Boletín Médico del - Hospital Infantil de México Federico Gómez

Boletín Médico del
ISSN-1665-1146

EDITORIAL
249 Thoracoscopy using ultrasonic scalpel: importance in the etiologic study of interstitial lung disease in children
Luis Jasso Gutiérrez
REVIEW ARTICLE
251 Efficacy and safety of omega 3 and omega 6 fatty acid supplementation in developmental neurological
disorders: systematic review
Antonio Calderón-Moore, Mariel Pizarro-Castellanos, Antonio Rizzoli-Córdoba
RESEARCH ARTICLES
257 Use of ultrasonic scalpel for pulmonary biopsy through thoracoscopy in pediatric patients with interstitial lung
disease
Ricardo Villalpando Canchola, Esmeralda Piedra Buena Muñoz, Isis Beatriz Medel Morales, Edgar Morales Juvera, Gabriel Reyes
García, Fortino Solórzano Santos
262 Risk factors associated with retinopathy of prematurity in preterm infants treated at a tertiary level hospital
Yolanda Vázquez Lara, Juan Carlos Bravo Ortiz, Claudia Hernández Galván, Narlly del Carmen Ruíz Quintero, Carlos Augusto
Soriano Beltrán
268 Association of steroid use with weight gain in pediatric patients with rheumatic disease
Sonia González-Muñiz, Donají Miranda-González, Miguel Ángel Villasís-Keever, Vicente Baca-Ruíz, Teresa Catalán-Sánchez,
Patricia Yañez-Sánchez
275 Analysis of sociodemographic features of patients with end-stage chronic renal disease: differences in a 6-year
period
Guillermo Cantú, Graciela Rodríguez, Mercedes Luque-Coqui, Benjamín Romero, Saúl Valverde, Silvia Vargas, Alfonso Reyes-
López, Mara Medeiros
CASE REPORTS
280 Bronchial mucoepidermoid carcinoma: a rare tumor in children
Luis Hernández-Motiño, Yarisa Brizuela, Verónica Vizcarra, Rubén Cruz, Lourdes Jamaica, José Karam
284 Hermansky-Pudlak syndrome: variable clinical expression in two cases
Rogelio Paredes Aguilera, Norma López Santiago, Angélica Monsiváis Orozco, Daniel Carrasco Daza, José Luis Salazar-Bailón
CLINICOPATHOLOGICAL CASE
Boletín Médico del
Hospital Infantil de México
BIMONTHLY PUBLICATION
Vol. 69 July-August, 2012 No.4
CONTENTS
291 Newborn with hypoplastic left heart syndrome
Luis Alexis Arévalo-Salas, Sandrino José Fuentes Alfaro, Jorge Omar Osorio Díaz, Begoña Segura Stanford, Mario Perezpeña
Diazconti

TOPICS IN PEDIATRICS
298 Shaping a new strategy against B. pertussis: a public health problem in Mexico
Lorena Suárez Idueta, Ilse Herbas-Rocha, César Misael Gómez Altamirano, Vesta Richardson López-Collada
VITAL STATISTICS
305 Mortality due to drowning in children less than 15 years of age in Mexico, 1998-2010
Sonia B. Fernández-Cantón, Ana María Hernández Martínez, Ricardo Viguri Uribe
Boletín Médico del Hospital Infantil de México
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editorial
Thoracoscopy using ultrasonic scalpel: importance in the etiologic
study of interstitial lung disease in children
Dr. Luis Jasso Gutiérrez
Interstitial lung disease (ILD) may present itself in
children of any age. However, it is most frequent
during the first 2 years of life and has a mortality
rate of ∼30%. The principal causes are lung injuries or
problems in lung development which, in good measure,
explains its frequency at this age and does not occur
in children of other ages. In past years, identifying a
patient and establishing a specific diagnosis has been a
challenge for pulmonologists, radiologists and pediatric
pathologists as well as for neonatologists and internists. 1
Among the principal and most frequent causes are diffuse
developmental anomalies such as the case of congenital
alveolar dysplasia, disorders of lung growth as well as
chronic pulmonary disease of prematurity, pulmonary
interstitial glycogenosis, hyperplasia of neuroendocrine
cells of infancy, dysfunction of the alveolar surfactant T
and E, host disorders (such as infections, hypersensitivity
or aspiration), systemic diseases such as metabolic
disorders, and collagen or autoimmune disorders, among
others. Independent of the causes, ILD can affect, in ad-
Departamento de Evaluación y Análisis de Medicamentos, Hospital
Infantil de México Federico Gómez, México, D.F., México
Correspondence to:
Dr. Luis Jasso Gutiérrez
Jefe del Departamento de Evaluación y Análisis de Medicamentos
Hospital Infantil de México Federico Gómez
México, D.F., México
E-mail: ljasso@himfg.edu.mx
Received for publication: 8-27-12
Accepted for publication: 8-28-12
Vol. 69, July-August 2012
Bol Med Hosp Infant Mex 2012;69(4):249-250
dition to the interstitium, different compartments of the
lung such as airways, alveolar space, lymphatic channels
and pleura. For this reason, the term diffuse parenchymal
lung disease was coined. 2
From the clinical viewpoint, its common manifestations
are tachypnea, exercise intolerance, growth delay,
cyanosis, resting dyspnea and, dependent on the time of
evolution, Hippocratic fingers. After clinical suspicion and
according to each case, it is necessary to perform chest xray,
high-resolution computed tomography, bronchoscopy
(that may include bronchial washings for investigation
of microorganisms or for genetic analysis of its content),
pulmonary function tests and, when required, lung biopsy.
With respect to lung biopsy, in the article published in
the present number of Boletin Medico del Hospital Infantil
de Mexico (BMHIM) by Villalpando et al., five cases are
described in a retrospective series of children subjected
to lung biopsies using thoracoscopy with three working
ports and ultrasonic scalpel during a 12-month period. 3
According to the authors' description, at least in these five
cases the result was satisfactory. For this reason we believe
that this innovation with respect to other techniques used
in thoracoscopy is the safest due to scant bleeding and to
the effect of aerostasia (absence of air leak). Although
the results were satisfactory, it would be appropriate to
increase the size of the sample to verify the findings. Also,
the results could be compared with experiences of thoracoscopies
performed in children using other methods. 4
It should be mentioned that, for the general pediatrician,
minimally invasive thoracoscopy is not only useful for
lung biopsies but also for aortopexies, repair of congenital
diaphragmatic hernias, excision of bronchogenic cysts,
249

Luis Jasso Gutiérrez
and exploratory thoracotomy or ligatures of the ductus
arteriosus, among other important procedures. 5,6
REFERENCES
1. Deutsch GH, Young LR, Deterding RR, Fan LL, Dell SD, Bean
JA, et al. Diffuse lung disease in young children: application
of a novel classification scheme. Am J Respir Crit Care Med
2007;176:1120-1128.
2. Deterding RR. Infants and young children with children’s
interstitial lung disease. Pediatr Allergy Immunol Pulmonol
2010;23:25-31.
3. Villalpando CR, Piedra BME, Medel MIB, Morales JE, Reyes
GG, Solórzano SF. Uso del bisturí ultrasónico para la toma de
biopsias pulmonares por toracoscopia en pacientes pediátricos
con enfermedad pulmonar intersticial. Bol Med Hosp Infant
Mex 2012;69:257-261
4. Ponsky TA, Rothenberg SS. Thoracoscopic lung biopsy in
infants and children with endoloops allows smaller trocar
sites and discreet biopsies. J Laparoendosc Adv Surg Tech
A 2008;18:120-122.
5. Ponsky TD, Rothenberg S, Tsao KJ, Ostlie DJ, St Peter SD,
Holcomb GW. Thoracoscopy in children: is a chest tube
necessary? J Laparoendosc Adv Surg Tech A 2009;19(suppl
1):S23-S25.
6. Glüer S, Schwerk N, Reismann M, Metzelder ML, Nustede R,
Ure BM, et al. Thoracoscopic biopsy in children with diffuse
parenchymal lung disease. Pediatr Pulmonol 2008;43:992-996.
doi: 10.1002/ppul.20896.
250 Bol Med Hosp Infant Mex

eview article
Efficacy and safety of omega 3 and omega 6 fatty acid supplementation
in developmental neurological disorders: systematic review
Antonio Calderón-Moore 1 , Mariel Pizarro-Castellanos 2 , Antonio Rizzoli-Córdoba 3
AbSTRACT
Vol. 69, July-August 2012
Bol Med Hosp Infant Mex 2012;69(4):251-256
background. Available information on clinical guidelines and review articles is controversial and is insufficient to determine the clinical
efficacy of supplementation with omega 3 and omega 6 fatty acids in neurodevelopmental disorders. Additional treatment may be effective
for treatment of these disorders.
methods. We conducted a systematic review based on the guidelines of the Cochrane group by searching for clinical trials in MEDLINE,
COCHRANE DATABASE in the time interval 1990 to 2011, in English and Spanish, and in pediatric patients that comply with the information
required by the CONSORT group. One hundred and two articles were obtained; 97 articles were excluded choosing five randomized,
double-blind, placebo-controlled trials to perform the review.
Results. In the trials analyzed we found no significant difference in the improvement of ADHD symptoms between placebo group and the
intervention, but there was clear clinical improvement. No serious adverse events were reported. There are no similar characteristics in
the reviewed articles to carry out a meta-analysis and accurate assessment of the effectiveness of supplementation.
Conclusions. With the results of this systematic review, we cannot state categorically that the use of this supplementation is significantly
effective due to the different characteristics of the studies described above. However, due to clinical improvement and adequate safety
profile, it may be useful without replacing pharmacological treatment.
Key words: essential fatty acids, omega 3, omega 6, attention deficit disorder.
INTRODuCTION
According to the Diagnostic and Statistical Manual
of Mental Disorders (DSM-IV), neurodevelopmental
disorders are classified in Axis I, which are the clinical
disorders that do not involve a syndrome. Among
these are the Attention Deficit Hyperactivity Disorder
(ADHD) and Developmental Coordination Disorder
(DCD). 1 Characteristics of attention deficit disorders are
mismatching, inattention and impulsivity–hyperactivity.
1 Departamento de Pediatría,
2 Departamento de Neurología Pediátrica,
3 Dirección de Investigación, Hospital Infantil de México Federico
Gómez, México, D.F., México
Correspondence: Dr. Antonio Rizzoli-Córdoba
Dirección de Investigación
Hospital Infantil de México Federico Gómez
México, D.F., México
E-mail: antoniorizzoli@hotmail.com
Received for publication: 2-2-12
Accepted for publication: 4-17-12
The recommended treatment options for ADHD include
pharmacological therapy with and without stimulant
medications, and nonpharmacological treatment, mainly
behavioral therapy. 2 The base treatment for DCD consists
of the acquisition of skills and problem solving, although
there is no established pharmacological treatment for this
disorder. Essential long-chain fatty acids are those that
the body cannot synthesize or are synthesized in small
amounts, so there is a need for dietary supplementation
to meet the metabolic functions that they perform such as
forming an important part of the cell membrane.
At present, according to the French Agency for Food
Sanitary Safety (AFSSA), the diet in developed countries
provides sufficient concentrations of omega 6 and very low
omega 3, with an omega 6/omega 3 ratio insufficient for
the proper functioning of neuroconduction. 3
Long-chain polyunsatured fatty acids (LC-PUFAs)
are metabolically very active. The highest concentrations
of these are found in the central nervous system (CNS),
predominantly in the neuronal membranes. The most
abundant is docosahexaenoic acid (DHA), which mainly
participates in neuronal synapses where it intervenes in
251

Antonio Calderón-Moore, Mariel Pizarro-Castellanos, Antonio Rizzoli-Córdoba
neuronal signaling and formation of neurotransmitters,
increasing neuronal permeability through the activation of
sodium channels, and eicosapentaenoic acid (EPA), which
is the precursor of DHA and an important activator of metabolism
in the CNS. In addition, it favors the generation
of eicosanoids and cytokines. 4 The relationship between
LC-PUFA deficiency and hyperactivity was initially proposed
by Colquhoun and Bunday. 5 In 1995, Stevens et al.
suggested a link between the deficiency of omega 3 and
omega 6 and ADHD, learning disabilities, reading disorders,
dyspraxia and ADHD-related symptoms. 6,7
In most neurodevelopmental disorders, first-line treatment
is pharmacological. However, up to 20% of the
patients with ADHD with pharmacological therapy have
side effects that hinder its effects, causing distrust in
parents over their use and resulting in treatment discontinuation.
As mentioned previously, DCD patients have
no established drug treatment.
It has been suggested that supplementation with omega
3 and omega 6 can function as an additional treatment to
those treatments already established, for improvement of
the clinical status of patients with ADHD and DCD.
Some authors have suggested that children with ADHD,
with and without a learning problem, respond differently
to fatty acid supplementation. A higher response was observed
in those children with learning disabilities. 8 It has
even been suggested that some combinations of omega 3,
omega 6, zinc and magnesium may be beneficial for these
patients. Huss et al. suggested that these combinations
have beneficial effects on attention and on behavioral and
emotional problems in children and adolescents with this
type of disorder. 9 There are research groups who have
reported that there is no hard evidence to justify this type
of supplement; therefore, they do not recommend omega
3 and omega 6 as adjuvant treatment options for ADHD. 10
Information available in clinical guidelines and review
articles are controversial and insufficient. Therefore, the
objective of this review was to assess the available information
on the efficacy and safety of supplementation with
omega 3 and omega 6 for neurodevelopmental disorders
using a systematic review of the literature.
mATERIALS AND mETHODS
A systematic review was conducted based on the guidelines
of the Cochrane systematic reviews, 11 in Medline/
PubMed database, Cochrane Database and Artemis, and
references of retrieved articles published between 1990
and 2011. The search was limited to clinical trials conducted
in English and Spanish by a pediatric group. Studies
were randomized and double-blind comparison was made
between administration of essential fatty acids and placebo
administration, which evaluate the clinical efficacy as well
as safety of the intervention described. We sought clinical
trials that complied with the required information in the
articles of clinical trials, developed by the CONSORT
Group (Consolidated Standards of Reporting Trials) in
2010. 12 From the research done by two reviewers, 102
articles were obtained. Of these, we selected five clinical
trials that met the requirements established initially to
perform the review.
RESuLTS
The design of the five articles analyzed was randomized,
double-blind, placebo-controlled clinical trials (Table
1). 3,7,13-15 In four of the five articles, the effect of fatty acid
supplementation in children with ADHD and symptoms
related to it was analyzed, whereas one study examined
the effect on children diagnosed with DCD. Interventions
performed, supplement given, doses and time of administration
were different in all studies, ranging from 2–6
months (Table 1).
To evaluate the effectiveness of the supplement, the
methods and scales used in the articles were diverse. No
significant difference was found in improving ADHD
symptoms between the placebo group and interventional
group (Table 2). However, when assessing the clinical
response in the intervention group, significant clinical
improvement was found. Because this improvement was
so significant, parents decided to continue with the PU-
EFAs supplement after study completion.
In the study conducted by Sinn et al. where a combination
of EPA, DHA, γ-linolenic acid and vitamin E
(558 mg of EPA + 174 mg of DHA + 60 mg γ-LA + 10.8
mg of vitamin E daily, for 15 weeks) was administered,
a statistically significant difference was demonstrated
between groups (supplement and placebo) in the Conners
test for parents, with improvement of more than one
standard deviation (SD) in 30 to 40% of children. In the
second phase, the same intervention was performed in both
groups and clinical improvement was found in Conners
252 Bol Med Hosp Infant Mex

Efficacy and safety of omega 3 and omega 6 fatty acid supplementation in developmental neurological disorders: systematic review
Table 1. Differences between type of supplement, dose and time of administration
Author (year) Intervention Dose (per day) Time of administration
Sinn, et al (2007) 7 EPA + DHA + GLA + Vit E 558 mg EPA + 174 mg DHA + Two periods, one of 15 and another of
60 mg GLA + 10.8mg Vit E 30 weeks
Jonhson, et al (2008) 13 EPA + DHA + GLA + Vit E 558 mg EPA + 174 mg DHA +
60 mg GLA + 10.8 mg Vit E
Two periods, each of 3 months
Hirayama, et al (2004) 14 DHA + EPA 100 mg EPA
+ 514 mg DHA
One period of 2 months
Voigt, et al (2001) 15 DHA 345 mg DHA One period of 4 months
Richardson, et al (2005) 3 EPA + DHA + GLA + Vit E 558 mg EPA + 174 mg DHA + Two periods, each of 3 months
(en DCD)
60 mg GLA + 9.6 mg Vit E
EPA, eicosapentaenoic acid; DHA, docosahexaenoic acid; GLA, gamma-linoleic acid; Vit E, vitamin E; DCD, developmental coordination
disorder.
test in all groups with supplement, with a decrease of >1
SD in 40 to 50% of the children. However, no significant
difference was observed in the Conners test given to the
teachers. 7 Likewise, Johnson et al. found a favorable
clinical response (not statistically significant) in the subgroup
of patients with predominantly inattentive ADHD
(26%). This group showed a reduction in symptoms of
50% in their
symptoms. 13 Upon analyzing the safety of administration
of the supplementation, no adverse effects were reported.
Adverse effects were observed only in the gastrointestinal
system (diarrhea and dyspepsia) in three patients, with no
clinical compromise.
DISCuSSION
As discussed above, there are no similar features in the analyzed
studies to perform a meta-analysis and an accurate
assessment of the effectiveness of supplementation with
LC-EPAs, omega 3 and omega 6 in neurodevelopmental
disorders.
The articles reviewed showed a wide age range (6–18
years). The supplement with which the intervention was
made, its dose and time of administration ranged from 2
to 6 months. Methods of evaluation of the efficacy were
diverse. This does not allow us to compare results between
studies or to measure the effectiveness of the supplement
used.
Vol. 69, July-August 2012
Although no statistically significant differences were
found in the articles that evaluated the effectiveness of the
supplement in ADHD patients, between the intervention
group and the placebo group, there was obvious clinical
improvement, mainly in the areas of hyperactivity/impulsivity,
inattention and coordination disorders.
The combination most used and recommended for
improvement of symptoms of ADHD is essential polyunsaturated
fatty acids omega 3 (EPA, DHA) and omega 6
(arachidonic acid and γ-LA). The most commonly used
dose is 558 mg of EPA + 174 mg of DHA + 60 mg γ-LA
+ 10.8 mg vitamin E/day.
Clinical improvement observed in the areas of hyperactivity/impulsivity,
inattention and coordination disorders,
although not statistically significant, was sufficient to
encourage parents to continue with the treatment of
supplemental essential long-chain fatty acids, omega-3
and omega 6, even after completion of studies. This is
coupled with its safety and no significant adverse effects.
Based on the results of this systematic review, we cannot
categorically state that supplementation with essential
long-chain fatty acids of omega 3 and omega 6 in neurodevelopmental
disorders present significant efficacy due
to the different characteristics of the previously described
studies. Although only statistically significant differences
were shown in reading and spelling skills in the placebo
group and the supplement group, it is suggested, for clinical
improvement in other aspects such as hyperactivity/
impulsivity and inattention, the possibility of supplementing
with omega 3 essential fatty acids and omega 6
when these symptoms predominate in the patient. For this
reason, and an appropriate safety profile, the treatment
may be useful in children with ADHD and DCD with the
253

Antonio Calderón-Moore, Mariel Pizarro-Castellanos, Antonio Rizzoli-Córdoba
Table 2. Description of analyzed studies
Author (year) Population Groups Intervention Evaluation Results
Sinn (2007) 7
ADHD
Voigt (2001) 15
ADHD
n=104
n=87
n= 54
Hirayama (2004) 14
ADHD n=40
Johnson (2008) 13
ADHD
n=75
PUFA +
MVM n=41
PUFA
n=36
Placebo
n=27
PUFA +
MVM
DHA
n=27
Placebo
n=27
DHA
n=20
Placebo
n=20
PUFA
n=37
Placebo
n=38
n=59 AGPI
558 mg EPA + 174
mg DHA + 60 mg
GLA + 10.8 mg vit E/
day + MVM
558 mg EPA + 174
mg DHA + 60 mg
GLA + 10.8 mg vit
E/day
First stage (15 weeks)
Improvement in inattention, impulsivity,
Conners scale, parents and hyperactivity in >1 SD in 30-40% of
children
Conners scale, teachers Without significant improvement
Improvement in inattention, impulsivity
Conners scale, parents and hyperactivity in >1 SD in 30-40% of
children
Conners scale, teachers Without significant improvement
Placebo Conners scale Without significant improvement
Second stage (30 weeks)
558 mg EPA + 174
mg DHA + 60 mg
Conners scale, parents
GLA + 10.8 mg vit E/
day +MVM
345 mg/day DHA for
4 months
Placebo
3,600 mg DHA+700
mg EPA/week for 2
months
Olive oil
558 mg EPA + 174
mg DHA/day, 60 mg
GLA, 10.8 mg Vit E
Olive oil
558 mg EPA + 174
mg DHA/day, 60 mg
GLA, 10.8 mg Vit E
TOVA (omission/
commission)
Improvement of 40-50% of patients in
regard to symptoms of inattention and
hyperactivity/impulsivity
Increase of 3 SD in errors of omission,
decrease of 1 SD in errors of commission,
time of response with increase of 2
SD (NS)
254 Bol Med Hosp Infant Mex
CCTT
Decrease of time of carrying out test 1 of
2 SD and of 3 SD in test 2 (NS)
Decrease in internalization of 2 SD,
outside behavior of 2 SD, socialization
CBCL
of 3 SD, thought processes of 2 SD,
inattention 1.5 SD (NS)
Conners No results shown (NS)
Attention No results shown (NS)
Auditory and visual
memory
Without increase in number of remembered
objects
Visuomotor integration Increase of 9 points in regard to normal age
Continuity
Without changes in errors of omission or
commission
Impatient Decrease of number of errors in 1
First stage (3 months)
26% presented >25% reduction in score
ADHD-RS-IV
and 12% presented >50% reduction in
score
ADHD-RS-IV 7% presented >25% improvement in
score
Second stage (3 months)
TDAH-RS-IV 47% improved their score and of these,
12% improved in >50% of symptoms

Efficacy and safety of omega 3 and omega 6 fatty acid supplementation in developmental neurological disorders: systematic review
Table 2. Description of analyzed studies
Author (year) Population Groups Intervention Evaluation Results
Richardson (2005) 3
DCD
n= 117
Vol. 69, July-August 2012
PUFA
n=60
Placebo
n=57
n=100
558 mg EPA + 174
mg DHA + 60 mg
GLA + 9.6 mg Vit E
Olive oil
558 mg EPA + 174
mg DHA + 60 mg
GLA + 9.6 mg Vit E
First stage (3 months)
Motor function (MABC)
Reading and spelling
(WORD)
ADH symptoms
teachers
CTRS-L
Increase of score from 6th to 12th percentile
(NS)
Increase in 1 SD in writing (z = 2.87, p

Antonio Calderón-Moore, Mariel Pizarro-Castellanos, Antonio Rizzoli-Córdoba
10. Aben A, Danckaerts M. Omega-3 and omega-6 fatty acids in
the treatment of children and adolescents with ADHD. Tijdschr
Psychiatr 2010;52:89-97.
11. Davey J, Turner RM, Clarke MJ, Higgins JP. Characteristics
of meta-analyses and their component studies in the Cochrane
Database of Systematic Reviews: a cross-sectional,
descriptive analysis. BMC Med Res Methodol 2011;11:160.
doi:10.1186/1471-2288-11-160.
12. Schulz K, Altman DG, Moher D, for the CONSORT Group.
CONSORT 2010 Statement: updated guidelines for reporting
parallel group randomised trials. PLoS Med 2010;7:e1000251.
doi:10.1371/journal.pmed.1000251.
13. Johnson M, Ostlund S, Fransson G, Kadesjo B, Gillberg C.
Omega-3/omega-6 fatty acids for attention deficit hyperactivity
disorder: a randomized placebo-controlled trial in children and
adolescents. J Atten Disord 2009;12:394-401.
14. Hirayama S, Hamazaki T, Terasawa K. Effect of docosahexaenoic
acid-containing food administration on symptoms of
attention-deficit/hyperactivity-disorder—a placebo-controlled
double-blind study. Eur J Clin Nutr 2004;58:467-473.
15. Voigt RG, Llorente AM, Jensen CL, Fraley JK, Berreta MC,
Heird WC. A randomized, double-blind, placebo-controlled trial
of docosahexanoic acid supplementation in children with attention-deficit/hyperactivity
disorder. J Pediatr 2001;139:189-196.
256 Bol Med Hosp Infant Mex

esearch article
use of ultrasonic scalpel for pulmonary biopsy through thoracoscopy in
pediatric patients with interstitial lung disease
Vol. 69, July-August 2012
Bol Med Hosp Infant Mex 2012;69(4):257-261
Ricardo Villalpando Canchola, 1 Esmeralda Piedra Buena Muñoz, 2 Isis Beatriz Medel Morales, 2
Edgar Morales Juvera, 3 Gabriel Reyes García, 4 Fortino Solórzano Santos 5
AbSTRACT
background. Diagnosis of interstitial lung disease (ILD) in children is challenging. Open lung biopsy was long considered to be the best
procedure to obtain lung tissue in children. Thoracoscopic biopsy may be equally effective and less aggressive. In this report we analyze
the results of the use of ultrasonic scalpel with the placement of three 5-mm trocars (one for thoracoscope and two working ports) for lung
biopsy through thoracoscopy.
methods. We present a retrospective case series of children undergoing lung biopsy through thoracoscopy using three working ports and
ultrasonic scalpel. The study was carried out from January 2011 to January 2012 in a third-level pediatric hospital.
Results. A total of five patients aged 1 to 13 years were included. There were no complications in the five cases analyzed. The sample obtained
was sufficient in all cases for histopathological study. During surgery, bleeding was reported on average of 4.3 ml (range: 0.5–10 ml).
Operative time ranged from 2 to 3 h. Two cases required chest tube placement. These were removed 2 to 3 days after the surgical event,
and patients were discharged without complications.
Conclusions. Feasibility is confirmed of a technique for lung biopsy using an ultrasonic scalpel, which is easily reproducible in any hospital
with the necessary resources to perform thoracoscopy. In this series there were no complications, bleeding was low and there was
opportune placement of transpleural chest tube.
Key words: lung biopsy, ultrasonic scalpel, interstitial lung disease.
INTRODuCTION
Diagnosis of interstitial lung disease (ILD) in infancy
constitutes a real challenge for the pediatrician.1 Within
the term ILD, a very heterogeneous group of subacute and
chronic lung diseases are grouped that share in common the
production of chronic inflammatory process with a diffuse
1 Cirugía de Tórax,
2 Residente de Cirugía Pediátrica,
3 Servicio de Urología,
4 Servicio de Gastrocirugía,
5 Pediatría Médica, Unidad Médica de Alta Especialidad Hospital
de Pediatría, Centro Médico Nacional Siglo XXI, Instituto Mexicano
del Seguro Social, México D.F., México
Correspondence: Dr. Ricardo Villalpando Canchola
Cirugía de Tórax, Unidad Médica de Alta Especialidad
Hospital de Pediatría, Centro Médico Nacional Siglo XXI
Instituto Mexicano del Seguro Social
México D.F., México
E-mail: drricvillalpando@me.com
Received for publication: 5-24-12
Accepted for publication: 6-12-12
lesion of the lung parenchyma, affecting the interstitium,
epithelium, alveolar spaces and capillary endothelium.
Because the interstitium is not affected alone, and the term
pulmonary interstitial disease can cause some confusion,
some authors prefer to refer to these groups as diffuse
parenchymatous lung disease. 2 The clinical picture is
predominantly characterized by tachypnea, hypoxia and
diffuse pulmonary infiltrates. Other pathologies also are
taken into consideration for the differential diagnosis such
as some infections, chronic aspiration, some cardiac diseases
and pulmonary vascular disease. 3 ILD is less frequent
in children than in adults, but with higher comorbidities
and mortality.4,5 By the time of development, it can be
defined as either acute or chronic (lasting >6 months), and
of known cause, unknown (idiopathic) or associated with
other processes.
From the histopathological point of view, the most
widely used classification is based on the predominant cell
type involved in thickening of the alveolar wall, so it can
be usual interstitial pneumonia, desquamative interstitial
pneumonia, giant cell interstitial pneumonia, plasma cell
interstitial pneumonia, interstitial lymphoid pneumonia or
257

Ricardo Villalpando Canchola, Esmeralda Piedra Buena Muñoz, Isis Beatriz Medel Morales, Edgar Morales Juvera, Gabriel Reyes García,
Fortino Solórzano Santos
bronchiolitis obliterans with interstitial pneumonia. The
histological appearance of usual interstitial pneumonia is
large heterogeneous lesions from alveolar inflammation
to diffuse interstitial fibrosis. During lung biopsy (LB),
lesions may be seen in various stages of development
with other areas of apparently healthy lung. It is very
rare in children; therefore, many of the cases would be
7, 8
diagnosed today as nonspecific interstitial pneumonitis.
Desquamative interstitial pneumonitis is characterized
by an inflammatory process, initially homogeneous, and
with abundant intraalveolar macrophage. This disease,
although rare, is well characterized in children. Most
cases have been reported in children

Vol. 69, July-August 2012
Use of ultrasonic scalpel for pulmonary biopsy through thoracoscopy in pediatric patients with interstitial lung disease
Figure 1. Tissue obtained with thorascopic grasper.
Figure 2. Cut with ultrasonic scalpel.
RESuLTS
Included in the analysis were five patients with a median
age of 9 years (1–13 years). No cases presented intra- or
postoperative complications. The material obtained from
the biopsy was considered sufficient in all cases by the
pathology department (Figure 3). Perioperative bleeding
was at minimum 0.5 ml and at maximum 10 ml. Median
operative time was 2 h 15 min (range: 2–3 h). In two of
the cases, placement of a chest tube was required, which
was removed after 2 days in one patient and 3 days after
surgery in the other patient. In all cases, therapeutic behavior
was modified in accordance with the histopathological
report of the LB (Table 1). One case presented neoplastic
disease. The remaining four were of infectious etiology.
Figure 3. Final sampling of the biopsied pulmonary tissue without
evidence of residual bleeding.
DISCuSSION
Obtaining an LB was a procedure that was considered to
be invasive for many years and remained as a last resort.
However, it is recognized that with LB the etiology, extent,
severity and aggressiveness of disease can be verified. 24
LB is carried out at the end of a sequence of decisions and
diagnostic procedures, not as the first choice. However,
in many instances, this has as a consequence a delayed
diagnosis and treatment, which may further deteriorate
the patient’s prognosis. 25
It is believed that in order to have a useful biopsy, the
tissue must be representative of the problem it seeks to
explore. The ideal situation is a biopsy performed by an
experienced thoracic surgeon who is familiar with the
patient and is aware of the diagnostic possibilities. Hence,
the surgeon’s experience during intraoperative lung evaluation
and of the possible pathological processes involved
will permit the surgeon to obtain tissue representative in
quality and quantity, without incipient or advanced alterations
that result in being nonspecific. This will allow
for an appropriate diagnosis to be made from the tissue
obtained. Also, it will be able to be determined at which
time tissue can be provided for cultures or special studies.
LB does not tend to be a procedure that allows for repetitions.
Therefore, perhaps more than other tissues obtained
for biopsy, it is of particular importance that the tissues
be managed carefully and appropriate measures used to
optimize their informative value. 26
For a long time, open LB was considered to be a major
procedure to obtain lung tissue in children. Contraindica-
259

Ricardo Villalpando Canchola, Esmeralda Piedra Buena Muñoz, Isis Beatriz Medel Morales, Edgar Morales Juvera, Gabriel Reyes García,
Fortino Solórzano Santos
Table 1. General characteristics of pediatric patients subjected to pulmonary biopsy with thorascopy using ultrasonic scalpel
Case Age
(years)
Complications Sufficient
sample
Bleeding
(ml)
tions for open LB via thoracotomy are essentially surgical.
The patient must be in optimal clinical and laboratory
condition to be able to cope with the surgical procedure
with the least possible risk. 20 Transbronchial LB is a
procedure that, up to a certain point, is considered blind
and with a greater risk of complications. Indication for a
transbronchial biopsy is geared for the most part towards
infectious and acute processes and is contraindicated in
chronic interstitial diseases as its discriminatory value
in these situations is limited. The usefulness of a transbronchial
biopsy in young children is debatable due to
the reduced size of the sample obtained because, in most
cases, it is insufficient to establish a diagnosis. In a study
in which percutaneous needle biopsies with an 18-gauge
needle guided by high-resolution CT were used, histological
diagnosis was achieved in only 58% of the cases. 23,27
In pediatrics, LB is a standard diagnostic method for
ILD. At present there is the possibility of offering the
patient the thoracoscopic procedure, which carries the
basic principles and benefits that endoscopic surgery
has demonstrated during the last decades. With respect
to surgical technique, the current reports encourage the
practice of obtaining biopsies by means of pre-knotted
loops (Endoloop) or mechanical sutures (stapler) with the
disadvantage of displacement of the pre-knotted loop when
the lung is re-expanded or the size of the stapler, which
makes it inadequate for pediatric patients. 28
Based on the results of the five cases reported, it is
considered that the technique described in this study is
the safest because of the small amount of bleeding and
the effect of the aerostasia (no air leak) with the use of the
described instrument. In these cases, placement of chest
tube is optional. If placed, it should always be removed
within

Vol. 69, July-August 2012
Use of ultrasonic scalpel for pulmonary biopsy through thoracoscopy in pediatric patients with interstitial lung disease
10. Whitsett JA, Wert SE, Weaver TE. Alveolar surfactant homeostasis
and the pathogenesis of pulmonary disease. Annu Rev
Med 2010;61:105-119.
11. Katzenstein AL, Gordon LP, Oliphant M, Swender PT.
Chronic pneumonitis of infancy. A unique form of interstitial
lung disease occurring in early childhood. Am J Surg Pathol
1995;19:439-447.
12. Copley SJ, Coren M, Nicholson AG, Rubens MB, Bush A,
Hansell DM. Diagnostic accuracy of thin-section CT and chest
radiography of pediatric interstitial lung disease. AJR Am J
Roentgenol 2000;174:549-554.
13. Koh DM, Hansell DM. Computed tomography of diffuse interstitial
lung disease in children. Clin Radiol 2000;55:659-667.
14. Bokulic RE, Hilman BC. Interstitial lung disease in children.
Pediatr Clin North Am 1994;41:543-567.
15. Redding GJ, Fan LL. Idiopathic pulmonary fibrosis and lymphocytic
interstitial pneumonia. In: Taussig LM, Landau LI,
eds. Pediatric Respiratory Medicine. St. Louis: Mosby; 1999.
pp. 794-804.
16. Chollet S, Soler P, Dournovo P, Richard MS, Ferrans VJ, Basset
F. Diagnosis of pulmonary histiocytosis X by immunodetection
of Langerhans cells in bronchoalveolar lavage fluid. Am J
Pathol 1984;115:225-232.
17. Martin RJ, Coalson JJ, Rogers RM, Horton FO, Manous LE.
Pulmonary alveolar proteinosis: the diagnosis by segmental
lavage. Am Rev Respir Dis 1980;121:819-825.
18. Fan LL, Lung MC, Wagener JS. The diagnostic value of
bronchoalveolar lavage in immunocompetent children with
chronic diffuse pulmonary infiltrates. Pediatr Pulmonol
1997;23:8-13.
19. Fan LL, Kozinetz CA, Deterding RR, Brugman SM. Evaluation
of a diagnostic approach to pediatric interstitial lung disease.
Pediatrics 1998;101:82-85.
20. Coren ME, Nicholson AG, Goldstraw P, Rosenthal M, Bush A.
Open lung biopsy for diffuse interstitial lung disease in children.
Eur Respir J 1999;14:817-821.
21. Hilman BC, Amaro-Galvez R. Diagnosis of interstitial lung
disease in children. Paediatr Respir Rev 2004;5:101-107.
22. Rothenberg SS, Wagner JS, Chang JH, Fan LL. The safety
and efficacy of thoracoscopic lung biopsy for diagnosis and
treatment in infants and children. J Pediatr Surg 1996;31:100-
103; discussion: 103-104.
23. Spencer DA, Alton HM, Raafat F, Weller PH. Combined percutaneous
lung biopsy and high-resolution computed tomography
in the diagnosis and management of lung disease in children.
Pediatr Pulmonol 1996;22:111-116.
24. Katzenstein AL, Fiorelli RF. Nonspecific interstitial pneumonia/
fibrosis. Histologic features and clinical significance. Am J Surg
Pathol 1994;18:136-147.
25. Dishop MK, Askin FB, Galambos C, White FV, Deterding RR,
Young LR, et al, for the chILD Network. Classification of diffuse
lung disease in older children and adolescents: a multiinstitutional
study of the Children’s Interstitial Lung Disease
(chILD) pathology working group. Mod Pathol 2007;2:2878.
26. Leslie KO, Viggiano RW, Trastek VF. Optimal processing of
diagnostic lung specimens. In: Leslie KO, Wick MR, eds. Practical
Pulmonary Pathology. A Diagnostic Approach. Philadelphia:
Churchill Livingstone; 2005. pp. 19-32.
27. Langston D, Patterson K, Dishop MK, chILD Pathology Co-operative
Group. A protocol for the handling of tissue obtained by
operative lung biopsy: recommendations of the chILD pathology
co-operative group. Pediatr Dev Pathol 2006;9:173-180.
28. Ponsky TA, Rothenberg SS. Thoracoscopic lung biopsy in
infants and children with endoloops allows smaller trocar
sites and discreet biopsies. J Laparoendosc Adv Surg Tech
A 2008;18:120-122.
261

esearch article
Bol Med Hosp Infant Mex 2012;69(4):262-267
Risk factors associated with retinopathy of prematurity in preterm
infants treated at a tertiary level hospital
Yolanda Vázquez Lara, 1 Juan Carlos Bravo Ortiz, 1 Claudia Hernández Galván, 1 Narlly del Carmen Ruíz
Quintero, 2 Carlos Augusto Soriano Beltrán 1
AbSTRACT
background. Retinopathy of prematurity (ROP) is defined as a peripheral proliferative vitreoretinopathy in which immaturity (determined
by gestational age and birth weight) and oxygen are more decisive factors. We undertook this study to analyze the relative risk for development
of ROP in relation to gestational age and birth weight in infants.
methods. We carried out a retrospective, analytical, cross-sectional, single center trial in preterm infants with a gestational age

PATIENTS AND mETHODS
Vol. 69, July-August 2012
Risk factors associated with retinopathy of prematurity in preterm infants treated at a tertiary level hospital
We conducted a retrospective, observational, descriptive,
cross-sectional, unicentric and open study of premature
newborns with a gestational age

Yolanda Vázquez Lara, Juan Carlos Bravo Ortiz, Claudia Hernández Galván, Narlly del Carmen Ruíz Quintero, Carlos Augusto Soriano
Beltrán
Table 1. International classification of PROP
Stage
• Stage 1. Line of demarcation: a fine white line that separates the vascular from the avascular retina
• Stage 2. Elevated ridge: line of demarcation that appears in stage I increases in volume and extends outside the plane of
the retina
• Stage 3.Increase in vascular tissue towards the vitreous space
• Stage 4. Subtotal retinal detachment—subdivided into 4A if the macula is attached and 4B if the macula is detached
• Stage 5. Total retinal detachment
• Disease “plus”. Refers to dilatation and tortuosity of the vessels of the posterior pole and indicates that there is activity—can
present in any stage of retinopathy
• Baseline retinopathy. Five continuous or 8 total clock hours of disease with a stage 3 “plus” in zone 1 or 2
Localization
• Zone 1. Circle whose radius is two times the distance between the papila and the fovea
• Zone 2. Comprises a band of retina from the limits of zone 1 up to the ora serrate nasally in the horizontal meridian
• Zone 3. The remaining semilunar space, outside zone 2
Extension
Extension of the retinopathy is described in clock sectors
ROP, retinopathy of prematurity.
Figure 1. Representation of the retina in hourly sectors and divided
according to zones.
In our population, 59.09% of all premature NB weighing
from 751-1,000 g developed ROP. The rest of the
sample population, depending on weight, had a relatively
lower risk of developing ROP as birth weight increased.
The factors that were related with a greater risk of developing
ROP were oxygen with a 1.30 times greater risk of
developing ROP, mechanical ventilation with 1.65 times
greater risk, pulmonary bronchodysplasia with a 1.60
times greater risk and sepsis with 1.27 times greater risk
of developing ROP. All these values were statistically
significant. The remaining factors analyzed did not present
a significant risk but should be followed up.
DISCuSSION
ROP is a peripheral proliferative vitreoretinopathy that
develops in premature children and in its most serious
forms can cause blindness. Survival of premature infants
has increased in the last decade; however, despite this it
appears that the prevalence of ROP has decreased. 17,18 It is
essential to use screening systems to detect all of cases of
severe newborn ROP and adapt them to the changes that
are present in the epidemiology of the disease.
It is difficult to try to unify the criteria regarding the
incidence of ROP among different populations because
different variables can influence the results such as immaturity
and the survival rate as well as the race of the
patients studied. 17,19,20
The incidence of ROP in this study was 36.9%, similar
to that observed by Bossi and Koerner 21 and Pallás et
al. 22 who found an incidence between 25 and 35%. In a
comparative study, Blair et al. 23 reported an incidence of
36.1% and in the UK an incidence of ROP was reported
in general as 31.2%. 12
However, our study showed an incidence less than
that found in the studies by Holmström et al., Palmer et
al. and Párraga et al. who reported incidences of between
40 and 60%. 24-26
In the study performed between 2000 and 2002 by the
Early Treatment for Retinopathy of Prematurity Coopera-
264 Bol Med Hosp Infant Mex

Vol. 69, July-August 2012
Risk factors associated with retinopathy of prematurity in preterm infants treated at a tertiary level hospital
Table 2. Evaluation of risk of ROP in accordance with gestational age
Gestational
age (weeks)
Without
ROP
With ROP Total RR (p) Incidence
(%)
24-25 2 0 2 — —
26-27 10 14 24 1.65
(0.008)*
58.33
28-29 33 59 92 2.37
(0.0005)*
64.13
30-31 71 29 100 0.72
(0.063)
29.00
32-33 75 23 98 0.55
(0.003)*
23.46
34-35 24 2 26 0.196
(0.017)*
7.6
≥36 2 0 2 — —
Total 217 127 344 — —
ROP: retinopathy of prematurity; RR: risk factor.
*p value statistically significant
Table 3. Evaluation of ROP risk with regard to weight
Weight (g) Without
ROP
With ROP RR Incidence (%)
501-750 4 6 1.65
(0.0600)
60
751-1,000 27 39 1.86
(0.0005)*
59.09
1,001-1,250 57 55 1.58
(0.001)*
49.10
1,251-1,500 87 25 0.508
(0.0005)*
22.32
1,501-1,750 40 2 0.115
(0.002)*
4.76
1,751-2,000 0 0 — —
>2,000 2 0 — —
Total 217 127 — —
ROP, retinopathy of prematurity; RR, relative risk.
*p value statistically significant.
tive Group (ETROP), an incidence of 68% was reported,
which was similar to that reported by the CRYO-ROP
group in 1986 and 1987. 25,27 The number of patients studied
and the screening parameters are different between the different
studies analyzed, which make comparisons difficult.
Screening for ROP should not only take into account
gestational age and weight at birth, but should be enlarged
to include other patients whose perinatal disease predisposes
them to an elevated risk for developing ROP. Efficient
care now requires that children at high risk receive retinal
exams carefully synchronized by an experienced ophthalmologist
with experience in examinations of premature
NB with risk of retinopathy, and that all pediatricians who
care for these patients in risk situations be aware of the
need for early examination. 28
In developed countries such as the U.S. and UK, guidelines
for screening of these children have been established.
However, it must be kept in mind that each region could
have different parameters for screening due to the characteristics
of the patients and that management is different
in each region. These guidelines recommend screening
for children born 1500 g was only 4.76%, although it resulted
to be statistically significant even when compared with
22.32% corresponding to those patients who weighed

Yolanda Vázquez Lara, Juan Carlos Bravo Ortiz, Claudia Hernández Galván, Narlly del Carmen Ruíz Quintero, Carlos Augusto Soriano
Beltrán
ROP continues to be a leading cause of blindness in
children worldwide. A significant number of children who
develop ROP will have serious visual problems (14.5%)
and unfavorable structural problems (9.1%) despite ablative
treatment with laser or cryotherapy. 30,31
It is important to emphasize that ophthalmological
control of these patients should not be limited to the
diagnosis and management of retinopathy until it progresses
or until treatment is indicated. We must control
these children in the early years due to the greater incidence
of late refractive errors, strabismus and retinal
detachments. 32-35 Based on the results, we can conclude
that preterm infants with gestational age between 28 and
29 weeks have a risk of up to 2.37 greater of developing
ROP. In infants with birth weights of 751 to 1,000 g, the
risk is up to 1.6 times of developing ROP. Supplemental
oxygen, mechanical ventilation and sepsis are risk factors
of up to 1.6 times for the development of ROP in
premature NB.
REFERENCES
1. Terry T. Extreme prematurity and fibroblastic overgrowth of
persistent vascular sheath behind each crystalline lens. I.
Preliminary report. Am J Ophthalmol 1942;25:203-204.
2. Campbell K. Intensive oxygen therapy as a possible cause
for retrolental fibroplasia. A clinical approach. Med J Aust
1951;2:48-50.
3. Heath P. Pathology of the retinopathy of prematurity: retrolental
fibroplasia. Am J Ophthalmol 1951;34:1249-1259.
4. Kinsey VE, Hemphill FM. Etiology of retrolental fibroplasia and
preliminary report of cooperative study of retrolental fibroplasia.
Trans Am Acad Ophthalmol Otolaryngol 1955;59:15-24.
5. Gibson DL, Sheps SB, Uh SH, Schechter MT, McCormick
AQ. Retinopathy of prematurity-induced blindness: birth
weight-specific survival and the new epidemic. Pediatrics
1990;86:405-412.
6. Gilbert C, Fielder F, Gordillo L, Quinn G, Semiglia R, Visintin P,
et al; for the International NO-ROP Group. Characteristics of
infants with severe retinopathy of prematurity in countries with
low, moderate, and high levels of development: implications
for screening programs. Pediatrics 2005;115:e518-e525.
7. Gilbert CE, Foster A. Childhood blindness in the context of
VISION 2020—the right to sight. Bull WHO 2001;79:227-232.
8. Gilbert C, Rahi J, Eckstein M, O´Sullivan J, Foster A. Retinopathy
of prematurity in middle-income countries. Lancet
1997;350:12-14.
9. Zimmermann CJ, Fortes FJB, Tartarella MB, Zin A, Dorneles JI
Jr. Prevalence of retinopathy of prematurity in Latin America.
Clin Ophthalmol 2011:5 1687-1695.
10. Zepeda RLC, Gutiérrez PJA, De la Fuente TMA, Angulo CE,
Ramos PE, Quinn GE. Detection and treatment for retinopathy
of prematurity in Mexico: need for effective programs. J AAPOS
2008;12:225-226.
11. Steinkuller PG, Du L, Gilbert C, Foster A, Collins ML, Coats
DK. Childhood blindness. J AAPOS 1999;3:26-32.
12. Mathew MR, Fern AI, Hill R. Retinopathy of prematurity: are
we screening too many babies? Eye (Lond) 2002;16:538-542.
13. Holmström G, Broberger U, Thomassen P. Neonatal risk factors
for retinopathy of prematurity —a population-based study.
Acta Ophthalmol Scand 1998;76:204-207.
14. Olea JL, Corretger FJ, Salvat M, Frau E, Galiana C, Fiol M.
Factores de riesgo en la retinopatía del prematuro. An Esp
Pediatr 1997;47:172-176.
15. Cryotherapy for Retinopathy of Prematurity Cooperative Group.
Multicentre trial of cryotherapy for retinopathy of prematurity.
Preliminary results. Arch Ophthalmol 1988;106:471-479.
16. Early Treatment for Retinopathy of Prematurity Cooperative
Group. Revised indications for the treatment of retinopathy
of prematurity: results of the early treatment for retinopathy of
prematurity randomized trial. Arch Ophthalmol 2003;121:1684-
1694.
17. Lim J, Fong DS, Dang Y. Decreased prevalence of retinopathy
of prematurity in an inner-city hospital. Ophtalmic Sur Lasers
1999;30:12-16.
18. Termote J, Schalij-Delfos NE, Brouwers HAA, Donders ART,
Cats BP. New developments in neonatology: less severe
retinopathy of prematurity? J Pediatr Ophthalmol Strabismus
2000;37:142-148.
19. Ng YK, Fielder AR, Shaw DE, Levene MI. Epidemiology of
retinopathy of prematurity. Lancet 1988;2:1235-1238.
20. Hameed B, Shyamanur K, Kotecha S, Manktelow B, Woodruff
G, Draper ES, et al. Trends in the incidence of severe retinopathy
of prematurity in a geographically defined population over
a 10-year period. Pediatrics 2004;113:1653-1657.
21. Bossi E, Koerner F. Retinopathy of prematurity. Intensive Care
Med 1995;21:241-246.
22. Pallás CR, Tejada P, Medina MC, Martín MJ, Orbea C, Barrios
MC. Retinopatía del prematuro: nuestra experiencia. An Esp
Pediatr 1995;42:52-56.
23. Blair BM, O'Halloran HS, Pauly TH, Stevens JL. Decreased
incidence of retinopathy of prematurity, 1995-1997. JAAPOS
2001;5:118-122.
24. Holmström G, El Azazi M, Jacobson L, Lennerstrand G. A
population-based, prospective study of the development of
ROP in prematurely born children in the Stockholm area of
Sweden. Br J Ophthalmol 1993;77:417-423.
25. Palmer EA, Flynn JT, Hardy RJ, Phelps DL, Phillips CL, Schaffer
DB, et al. Incidence and early course of retinopathy of
prematurity. The Cryotherapy for Retinopathy of Prematurity
Cooperative Group. Ophthalmology 1991;98:1628-1640.
26. Párraga QMJ, Sánchez PR, Barreiro LJC, Cañete ER,
Fernández GF, Zapatero MM, et al. Retinopatía del prematuro.
Resultados tras un año de seguimiento. An Esp Pediatr
1996;44:482-484.
27. Good WV, Hardy RJ, Dobson V, Palmer EA, Phelps DL, Quitos
M, et al; for the Early Treatment for Retinopathy of Prematurity
Cooperative Group. The incidence and course of retinopathy
of prematurity: findings from the early treatment for retinopathy
of prematurity study. Pediatrics 2005;116:15-23.
28. American Academy of Pediatrics, Section on Ophthalmology;
American Academy of Ophthalmology; American Association
266 Bol Med Hosp Infant Mex

Vol. 69, July-August 2012
Risk factors associated with retinopathy of prematurity in preterm infants treated at a tertiary level hospital
for Pediatric Ophthalmology and Strabismus. Screening examination
of premature infants for retinopathy of prematurity.
Pediatrics 2006;117:572-576.
29. Secretaría de Salud. Manejo de la retinopatía del recién
nacido prematuro. Lineamiento técnico. Available at: http://
saludmaternamedicos.blogspot.mx/2011/09/lineamientotecnico-manejo-de-la.html#!/2011/09/lineamiento-tecnicomanejo-de-la.html
30. Smith LE. Pathogenesis of retinopathy of prematurity. Growth
Horm IGF Res 2004;14(suppl A):S140-S144.
31. Msall ME, Phelps DL, Hardy RJ, Dobson V, Quinn GE, Summers
CG, et al. Educational and social competencies at 8
years in children with threshold retinopathy of prematurity in
the CRYO-ROP multicenter study. Pediatrics 2004;113:790-
799.
32. Holmström G, El Azazi M, Kugelberg U. Ophthalmological
long term follow up of preterm infants: a population based,
prospective study of the refraction and its development. Br J
Ophthalmol 1998;82:1265-1271.
33. Ricci B. Refractive errors and ocular motility disorders in
preterm babies with and without retinopathy of prematurity.
Ophthalmologica 1999;213:295-299.
34. Good WV. Early treatment for Retinopathy of Prematurity
Cooperative Group. The Early Treatment for Retinopathy of
Prematurity Study: structural findings at age 2 years. Br J
Ophthalmol 2006;90:1378-1382.
35. Larsson EK, Holmström GE. Development of astigmatism
and anisometropia in preterm children during the first 10
years of life: a population based study. Arch Ophthalmol
2006;124:1608-1614.
267

esearch article
Bol Med Hosp Infant Mex 2012;69(4):268-274
Association of steroid use with weight gain in pediatric patients with
rheumatic disease
Sonia González-Muñiz, 1 Donají Miranda-González, 2 Miguel Ángel Villasis-Keever, 3 Vicente Baca-Ruíz, 4
Teresa Catalán-Sánchez, 4 Patricia Yañez-Sánchez 4
AbSTRACT
background: Prevalence of obesity in pediatric patients with rheumatic disease (RD) receiving steroids can be as high as 43%. The aim
of this study was to determine the association between low dose of prednisone and weight gain among children with RD.
methods: We carried out a prospective cohort study. One cohort was comprised of patients exposed to steroids (group B) and the other
group was comprised of patients not exposed to steroids (group A). After standardization, all patients were followed for 24 weeks and
weight, height, waist circumference, arm circumference and body fat percentage were assessed.
Results: There were 20 patients in group A and 32 in group B. In the first group, juvenile rheumatoid arthritis was the main diagnosis (40%)
and systemic lupus erythematosus (56%) in the second group. Between groups, from the beginning and during the entire study period
there was no difference in the averages of each anthropometric variable, but there were four (12.5%) new cases of obesity in group B and
none in group A. Eleven (55%) patients in group A and 18 (56%) patients of group B showed an increase in fat percentage. Of these, only
in group B patients was there was a statistically significant gain (p 60 days with prednisone. It was concluded that the risk
of obesity was low among children who were at their
normal weight at baseline as a result of continuous use of
steroids. 2 In 1988, a study in Kuwait evaluated the effects
of chronic therapy with low-doses of prednisone on stature
and obesity of 37 patients aged 2–15 years with nephrotic
syndrome who had frequent relapses. Serial measurements
of height and weight showed the persistence of obesity
in only 2/13 of the children who were initially obese. 3 In
2006, a Canadian study reported in a group of patients
with nephrotic syndrome that the incidence of obesity was
35 to 43% during GC treatment and found that the weight
decreased when the GC dose was reduced or suspended. 4
Obesity is defined as a chronic metabolic disorder
characterized by excessive body fat. A child is considered
obese when his/her weight is >20% of the ideal. 5
According to the growth charts published in 2000 by the
Centers for Disease Control and Prevention (CDC) in the
268 Bol Med Hosp Infant Mex

U.S., obesity is defined as body mass index (BMI) ≥95th
percentile for age and gender and overweight is defined
when the percentile is ≥85 and ≤94. 6-8 Worldwide, obesity
and overweight are considered a public health problem.
In Mexico, beginning with the National Health Survey
in 2000, it was determined that this was a problem that
also occurs in the pediatric population. Prevalence of
overweight was documented in children between 10 and
17 years of age: 10.8–16.1% in males and 14.3–19.1% in
females. Prevalence of obesity was 9.2–14.7% in males
and 6.8–10.6 % in females. 9-11
In clinical practice, the most frequently used indicator
for diagnosis of obesity is the BMI. However, when the
BMI is high, it is not distinguished whether the increase
in weight with respect to height is a function of fat mass
or fat-free mass. 8 Therefore, other measurement methods
should be used to assess the total body composition such
as biompedance. 4,12
The aim of this study was to determine whether there is
a relationship between low-dose steroid use and changes
in nutritional status in children with RD during the first
months after establishing the diagnosis.
PATIENTS AND mETHODS
We conducted an observational, longitudinal, prospective
and analytical cohort study with patients between 2
and 16 years of age who were recruited in the Service of
Rheumatology of the Pediatric Hospital, Centro Medico
Nacional Siglo XXI. Patients who were included had to
have a certain initial diagnosis of RD. Patients were divided
into two groups: group A patients who did not require
steroids for a minimum of 24 weeks and group B included
patients with RD who initiated treatment with steroids
(prednisone) and in whom it was necessary to continue
treatment for at least 24 weeks. The decision of whether or
not to administer prednisone was made by the physician in
charge of each patient. We excluded patients who received
additional doses of steroids (such as methylprednisolone)
as a result of complications of the disease itself during
the monitoring period. The protocol was approved by the
Local Committee for Health Research of the hospital. For
admission to the study, parents signed an informed consent
and patients >8 years provided informed assent.
Prior to the initiation of the study, one of the investigators
(SGM) conducted a standardization process for
Vol. 69, July-August 2012
Association of steroid use with weight gain in pediatric patients with rheumatic disease
assessment of weight, height, waist circumference (WC),
arm circumference and electrical bioimpedance to determine
total body composition, in particular the percentage
of fat mass. Weight was determined using a mechanical
scale (BAME, Puebla, Mexico) with 140-kg maximum
range and minimum weight of 1 kg. Height was measured
using a stadiometer and a maximum range of 194 cm. Waist
circumference (WC) and mid-upper arm circumference
(MUAC) were measured with a fiberglass tape measure
with a maximum length of 150 cm. Electrical bioimpedance
was assessed with a four derivation model (325F,
Omron Healthcare, Bannockburn, IL). All measurements
were performed at the time of confirmation of diagnosis
and were repeated four times every 6 weeks during the 24
weeks of surveillance. We defined overweight when BMI
was between the 85 th and 94 th percentile and as obese when
it was ≥95 th percentile.
Statistical Analysis
Information was captured in a database. Subsequently,
statistical analysis was performed using SPSS v.13.
For descriptive analysis, we used measures of central
tendency according to the scale of measurement variables.
Qualitative variables were presented as modes and
simple frequencies, whereas quantitative variables such
as average and standard deviation (SD) showed a normal
distribution after making a logarithmic conversion. For
inferential analysis, we used the χ 2 test. For independent
and dependent samples, t test was performed as well as
one- and two-way analyses of variance (ANOVA). Furthermore,
Pearson r correlation test was conducted; p

Sonia González-Muñiz, Donají Miranda-González, Miguel Ángel Villasis-Keever, Vicente Baca-Ruíz, Teresa Catalán-Sánchez, Patricia Yañez-
Sánchez
Table 1. Comparison of the characteristics of patient with rheumatic
disease with or without steroid exposure
Characteristics Group A
(without steroids)
n = 20
Group B
(with steroids)
n = 32
Age (years) Average ± SD 11.6 (± 3.3) 12.0 (± 3.2) 0.7
Pediatric stage (n)
• Preschool 1 1
• School age 4 5
• Adolescents 15 26
Gender n (%)
• Female
• Male
Type of RD n (%)
14 (70)
6 (30)
22 (68.8)
10 (31.2)
• SLE 4 (20) 18 (56.2)
• JIA 8 (40) 4 (12.5)
• Vasculitis 1 (5) 4 (12.5)
• Dermatomyositis 2 (10) 2 (6.2)
• DEL 3 (15) —
• APS 1 (5) 1 (3.1)
• Progressive systemic
sclerosis
— 1 (3.1)
• Overlap syndrome — 1 (3.1)
• Scleroderma 1 (5) —
With respect to the amount of steroid prescribed in
group B, there was little difference observed during the
study period. The average dose at baseline was 0.32 mg/
kg/day (range: 0.05–1.4 mg/kg/day), whereas for the fourth
measurement, the average was 0.25 mg/kg/day (variation
of 0.05–1.2 mg/kg/day).
Table 2 compares the anthropometric measurements in
the two groups: at baseline and at the end of the 24-week
monitoring period. As noted, there were no differences
between groups with respect to baseline and final measurements.
However, it is worth noting that in both groups
there was a slight increase in weight, WC, MUAC and fat
percentage, which was a little higher in the steroid group.
Figure 1 shows the behavior of the latter four variables.
The remaining did not show changes of the four measurements
at any given time. In terms of weight, compared
with group A (which remained unchanged), group B had
progressive increases. This was also observed in the WC
and MUAC. Regarding the percentage of fat, group B
p
0.9
0.03
SD, standard deviation; SLE, systemic lupus erythematosus;
JIA, juvenile idiopathic arthritis; APS, antiphospholipid syndrome;
DLE, discoid lupus erythematosus; RD, rheumatic disease.
had a lower percentage at the beginning, but in the end
it nearly equaled the other group. According to ANOVA,
the behavior of these variables between groups over time
was not statistically significant (p >0.05).
The average weight gain was higher in group B (0.3 kg
vs. 1.3 kg) but was not statistically significant (p = 0.2);
however, during the observation period, one patient from
group A (5%) and five patients from group B (15%) showed
an increase in weight much more than the average for the
rest of the group (Figure 2). In the latter group, two patients
increased their weight almost 15 kg as compared with the
patient in group A who only showed an increase of 4.1 kg.
Furthermore, according to the BMI, group A had four
overweight patients (20%) and three obese patients (15%)
from the first evaluation and who did not change their
status during the study. In contrast, at baseline, group B
had four overweight patients (12.5%) and seven obese
patients (21.8%), but at the end there were six (18.7%) and
eight (25%) patients, respectively. It should be noted that
in these eight children with obesity, one patient had BMI
within normal limits at the beginning of the surveillance
period and another child was overweight, so the change
in BMI percentile occurred during the steroid treatment
period. Likewise, of the six patients who were detected
with overweight at the end of the study, their BMI (in three
cases) was normal at initiation of the monitoring period. At
the beginning and at the end of the study, the prevalence
of overweight and obesity increased from 34 to 43%, and
the incidence was 20%. In other words, there were five
new cases of overweight or obesity. In contrast, it was
also observed that the BMI improved in two patients: a
patient with obesity changed to overweight and another
overweight patient lowered to normal status.
By analyzing the variation in fat percentage, we identified
11 patients in group A (55%) and 18 in group B (56%)
with some increase in the percentage of fat during the 24week
follow-up. Of these patients, only those from group
B showed a statistically significant gain (p

Vol. 69, July-August 2012
Association of steroid use with weight gain in pediatric patients with rheumatic disease
Table 2. Basal and final measurements of patients with generalized rheumatic disease according to steroid exposure
Variable No steroids
n=20
Basal Final*
With steroids
n=32
No steroids
n=20
With steroids
n=32
Average ± SD Average ± SD Average ± SD Average ± SD
Weght (kg) 45.4 (17.0) 46.8 (16.7) 45.7 (16.5) 48.1 (17.1)
Length (cm) 145.4 (18) 145.4 (16.8) 145.7 (17.7) 145.9 (16.5)
BMI 20.5 (3.1) 21.4 (3.2) 20.6 (2.3) 21.8 (0.6)
WC (cm) 72.6 (14.0) 74.2 (13.8) 72.7 (13.3) 75.6 (14.2)
Arm circumference (cm) 23.6 (4.7) 23.9 (4.9) 23.7 (4.4) 24.7 (5.2)
Fat (%) 31.7 (10.0) 30.0 (10.0) 32.3 (9.3) 30.8 (8.2)
*No statistical difference between groups or before or after in the same group.
Figure 1. Comparison of four variables during the study period according to each group. BPI, brachial perimeter index.
271

Sonia González-Muñiz, Donají Miranda-González, Miguel Ángel Villasis-Keever, Vicente Baca-Ruíz, Teresa Catalán-Sánchez, Patricia Yañez-
Sánchez
Figure 2. Comparison of the weight increment between groups.
performing the correlation between cumulative steroid dose
and weight change, fat, WC and arm circumference, we only
obtained a low correlation between steroid dose with the
fat percentage (r = 0.31, p = 0.08); the other three variables
did not show any correlation.
DISCuSSION
With the results of this investigation we observed that there
is a relationship between administration of steroids and
weight gain in pediatric patients with RD receiving low
doses of steroids. This observation was seen particularly
in five patients (15.6%) because their weight increase
was significant (5 kg–13 kg during a 6-month period).
These findings were in spite of the fact that in the group
exposed to steroid use since the beginning of the surveillance
period, 11 patients were already overweight or
obese (34%), whereas at the end of the study there were
14 patients (43%). The weight gain in these five patients
was as significant from the clinical point of view. In four
of these patients who initially had normal BMI, at the end
of the follow-up period three were overweight and one
was obese, whereas the fifth patient changed from being
overweight to obesity.
The results of this study are similar to other studies such
as the one by Merrit et al. where there was an increased
incidence of obesity over a period of about 2 years, but in
children with nephrotic syndrome; nevertheless, the steroid
dose administered was not clearly specified. 2 Likewise, it
has also been described that upon discontinuation of steroids,
the opposite effect was observed. In other words, it
decreases the frequency of overweight or obese patients. 3
In particular, in the case of patients with RD information
on the modification of nutritional status has not been
previously published. The only related studies refer to the
possible impact of steroids in terms of stature. 13,14 However,
the results of this study cannot be compared because
the patients included in this study had a minimal change
in their height, which is related to the monitoring time of
our study (6 months) compared to previous studies with
a much longer surveillance period.
Another aspect used in this study that has not been
described previously was the analysis of body composition
by measurement of the percentage of body fat using
impedance. As described, averages obtained between
groups did not differ because during the study week there
were patients who increased and others who decreased
the amount of fat. Therefore, we proceeded to analyze the
29 patients separately (n = 11, without steroids; n = 18,
with steroids) in whom the amount of body fat increased.
Although there was no difference in the rate of increase
of fat between groups (55% vs. 56.2%), interestingly, it
was determined that in this subgroup the patients who
received steroids gained more weight and had a greater
increase in WC and arm circumference compared to the
group without steroid use (Table 3). This would support
the fact that the weight gain in patients who use prednisone
would be related to the higher fat deposition. Furthermore,
it is worth mentioning the manner in which fat accumulates
with steroid use. Based on data from this study, it is
possible to assume that there is no preference for either
central or peripheral fat accumulation when it is expected
that the accumulation of fat would be predominantly
central, as occurs in Cushing’s syndrome. However, it
must be noted that this syndrome is associated with high
doses of steroids. The findings on how fat accumulates in
patients using steroids, which is described in this study,
is consistent with those reported by other authors using
other assessment tools such as DEXA. 15-17
Although in this study we considered important aspects,
it is appropriate to mention that the study had some weaknesses.
For example, although SLE patients who require
high doses of steroids are not included, monitoring of
patients who participated in this study took about 3 to 6
months to be initiated after the conclusive diagnosis. The
272 Bol Med Hosp Infant Mex

greater proportion of patients with SLE required high doses
of steroids at the beginning of treatment for disease control.
Thereafter, the dose is progressively reduced. Thus, it is
possible that, in some patients, the cause of overweight
or obesity prior to the study was due to the use of high
doses of steroids. Another important point is that during
the time the study was conducted, there was no control of
food intake or physical activity of the patients. Of these
two confounding variables, physical activity is probably
the most important according to the type of disease
because it is possible that the weight gain is due to lack
of activities commonly carried out by children. In these
patients, clinical manifestations can cause a decrease in
physical activity due to pain or musculoskeletal disability
or articulation. It is also possible that during the different
phases of treatment, family members do not allow the
child to perform physical activities, work, or go to school
without specific medical advice. In this regard, it should
be noted that there are studies in pediatric patients with
chronic diseases that note that it is common for the patients
to frequently miss school, which is not necessarily related
to functional or organic problems. 18 Finally, this study
did not consider adherence to the treatment as a possible
confounding variable, although it could support the findings.
In view of the above, and in order to explore and
determine the most clear relationship between low doses of
steroids and weight gain, further studies are necessary that
would take into account the nutritional status of children
prior to the initiation of steroids, their growth rate, time
of exposure to steroids, and therapeutic adherence as well
as dietary habits and physical activity.
Vol. 69, July-August 2012
Association of steroid use with weight gain in pediatric patients with rheumatic disease
Table 3. Baseline and final anthropometric evaluation of patients with increase in the percentage of fat in accordance with steroid exposure
Variable Without steroids
n = 11
Basal Final*
With steroids
n = 18
In conclusion, according to the results obtained in this
study, it appears that there is a greater likelihood that children
with RD receiving low dose steroids are exposed to a
significant increase in weight. These findings should be an
alert to healthcare workers caring for these patients in order
to offer precautionary measures to prevent overweight and
obesity as well as dietary guidelines.
REFERENCIAS
Without steroids
n = 11
With steroids**
n = 18
Average ± SD Average ± SD Average ± SD Average ± SD
Weight (kg) 39.9 (14.9) 45.7 (16.9) 41.23 (15.3) 48.7 (17.9)
WC (cm) 65.5 (9.2) 71.3 (13.4) 67.8 (9.6) 75.3 (14.8)
Arm circumference (cm) 23.8 (4.2) 23.6 (4.3) 23.7 (3.8) 25.4 (5.1)
Fat (%) 28.9 (9.4) 23.8 (8.4) 31.3 (9.1) 29.6 (7.1)
*No statistically significant differences between groups (p >0.05).
**p

Sonia González-Muñiz, Donají Miranda-González, Miguel Ángel Villasis-Keever, Vicente Baca-Ruíz, Teresa Catalán-Sánchez, Patricia Yañez-
Sánchez
index cut offs to define thinness in children and adolescents:
international survey. BMJ 2007;335:194.
9. Rudolf MC. The obese child. Arch Dis Child Educ Pract Ed
2004;89:ep57-ep62.
10. del Río-Navarro BE, Velázquez-Monroy O, Sánchez-Castillo
P, Lara-Esqueda A, Berber A, Fanghänel G, et al. The high
prevalence of overweight and obesity in Mexican children.
Obes Res 2004;2:217-223.
11. Centers for Disease Control and Prevention. About BMI for children
and teens. Disponible en: http://www.cdc.gov/healthyweight/
assessing/bmi/childrens_bmi/about_childrens_bmi.html
12. Pi-Sunyer FX. Obesity: criteria and classification. Proc Nutr
Soc 2000;59:505-509.
13. Simon D, Lucidarme N, Prieur AM, Ruiz JC, Czemichow P.
Linear growth in children suffering from juvenile idiopathic
arthritis requiring steroid therapy: natural history and effects
of growth hormone treatment on linear growth. J Pediatr Endrocrinol
Metab 2001;14(suppl 6):1483-1486.
14. Simon D, Fernando C, Czernichow P, Prieur AM. Linear growth
and final height in patients with systemic juvenile idiopathic
arthritis treated with longterm glucocorticoids. J Rheumatol
2002;29:1296-1300.
15. Foster BJ, Shults J, Zemel BS, Leonard MB. Interactions
between growth and body composition in children treated
with high-dose chronic glucocorticoids. Am J Clin Nutr
2004;80:1334–1341.
16. Leonard MB, Feldman HI, Shults J, Zemel BS, Foster BJ,
Stallings VA. Long-term, high-dose glucocorticoids and bone
mineral content in childhood glucocorticoid-sensitive nephrotic
syndrome. N Engl J Med 2004;351:868-875.
17. Czock D, Keller F, Rasche FM, Häussler U. Pharmacokinetics
and pharmacodynamics of systemically administered glucocorticoids.
Clin Pharmacokinet 2005;44:61-98.
18. Lollar DJ, Hartzell MS, Evans MA. Functional difficulties and
health conditions among children with special needs. Pediatrics
2012; 129: e714-e722.
274 Bol Med Hosp Infant Mex

esearch article
Analysis of sociodemographic features of patients with end-stage chronic
renal disease: differences in a 6-year period
Vol. 69, July-August 2012
Bol Med Hosp Infant Mex 2012;69(4):275-279
Guillermo Cantú, 1 Graciela Rodríguez, 2 Mercedes Luque-Coqui, 3 Benjamín Romero, 3 Saúl Valverde, 3 Silvia
Vargas, 4 Alfonso Reyes-López, 4 Mara Medeiros 3
AbSTRACT
background. Chronic renal disease (CRD) has a strong impact on the Mexican childhood population with short-range limiting and serious
consequences. Poverty and a social environment devoid of social justice hinder timely medical attention and long-range rehabilitation. The
aim of this study was to determine the differences regarding sociodemographic features in patients under treatment at Hospital Infantil de
México Federico Gómez, with a 6-year difference: patients diagnosed in 2003 as compared to those diagnosed in 2009.
methods. A retrospective comparative study was carried out with end-stage chronic renal disease (ESRD) patients with information obtained
from the clinical files. Data were obtained on age, gender, renal insufficiency etiology, socioeconomic level, type of financing, place
of origin, and whether patient entered a rehabilitation program (dialysis or transplant).
Results. In 2003, 69 patients with ESRD were treated, whereas 50 patients were treated in 2009. There were no differences in age or
gender between dates. Etiology of uremia was determined in 40% of the children in 2003 and 50% in 2009. Most patients in the assessed
years belong to the lowest socioeconomic levels, coming from the State of Mexico and metropolitan Mexico City. There was a decreasing
trend in the number of patients coming from other states of the country: 30% in 2003 and 16% in 2009. Twenty-three patients (33%)
entered the rehabilitation program in 2003 and 29 patients (58%) in 2009 (p = 0.007).
Conclusions. There was a 28% decrease between 2003 and 2009 in the number of cases being managed. Attention has been focused on
the State of Mexico and metropolitan Mexico City area. In spite of socioeconomic level being apparently similar in the studied years, there
was a significant increase in the proportion of children entering a long-range rehabilitation program (from 33% in 2003 to 58% in 2009).
Key words: renal insufficiency, pediatrics, distributive justice, bioethics.
INTRODuCTION
Chronic renal disease (CRD) is considered to be a public
health problem in our country, in children as well as in
adults. 1,2 At a worldwide level it tends to increase. According
to international guidelines, CRD in pediatrics is
defined as structural or functional damage to the kidneys
1 Escuela de Medicina, Universidad Panamericana, Mexico, D.F.,
Mexico
2 Facultad de Psicología, Universidad Nacional Autónoma de
México, Mexico, D.F., Mexico
3 4 Departamento de Nefrología, Subdirección de Investigación,
Hospital Infantil de México Federico Gómez,
México D.F., México
Correspondence: Dra. Mara Medeiros Domingo
Departamento de Nefrología
Hospital Infantil de México Federico Gómez
México, D.F., México
E-mail: medeiro.mara@gmail.com
Received for publication: 5-31-12
Accepted for publication: 8-21-12
for a period of 3 months or more, which may decrease
the glomerular filtration rate, and the presence of any of
the following findings: 1) alteration in the composition
of the blood or urine, 2) alteration in imaging studies and
3) impaired renal biopsy, or those patients who have a
glomerular filtration rate

Guillermo Cantú, Graciela Rodríguez, Mercedes Luque-Coqui, Benjamín Romero, Saúl Valverde, Silvia Vargas, Alfonso Reyes-López,
Mara Medeiros
are reported and in Japan 16.6% of its population of

Vol. 69, July-August 2012
Analysis of sociodemographic features of patients with end-stage chronic renal disease: differences in a 6-year period
an unspecified level (42%), probably because they were not
treated in the emergency department and were not admitted
into a rehabilitation program. In 2009 there were 32 level 1
patients (64%), nine patients from level 2 (18%) and only
one patient (2%) at an unspecified level (Table 2).
With regard to type of financial support, in 2003 (as
well as in 2009) the father was the main provider. The
most frequent trades were tradesman, businessman, driver
and bricklayer. In regard to maternal financial support,
the most frequently reported type of work was that of
housekeeper (Table 2).
In the years evaluated, most patients came from the
State of Mexico and from the Federal District. There was
a downward trend in the number of patients from other
states, with 30% in 2003 and 16% in 2009 (p = 0.06) (Table
2). In 2003, in addition to the 48 patients from the Federal
District and State of Mexico, there were six patients
from the state of Guanajuato (7%), three from the state
of Guerrero (4%) and 12 patients representing more than
nine different states. Moreover, in 2009 there were only
eight patients from seven different states.
Table 2. Socioeconomic level, type of financing, place of residence
and admission to long-term rehabilitation program for children with
CRI attended in 2003 and 2009
2003
(n=69)
2009
(n=50)
Socioeconomic level (n,%) 0.01
• 1 31 (45%) 32 (64%)
• 2 8 (12%) 9 (18%)
• Other 0 8 (16%)
• Not specified 29 (42%) 1 (2%)
Type of financing (n,%) 0.28
• Paternal 56 (81.2%) 34 (68%)
• Maternal 10 (14.5%) 12 (24%)
• Not specified 3 (4.3%) 1 (2%)
Place of residence (n,%) 0.06
• State of México 44 (64%) 34 (68%)
• Federal District 4 (6%) 8 (16%)
• 34 Other states 21 (30%) 8 (16%)
Admission to long-term
rehabilitation program (n,%)
23 (33%) 29 (58%) 0.007
*p value obtained using c 2 .
CRD, chronic renal disease.
p*
In 2003, only 33% of patients were able to enter a longterm
rehabilitation program. This means that 46 patients
returned home with ESRD due to lack of socioeconomic
resources. Of the 23 patients who managed to enter the
rehabilitation program, 16 were transplanted within 12
months. Admission into the rehabilitation program increased
significantly in 2009 with 29 patients (58%). Of
these, 13 patients were transplanted during a 12-month
span (Table 2).
DISCuSSION
In accordance with theories of distributive justice in health
care such as that provided in the HIMFG, one can conclude
that liberal theory seeks to give every person according
to his right and property. The criticism of this approach
is that it benefits only patients whose families have the
financial resources to receive medical care, which does not
correspond to the reality of our environment. 17,18
This report documents that the number of patients
who presented to the HIMFG for ESRD was lower, with
a decrease of 28% between 2003 and 2009. This may
be because other highly specialized hospitals have been
created in several states, along with the phenomenon of
epidemiological inversion by reducing the number of
births. Although most patients came from the State of
Mexico, the percentage of patients from other states decreased
significantly (from 30% in 2003 to 16% in 2009).
There were no differences in age at diagnosis. The average
age was 11 years. This may indicate that there has
been progress in the early diagnosis of the disease. There
were no differences regarding gender.
Regarding the etiology of renal failure, in 2009 the
primary cause in 54% of children was able to be achieved,
whereas in 2003 it was only 40%. This is important
because some conditions may recur in the transplanted
kidney, and knowing the epidemiology of renal failure
can allow for developing strategies for timely detection
and treatment. 6,19,20
In adults, early detection of risk groups (diabetic patients,
obese patients, hypertensive patients or relatives
with kidney disease) has been implemented by the National
Kidney Foundation program called KEEP (Kidney Early
Evaluation Program). To date the program is the most effective
community screening to identify individuals >18
years of age with risk of renal disease. 20, 21 In Mexico, us-
277

Guillermo Cantú, Graciela Rodríguez, Mercedes Luque-Coqui, Benjamín Romero, Saúl Valverde, Silvia Vargas, Alfonso Reyes-López,
Mara Medeiros
ing this program we have detected a prevalence of chronic
kidney disease of 22% in the Federal District and of 33%
in the state of Jalisco. The high prevalence is highlighted,
little known even in subjects with high risk factors. 8 A
similar program for the pediatric population does not
exist, and given that the causes of uremia are different in
children, one would have to select the specific risk factors
for screening in this population. History of prematurity,
acute renal insufficiency, urinary tract infections, congenital
malformations, type I diabetes mellitus, obesity, and
hypertension, among others, are suggested. 1
Regarding socioeconomic status, there was an increase
in the level of poverty (socioeconomic levels 1 and 2) from
57 to 84% in patients who were treated at the hospital. It
is noteworthy that in 2003 there was a high percentage of
patients at an unspecified level, so the data are now more
representative.
Although a greater number of patients with low socioeconomic
status are seen, the number of patients who
entered a long-term rehabilitation program (dialysis or
transplantation) increased from 33% in 2003 to 58% in
2009.
It is gratifying to report that more than half of the
children entering rehabilitation programs are transplanted
during the 12 months following diagnosis. Kidney transplantation
is the optimal treatment for these patients
because it allows better growth and development and
impacts on the quality of life. 9 It is also noted as the best
method for low-income countries because the cost of
maintaining an immunosuppressed patient is less than
maintaining them under dialysis. 22
We hope that the Seguro Popular program in Mexico
will soon include renal transplantation as the universal
treatment for children with renal insufficiency as in other
countries in Latin America and the Caribbean. 17
REFERENCES
1. Medeiros M, Muñoz-Arizpe R. Enfermedad renal en niños.
Un problema de salud pública. Bol Med Hosp Infant Mex
2011;68:259-261.
2. López-Cervantes M, Rojas-Russell M, Tirado-Gómez LL,
Durán-Arenas L, Pacheco-Domínguez RL, Venado-Estrada
AA, et al. Enfermedad renal crónica y su atención mediante
tratamiento sustitutivo en México. Facultad de Medicina, Universidad
Nacional Autónoma de México, México D.F. México;
2009.
3. Hogg RJ, Furth S, Lemley KV, Portman R, Schwartz GJ,
Coresh J, et al. National Kidney Foundation's Kidney Disease
Outcomes Quality Initiative clinical practice guidelines for
chronic kidney disease in children and adolescents: evaluation,
classification, and stratification. Pediatrics 2003;111:1416-
1421.
4. Klarenbach S, Manns B. Economic evaluation of dialysis
therapies. Semin Nephrol 2009;29:524-532.
5. Harambat J, van Stralen KJ, Kim JJ, Tizard EJ. Epidemiology
of chronic kidney disease in children. Pediatr Nephrol
2012;27:363-373.
6. Warady BA, Chadha V. Chronic kidney disease in children:
the global perspective. Pediatr Nephrol 2007;22:1999-2009.
7. Ardissino G, Dacco V, Testa S, Bonaudo R, Claris-Appiani A,
Taioli E, et al. Epidemiology of chronic renal failure in children:
data from the ItalKid project. Pediatrics 2003;111:e382-e387.
8. Obrador GT, García-García G, Villa AR, Rubilar X, Olvera N,
Ferreira E, et al. Prevalence of chronic kidney disease in the
Kidney Early Evaluation Program (KEEP) México and comparison
with KEEP US. Kidney Int Suppl 2010:S2-S8.
9. Medeiros-Domingo M, Romero-Navarro B, Valverde-Rosas
S, Delgadillo R, Varela-Fascinetto G, Muñoz-Arizpe R. [Renal
transplantation in children]. Rev Invest Clin 2005;57:230-236.
10. Beauchamp TL. Methods and principles in biomedical ethics.
J Med Ethics 2003;29:269-274.
11. Buchanan A. A health-care delivery and resource allocation.
In: Veatch RM, ed. Medical Ethics. Boston: Jones and Bartlett
Publishers; 1997. pp. 321-358.
12. Sakhuja V, Sud K. End-stage renal disease in India and Pakistan:
burden of disease and management issues. Kidney Int
Suppl 2003:S115-S118.
13. Yeates K. Health disparities in renal disease in Canada. Semin
Nephrol 2010;30:12-18.
14. Xue JL, Eggers PW, Agodoa LY, Foley RN, Collins AJ. Longitudinal
study of racial and ethnic differences in developing
end-stage renal disease among aged medicare beneficiaries.
J Am Soc Nephrol 2007;18:1299-1306.
15. Franco-Marina F, Tirado-Gómez LL, Venado-Estrada A,
Moreno-López JA, Pacheco-Domínguez RL, Durán-Arenas L,
et al. Una estimación indirecta de las desigualdades actuales y
futuras de la frecuencia de enfermedad renal crónica terminal
en México. Salud Publica Mex 2011;53(suppl 4):506-515.
16. García-García G, Renoirte-López K, Márquez-Magaña I.
Disparities in renal care in Jalisco, Mexico. Semin Nephrol
2010;30:3-7.
17. Cantú-Quintanilla G, Orta-Sibú N, Romero-Navarro B, Luque-
Coqui M, Medeiros-Domingo M, Grimoldi I, et al. Patrones de
suficiencia y prioridad de la justicia distributiva en atención
de los pacientes pediátricos con enfermedad renal crónica
terminal en América Latina y el Caribe. Arch Latin Nefr Ped
2010;10:25-33.
18. Cantú-Quintanilla G, Orta-Sibu N, Romero-Navarro B, Luque-
Coqui M, Rodríguez-Ortega EG, Reyes-López A, et al. Acceso
a trasplante renal de donante fallecido en pacientes pediátricos
de América Latina y el Caribe. Pers Bioét 2010;14:151-162.
19. Staples A, Wong C. Risk factors for progression of chronic
kidney disease. Curr Opin Pediatr 2010;22:161-169.
20. Whaley-Connell AT, Vassalotti JA, Collins AJ, Chen SC,
McCullough PA. National Kidney Foundation's Kidney Early
278 Bol Med Hosp Infant Mex

Vol. 69, July-August 2012
Analysis of sociodemographic features of patients with end-stage chronic renal disease: differences in a 6-year period
Evaluation Program (KEEP) annual data report 2011: executive
summary. Am J Kidney Dis 2012;59(suppl 2):S1-S4.
21. Obrador GT, Mahdavi-Mazdeh M, Collins AJ; Global Kidney
Disease Prevention Network. Establishing the Global Kidney
Disease Prevention Network (KDPN): a position statement
from the National Kidney Foundation. Am J Kidney Dis
2011;57:361-370.
22. Garcia GG, Harden P, Chapman J; for the World Kidney Day
Steering Committee. The global role of kidney transplantation.
Transplantation 2012;93:337-341.
279

clinical case
Bol Med Hosp Infant Mex 2012;69(4):280-283
bronchial mucoepidermoid carcinoma: a rare tumor in children
Luis Hernández-Motiño, Yarisa Brizuela, Verónica Vizcarra, Rubén Cruz, Lourdes Jamaica, José Karam
AbSTRACT
background. Lung neoplasms are rare in children. Mucous and serous glands from trachea and upper airway contain cells similar to those
of the major salivary glands. Of these glands there is a group of very rare tumors including adenoid cystic carcinoma, mucoepidermoid
carcinoma, pleomorphic adenoma, acinic cell carcinoma and oncocytoma. Mucoepidermoid carcinomas (MEC) represent 0.2% of cases
of lung cancer at any age, and slightly more than 100 children have been reported with this entity in the international literature. Formerly
classified as bronchial adenoma, this term is inappropriate for a slow-growing neoplasm and may be locally invasive. These tumors present
a relatively benign course when they correspond to tumors of low-grade malignancy and may be manifested as recurrent pneumonia or
slow resolution. Children with these clinical manifestations should be thoroughly evaluated including endoscopic and tomographic studies.
Surgical resection of the affected lung lobe with the respective lobar hilar lymph nodes is the most accepted treatment.
Case Report. We report the case of a 10-year-old female with a history of recurrent airway infection and two left lung pneumonias. Chest
tomography showed a left bronchus stenosis confirmed by endoscopy. Following pneumonectomy, histopathological and immunohistochemical
findings reported a low-grade MEC.
Conclusions. MEC of low-grade malignancy has a good prognosis with complete tumor excision that requires a comprehensive approach
that includes bronchoscopy.
Key words: mucoepidermoid carcinoma, cancer, lung.
INTRODuCTION
Primary pulmonary neoplasms are rare in children. 1
Because symptoms are nonspecific, diagnosis and
management may be delayed, thus worsening the prognosis.
These tumors should be suspected when there are
persistent or recurrent respiratory symptoms. Initially,
common causes should be ruled out such as infectious,
immunodeficiencies, and cystic fibrosis, among others.
Diagnostic approach should include imaging studies such
as plain chest x-rays and, if necessary, other studies such
as chest computed tomography (CT) or bronchoscopy,
which determine the nature of the process. 2 Among the
bronchial tumors, the most frequent are carcinoid tumors
Servicio de Neumología Pediátrica, Hospital Infantil de México
Federico Gómez, México D.F., México
Correspondence: Dr. Luis Carlos Hernández Motiño
Servicio de Neumología Pediátrica
Hospital Infantil de México Federico Gómez
México D.F., México
E-mail: luismotino@yahoo.com; luischmotino@hotmail.com
Received for publication: 1-9-12
Accepted for publication: 6-8-12
(in 80–90% of the cases). The remaining tumors (10–20%)
are those described as carcinomas of the salivary glands
(adenocystic and mucoepidermal carcinomas). 3 Pulmonary
mucoepidermoid carcinoma (MEC) is a rare malignant
tumor (0.2%). It may originate in the trachea, main bronchus,
or in the lobes or segmental bronchi. Despite its low
malignant potential, it has a benign behavior. Therefore, in
the majority of the cases conservative pulmonary resection
is an adequate and sufficient treatment with an eventual
good prognosis. 1,3-5
CLINICAL CASE
We present the case of a 10-year-old previously healthy
female student who from 2008 presented with recurrent
airway infections (RAI) and was hospitalized twice for
left lung pneumonia. She has been treated at our service
since June 2011. She was referred due to RAI with occasional
episodes of hemoptysis. An approach to rule
out common causes of RAI was begun, e.g., sinusitis,
immunodeficiencies, cystic fibrosis, among others. Chest
x-ray was done and demonstrated total left atelectasis with
an area of consolidation at the left base (Figure 1). The
patient was initially managed with antibiotics, steroids and
280 Bol Med Hosp Infant Mex

Figure 1. Posteroanterior chest x-ray where atelectasis of the left
lower lobe is seen with overdistention of the right lung.
bronchodilators with no improvement and with persistence
of total atelectasis. High-resolution chest CT reported left
bronchial stenosis, left pulmonary necrosis, areas of bronchiectasis
and fibrosis (Figure 2). The diagnostic approach
was later complemented with bronchoscopy. The findings
in the left bronchus were as follows: ill-defined reddishcolored,
solid granulomatous mass completely occluding
the lumen of the left bronchus without allowing passage of
the bronchoscope (Figure 3). Biopsy of the lesion reported
left bronchial granuloma. A ventilation/perfusion scan of
the lung was done that showed functional absence of the
left lung and the right lung with normal perfusion and
ventilation. Total pneumonectomy was performed. The
pathology report was as follows:
1. Left bronchial tumor. Low-grade MEC with vascular
permeation and lesion on the surgical margins
(pancytokeratin, EMA, CD 31, CD 34, FACTOR
VIII positive, adequate controls).
2. Hypoplastic left lung.
It was later decided, in conjunction with the Oncology
Service, to keep the patient under observation because of
the low grade of malignancy of the tumor. During outpatient
pulmonary follow-up there have been no episodes of
pneumonia or RAI.
Vol. 69, July-August 2012
A
b
Bronchial mucoepidermoid carcinoma: a rare tumor in children
Figure 2. Axial cut (A) and coronal cut (B) chest computed tomography
(CT). Total obstruction of the left bronchus with total left
atelectasis is seen (black arrow) and areas of necrosis within the
interior (arrowhead).
DISCuSSION
Primary lung tumors are rare in the pediatric population.
The majority correspond to carcinoid tumors, adenocystic
carcinoma and MEC. 6,7 Of these, mucoepidermoid tumors
are the least frequent. It has been proposed that the MEC
originates in the mucosal and serosal glands of the central
tracheobronchial tree. Other structures can develop
MEC such as the salivary, mammary, thyroid gland or
skin. 2,3 Histologically, two types of MEC are characterized
according to the degree of malignancy as proposed
by Heitmiller et al. 8
281

Luis Hernández-Motiño, Yarisa Brizuela, Verónica Vizcarra, Rubén Cruz, Lourdes Jamaica, José Karam
Figure 3. Fiberoptic bronchoscopy where tumor is observed occluding
the left main bronchus (arrow).
1) Low grade⎯present macroscopically as well-delineated
endobronchial polypoid tumors covered with a thin
mucosa. Microscopically they are heterogeneous with predominance
of glandular elements with muocoid content.
Benign tumors represent the majority of pediatric cases.
In the international literature only one case that developed
metastasis to peribronchial nodes has been reported.
2) High-grade macroscopically infiltrating. Microscopic
study reveals a predominance of epidermoid
elements, atypias, hyperchromatism and elevated mitotic
activity. This type of MEC is less common and with a poor
prognosis and almost always presents in adults. Only two
cases of this type have been reported in the pediatric age.
Symptoms produced by endobronchial tumors are
irritation (cough and hemoptysis) or bronchial obstruction.
9,10 The insidious evolution with nonspecific clinical
manifestations are generally suggestive of other diagnoses
such as asthma, obstructive pneumonia or foreign body. 11
They can present as pulmonary phenomena in the zones
distal to the bronchial obstruction, as recurrent pneumonia,
bronchiectasis, pulmonary hyperinsufflation (in case of
partial obstruction) and atelectasis (if there is total bronchial
obstruction). 11,12 Prolonged evolution of the patient
resulted in total obstruction of the bronchus and total col-
lapse of the left lung. This prolonged evolution of almost 2
years was due to lack of an adequate diagnostic approach
before arrival at our hospital and delayed the diagnosis 18
months, resulting in pneumonectomy.
The most common radiological manifestation is the
presence of an intraluminal mass in the tracheobronchial
tree, although it is difficult to predict its endobronchial
situation when it is found in the segmental bronchus.
Pulmonary lesion secondary to obstruction such as the
atelectasis presented by our patient is found in one third
of the cases. 13,14 On chest CT it may appear as an oval or
lobulated mass with well-defined borders with puntiform
calcifications in half of the cases, and slight reinforcement
with contrast media. The greatest diameter of the
tumor is parallel to the direction of the branches of the
airway in which it is found. 1,2 In this case, no well-defined
mass was seen, only stenosis of the left main bronchus,
total left atelectasis and left pulmonary necrosis secondary
to the prior events of pneumonia. For this reason,
it was decided to do an exploratory endoscopy, which
corroborated the presence of a mass that occluded the
entire left bronchus.
A biopsy was carried out followed by scheduling of
pneumonectomy. This reinforces the importance of carrying
out endoscopic study for the diagnostic approach of
these patients. 4,11 For a low-grade malignant pulmonary
MEC, lobectomy or segmentectomy is sufficient for cure.
Bronchoscopic laser resection may be indicated in the case
of small tumors where there is no question of compromise
of the parenchyma. 7,15-18 The prognosis for mucoepidermoid
bronchial tumors is closely related with tumor grade
and extension at the time of diagnosis. Unlike high-grade
MECs, progression of low-grade MECs predominantly
in children is slow, which allows for a good prognosis
at the time of diagnosis (if established at the beginning
of the diagnostic process). Diagnosis can be made more
rapidly with the early search of these tumors in patients
with chronic cough or RAI, improving the prognosis. 5,7,14
In conclusion, primary lung neoplasms, although rare in
children, should be included in the differential diagnosis of
patients with chronic lung disease. With the presentation
of persistent respiratory symptoms, chest x-ray should be
done. Diagnosis of lung atelectasis that does not improve
with conservative treatment warrants diagnostic bronchoscopy.
Among the list of endobronchial lesions, one must
consider MEC and confirm its diagnosis with endoscopic
282 Bol Med Hosp Infant Mex

iopsy. During pediatric age, with complete excision, MEC
has a good prognosis.
REFERENCES
1. Alves dos Santos JW, Licks da Silveira M, Tonello C, Dubermann
M. Carcinoma mucoepidermoide de bajo grado:
una causa rara de neumonía recurrente. Rev Am Med Resp
2005;1:52-54.
2. Sánchez RI, Arce QM. Carcinoma mucoepidermoide bronquial.
Diagnóstico diferencial de neumonía recurrente. Rev Med
Costa Rica Centroamérica 2007;64:113-117.
3. Reyes-Kattar J, Gómez M, Gómez L, Mota D, Giménez C,
Arcamone G, et al. Carcinoma mucoepidermoide de pulmón
en la infancia. Reporte de caso, revisión de la literatura. Rev
Venez Oncol 2007;19:344-348.
4. Oura H, Ishida I, Niikawa H, Mori Y, Ube K, Sasajima T, et
al. Sleeve resection of the left main bronchus for bronchogenic
carcinoid for preserving lung parenchyma. Kyobu Geka
2010;63:795-799.
5. El Mezni F, Ben Salha I, Ismaïl O, Braham E, Zeddini A, Ayadi-
Kaddour A, et al. Mucoepidermoid carcinoma of the lung. A
series of 10 cases. Rev Pneumol Clin 2005;61:78-82.
6. Fujita K. Mucoepidermoid carcinoma in a 13-year-old girl;
report of a case. Kyobu Geka 2009;62:423-426.
7. Ghraïri H, Kartas S, Ammar J, Abid H, Ayadi A, Kilani T, et al.
Prognosis of mucoepidermoid carcinoma of the bronchi. Rev
Pneumol Clin 2007;63:29-34.
8. Heitmiller RF, Mathisen DJ, Ferry JA, Mark EJ, Grillo HC.
Mucoepidermoid lung tumors. Ann Thorac Surg 1989;47:394-
399.
Vol. 69, July-August 2012
Bronchial mucoepidermoid carcinoma: a rare tumor in children
9. Wu M, Wang Q, Xu XF, Xiang JJ. Bronchial mucoepidermoid
carcinoma in children. Thorac Cardiovasc Surg 2011;59:443-
445.
10. Vogelberg C, Mohr B, Fitze G, Friedrich K, Hahn G, Roesner
D, et al. Mucoepidermoid carcinoma as an unusual cause for
recurrent respiratory infections in a child. J Pediatr Hematol
Oncol 2005;27:162-165.
11. Andersen JB, Mortensen J, Damgaard K, Skov M, Sparup J,
Petersen BL, et al. Fourteen-year-old girl with endobronchial
carcinoid tumour presenting with asthma and lobar emphysema.
Clin Respir J 2010;4:120-124.
12. Yu CH, Li J, Yu JQ, Wang B, Wang T, Wang DJ. Clinicopathological
features and prognosis of bronchial mucoepidermoid
carcinoma: analysis of 21 cases. Zhonghua Yi Xue Za Zhi
2007;87:41-43.
13. Firinci F, Ates O, Karaman O, Tekin A, Ozer E, Cakmakci H, et
al. A 7-year-old girl with cough, fever, pneumonia. Diagnosis:
mucoepidermoid carcinoma (MEC). Pediatr Ann 2011;40:124-
127.
14. Sogut A, Yilmaz O, Yuksel H. A rare cause of persistent atelectasis
in childhood: mucoepidermoid carcinoma. Tuberk Toraks
2008;56:325-328.
15. Lei J. Successful treatment of bronchial mucoepidermoid
carcinoma in a longstanding collapsed lung. Ann Thorac Surg
2010;90:655-657.
16. Fauroux B, Aynie V, Larroquet M, Boccon-Gibod L, Ducau le
Pointe H, Tamalet A, et al. Carcinoid and mucoepidermoid
bronchial tumours in children. Eur J Pediatr 2005;164:748-752.
17. Roby BB, Drehner D, Sidman JD. Pediatric tracheal and endobronchial
tumors: an institutional experience. Arch Otolaryngol
Head Neck Surg 2011;137:925-929.
18. Al-Qahtani AR, Di Lorenzo M, Yazbeck S. Endobronchial tumors
in children: institutional experience and literature review.
J Pediatr Surg 2003;38:733-736.
283

clinical case
Bol Med Hosp Infant Mex 2012;69(4):284-290
Hermansky-Pudlak syndrome: variable clinical expression in two cases
Rogelio Paredes Aguilera, 1 Norma López Santiago, 1 Angélica Monsiváis Orozco, 2 Daniel Carrasco Daza, 2
José Luis Salazar-Bailón 1
AbSTRACT
background. Hermansky-Pudlak syndrome is a genetic disorder characterized by albinism and bleeding of varying degrees due to alteration
in the structure of the platelets. The disorder may be accompanied by pulmonary, intestinal or kidney involvement. Identification of
several genetic alterations in this syndrome has been reported.
Case reports. We present two cases: the first of an adolescent male with mucocutaneous albinism and renal involvement. Bleeding episodes
started after being subjected to invasive studies and venipunctures, developing a perinephric hematoma. After severe sepsis, the
patient developed hemoperitoneum and pulmonary hemorrhage, which precipitated the patient’s death. Diagnosis was made postmortem.
In the second case, a female patient was diagnosed during infancy due to albinism and bleeding episodes, with progressive pulmonary
fibrosis that to date has limited her vital lung capacity.
Conclusions. Early diagnosis of the syndrome as well as the correct approach may prevent the development of complications or limit
the evolution. It is still under debate whether the genetic alterations described are associated with the expression of any particular clinical
manifestation.
Key words: Hermansky-Pudlak syndrome, albinism, hemorrhage, pulmonary fibrosis, renal failure.
INTRODuCTION
Hermansky-Pudlak Syndrome (HPS) is a multisystemic
disorder characterized by the presence of tyrosinase-positive
oculocutaneous albinism, hemorrhagic disease with
impaired platelet structure and, in some cases, pulmonary
fibrosis, colitis granulomatous or enteropathic granulomatous
renal disease secondary to disease due to lysosomal
storage of ceroid lipofuscin. HPS was first described in
1959. Initially, it was believed to be a single disease;
however, it is now considered to be a heterogeneous group
of at least eight autosomal recessive linked disorders that
share a common genetic pathway.
A diverse number of experimental studies have recognized
the association of HPS1, AP3B1, HPS3, HPS4,
1 Servicio de Hematología Pediátrica, 2 Servicio de Patología
Clínica, Instituto Nacional de Pediatría, México, D.F., México
Correspondencia: Dr. José Luis Salazar Bailón
Servicio de Hematología Pediátrica, Instituto Nacional de Pediatría
México, D.F., México
E-mail: drluissalazar@gmail.com
Received for publication: 7-6-11
Accepted for publication: 4-12-12
HPS5, HPS6, DTNBP1 and BLOC1S3 genes with HPS.
However, to date there is a debate about whether any
particular expression is directly related to a determined
clinical picture. We are presenting two clinical cases of
patients with this syndrome in which classic clinical signs
were observed, but seriously affected two different organs.
CLINICAL CASES
Case 1
We present the case of a 13-year-old male who was the
second child in his family and a descendant of Mexican
origin. His parents are healthy and a natural birth was
recorded with weight and height in the 50th percentile for
age. The patient experienced normal growth and development
with an albino phenotype, for which no specific
diagnosis was made. His clinical condition initiated with
a high fever without predominance of occurrence, general
malaise, fatigue, weakness, nonproductive cough, sore
throat and ascending and rapidly progressive lower limb
edema. He was prescribed intramuscular gentamicin treatment
for 4 consecutive days, furosemide (20 mg/12 h for
8 days), trimethoprim with sulfamethoxazole (unspecified
dose for 5 days) and prednisone (10 mg/24 h for 8 days).
284 Bol Med Hosp Infant Mex

The patient experienced a torpid evolution that progressed
insidiously. One month after the onset of fever, the parents
brought the patient to the emergency room of the National
Institute of Pediatrics in Mexico City (INP) because of
shortness of breath and orthopnea. Physical examination
documented widespread lack of skin pigment, widespread
poliosis, high-speed horizontal nystagmus, iris atrophy
with gray/blue coloring, positive transillumination, and
retina with macular bilateral hypoplasia without pigment
in the right eye. They also corroborated further clinical data
such as acute renal illness, anasarca, nephritis, congestive
heart failure due to hypervolemia, arterial hypertension,
pulmonary edema, and ascites.
Laboratory analysis showed the following results: 7.0
Hg, Hct 21%, MCV 90, MCH 28, 11,700 leukocytes, neutrophils
83%, bands 2%, lymphocytes 15%, and platelets
265,000. Blood chemistry results were as follows: serum
creatinine 9.96, BUN 190, glucose 153, sodium 131,
potassium 6.1, and chloride 106. Urinalysis was cloudy
yellow, urine specific gravity 1.020, pH 5, protein 75,
blood 250, leukocytes 5, erythrocytes 75. Venous blood
gases were pH 7.26, pCO 2 20.0, pO 2 39, HCO 3 8.9, base
excess -16.9, lactate 6.
With the above, the following diagnoses were integrated:
normochromic normocytic anemia, uremia, proteinuria,
hematuria, compensated metabolic acidosis and symptomatic
hyperkalaemia. The patient received medical treatment
based on loop diuretics, acute peritoneal dialysis, and prazosin
for arterial tension management. The patient exhibited
a successful evolution over a 3-week period.
To achieve stabilization of the patient, ultrasoundguided
percutaneous renal biopsy was performed. During
the immediate postoperative period, the patient developed
a left perirenal hematoma of 5 x 4 x 2 cm with 38 mL fluid.
This was corroborated with an ultrasound and involved the
renal capsule, fascia and adjacent muscle (Figure 1). It was
reabsorbed after 15 days of conservative treatment. The
biopsy material obtained was insufficient or inconclusive
to establish a diagnosis.
Based on the suspicion of a multisystemic disease
(kidney, lung, hematologic) with decreased C4 and normal
C3, the patient was initially treated for systemic lupus
erythematosus (SLE) and consisted of boluses of methylprednisolone
at 30 mg/kg of weight for 7 consecutive days.
When the patient was discharged due to improvement,
primary and secondary outpatient coagulation tests were
Vol. 69, July-August 2012
Hermansky-Pudlak syndrome: variable clinical expression in two cases
conducted and normal clot retraction was found, positive
tourniquet, normal bleeding time and aggregometry with
a slight decrease in the ADP (adenosine diphosphate)
curve and epinephrine. From the time of symptom onset,
the patient showed normochromic normocytic anemia
(chronic disease). Total neutrophils ranged from 1,800 to
2,600 and platelets between 146,000 and 334,000. Clotting
times were always normal. Bone marrow presented data of
red cell hyperplasia without evidence of blue histiocytes
or alterations in megakaryocytes (Table 1).
One month after discharge, the patient was readmitted
to the emergency room with symptoms of acute hypertension
secondary to renal failure. The event was controlled
with prazosin and diuretics for 3 days, for which the patient
had a favorable outcome.
As a consequence to the progressive decline in renal
function, it was necessary to place a permanent catheter
for dialysis. This became infected three times with
Staphylococcus epidermidis, thus requiring treatment with
vancomycin i.v. and i.p. for 10 days without complications.
Figure 1. Renal ultrasound showing the size and the relationship
between the cortex and normal marrow.
Table 1. Results of patient aggregometry
Patient (%) Control (%)
ADP 62 84
Collagen 64 78
Epinephrine 60 86
Ristocetin 78 70
AA 70 70
ADP, adenosine diphosphate; AA, arachidonic acid.
285

Rogelio Paredes Aguilera, Norma López Santiago, Angélica Monsiváis Orozco, Daniel Carrasco Daza, José Luis Salazar-Bailón
During the third colonization, the patient developed
bacterial peritonitis complicated with bilateral pneumonia.
Despite treatment with specific antibiotics according to the
culture and sensitivity, the patient experienced deterioration
in his condition and eventually led to septic shock.
Deterioration of the patient’s general condition persisted
despite supportive treatment. Disseminated intravascular
coagulation (DIC) was presented with organ dysfunction
involving the heart, lung and liver. Peritonitis was
documented due to Candida albicans and Enterococcus
faecium, as well as a right lung abscess with empyema.
Treatment included broad spectrum antibiotics (meropenem
and vancomycin) for 21 days, with doses adjusted for
renal function. The patient demonstrated whitish, hyperemic
lesions on gums and cheeks, with a necrotic aspect on
the nose, which led to suspicion of fungal infection. Nasal
and oral aspergillosis secondary to DIC was confirmed
by culture, and bleeding developed in venipuncture sites
along with malignant hemoperitoneum.
The patient died as a result of massive pulmonary
hemorrhage and cardiac arrest despite the treatment he
received.
During postmortem study and conducting an intentional
search, bone marrow and patient’s blood were analyzed by
electronic microscopy. Platelets showed an irregular discoid
shape, granulations, canalicular system, mitochondria
and normal structure microtubules (Figure 2). Absence of
dense granules in the platelet structure was noted as well
as replacement by collagen fragments (Figure 3). These
data, together with the clinical course of the patient, allowed
us to establish the diagnosis of HPS in this patient.
Case 2
We present the case of a 5-year-old female who was admitted
without relevant perinatal history. The patient was
of Mexican origin and descent. Her father had sequelae
of neurocysticercosis and a paternal aunt was reported to
have lupus erythematosus. The patient’s two brothers are
apparently healthy.
Among her important clinical events, the patient presented
a Henoch-Schönlein blister at the age of 1 year
and 3 months, for which she received unspecified hospital
treatment. She was discharged at 2 weeks without apparent
sequelae.
During her follow-up and while performing serial blood
counts, mild transient neutropenic events were docu-
Figure 2. Electron microscopy showing granulations (1), canalicular
system (2), mitochondria (3) and microtubules (4). Irregular collagen
fragments replacing dense granules are also seen.
mented without cyclical pattern and with total neutrophil
nadir between 1,500 and 1,800. For this reason, the patient
was referred to the pediatric hematologist who initiated
treatment with granulocyte-stimulating colony factor
(GSCF) at a dose of 5 µg/kg/weight during alternating
periods. With this treatment, the numbers of neutrophils
rose to normal levels. No specific alterations were seen in
the platelet counts. There was an intentionally search of
structural alterations in the platelet number. Using electron
microscopy, 32 platelets were studied of which 27 lacked
dense granules, i.e., an average of 0.27 dense bodies per
platelet, which is well below the normal values (Figure 4).
Again, during routine examination, hepatomegaly was
found. An ultrasound determined the presence of a 3 x 4
x 3 cm liver mass. Liver biopsy was performed at the age
of 2 years and 3 months. It was concluded that the mass
was secondary to infection caused by Epstein-Barr virus.
To date the patient receives monthly treatment with i.v.
doses of immuomodulatory gammaglobulin.
At 3 years of age the patient demonstrated severe
mucositis with sloughing of both cheeks and mucosal
286 Bol Med Hosp Infant Mex

Figure 3. Replacement of missing collagen-dense granules is
clearly shown.
detachment, compromising gums and tongue. She was
treated with clindamycin and fluconazole for 10 days with
favorable results.
The patient has presented multiple cases of lower
respiratory tract infection with varying severity. The
first event was pneumonia was at 11 months of age with
unspecified treatment. At 2 years of age, pneumonia was
complicated by pleural effusion, which required hospital
treatment for 6 weeks. The third case of pneumonia was
2 months after discharge from the hospital and required
treatment with mechanical ventilation and 15 days of
treatment with unspecified broad-spectrum antibiotics.
The fourth event of pneumonia was presented at 2 years
and 8 months of age, with a torpid evolution despite
management with broad-spectrum antibiotics. Bronchoscopy
was performed with bronchoalveolar lavage, and
pulmonary candidiasis was reported. On this ocassion,
the patient was treated with itraconazole (50 mg/kg of
weight for 21 days) and subsequently with continuous
prophylaxis. She persisted with a sporadic, productive
Vol. 69, July-August 2012
Hermansky-Pudlak syndrome: variable clinical expression in two cases
Figure 4. Electron microscopy performed in blood. Normal platelet
structures are observed as well as the absence of dense granules.
cough for >2 years, progressive wheezing with medium
efforts and later with lower efforts. At 3 years of age the
patient already showed signs of chronic hypoxia with
clubbing fingers and pectus carinatum. She also had
recurrent cases of bronchospasm necessitating hospital
treatment with supplemental oxygen, bronchodilators
and antibiotics. For this reason she was referred to the
National Pediatric Institute (INP).
Physical examination of the patient revealed light tan
skin color, silver-colored hair with dark brown eyebrows
and eyelashes, coarse facies with bulbous nose, prominent
forehead at the level of the metopic suture, bilateral epicanthus,
eyes with isochoric pupils and normal reflexes,
fundus of the eye with 30 to 40% excavation of the papilla,
macula with no foveolar brightness, gingival hyperplasia,
no cardiovascular compromise, hepatomegaly of 4-4-1 cm
below the costal margin and generalized hypotonia, pectus
carinatum, normal inspiration and expiration, bilateral
crepitant rales with “sail sign” and bilateral reticulonodular
infiltrates on chest x-ray (Figure 5). At 5 years of age the
287

Rogelio Paredes Aguilera, Norma López Santiago, Angélica Monsiváis Orozco, Daniel Carrasco Daza, José Luis Salazar-Bailón
Figure 5. AP chest x-ray showing bilateral reticulonodular infiltration
and prominent pulmonary artery is demonstrated.
patient presented with a new case of pneumonia, which
was treated with meropenem for 14 days.
Bilateral micronodular infiltrate was observed with
chest CAT (with no apparent subpleural affection) and leftsided
rounded pulmonary nodule (with well-defined edges)
(Figure 6). Bronchoscopy was performed, demonstrating
normal results. Bronchoalveolar lavage reported the presence
of abundant hemosiderophages and compatible data
with lymphocytic interstitial pneumonia. Angioresonance
reported vasculitis data with posterior bilateral basal consolidation,
suggestive of bronchiectasis.
Lung biopsy was performed where data were consistent
with pulmonary fibrosis. To complement the data,
echocardiogram was performed, which showed evidence
of pulmonary hypertension with pulmonary artery pressure
of 87 mmHg. The patient was was treated with
sildenafil.
Respiratory function showed progressive deterioration,
increasing dyspnea with less stress, persistent rales,
acrocyanosis, and clubbing. Treatment was initiated with
supplemental oxygen when necessary, methotrexate 500
mg/kg monthly and 18 mg of deflazacort daily, nebulization
with budesonide and salbutamol with ipratropium
bromide as needed and i.v. gammaglobulin to 500 mg
monthly. With this treatment, respiratory symptoms have
decreased and the breathlessness improved as well as
the overall status of the patient. In addition, the patient
changed her residence to a location at sea level. Her
other laboratory studies were normal except for mild
persistent neutropenia and discreetly decreased NK cell
cytotoxicity.
Figure 6. Lateral chest x-ray confirming the presence of reticulonodular
infiltrate.
DISCuSSION
The classic form and description of diagnostic criteria
of HPS are the presence of mucocutaneous albinism and
bleeding diathesis of variable severity. 1,2 It is of high diagnostic
value to document the decreased index of dense
granular bodies in platelets using electron microscopy.
This was carried out in both patients. In an optional and
complementary form we can determine the presence of a
complex amorphous lipid protein and ceroid-lipofuscin
autofluorescence in urinary sediment and in parenchymal
cells. However, this is not essential for diagnosis. 1,3-9
Albinism in this syndrome is characterized with the
skin having a white to olive color, but always in a lighter
shade than the rest of the family. In addition, hair color is
usually between white and light brown, with a tendency to
become darker over the years. 1,4-6 A constant is the presence
of nystagmus from birth that, generally, is decreased alternating
with visual acuity. It is fast moving with a tendency
to decrease with age, and it is usually most severe when the
patient is tired or under stress. The iris color is bluish and
288 Bol Med Hosp Infant Mex

arely does it turn blue or brown. Visual acuity is found
between 20/50 and 20/400, but it is typically 20/200 and
usually remains constant after early childhood. 1
From the hematological viewpoint, bleeding is secondary
to the lack of dense granules in the platelets. In the
normal structure, these granules contain calcium, serotonin,
ADP, ATP, pyrophosphate and lysosomal membrane
proteins. Once the platelets are activated, the granules fuse
with the plasma membrane via the soluble receptor of the
protein factor of the fixative sensitive to N-ethylmaleimide
and undergo exocytosis, resulting in platelet recruitment.
In the absence of this mechanism (secondary aggregation
response), patients have prolonged bleeding time, absence
of secondary wave in the ADP test and epinephrine in aggregometry
results, as well as absence of ATP secretion
in lumi-aggregometry. These studies are not suitable for
diagnosis because they present a high rate of variation.
However, demonstration of platelet hypogranulation in
electron microscopy is considered, along with the clinical
features, in the definitive diagnosis of HPS. 1,3,8,9
Pulmonary fibrosis consists of a progressive lung disease
with a highly variable course, although symptoms
generally worsen during the fourth decade of life due to the
deposition of ceroid lipofuscin. 1,10 Granulomatous colitis
presents with clinical resemblance to Crohn’s disease due
to widespread inflammation and is not infrequent to be seen
in the entire digestive tract. Renal failure has been reported
in cases with an isolated syndrome or even associated with
lupus nephritis. However, renal dysfunction, colitis and
pulmonary fibrosis have been associated with infiltration
by lysosomal deposits of ceroid lipofuscin. 1,11,12 Through
genetic analysis we can sequence the genes involved in the
origin of the syndrome, although it is still debated whether
there is direct correlation with the clinical scenario of
each patient. Therefore, it is only applied in experimental
studies and not in daily clinical practice. 1,3-9
HPS1-mutation is common among homozygous patients
from Puerto Rico. It is associated with pulmonary
fibrosis; likewise, the HPS4 in European individuals
confers a similar predisposition so it is suggested that the
mutation of these genes may cause lung and hemorrhagic
disease. The AP3B1 mutation is associated with persistent
neutropenia and recurrent infectious conditions in the
patient. Congenital neutropenia tends to be less severe
than in patients with severe or cyclic chronic neutropenia
and presents a tendency to develop syndromes of activa-
Vol. 69, July-August 2012
Hermansky-Pudlak syndrome: variable clinical expression in two cases
tion of macrophages and NK cell function. Patients with
HPS3 usually have slightly marked symptoms. Albinism
is characterized by minimal cutaneous hypopigmentation
and even the only condition becomes ocular. Mutations
of HP5, HP6, HPS7 and HPS8 have been sporadically
reported. 1,11-23
The patients described in this study met the diagnostic
criteria of HPS and illustrated the heterogeneity of possible
manifestations. Our data are consistent with those reported
by Gamboa et al. which, due to the prominence of hematologic
and pulmonary manifestations, can be considered
as type 1. However, lack of purposeful approach causes
a subdiagnosis and lacks most representative cases. We
must always consider HPS in the differential diagnosis
of newborns with oculocutaneous albinism so as to not
overlook the determination of a deficiency in clotting that
could lead to serious complications in the patient.
REFERENCES
1. Gahl WA. Hermansky Pudlak Syndrome. Gene Reviews.
Available at: http://www.ncbi.nlm.nih.gov/books/NBK1287
2. Gamboa-Marrufo JD, Loperena-Anzaldúa L, Bello-González
A. Albinismo y enfermedad hemorrágica. Síndrome de Hermansky
y Pudlak. Presentación de un caso. Bol Med Hosp Inf
Mex 1984;41:53-55.
3. Boztug K, Welte K, Zeidler C, Klein C. Congenital neutropenia
syndromes. Immunol Allergy Clin North Am 2008;28:259-275.
4. Bomalaski JS, Greene D, Carone F. Oculocutaneous albinism,
platelet storage pool disease, and progressive lupus nephritis.
Arch Intern Med 1983;143:809-811.
5. Schachne JP, Glaser N, Lee SH, Kress Y, Fisher M. Hermansky-Pudlak
syndrome: case report and clinicopathologic
review. J Am Acad Dermatol 1990;22:926-932.
6. Sánchez MR. Cutaneous diseases in Latinos. Dermatol Clin
2003;21:689-697.
7. El-Molfy MA, Esmat SM, Abdel-Halim MR. Pigmentary disorders
in the Mediterranean area. Dermatol Clin 2007;25:401-
417.
8. Neunert CE, Journeycake JM. Congenital platelet disorders.
Hematol Oncol Clin North Am 2007;21:663-684.
9. Córdova A, Barrios NJ, Ortiz I, Rivera E, Cadilla C, Santiago-
Borrero PJ. Poor response to desmopressin acetate (DDAVP)
in children with Hermansky-Pudlak syndrome. Pediatr Blood
Cancer 2005;44:51-54.
10. Brantly M, Avila NA, Shotelersuk V, Lucero C, Huizing M,
Gahl WA. Pulmonary function and high-resolution CT findings
in patients with an inherited form of pulmonary fibrosis,
Hermansky-Pudlak syndrome, due to mutations in HPS-1.
Chest 2000;117:129-136.
11. Sandrok K, Bartsch I, Rombach N, Schmidt K, Nakamura
L, Hainmann I, et al. Compound heterozygous mutations in
289

Rogelio Paredes Aguilera, Norma López Santiago, Angélica Monsiváis Orozco, Daniel Carrasco Daza, José Luis Salazar-Bailón
siblings with Hermansky-Pudlak syndrome type 1 (HPS1). Klin
Padriatr 2010;3:168-174.
12. Morra M, Geigenmuller U, Curran J, Rainville IR, Brennan T,
Curtis J, et al. Genetic diagnosis of primary immune deficiencies.
Immunol Allergy Clin North Am 2008;28:387-412.
13. Dessinioti C, Stratigos AJ, Rigopoulus D, Katsambas AD. A review
of genetic disorders of hypopigmentation: lessons learned
from the biology of melanocytes. Exp Dermatol 2009;18:741-
749.
14. Ciciotte S, Gwynn B, Moriyama K, Huizing M, Gahl WA, Bonifacino
JS, et al. Cappuccino, a mouse model of Hermansky-
Pudlak syndrome, encodes a novel protein that is part of the
pallidin-muted complex (BLOC-1). Blood 2003;101:4402-4407.
15. Huizing M, Anikster Y, Gahl WA. Hermansky-Pudlak syndrome
and related disorders of organelle formation. Traffic
2000;1:823-835.
16. Jung J, Bohn G, Allroth A, Boztug K, Brandes G, Sandrock
I, et al. Identification of a homozygous deletion in the AP3B1
gene causing Hermansky-Pudlak syndrome, type 2. Blood
2006;108:362-369.
17. Gerrard JM, Lint, D, Sims PJ, Wiedmer T, Fugate RD, McMillan
E, et al. Identification of a platelet dense granule membrane
protein that is deficient in a patient with the Hermansky Pudlak
syndrome. Blood 1991;1:101-112.
18. Fontana S, Parolini S, Vermi W, Booth S, Gallo F, Donini M,
et al. Innate immunity defects in Hermansky Pudlak type 2
syndrome. Blood 2006;107:4857-4864.
19. Enders A, Zieger B, Schwarz K, Yoshimi A, Speckmann
C, Knoepfle EM, et al. Lethal hemophagocytic lymphohistiocytosis
in Hermansky-Pudlak syndrome type II. Blood
2006;108:81-87.
20. Gunay-Aygun M, Huizing M, Gahl WA. Molecular defects
that affect platelet dense granules. Semin Thromb Hemost
2004;30:537-547.
21. White JG, Edson JR, Desnick SJ, Witkop CJ Jr. Studies of
platelets in a variant of the Hermansky-Pudlak syndrome. Am
J Pathol 1971;63:319-332.
22. Feng L, Novak EK, Hartnell LM, Bonifacino JS, Collinson
LM, Swank RT. The Hermansky Pudlak syndrome 1 (HPS1)
and HPS2 genes independently contribute to the production
and function of platelet dense granules, melanosomes, and
lysosomes. Blood 2002;99:1651-1658.
23. Carmona-Rivera C, Golas G, Hess R, Cardillo ND, Martin
EH, O’Brien K, et al. Clinical, molecular, and cellular features
of non-Puerto Rican Hermansky-Pudlak syndrome patients
of Hispanic descent. J Invest Dermatol 2011;131:2394-2400.
doi: 10.1038/jid.2011.228.
290 Bol Med Hosp Infant Mex

clinicopathological case
Newborn with hypoplastic left heart syndrome
Vol. 69, July-August 2012
Bol Med Hosp Infant Mex 2012;69(4):291-297
Luis Alexis Arévalo Salas, 1 Sandrino José Fuentes Alfaro, 1 Jorge Omar Osorio Díaz, 1 Begoña Segura
Stanford, 1 Mario Pérezpeña Díazconti 2
Summary of the Clinical History
We present the case of a male newborn (NB) 4 days of age
who was referred to a tertiary hospital due to polypnea and
cyanosis. The infant was the product of a first pregnancy
of a 17-year-old mother who reported prenatal care from
the second month of pregnancy. At 20 weeks an obstetric
ultrasound noted a cardiac alteration. For this reason the
mother was sent to a high specialty hospital where the
condition was confirmed. Treatment based on folic acid
and ferrous sulfate and two doses of anti-tetanus vaccine
was provided. At 38.6 weeks of gestation there was
spontaneous rupture of membranes with onset of labor.
The NB was born via eutocic labor with spontaneous cry
and respiration: Apgar 9/9, weight 2515 g, height 47.5 cm.
Cyanosis was noted and the newborn was transferred to
the neonatal intensive care unit (NICU) where treatment
with prostaglandin E1 (PGE1) was begun at an initial dose
of 0.05 μg/kg/min until a maintenance dose of 0.01 μg/kg/
min was reached. On the fourth day of life, the NB was
transferred to the Hospital Infantil de Mexico Federico
Gomez (HIMFG) for cardiac management.
On admission the NB was found to be active and
reactive, without characteristic facies, perioral and nail
cyanosis I/IV, and decreased pulses in all four extremities.
1 Departamento de Cardiología,
2 Departamento de Patología Clínica y Experimental, Hospital
Infantil de México Federico Gómez, México, D.F., México
Correspondence: Dr. Luis Alexis Arévalo Salas
Departamento de Cardiología
Hospital Infantil de México Federico Gómez
México, D.F., México
E-mail: luisalas17@hotmail.com
Received for publication: 2-9-12
Accepted for publication: 3-22-12
Blood pressure on the right arm was 72/36/48 and oxygen
saturation was 85%. The infant was normocephalic,
anterior fontanelle 2 x 2 cm, and normotensive. There
was polypnea at rest, xiphoid retraction and intercostal
retraction, intense left parasternal precordial hyperactivity
and palpable S2. On auscultation there were rhythmic
heart sounds, intense and single second sound, and a 2/6
systolic murmur in the 4th left intercostal parasternal
space. Pulmonary fields were clear. Abdomen was soft
with mummified umbilical stump without evidence of
infection. Liver was 3 cm below the right costal margin
and of firm consistency. Spleen was nonpalpable. Normal
male genitalia were reported.
X-ray on admission showed situs solitus, levocardia
and grade III cardiomegaly with evidence of venocapillary
congestion. Electrocardiogram (EKG) showed right atrial
enlargement and right ventricular hypertrophy. Transfontanelle
and renal ultrasound were done with normal results.
Laboratory tests were considered within normal limits.
Two-dimensional Echocardiography with Doppler Color
Flow (Eco-bi)
In the subcostal axis there was situs solitus, levocardia,
and normal systemic and pulmonary venous return.
Atresia of the left A-V valve was documented as well as
an interatrial septal defect of 4.8 mm in diameter with left
to right shunt without gradient.
In the apical four-chamber cut a dominant right ventricular
cavity was demonstrated with moderate tricuspid
valve insufficiency with hypoplastic left ventricular cavity
(Figure 1).
In the parasternal long axis, a hypoplastic left ventricular
cavity is seen from which emerges the aorta with severe
hypoplasia with a 2-mm diameter (Z = -9.6). On color
flow Doppler, no flow was observed through the aortic and
291

Luis Alexis Arévalo Salas, Sandrino José Fuentes Alfaro, Jorge Omar Osorio Díaz, Begoña Segura Stanford, Mario Pérezpeña Díazconti
A b
Figure 1. (A) Four-chamber apical view where a dominant right
ventricular cavity and a hypoplastic left ventricle chamber are seen.
(B) Schematically, right atrium (RA), left atrium (LA), right ventricle
(RV) and hypoplastic left ventricle (LV) are seen.
mitral valves. In the parasternal short axis the diameter of
the aortic ring was observed to be 2.8 mm (Z = -8.47) and
pulmonary ring 12.3 mm (Z = +3.34) in anterior and left
position. The ratio of the rings was 4.3:1 in favor of the
pulmonary ring. The pulmonary branches were confluent.
On color flow Doppler, systolic flow from a large patent
ductus arteriosus (PDA) was observed. In the suprasternal
axis was appreciated a suprasternal narrowing at the level
of the aortic isthmus (Figure 2) suggesting juxtaductal
aortic coarctation. There is a large PDA that showed a short
circuit from right to left into the aorta, with retrograde flow
to the aortic arch and ascending aorta.
On admission, management was begun by restricting
parenteral fluids to 80 ml/kg/day, glucose 6 g/kg/min,
sodium 3 mEq/kg day, 4% potassium, calcium 100 mEq/
kg/ day, PGE1 0.01 μg/kg/min, furosemide 1 mg/kg/dose
every 12 h, and captopril 0.2 mg/kg/dose every 8 h. During
the second day of hospital stay, jaundice was detected with
indirect bilirubin 12.68 mg dL, direct bilirubin 0.67 mg
dL, albumin 3.2 g/dL, and globulin 2.6 g dL. Phototherapy
was begun and was maintained for 3 days.
A b
Figure 2. (A) Suprasternal projection with color Doppler where the
anatomy of the aortic arch is observed as well as retrograde filling
(red) of the isthmus, transverse portion and ascending portion of
the aortic arch. (B) In the same suprasternal projection the position
of the ascending aorta (AoA), the transverse portion and the
isthmus of the aortic arch (Ao Arco), the relationship of the trunk
of the pulmonary artery (TAP) with patent ductus arteriosus (PDA)
and the descending aorta (AoD) are diagrammed. The area of aortic
coarctation (CoA) is noted (arrow).
The case was discussed in a joint session with the Cardiovascular
Surgery Service concluding that the patient
was a candidate for total correction using the Norwood
technique, which was done 10 days after admission.
Operative report notes a perfusion of 1 h 55 min with a
minimum temperature of 16-18°C. Surgery was without
complications or incidents. However, on attempting to
wean from the cardiopulmonary bypass pump, the patient
showed persistent hypotension, bradycardia and desaturation
without recovery and died in the operating room.
During the surgical waiting period, the NB remained in
good general condition without signs of acute heart failure
and was under oral feeding until the surgical event.
Case Discussion
This was a NB who was the product of a first pregnancy
of a healthy young mother who had satisfactory prenatal
care. At 20 weeks of gestation (WG), congenital heart
disease was detected by fetal echocardiography. For this
reason the patient was sent to a tertiary level institution for
management where the impression of cardiac dysfunction
was confirmed. At 38 weeks there was spontaneous rupture
of membranes and the NB was vaginally delivered with
Apgar scores of 9/9.
The reason for admission to our service was the presence
of generalized cyanosis and resting polypnea with
intercostal retractions, along with findings of intense precordial
hyperactivity and a second palpable tone, which are
significant conditions for diagnosis of severe congenital
heart disease. These alterations during the neonatal stage
are characterized by the condition of relying on a PDA
for survival because, upon closure, signs and symptoms
that tend to be lethal appear. At this point three physiopathological
conditions should be mentioned in which this
may occur: a) pulmonary flow is dependent on the PDA
whose clinical manifestation is hypoxia, b) with an inappropriate
mixture of blood, a state of metabolic acidosis
will develop when there is closure of the PDA and c) when
the systemic flow depends on a PDA and when it closes
there is cardiogenic shock.
In the condition mentioned, congenital heart disease
is characterized by an obstruction present at the outflow
tract of the right ventricle (stenosis or atresia) and a defect
that allows mixing of intracardiac blood (ventricular
septal defect, atrioseptal defect) or extracardiac (PDA).
This group is characterized by reduced pulmonary flow,
292 Bol Med Hosp Infant Mex

and clinical data in addition to cyanosis are tachypnea at
rest and a second pulmonary sound that is inaudible or
difficult to detect, which is occasionally associated with
an ejection murmur specifically in the tetralogy of Fallot.
Other abnormalities in this group such as pulmonary
atresia or Ebstein’s disease may present without murmurs.
This group can be ruled out by the respiratory pattern,
auscultation and cardiomegaly, in addition to the fact that
the clinical manifestation is the hypoxic crisis.
The second group mentioned are heart diseases in which
there may be no intracardiac defects, but there is a ventricular
arterial discordance in the case of D-transposition of
the great vessels or double outlet of the right ventricle with
subpulmonary interventricular communication (Taussig-
Bing disease) in which the circulation is parallel. By force,
a defect is needed so that the mixture can “oxygenate” the
blood in the aorta. Symptoms are cyanosis and metabolic
acidosis but usually the cardiomegaly is small or nonexistent
and associated with a narrow vascular pedicle, for
which this group of symptoms can also be ruled out.
The third group includes those heart diseases in which
some type of left obstruction predominates and is manifested
by cardiac insufficiency, pulmonary edema and,
under extreme conditions, by cardiogenic shock. In this
group, the PDA allows a right to left shunt that retains
systemic output to the extent possible with possible cardiac
diseases such as critical aortic stenosis of the NB, Shone
Syndrome, hypoplastic left heart syndrome (HLHS),
and total anomalous connection of infradiaphragmatic
pulmonary veins. 1
Physical examination is a crucial weapon to establish
the diagnosis of cardiac disorders. In the case in question,
pulses were decreased in all four extremities; therefore,
aortic coarctation can be ruled out because one would
find intense pulses in the arms and neck and absent or
diminished in the lower extremities with a pressure gradient
between arm and leg. However, coarctation of the
aorta may accompany other left-sided obstructions and
the classic clinical picture may be modified, particularly
in the presence of a PDA that allows improvement of
cardiac systemic pulses, which may be felt even in the
legs. Furthermore, in the case of critical aortic stenosis,
whereas the pulses may be filiform in all four extremities
and be accompanied by variable cardiomegaly, there is
often an ejection murmur in the second right intercostal
space, sometimes accompanied by an opening snap. This
Vol. 69, July-August 2012
Newborn with hypoplastic left heart syndrome
is different from what was described for this patient
whose auscultatory focus was the fourth left intercostal
parasternal space (tricuspid), very possibly related to
tricuspid regurgitation. Therefore, diagnosis of critical
aortic stenosis can be eliminated.
In 1963 an anomaly called Shone syndrome 2 was
described and characterized by serial left obstructions
(aortic coarctation, subaortic stenosis, parachute mitral
valve and mitral supraventricular ring) that could imply
a diagnostic complexity similar to that shown in extreme
cases of left-side obstruction such as HLHS. Clinical data
may be similar with regard to the magnitude of cardiac
insufficiency, pulmonary edema or shock under great
precordial hyperactivity and pulmonary hypertension,
which is manifested by an intense second pulmonary
sound. However, in Shone syndrome it is possible to detect
murmurs due to aortic obstruction. In HLHS the clinical
severity will be related to the size of the foramen ovale.
If it is restricted or absent, symptoms will begin minutes
after birth. 3 In this case there was an interatrial communication
of 4.8 mm in diameter that allowed early treatment of
PGE1 as well as demonstrating clinical stability for some
days. Closure of PDA is crucial to the survival of these
patients because it allows decongestion of the pulmonary
vasculature by decreasing pulmonary edema. If the patient
becomes lethargic, more dyspneic, with desaturation and
increased heart failure, then the PDA has certainly started
to close. 4 In order to be able to establish the differential
diagnosis between these conditions, imaging studies are
mandatory. X-rays as well as EKG are nonspecific in
both conditions because they show diverse degrees of
cardiomegaly as well as right ventricular hypertrophy.
Undoubtedly, accurate diagnosis is provided by an Eco-Bi
because it reports extreme hypoplasia of the left ventricle
associated with aortic and mitral atresia and it is the one
examination that determines an ascending aorta of 2 mm
in diameter, which is a relevant prognostic factor for postoperative
survival. 5 Interatrial communication of 4.8 mm
in diameter possibly provided hemodynamic stability by
allowing a free short circuit from left to right. In this way,
there was decongestion of the lungs and tricuspid evidence
that could eventually contraindicate a Fontan circulation.
It is relevant to mention that this case had a prenatal
diagnosis and that from birth the patient received optimal
treatment due to the infusion of PGE1, 6 which allowed
for transfer without incidence, maintaining hemodynamic
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Luis Alexis Arévalo Salas, Sandrino José Fuentes Alfaro, Jorge Omar Osorio Díaz, Begoña Segura Stanford, Mario Pérezpeña Díazconti
stability and acid-base equilibrium during the patient’s
admission. It also allowed the surgical team, together
with the family, to decide on the type of correction that
was finally provided. When the available treatment options
were evaluated, hybrid palliation was ruled out
because of the echographically demonstrated association
with aortic coarctation which, at the same time, could
impede a waiting period for heart transplant so that the
only option was to perform a Norwood-type correction.
This option had a poor prognosis due to the weight limits
for this procedure (2515 g) and an ascending aorta of 2
mm in diameter, which are factors associated with a rate
of mortality. 5
At 16 days of life, a stage I Norwood procedure was
performed that consisted of reconstructing the ascending
aorta, creating an anastomosis with the trunk of the pulmonary
artery including release of the coarctation, placing
a bandage in each pulmonary branch with the goal of
regulating pulmonary flow and placing a tube under Sano
technique between the right ventricle and the pulmonary
artery to provide pulmonary flow. At this time, a perfusion
time of 1 h 55 min was reported with hypothermia of 16 to
18°. This is relevant because the complications related to
circulatory failure are greater after 40 min and are inherent
to a greater metabolic suppression. Although this scenario
was predictable because of the anatomic characteristics
of the case, this was possibly the reason why the patient
could not be weaned from the pump. The final diagnoses
were as follows:
1. Term NB with weight appropriate for gestational
age
2. HLHS associated with mitral-aortic atresia and
aortic coarctation
3. Norwood type surgery with Sano tube
4. Cardiogenic shock as cause of death.
Histopathological Description
Autopsy was performed on the NB in the Pathology Department
with an incision over the sternal line of 10 cm in
length. On opening the chest and abdominal cavity, there
was 13 mL of bloody material coming from the left pleural
cavity and 15 mL in the abdominal cavity. The heart was
in levocardia with situs solitu, the cardiopulmonary block
weighed 99 g (for an expected 66 g). This increase was
at the expense of the heart that showed dilatation of the
right ventricle as well as right atrium and vena cavas. The
external surface of the right ventricle showed hemorrhagic
zones and a sutured surgical wound.
On atrial dissection there was atrioventricular concordance
observed and a surgically widened foramen ovale
of 1 cm in its greatest axis. When the right ventricle
was opened, the right morphology in a very dilated and
hypertrophic cavity was documented with a thickness of
0.6 mm as well as zones of different colors throughout the
length of the myocardium in this ventricle. The tricuspid
valve was redundant and its output had a pulmonary valve
with a 1-cm diameter ring with normal-appearing valves.
The trunk of the pulmonary artery was anastomosed to
the aorta up to the level of the arch. There was no ductus
arteriosus seen and the supraaortic trunk arose normally.
There was a widened aortic arch and descending aorta
seen. At the level of the infundibulum the exit of the
polytetrafluoroethylene (Gore-Tex) tube was found, which
connected with the proximal third of the left pulmonary
branch without obstructions. Five right pulmonary veins
were discovered: three right and two left, which connect
to the left atrium. The mitral valve was atresic and communicated
with a small cavity that corresponded to the
left ventricle without demonstrating permeability towards
the aorta (Figure 3). The histological sections carried out
in the right ventricular myocardium showed multiple
areas of infarction of ∼4 h of evolution in which areas of
hemorrhage, edema, erythrocytes between myofibrils and
disruption of the fibers was seen, which correlate with
findings of color changes described macroscopically. In
addition to the above, there were myocytolysis cellular
changes that translate into cardiogenic shock (Figure 4).
In the lungs there was emphysema with rupture of
alveolar walls and enlargement of the air spaces. No inflammation,
edema or hemorrhage was noted; however,
small- and medium-caliber vessels showed changes in
the arterial media by muscularization secondary to pulmonary
hypertension. When these cells were stained with
Masson trichrome, there was fibrosis around the vessel
and decreased lumen. Elastic fiber disorganization and
rupture of the muscle were demonstrated by staining that
corresponded to changes due to grade A pulmonary arterial
hypertension according to the Rabinovitch classification
(Figure 5). 7
The enlarged liver was congested microscopically, with
extramedullary hematopoiesis and steatosis. Portal spaces
were normal and liver and kidneys showed an increase
294 Bol Med Hosp Infant Mex

A b
C D
Figure 3. (A) Cardiopulmonary block weighing 99 g (expected
weight 66 g) due to the increased size and weight of the heart.
Changes in the color of the cardiac surface are observed, which
correlate with histological changes of extensive infarction. (B)
Pulmonary veins, three right and two left, show no alterations.
(C) Gore-Tex tube extends from the middle third ventricle into the
pulmonary artery on the left side. (D) At the opening of the heart
chambers, the atrium and right ventricle are of right morphology.
The first is very dilated, and there is ventricular wall hypertrophy.
There is interatrial communication (blue arrow) that is enlarged
during surgery and measures 1 cm on the long axis. Wall thickness
demonstrates changes in coloration.
A b
Figure 4. (A) Histological sections of the left ventricular wall show
changes of acute infarction of ∼4 h. Changes are extensive and are
observed in all studied sections. There is disorganization of the myofibrils,
recent hemorrhage, edema and shock changes represented
by myocytolysis. (B) Intense edema is shown in this field (arrows).
in size and weight due to intense congestion. All these
changes were secondary to cardiac insufficiency. The brain
showed a normal weight and development with congestion
of the blood vessels. Two zones of hemorrhage were
detected in the brain, possibly secondary to congestion.
The digestive tract showed bands of contraction caused
by the shock status (Table 1).
Vol. 69, July-August 2012
A b
Newborn with hypoplastic left heart syndrome
Figure 5. (A) Pulmonary parenchyma cuts show rupture of alveolar
walls forming large air spaces, which represent areas of
emphysema. (B) In this Masson trichrome stain, small and mid-size
vessels demonstrate perivascular fibrosis and muscularization of
the median.
Table 1. Final anatomic diagnoses
PRINCIPAL DISEASE
HLHS
CONCOmITANT ALTERATIONS
Status postsurgery of Norwood/Sano
Mitral atresia
Aortic atresia
Widened foramen ovale 1 cm
Left hemithorax 15 ml
Recent hemorrhage in visceral and parietal pericardium
RVH
Recent hemorrhage in myocardium of right atrium and
ventricle
Pulmonary arterial hypertension (grade A Rabinovitch)
Acute extensive infarct to myocardium
(~4 h of evolution)
Serosanguineous ascitic fluid 13 ml
Recent sutured surgical wound in the anterior chest of 10 cm
in length
Partial surgical absence of the thymus
Hemorrhagic areas in the brain
Panlobular steatosis affecting 30% of the hepatic parenchyma
Anatomic data of shock
Ischemic visceral hypoxic myopathy affecting the esophagus,
stomach, colon and bladder
Decrease in the lymphoid tissue of the thymus
Recent subarachnoid cerebellar hematoma
HLHS, hypoplastic left heart syndrome: RVH, right ventricular
hypertrophy.
Comment
This case reported here is of particular interest according to
two aspects. The first, because the diagnosis of congenital
heart disease was made at 20 weeks of gestation with fetal
echocardiography, and second because the patient was
treated immediately with PGE1 from the time of birth. Referring
to the echocardiography, it is important to note that
295

Luis Alexis Arévalo Salas, Sandrino José Fuentes Alfaro, Jorge Omar Osorio Díaz, Begoña Segura Stanford, Mario Pérezpeña Díazconti
from 2002 8 there have been high percentages reported of
high diagnostic accuracy in fetal echocardiography. It has
been mentioned that among the most frequently diagnosed
heart diseases, HLHS is the most notable. 9 However, there
are diagnostic failures related to the skill and experience
of the radiologist and even to the quality of the equipment.
In the second aspect, it is of utmost importance to provide
adequate treatment from the time of birth that leads to
maintaining stable conditions in these children, decreasing
as much as possible development of cardiac insufficiency.
For this reason, we must emphasize that multidisciplinary
management is required that involves obstetricians, neonatologists,
nurses, cardiologists, surgeons and intensivists
trained in severe congenital heart disease.
The priority is the PGE1 infusion at doses of 0.01 to 0.05
μg/kg/min. This is used to maintain PDA with the intention
of allowing a proper systemic output and to reduce, as far
as possible, heart failure and underlying pulmonary edema.
On occasions, orotracheal intubation is necessary in which
case it is fundamental to keep these patients in hypercarbia
trying to maintain a pCO 2 between 35 and 45 mmHg and
a PaO 2 between 30 and 40 mmHg in order to safeguard
the high pulmonary vascular resistance and prevent the
pulmonary vasodilator effect of oxygen. As secondary
effects, an improved cerebral perfusion is obtained (beneficial)
and the possibility of developing metabolic acidosis
that can be treated by administering sodium bicarbonate at
conventional doses of 1 to 2 mEq/kg/dose. It is noteworthy
that parenteral fluids should be restricted and rapid boluses
avoided. When there is need of providing inotropic support,
it is recommended that it be a combination of dobutamine
and dopamine, with the latter a dopaminergic dose with the
goal of favoring renal circulation. On the other hand, higher
doses of these inotropes (>5 μg/kg/min) tend to increase the
systemic vascular resistence with deleterious effects on the
systemic flow and tissue perfusion. 3
In this case, once the fetal diagnosis was made, therapeutic
options can be presented to the parents: interruption
of pregnancy, carry pregnancy to term and offer only compassionate
support, plan a surgical intervention (Norwood)
or the possibility of heart transplantation. It is essential
to clearly explain the options to parents, emphasizing the
high mortality rate of the Norwood procedure, the shortage
of donor hearts and the high possibility of neurological
sequelae, even if patient survival is achieved. With this
information a joint decision can be made.
Upon acceptance to a particular therapeutic program,
the best option then needs to be considered according to
the anatomy of the lesion. In the present case, moderate
tricuspid regurgitation, ascending aortic diameter of 2 mm
and juxtaductal aortic coarctation are described. There
are elements to consider when determining a therapeutic
approach. To plan a corrective Norwood-type surgery
has the disadvantage that when tricuspid regurgitation
is severe, it practically contraindicates the second stage
(cavopulmonary connection).
The hybrid treatment option (surgical/interventional)
aims to first control pulmonary flow by performing a cerclage
of each pulmonary branch, ensuring systemic flow
by means of stent implantation in the ductus arteriosus and
freeing the obstruction of pulmonary flow by performing
a medical or surgical atrial septostomy. This option was
considered to be contraindicated due to the fact of having
an ascending aorta of 2 mm in diameter as well as an aortic
coarctation because these inhibit retrograde circulation
towards the ascending and coronary aorta, thereby ruling
out this procedure. 10.11
When discussing the anatomic conditions of this case
that has several adverse factors for success in any type of
surgery, the obligation to treat or not treat these patients
should be considered. This discussion is not new and
there are literature reports that support or do not support
intervention 12 with the conclusion that it is not necessarily
the disease that leads to death and that the options depend
on the experience of the responsible physicians 13 to the
point that extreme cases are offered only palliative care.
It is without a doubt an obligation to clearly inform
parents of the surgical and medical possibilities of longterm
results that may include psychomotor retardation,
high mortality in each of the three surgeries that make
up the Norwood program and the almost nil donation of
neonatal heart, so jointly parents as well as the physicians,
social worker and psychologists make a consensus decision
to accept or reject the therapeutic option. It is a medical
obligation to act with a deep sense of ethics to address
cases such as the one presented to offer the best action in
the face of conflicting decisions. Ethical principles should
not be ignored, such as autonomy as well as the right to
self-determination and the benefit to provide truthful
information of the medical group’s surgical experience. 14
Finally, from the medical point of view, it is extremely
important to formalize the treatment of these cases by
296 Bol Med Hosp Infant Mex

taking into consideration the best possibilities. We must
remember that this particular surgery has a long learning
curve. Diagnosis should be made as early as possible, and
a transfer system should be established to ensure the use
of PGE1 and to maintain metabolic constants in order to
achieve a better prognosis.
REFERENCES
1. Lees MH. Cyanosis of the newborn infant. Recognition and
clinical evaluation. J Pediatr 1970;77:484-498.
2. Shone JD, Sellers RD, Anderson RC, Adams P, Lillehei C,
Edwards JE. The developmental complex of “parachute mitral
valve”, supravalvular ring of left atrium, subaortic stenosis, and
coarctation of the aorta. Am J Cardiol 1963;11:714-725.
3. Rudolph A. Aortic atresia, mitral atresia, and hypoplastic left
ventricle. In: Rudolph A, ed. Congenital Diseases of the Heart.
Clinical-Physiological Considerations. West Sussex: Wiley-
Blackwell; 2009. pp. 257-288.
4. Marino BS, Bird GL, Wernovsky G. Diagnosis and management
of the newborn with suspected congenital heart disease. Clin
Perinatol 2001;28:91-136.
5. Jenkins KJ. Risk adjustment for congenital heart surgery: the
RACHS-1 method. Semin Thorac Cardiovasc Surg Pediatr
Card Surg Annu 2004;7:180-184.
Vol. 69, July-August 2012
Newborn with hypoplastic left heart syndrome
6. Browning Carmo KJ, Barr P, West M, Hopper NW, White JP,
Badawi N. Transporting newborn infants with suspected duct
dependent congenital heart disease on low-dose prostaglandin
E1 without routine mechanical ventilation. Arch Dis Child Fetal
Neonatal Ed 2007;92:F117-F119.
7. Rabinovitch M. Pathobiology of pulmonary hypertension:
impact on clinical management. Semin Thorac Cardiovasc
Surg Pediatr Card Surg Annu 2000;3:63-81.
8. Haak MC, Twisk JW, Van Vugt JM. How successful is fetal
echocardiographic examination in the first trimester of pregnancy?
Ultrasound Obstet Gynecol 2002;20:9-13.
9. Marantz P, García-Guevara C. Ecocardiografía fetal. Rev
Argent Cardiol 2008;76:392-398.
10. Bacha E. Hybrid therapy for hypoplastic left heart syndrome:
system-wide approach is vital. Pediatr Cardiol 2008;29:479-
480.
11. Hoffman J. Hypoplastic left heart syndrome. In: Hoffman J,
ed. The Natural and Unnatural History of Congenital Heart
Disease. West Sussex: Wiley-Blackwell; 2009. pp. 531-545.
12. Osiovich H, Phillipos E, Byrne P, Robertson M. Hypoplastic
left heart syndrome: “to treat or not to treat”. J Perinatol
2000;20:363-365.
13. Feinstein JA, Benson DW, Dubin AM, Cohen MS, Maxey DM,
Mahle WT, et al. Hypoplastic left heart syndrome: current considerations
and expectations. J Am Coll Cardiol 2012;59(suppl
1):S1-S42.
14. Zeigler VL. Ethical principles and parental choice: treatment
options for neonates with hypoplastic left heart syndrome.
Pediatr Nurs 2003;29:65-69.
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pediatric theMe
Bol Med Hosp Infant Mex 2012;69(4):298-304
Shaping a new strategy against B. pertussis: a public health problem in
mexico
Lorena Suárez-Idueta, 1 Ilse Herbas-Rocha, 2 César Misael Gómez-Altamirano, 3 Vesta Richardson-López
Collada 4
AbSTRACT
Despite vaccination against pertussis, there are still a large number of pertussis deaths worldwide. Waning vaccine-induced immunity and
the gradual increase in reported incidence among adolescents and adults have supported the role of these age groups in the transmission.
Several countries have implemented a booster vaccination in order to reduce transmission and clinical significance. Pertussis is a current
public health problem in Mexico. The clinical suspicion in toddlers, adolescents and adults, delayed or incomplete vaccination series and
diagnostic confirmation are the most important challenges for pertussis control. The introduction of new vaccination strategies in adults
and adolescents as well as pregnant women should improve disease control.
Key words: Pertussis, whooping cough, B. pertussis, immunization, vaccines.
INTRODuCTION
Pertussis is a disease of worldwide distribution 1 that
continues to cause a large number of deaths despite the
existence of a vaccination against Bordetella pertussis
that has been in existence for >50 years. In 2008, the
World Health Organization (WHO) estimated 195,000
annual deaths attributed to the disease. In relation to other
vaccine-preventable diseases, it ranks as the fifth leading
cause of death in children

Table 1. Operational definitions, coqueluchoide syndrome and pertussis 12
inhabitants) and the year 2009 (five cases/million population)
(Figure 1). 14 The most affected region during the last
epidemic year (2009) was the northern border. During that
year, 1,959 suspected cases or coqueluchoide syndrome
were documented, confirming 579 cases of pertussis. The
states of Nuevo Leon, Sonora and Tamaulipas had the highest
incidence rates: 44.5, 42.6 and 16.6/million inhabitants,
respectively, corresponding to 62% of all confirmed cases
during that year for the country. 14
The real burden of disease is underestimated both by
the low diagnostic suspicion as well as the low percentage
of confirmation. In Mexico, we diagnosed two cases of
pertussis per every 10 cases of coqueluchoide syndrome
that are studied. In the last 10 years, the percentage of
confirmation was maintained uniform (~20%) (Figure 1).
Difficulties of laboratory diagnosis through culture include
inadequate sample collection, collection of the sample
after starting antibiotics and late sample collection (third
week after the onset of cough). Despite the heterogeneity
in epidemiological surveillance of pertussis worldwide,
different operational definitions and diagnostic methods
used, 15 the percentages of confirmation from countries
like Australia, 16 U.S., 6 Canada, 17 Spain 18 and Switzerland 19
are reported in 90%, 55%, 25.6%, 57.6% and 24.3%,
respectively.
The age group most affected was that of

Lorena Suárez-Idueta, Ilse Herbas-Rocha, César Misael Gómez-Altamirano, Vesta Richardson-López Collada
Figure 1. Probable and confirmed cases and incidence of pertussis (México, 1995-2011). 14
Since 1991, national coverage with these immunogens
has remained close to 90% at 1 year of age; 24,25 nevertheless,
the main difficulty was the late implementation of
the series of immunogens. According to the National
Immunization Coverage Survey (ENCOVA) carried out
between April and June, 2010 by the National Public
Health Institute, among children

Figure 2. Age distribution of confirmed cases of pertussis (México, 2000-2010). 14
pediatric DTaP vaccine, but with a lower concentration of
antigen. 43 Ward et al. described it as a safe vaccine with
an efficacy of 92% (95% CI 32-99%). 44 A 5-year followup
of post-adolescents after a Tdap reinforcement has
shown an adequate response in both humoral as well as
cell-mediated immunity. 45
Both the Global Pertussis Initiative 15,46 as well as the
Advisory Committee on Immunization of the United
States of America (ACIP) 47 have recommended a booster
of Tdap in adolescents and adults, as well as a vaccination
of healthcare staff and pregnant women, based on the loss
of acquired immunity through vaccination in these specific
Vol. 69, July-August 2012
Shaping a new strategy against B. pertussis: a public health problem in Mexico
Figure 3. Vaccination coverage with pentavalent acellular vaccine in Mexico and vaccine effectivity. 26,27
age groups, the increase in incidence, 10,12,31 their role in the
transmission of the disease 37,38 and as a potential measure
to reduce morbidity and mortality, especially in infants. 48
Countries like the U.S., Canada, Australia, France, Costa
Rica, and Argentina have recognized and implemented
these new vaccination strategies into their schemes. 8,49
The introduction of Tdap as a booster in the adolescent
population has proven effective in reducing the
incidence of pertussis in this age group. Kandola et al.
evaluated the impact of the introduction of Tdap in adolescents
of 14–16 years of age and found an incidence
of pertussis before the introduction of the vaccine in
301

Lorena Suárez-Idueta, Ilse Herbas-Rocha, César Misael Gómez-Altamirano, Vesta Richardson-López Collada
18/100,000 of the population compared to 0.2/100,000
of the population after its introduction. 50 Quinn et al.
demonstrated the impact of vaccination with Tdap in
the adolescent population in the reduction of reported
cases of pertussis in the group of adolescents and in
children 95% coverage with pentavalent acellular vaccine
is recognized, as well as to ensure timely vaccination of
the first dose of biological to the population 36 million diapers with the logo of
"vaccinate on time," and they produced 1 million collars to
adhere to baby products. They trained over 400 hospitals
with a range of >7,000 nurses as well as dissemination
through leaflets and posters in the hospital. However, it is
clear that effective vaccination for infants and toddlers will
not be a sufficient measure to control the disease. There is
a need to implement new strategies for vaccination in the
adolescent and adult population, such as a strategy to reduce
transmission to the group of infants

2008;9:201-211; quiz 211-212. Available at: http://www.sepeap.
org/archivos/pdf/10885.pdf
6. Tanaka M, Vitek CR, Pascual FB, Bisgard KM, Tate JE, Murphy
TV. Trends in pertussis among infants in the United States,
1980-1999. JAMA 2003;290:2968-2975.
7. Mooi FR, van Loo IH, King AJ. Adaptation of Bordetella pertussis
to vaccination: a cause for its reemergence? Emerg Infect
Dis 2001;7(3 suppl):526-528.
8. Tan T, Trindade E, Skowronski D. Epidemiology of pertussis.
Pediatr Infect Dis J 2005;24(suppl 5):S10-S18.
9. Singh M, Lingappan K. Whooping cough: the current scene.
Chest 2006;130:1547-1553.
10. Halperin SA. Pertussis immunization for adolescents: what
are we waiting for? Can J Infect Dis 2001;12:74-76.
11. Edwards KM. Overview of pertussis: focus on epidemiology,
sources of infection, and long term protection after infant vaccination.
Pediatr Infect Dis J 2005;24(suppl 6):S104-S108.
12. Dirección General de Epidemiología. Manuales Simplificados
Enfermedades Prevenibles por Vacunación. Secretaría de
Salud. México; 2005.
13. Dirección General de Epidemiología. Programa de Acción
Sistema Nacional de Vigilancia Epidemiológica SINAVE.
Secretaría de Salud. México; 2001.
14. Anuarios de morbilidad. Dirección General de Epidemiología.
Secretaría de Salud.
15. Guiso N, Wirsing von König CH, Forsyth K, Tan T, Plotkin
SA. The Global Pertussis Initiative: report from a round
table meeting to discuss the epidemiology and detection
of pertussis, Paris, France, 11-12 January 2010. Vaccine
2011;29:1115-1121.
16. Quinn HE, McIntyre PB. The impact of adolescent pertussis
immunization, 2004-2009: lessons from Australia. Bull World
Health Organ 2011;89:666-674.
17. Rivest P, Richer F, Bédard L. Difficulties associated with pertussis
surveillance. Can Commun Dis Rep 2004;30:29-33,36.
18. Crespo I, Cardeñosa N, Godoy P, Carmona G, Sala MR, et al.
Epidemiology of pertussis in a country with high vaccination
coverage. Vaccine 2011;29:4244-4248.
19. Wymann MN, Richard JL, Vidondo B, Heininger U. Prospective
pertussis surveillance in Switzerland, 1991-2006. Vaccine
2011;29:2058-2065.
20. Sapián-López LA, Valdespino JL, Salvatierra B, Tapia-Conyer
R, Gutiérrez G, Macedo J, et al. Seroepidemiology of whooping
cough in Mexico. Salud Publica Mex1992;34:177-185.
21. Sandoval PT, Arreola L del P, Quechol GR, Gallardo HG.
Bordetella pertussis in adolescent students in Mexico City.
Rev Saude Publica 2008;42:679-683.
22. Ruiz Palacios, et al. A prospective cohort study of pertussis in
adolescents attending middle school in Mexico City (ICAAC
2010) (unpublished data).
23. Centro Nacional para la Salud de la Infancia y la Adolescencia.
Manual de Vacunación 2008-2009. Secretaria de Salud.
México; 2008.
24. Organización Mundial de la Salud. Estadísticas Sanitarias
Mundiales; 2010. Available at: http://www.who.int/whosis/
whostat/ES_WHS10_Full.pdf
25. WHO/UNICEF. Regional Global Coverage; 2010. Available
at: http://www.who.int/immunization_monitoring/routine/immunization_coverage/en/index4.html
Vol. 69, July-August 2012
Shaping a new strategy against B. pertussis: a public health problem in Mexico
26. Instituto Nacional de Salud Pública. Encuesta Nacional de
Cobertura de Vacunación. Informe Final de Resultados.
México; 2010.
27. Bisgard KM, Rhodes P, Connelly BL, Bi D, Hahn C, Patrick
S, et al. Pertussis vaccine effectiveness among children 6 to
59 months of age in the United States, 1998-2001. Pediatrics
2005;116:e285-e294.
28. Juretzko P, von Kries R, Hermann M, Wirsing von König CH,
Weil J, Giani G. Effectiveness of acellular pertussis vaccine
assessed by hospital-based active surveillance in Germany.
Clin Infect Dis 2002;35:162-167.
29. Salmaso S, Mastrantonio P, Tozzi AE, Stefanelli P, Anemona
A, Ciofidegliatti ML, et al. Sustained efficacy during the first
6 years of life of 3-component acellular pertussis vaccines
administered in infancy: the Italian experience. Pediatrics
2001;108:e81.
30. Gustafsson L, Hessel L, Storsaeter J, Olin P. Long-term followup
of Swedish children vaccinated with acellular pertussis
vaccines at 3, 5, and 12 months of age indicates the need for
a booster dose at 5 to 7 years of age. Pediatrics 2006;118:978-
984.
31. Wendelboe AM, Van Rie A, Salmaso S, Englund JA. Duration
of immunity against pertussis after natural infection or vaccination.
Pediatr Infect Dis J 2005;24(suppl 5):S58-S61.
32. Jenkinson D. Duration of effectiveness of pertussis vaccine:
evidence from a 10 year community study. Br Med J (Clin Res
Ed) 1988;296:612-614.
33. Ramsay ME, Farrington CP, Miller E. Age-specific efficacy of
pertussis vaccine during epidemic and non-epidemic periods.
Epidemiol Infect 1993;111:41-48.
34. Van Buynder PG, Owen D, Vurdien JE, Andrews NJ, Matthews
RC, Miller E. Bordetella pertussis surveillance in England and
Wales: 1995-7. Epidemiol Infect 1999;123:403-411.
35. Tindberg Y, Blennow M, Granström M. A ten year follow-up
after immunization with a two component acellular pertussis
vaccine. Pediatr Infect Dis J 1999;18:361-365.
36. Lugauer S, Heininger U, Cherry JD, Stehr K. Long-term clinical
effectiveness of an acellular pertussis component vaccine
and a whole cell pertussis component vaccine. Eur J Pediatr
2002;161:142-146.
37. Kowalzik F, Barbosa AP, Fernandes VR, Carvalho PR, Avila-
Aguero ML, et al. Prospective multinational study of pertussis
infection in hospitalized infants and their household contacts.
Pediatr Infect Dis J 2007;26:238-242.
38. Wendelboe AM, Njamkepo E, Bourillon A, Floret DD, Gaudelus
J, Gerber M, et al. Transmission of Bordetella pertussis to
young infants. Pediatr Infect Dis J 2007;26:293-299.
39. Bisgard KM, Pascual FB, Ehresmann KR, Miller CA, Cianfrini
C, Jennings CE, et al. Infant pertussis: who was the source?
Pediatr Infect Dis J 2004;23:985-989.
40. Deen JL, Mink CA, Cherry JD, Christenson PD, Pineda EF,
Lewis K, et al. Household contact study of Bordetella pertussis
infections. Clin Infect Dis 1995;21:1211-1219.
41. Elliott E, McIntyre P, Ridley G, Morris A, Massie J, McEniery
J, et al. National study of infants hospitalized with pertussis in
the acellular vaccine era. Pediatr Infect Dis J 2004;23:246-252.
42. Perret C, Viviani T, Peña A, Abarca K, Ferrés M. Source of
infection in young infants hospitalized with Bordetella pertussis.
Rev Med Chil 2011;139:448-454.
303

Lorena Suárez-Idueta, Ilse Herbas-Rocha, César Misael Gómez-Altamirano, Vesta Richardson-López Collada
43. Broder KR, Cortese MM, Iskander JK, Kretsinger K, Slade BA,
Brown KH, et al. Preventing tetanus, diphtheria, and pertussis
among adolescents: use of tetanus toxoid, reduced diphtheria
toxoid and acellular pertussis vaccines recommendations of
the Advisory Committee on Immunization Practices (ACIP).
MMWR Recomm Rep 2006;55(RR-3):1-34.
44. Ward JI, Cherry JD, Chang SJ, Partridge S, Lee H, Treanor
J, et al. Efficacy of an acellular pertussis vaccine among adolescents
and adults. N Engl J Med 2005;353:1555-1563.
45. Edelman K, He Q, Mäkinen J, Sahlberg A, Haanperä M,
Schuerman L, et al. Immunity to pertussis 5 years after
booster immunization during adolescence. Clin Infect Dis
2007;44:1271-1277.
46. Ulloa-Gutierrez R, Hozbor D, Avila-Aguero ML, Caro J, Wirsing
von König CH, Tan T, et al. The global pertussis initiative:
meeting report from the Regional Latin America Meeting,
Costa Rica, 5-6 December, 2008. Hum Vaccin 2010;6:876-
880.
47. Updated recommendations for use of tetanus toxoid, reduced
diphtheria toxoid and acellular pertussis vaccine (Tdap)
in pregnant women and persons who have or anticipate
having close contact with an infant aged

vital statistics
mortality due to drowning in children less than 15 years of age in
mexico, 1998-2010
Sonia Fernández Cantón, 1 Ana María Hernández Martínez, 1 Ricardo Viguri Uribe 2
Nationally in Mexico, accidents are the fourth
leading cause of death for the general population.
When we refer to children

Sonia Fernández Cantón, Ana María Hernández Martínez, Ricardo Viguri Uribe
Table 1. Deaths caused by drowning and accidental submersion in the population

Vol. 69, July-August 2012
Mortality due to drowning in children less than 15 years of age in Mexico, 1998-2010
Figure 1. Relative weight of deaths by drowning and accidental submersion in regard to the total deaths due to accidents in children

Sonia Fernández Cantón, Ana María Hernández Martínez, Ricardo Viguri Uribe
Figure 2. Mortality rate and deaths due to drowning and accidental submersion in children

Boletín Médico del Hospital Infantil de México is the official
publication of the Hospital Infantil de México “Federico Gómez.”
The journal has been continuously published on a bi-monthly
basis since 1944 and publishes studies relating to pediatrics according
to the following areas: biomedical, clinical, public health,
clinical epidemiology, health education and clinical ethics. The
following guidelines are in accordance with the “Uniform Requirements
for Manuscripts Submitted to Biomedical Journals,”
published by the International Committee of Medical Journal
Editors (http://www.icmje.org).
Types of articles
Types of articles published are as follows: Review Articles, Clinical
Case Reports, Clinicopathological Cases, Pediatric Themes
and Letters to the Editor. Published articles appear both in print
and on-line in Spanish and on-line in English.
Submissions should be sent via electronic mail to: bolmedhim@
yahoo.com.mx with the following requirements:
1. Letter addressed to Dr. Gonzalo Gutiérrez Trujillo, Editor,
Boletín Médico del Hospital Infantil de México, Departamento
de Ediciones Médicas. The letter, signed by the corresponding
author, should include the following information:
a) The enclosed article is being submitted for evaluation
for eventual publication in Boletín Médico del Hospital
Infantil de México.
b) The authors declare that the work has not been previously
published, has not been previously accepted for
publication and has not been submitted simultaneously
to another publication.
c) Type of study should be indicated along with the corresponding
pertinent area of pediatrics.
d) Confirm that the Guidelines to Authors have been reviewed
and adhered to prior to submission.
e) If applicable, the authors should declare any conflict of
interest or submit a statement that no conflict of interest
exists. In the event of a conflict of interest, the authors
must disclose any external financial or economic interest.
f) All external funding sources should be clearly indicated.
g) All authors must affirm that they are in agreement with
the submission of the manuscript and that they have
reviewed and approved the work.
Please be reminded that without the appropriately signed author
letter, the initial editorial process will be delayed.
manuscript preparation
All manuscripts should be prepared with standard programs
(Word 97 or higher) using the word processor function of your
computer. Double space all sections of the manuscript including
References, Tables and Figure Legends. Do not justify right margins
and use one-inch margins all around. Keep formatting to a
minimum. Pages should be numbered consecutively beginning
with the first page and numbers should appear in the lower right
corner of the page.
Abbreviations
Complex terms used frequently in the manuscript may be abbreviated.
Abbreviations are placed in parentheses at first use in
the abstract and again at first use in the text. Confirm that any
Guidelines to authors
abbreviations used in Tables are appropriately spelled-out in the
Table legend underneath.
Organization of the manuscript
The first page should include the following:
a) Title of the manuscript (Spanish and English)
b) Type of manuscript: Original Article, Review Article,
Clinical Case Report, etc.
c) Name(s) of all authors in their order of appearance in
relation to the publication
d) Affiliation of each author (degrees and honors should
be omitted)
e) Name, E-mail address, postal address and telephone
number of the corresponding author to whom any correspondence
can be directed during the review process
of the manuscript.
The second page should contain the Abstract. Note that the
Abstract is the most-often read part of the manuscript. For this
reason, it must be clear, concise and contain information relevant
to the article. Do not use references in the Abstract. In the case of
Original Articles and Clinical Case Reports, the Abstract should
be structured according to the following sections: Background,
Methods, Results, Conclusions, or Background, Clinical Case
and Conclusions. Abstracts for Review Articles and Pediatric
Themes should be unstructured and include only one paragraph.
The Abstract should be limited to 200 words and include only
relevant aspects of each of the principal sections of the body of
the manuscript. Authors should provide 3–6 keywords following
the Abstract and use Medical Subject Headings (MeSH) terms
as a guide. Visit: http://www.nlm.nih.gov/mesh/meshhome.html.
The manuscript should include the following sections:
1) Original articles: Introduction, Methods, Results, Discussion
and References.
2) Clinical case reports: Introduction, Clinical case, Discussion
and References.
3) Clinicopathological cases: Clinical case, Discussion and
References.
An Acknowledgment section may be included directly following
the Reference section. Granting institutions or other financial aid
may be listed under Acknowledgments. If there are persons, other
than the authors, who assisted with the study or preparation of the
manuscript (i.e., technicians, nurses, ancillary health personnel,
editorial assistance), they may be listed here.
References
References should be numbered consecutively, double spaced,
and listed in the order in which they appear in the text using arabic
numbers (in the text, references are indicated by superscript
arabic numbers after any punctuation). The Reference section
should follow the last section of the manuscript. It is not necessary
to begin the References on a separate page. The references
should be formatted according to the instructions from the U.S.
National Library of Medicine. Abbreviated journal names should
reflect the style of Index Medicus (visit http://www.nlm.nih.gov/
tsd/serials/lji.html) When a reference cites six or fewer authors,
names should be included for all authors. When there are seven or
more authors, use the first six names followed by et al. Authors
are responsible for the accuracy of references. Please use the
following examples for presentation of references:

Journals:
• Klimo P, Rao G, Brockmeyer D. Congenital anomalies of
the cervical spine. Neurosurg Clin North Am 2007;18:463-
478.
• Published book:
• Bell RM. Holy Anorexia. Chicago: University of Chicago
Press; 1985.
• Book chapter:
• Hudson JI, Hudson RA, Pope HG. Psychiatric comorbidity
and eating disorders. In: Wonderlich S, Mitchell J, eds.
Eating Disorders Review. Part 1. Oxford: Radcliffe Publishing;
2005. pp. 43-58.
• Internet consult:
• McKusick VA. Klippel Feil syndrome. Online. Mendelian
inheritance in man (accessed: March 26, 2008). Available
at: http://www.ncbi.nlm.nih.gov/entrez/dispomim.
cgi?id=148900.
Tables and Figures All tables and figures including schemes,
diagrams and table legends must be presented in an editable
form. Do not “copy and paste” material from external sources.
Tables
Tables should be numbered using arabic numbers in the order in
which they are cited in the text and include a short descriptive
title. Tables should not reiterate information presented in the
Results section. For preparation of Tables containing only data,
use the “Table Editor” function of your word processing program.
Do not insert any vertical lines. Use horizontal lines only for
clarity of information under table headings. Confirm that information
provided below each table heading is properly aligned
and clearly identifiable. Tables containing schemes or diagrams
should be prepared in PowerPoint; graphics with shading, bars,
dispersions, etc. should be prepared using Excel. Each Table
should be prepared on a separate page, following the Reference
section. Table footnotes should include any abbreviations that
need to be explained and notes relating to the Table should be
presented alphabetically using superscript letters.
Figures
Authors should number figures in the order in which they
appear in the text. Figures include graphs, charts, photographs,
and illustrations. Each figure should be accompanied by a selfexplanatory
legend. Digital images should be legible and printed
with a resolution of not less than 300 dpi, using .jpg (jpeg) or
.bmp extension.
If photographs submitted correspond to actual patients, the
anonymity of the patients should be protected or written permission
from the patient and/or family/legal guardian to publish
the photograph(s) should be submitted. Figure legends with
corresponding figure numbers should be typed consecutively
on a separate page following the last Table (or following the
Acknowledgments if there are no Tables).
Note: For periodic up-to-dates of "Guidelines to Authors",
please consult our internet page: www.himfg.edu.mx
Permission to use previously published Tables or
Figures
If the manuscript contains Tables or Figures that have been previously
published, permission must be obtained from the original
Publisher in order to reproduce the material. This applies to Tables
or Figures that have been modified, adapted or translated. A
sample “permission” letter is available from the Editorial Office
of Boletín Médico del Hospital Infantil de México. Appropriate
credit must be written per the following example:
Reprinted (or Adapted, Modified, Translated) from Castilloux J,
Noble AJ, Faure C. Risk factors for short- and long-term morbidity
in children with esophageal atresia. J Pediatr 2010;156:755-760.
With permission.
Ethical approval of studies and informed consent
In regard to possible ethical conflicts, the rights of patients of
privacy and confidentiality shall be maintained. For studies
involving human subjects, state the manner in which informed
consent was obtained from the study participants (i.e., oral or
written). All manuscripts reporting data from studies involving
humans or animals are subject to formal review and approval
by an appropriate institutional review board or ethics committee
and should be described at the end of the Methods section. For
investigators who do not have formal ethics review committees,
the principles outlined in the Declaration of Helsinki as well as in
the Guide for the Care and Use of Laboratory Animals (Institute
of Laboratory Animal Resources, Commission on Life Sciences,
National Research Council) should be followed.
Review process
The first review of the manuscript is performed by the Editor
to assure that the manuscript corresponds to the theme of the
journal and that all required information has been properly
submitted in accordance with the Guidelines to Authors. The
second review is carried out by two independent reviewers
who have been assigned to the manuscript on the basis of their
field of expertise. The identities of authors’ and reviewers’ are
kept confidential.
Copyright
All accepted manuscripts become the permanent property of the
Boletín Médico del Hospital Infantil de México and may not be
published elsewhere, in whole or in part, without prior written
permission from the Editor and appropriate credit to the authors
and to Boletín Médico del Hospital Infantil de México. Upon
acceptance of an article for publication in Boletín Médico del
Hospital Infantil de México, a letter signed by all authors shall
be submitted transferring copyright of the published article to
Boletín Médico del Hospital Infantil de México. If the author(s)
wishes to reprint any of the material already published in Boletín
Médico del Hospital Infantil de México, prior authorization is
required from the Editor.