Micronutrients and Pregnancy Outcomes: Implications and Challenges

MATERNAL-FETAL
MEDICINE
Micronutrients and
Pregnancy Outcomes:
Implications and Challenges
Prakesh S. Shah, MBBS, DCH, MRCP, MRCPCH
FOCUSPOINT
Given the
long-term consequences
of LBW
in child health, this
review identifies
MMN as a major
factor in reducing
the risk for LBW.
New evidence shows that pregnant women
who supplement their diet with multiple
micronutrients, as opposed to just iron and
folic acid, have lower risks for low-birthweight
infants. What are the implications
and challenges associated with improving
fetal growth rates through the use of this
supplementation?
Dietary insufficiency of major and minor
nutrients is widely prevalent among
women of child-bearing age. 1 The rates
vary globally; however, no areas of the
world are immune. 2 Periconceptional nutritional
status has major and direct influence on
maternal and child health. Iron
deficiency anemia is the most
prevalent nutritional deficiency
among pregnant women.
Based on existing knowledge
at the time, the World Health
Organization (WHO) in 2003
recommended and promoted
supplementation of iron and
folic acid to pregnant women
rather than multiple micronutrients
(MMN). With the joint
efforts of UNICEF, WHO, and
other regional partners, pregnant
women receive iron–folic
acid combination (IFA) free of
charge during pregnancy in
many parts of the world. 3
WHAT IS THE EVIDENCE
OF EFFECTIVENESS OF MMN?
With the increasing awareness of coexisting
major and minor nutrient deficiencies, several
randomized controlled trials have recently
evaluated the effectiveness of MMN during
pregnancy. In a systematic review and metaanalyses
of 13 randomized controlled trials of
more than 30,000 women, Shah and Ohlsson
compared traditional IFA with MMN (containing
IFA). 4 A clinically and statistically significant
reduction in the risk for low-birth-weight
(LBW) births was identified among women
who received MMN compared to IFA (relative
risk [RR], 0.82; 95% CI, 0.73-0.92). Birth weight
was higher among infants whose mothers
received MMN compared to IFA, by an average
of 62 g (95% CI, 49-75 g). There was no difference
in the risk for preterm and small-forgestational-age
births between the two groups.
This translates to an 18% (95% CI, 8%-27%)
reduction in LBW births with MMN supplementation.
The number of women required to receive
supplementation to prevent one LBW infant
was 50 (95% CI, 33-100). Comparison of MMN
with placebo also revealed similar results.
Globally, a staggering 1.5 million LBW births
could be avoided annually if all pregnant
women received MMN during pregnancy. 4
Given the long-term consequences of LBW
births throughout the entire life span of the survivors,
this intervention has a major healthpromoting
impact. 5 Interestingly, it was noticed
from trials that time of initiation of MMN
during pregnancy had little effect; ie, women
who started MMN before 20 weeks’ gestational
age had similar benefit to those who started
MMN after 20 weeks of gestation.
Prakesh S. Shah, MBBS, DCH, MRCP, MRCPCH, is Staff
Neonatologist and Clinical Epidemiologist, Department of
Pediatrics, Mount Sinai Hospital, Toronto, Ontario; and
Associate Professor, Division of Neonatology, Department
of Pediatrics, and Department of Health Policy, Management,
and Evaluation, University of Toronto, Ontario.
32 The Female Patient | VOL 35 JULY 2010 All articles are available online at www.femalepatient.com.

Shah
The components of MMN present in the majority
of studies that showed effectiveness included
vitamin A ≥2,640 IU, vitamin D ≥200 IU,
vitamin E ≥10 mg, vitamin B 1
≥1.4 mg, folic acid
≥400 μg, vitamin C ≥70 mg, zinc ≥15 mg, and
iron ≥30 mg; however, authors were unable to
distinguish a clear composition of MMN that
was essential. It is important to note that the
MMN composition includes IFA. 4
Mechanisms of beneficial action of MMN
during pregnancy are most likely multifactorial.
A generalized improvement in the immune
function, reduction of risk of infection,
improvement in energy metabolism, improvement
in anabolic processes, appropriate reactions
to stressors (as compared to heightened
stress exhibited by malnourished mothers),
higher fluid retention, increased plasma volume
expansion, and improved hemoglobin are
proposed mechanisms. 6,7
WHAT ARE THE IMPLICATIONS
OF NEW EVIDENCE?
These findings have clear implications for maternal-child
health initiatives in North America
and around the world. All of these trials were
conducted in areas of the world where nutritional
deficiencies are highly prevalent and
where the majority of births occur. Current practice
of IFA supplementation needs to be challenged
in light of this new evidence.
Women require additional supplementation
during pregnancy, and selective supplementation
to target only anemia may not be adequate.
2 Based on common practice, the majority
of women in the Western world receive
MMN as a supplement in addition to IFA. Approximately
75% to 80% of women in Canada
receive MMN during pregnancy. However, the
numbers may not be similar in all developed
nations, particularly in women who are socially
disadvantaged, who do not have adequate
medical insurance coverage, or who are malnourished
at the beginning of their pregnancy. 2
Such women should be targeted to receive
MMN supplementation as soon as pregnancy
is detected. There is even an argument for prenatal
supplementation for these women similar
to that of folic acid. Improvement of the
nutritional milieu of these mothers during the
preconceptional period may prepare them to
sustain pregnancy and reduce adverse
consequences. 2
The interaction of various components of
MMN should be considered when combining
multiple nutrients and preparing formulations.
For example, absorption of iron is affected by
the presence of vitamin C; high intake of iron
can affect zinc and copper absorption; selenium
and vitamin E interact with each other; and
plasma folate can affect zinc absorption. 2
CHALLENGES
Individual Level Challenges
Awareness, access, and tolerability are issues at
an individual level. Knowledge of the importance
of MMN during or even before pregnancy is lacking
among women of childbearing age. It has
taken 10 years for increased
awareness of the importance of
folic acid in the preconceptional
period. Programs to highlight
the importance of MMN would
include educational campaigns
in high school, public events,
advertisements at local pharmacies,
use of media, and promotion
in prenatal clinics.
The majority of malnourished
women live in socially
disadvantaged community sectors
where medical or health
insurance coverage may not be
adequate to cover the cost of
MMN. In addition, lack of prenatal
care, unplanned pregnancy,
shorter interpregnancy interval, young
maternal age, and preexisting malnutrition are
common issues among women in low-income
neighborhoods. Tolerance of MMN could be an
issue for women with coexisting nausea and
vomiting during pregnancy. This may preclude
certain women from taking any additional tablets.
They should be encouraged to take MMN
when their symptoms subside, as benefits of
MMN are shown when it is initiated at any time
during pregnancy.
FOCUSPOINT
Women require
additional supplementation
during
pregnancy, and
selective supplementation
to target only
anemia may not
be adequate.
Regional/National Level Challenges
Improvement in maternal and child health has
been the least attractive portfolio for many national
health care sectors. 2 Additional costs of
making MMN free to all pregnant women in the
entire nation can be a very challenging prospect
for some of the populous countries, and
the total cost may exceed the entire health care
budget. 2 However, in the US, Canada, and other
developed countries, practitioners should be
made aware of the benefits and encouraged to
identify at-risk mothers. Public health initia-
Follow The Female Patient on and The Female Patient | VOL 35 JULY 2010 33

MATERNAL-FETALMEDICINE
Micronutrients and Pregnancy Outcomes: Implications and Challenges
tives to support, promote, and improve availability
of MMN for pregnant women who cannot
afford to purchase them will be needed. It is
important that these issues be identified and
openly debated with the public to determine
strategic directions in the improvement of maternal-child
health.
Global Challenges
It is also important that WHO or UNICEF undertake
positive steps. Change may be required in
the content of their programs without affecting
the infrastructure of these programs. Recent successes
of large-scale beneficial experimentations
at community levels have shown that this is
achievable. 8,9 At the same time, care must be
taken not to affect existing infant and child nutrition
programs, as maternal and childhood malnutrition
accompany each other.
WHAT ARE THE NEXT STEPS?
The most important step in knowledge translation
is the action on a synthesized knowledge.
Notwithstanding the challenges mentioned
above regarding implementation of routine
MMN supplementation to all pregnant women,
the most important issue will be cost. 2 However,
in the long run, the cost of managing one LBW
child during the neonatal and postneonatal periods
is much higher to society than the cost of
supplementing MMN to 50 pregnant women.
Partnership with industries in reducing the cost
of preparation, formulation, packaging, and
supplying MMN may make this an affordable
and highly rewarding program. Local governments,
nonprofit agencies, national academic
societies, pharmaceutical industry, and public
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partnership are crucial building stones in moving
forward this agenda.
The take-home message for individual health
care professionals involved in maternal-child
health in any part of the world is that MMN supplementation
initiated at any time during pregnancy
could be beneficial in reducing LBW rates
and improving fetal growth.
The author reports no actual or potential conflict
of interest in relationship to this article.
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34 The Female Patient | VOL 35 JULY 2010 All articles are available online at www.femalepatient.com.