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'Multiple
Micronutrient
Supplementation In
Pregnancy'
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by
C. Gopalan, April
2000 |
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Nearly a
third of full-term babies born in India
are reported to be of low birth-weight
(less than 2.5 kg)1,2. This
figure has remained more or less
stationary for the last few decades in
spite of striking declines in neonatal
and infant mortality, giving the
impression that India has not made much
progress with respect to the improvement
of nutritional status of its women.
However,
the validity of the present estimate of
low birth-weight in the country as a
whole needs to be carefully checked.
This estimate is almost completely
derived from births taking place in
government-owned public hospitals, which
cater to the poorest sections of the
population. With the springing up of
numerous nursing homes and private
hospitals, presently, most deliveries of
the relatively affluent middle class and
well-to-do women (who together
constitute two-thirds of the population)
take place outside government hospitals.
Therefore, the present estimate could be
considered as reflecting the position
with regard to the poorest section of
India’s population. Even so, a
striking difference can be seen between
different states of India, the incidence
of low birth-weights in Kerala -- for
example -- being low as compared to the
central Hindi-speaking states of the
country. The preliminary results of a
study now being undertaken by the
Nutrition Foundation of India show that
incidence of low birth-weight deliveries
among the middle class is strikingly low
(as low as 5.7 per cent). Under the
circumstances, comparison of low
birth-weight incidence between different
countries where the source of data may
be different, may not be valid. Here is
an area for further research.
Factors
Contributing to Low Birth-Weight
Low
birth-weight and poor pregnancy outcome
are the result of a multiplicity of
factors. Maternal pre-pregnancy weight
and maternal weight gain during
pregnancy are very important
determinants. Poor antenatal care,
anaemia, heavy physical work till late
in pregnancy, smoking and poor diets are
other important factors.
In most
public health programmes in India so
far, the emphasis has been on infants
and children. While lip service had
often been paid to mothers, not much was
done towards improving the diets of
mothers during pregnancy and antenatal
care. Though emphasis had been placed on
growth monitoring in children there were
no parallel efforts at assessment of
weight gains of women during pregnancy.
This relative neglect of women during
pregnancy now needs to be corrected.
Poor
pre-pregnancy weights of mothers and
poor nutritional status are but a
reflection of the poor status of girls
during childhood and adolescence. Little
attention has been paid to the health
and nutrition care of adolescent girls,
with the result that many adolescent
girls are anaemic even at the time of
conception. Under this circumstance,
current programmes of distribution of
iron and folate tablets during the last
100 days of pregnancy are hardly
adequate to correct the prevalent
anaemia. Anaemia in pregnancy,
especially severe anaemia, is an
important determinant of poor pregnancy
outcome. It is only recently that the
shortsightedness of the policy of
relative neglect of adolescent girls and
mothers has been recognised.
National
Nutrition Monitoring Bureau data now
show that weights and heights of
adolescent girls of today are better
than what they were 15 years ago -- a
positive secular trend3. The
recent proposals by the Planning
Commission4 and the Ministry
of Health to intensify healthcare and
antenatal care during adolescence with
special focus and specific treatment of
severe anaemia should yield results
within the next few years. Diets,
particularly of pregnant women, are
deficient both in energy and
(consequently) in several micronutrients
as well. Energy intake ranges between
1,200 to 1,600 kcal in the poor groups.
Any proposal for correction of dietary
deficiency in pregnant women should take
note of this fact. Poor energy intake,
coupled with high energy expenditure --
what with women having to perform heavy
physical work till the last days of
pregnancy -- is a major factor. Under
these circumstances, the logical
approach towards correcting poor
pregnancy outcome is to strive for
all-round improvement in diets during
pregnancy so as to ensure proper weight
gain and better antenatal care.
Multiple
Micronutrient Supplementation
In recent
months, some international and bilateral
groups have been proposing that health
administrations of poor developing
countries of South Asia and Africa be
persuaded to adopt a blunderbuss
polypharmacy approach of distribution of
a capsule containing a cocktail of about
15-17 micronutrients, daily, to all
pregnant women and adolescent girls.
This is being claimed to be the instant
public health solution to the problem of
poor pregnancy outcome in these
countries. A group of experts from the
USA and Europe, in a meeting in July
1999 in the USA, is reported to have ‘decided’
as follows:
“A
supplement containing 15 micronutrients
at levels based on the US/Canada RDAs
should be promoted for use on a daily
basis as soon as the woman is known to
be pregnant, and followed through
for a minimum of three months post-partum
and if possible throughout
breast-feeding. The same supplement is
also to be promoted on once or twice
weekly basis to all non-pregnant,
non-lactating women and adolescents.”
According
to the proposal, this ‘cocktail’ is
to be capsuled in Denmark and
distributed by an international agency
(fortunately not the WHO and certainly
not the FAO) to 10 countries of South
Asia (including India) and Africa. This
proposal must indeed be music to the
ears of the vitamin cartels! Strangely
enough, no representative of any of
the 10 developing countries who were the
intended ‘ostensible’ beneficiaries
of this approach was invited to this
meeting! Apparently, though we are
in the 21st century, 19th century
mindsets still prevail in some
quarters!!
We will,
however, examine this proposal for
multiple micronutrient supplementation
now being promoted purely on its
scientific merits. There have been some
excellent reviews on this subject in
recent years5,6, which have
been taken note of.
Points
for Consideration
The
following points need careful attention
in this regard:
Poor pregnancy outcome is the
result of a multiplicity of factors and
cannot be corrected by a narrow
pharmaceutical short cut. It calls for
overall improvement in antenatal care
and dietary diversification. This task
cannot be evaded and there are no magic
bullets.
Diets of pregnant women in poor
income groups are deficient not only in
micronutrients but in energy as well.
What women require is food of good
nutritive value, not just a capsule of
arbitrarily selected synthetic
nutrients. Foods provide, besides the
vitamins which are envisaged to be
supplied by the capsule, a whole range
of bioactive phytochemicals (so called
non-nutrients). Many more such
non-nutrients in food are likely to be
discovered in the future.
The famous ATBC study in Finland7
had shown that while GLVs and fruits
protect against epithelial cancers, a
combination of alpha-tocopherol and
beta-carotene was found to actually
aggravate the development of epithelial
cancer.
At present, there is a lack of
clear knowledge and information on
baseline micronutrient status or even of
suitable outcome indices in poor Indian
populations to whom these interventions
are proposed to be targeted. What
precisely are the micronutrient
deficiencies in Indian women that have a
bearing on their poor pregnancy outcome?
If there are any specific micronutrient
deficiencies responsible for poor
pregnancy outcome, are these
deficiencies such that they cannot be
combated through dietary improvement,
using locally available inexpensive
foods? We have, presently, no answers to
these questions.
The assumption that the
micronutrient requirements of
populations in developing countries such
as India are identical to those of
America or Canada may be totally
unwarranted. The suggested composition
of the recommended multiple
micronutrient supplement, based on the
US/Canadian RDA, is very likely to be
substantially in excess of the
requirements of populations in
developing countries, even though there
may be individuals in the population who
are likely to be in a depleted state in
terms of a number of micronutrients.
Since it is intended that the supplement
is to be taken on a daily basis, a
significant proportion of pregnant women
will end up with intakes which are
substantially in excess of their
individual requirements. There is
evidence that micronutrients given in
high doses during pregnancy may be
harmful to either the mother or the
foetus -- for example vitamin A and
zinc.
The micronutrient requirements of
populations in developing countries
where staple diets are different from
those of the USA and Canada could be
totally different from those of other
populations. Calcium requirements, for
example, have been shown to be higher in
populations subsisting on diets high in
animal proteins as compared to those
consuming primarily vegetable protein
diets. Several decades ago, Najjar and
Holt had suggested that some essential
micronutrients can be synthesised in the
large gut. Their suggestion was
dismissed by later investigators, who
failed to find evidence of such
synthesis in subjects subsisting on
usual Western diets. It is high time
that this whole question is
reinvestigated in populations subsisting
on predominantly cereal-based diets. It
is known now that a substantial
proportion of carbohydrates ingested as
cereals reach the large gut where they
undergo fermentation with production of
short-chain fatty acids such as butyric
acid, which are beneficial to the
integrity of the colonic epithelium.
Najjar and Holt’s observation may
still prove to be right in predominantly
cereal-eating populations.
However, this line of thinking may be no
more than speculation at this stage.
Even if this possibility is ruled out,
the need for proper re-examination of
micronutrient requirements in
populations of developing countries on
different staple diets should not be
ignored. The supplementation levels
currently being recommended on the basis
of the American RDA may be largely
inapplicable to populations in
developing countries.
- Increasing
micronutrient intakes to high levels
will bring about changes in cellular
metabolism. Supplementing
micronutrients at levels higher than
the habitual intake levels for a
short period, then abruptly
reversing to earlier lower levels,
could prove counter-productive and
harmful. In a Harvard study on
HIV-infected pregnant women in
Africa, it was claimed that multiple
micronutrient supplementation
brought about significant increase
in birth-weight of infants. It will
be wrong to extrapolate the result
of a study on HIV-infected mothers
to non-infected pregnant women. It
is also not known as to what
happened to the pregnant women in
the Harvard study after the
supplementation had finally ceased.
One wonders whether the short period
of high multiple micronutrient
supplementation, followed by sudden
cessation, hastened their end!
- RDAs
are usually estimated in healthy
populations free from infections. It
is known that in the presence of
infections, some micronutrients are
preferentially lost -- for example,
vitamin A in respiratory infections
and riboflavin in many infections
associated with negative nitrogen
balance. So, under real-life
situations in poor communities the
micronutrient requirements could be
totally different.
- Complex
interactions between micronutrients
(for example, between zinc and
copper, iron and zinc, and vitamin C
and zinc) are known and are likely
to be evident at higher doses. The
specific nutrient-nutrient
interactions in this mixture are
unknown, especially in
undernourished populations.
- The
proposal is apparently based on the
view that pregnant women in poor
developing countries are unlikely to
overcome their dietary deficiencies
through improved food intake using
locally available foods and,
therefore, they have to depend on
imported tablets and pills. This is
clearly an unjustified and defeatist
approach which will prove to be
unsustainable in the long run and
not conducive to promotion of
self-reliance.
- There
is currently no evidence based on
well-conducted Randomised Controlled
Trials (RCTs) in developing
countries that justify the use of
multiple micronutrient
supplementation on grounds of
efficacy, compliance and clearly
defined explicit outcome measures.
There is no convincing evidence
drawn from RCTs to intervene on
programmatic or pilot basis with
respect to multiple micronutrients
in pregnancy. Under the
circumstances, any pilot study of
the nature proposed by the group at
the US meeting would raise ethical
issues, and commit governments to
unnecessary expenditure on
interventions which are not based on
reliable scientific evidence. The
proposal, as it stands, will no
doubt save vitamin cartels from the
need for expensive experimental
studies and RCTs. It will, however,
be wrong to use pregnant women of
poor countries as human guinea pigs
for their benefit.
All this is not to say that there
are no micronutrient deficiencies
involved in poor pregnancy outcomes.
In all probability there are. But
the way to overcome these
deficiencies is not to resort to a
fishing expedition -- a hit or miss
blunderbuss polypharmacy approach
involving a few micronutrients which
may be necessary, quite a few which
may not be, and a few which may even
be harmful. It is also possible that
the proposed composition does not
include quite a few other
micronutrients, phytochemicals and
antioxidants, which may, in fact, be
useful.
For
this reason, this proposal for
multiple micronutrient
supplementation as it now stands is unscientific,
unethical and unsustainable.
It is not surprising that under the
circumstances the Indian Council of
Medical Research (ICMR) Expert Group
Committee meeting held on January
15-16, 2000 under the chairmanship
of the Director General of ICMR,
came to the unanimous conclusions
indicated in the box above.
We
are deeply appreciative of the
contributions that the
pharmaceutical industry is making
towards the advancement of medical
science, combating diseases and to
national development. We also
recognise that some major public
health programmes such as goiter and
iron deficiency and anaemia require
the use of supplements. There is a
vast legitimate scope for
contributions from the
pharmaceutical industry towards
health promotion in developing
countries. What we are emphasising
here, however, is that:
- the
specific multiple micronutrients
responsible for poor pregnancy
outcome in Indian women must first
be scientifically established;
- the
level at which these nutrients will
be needed to correct these
deficiencies must be carefully
identified; and
most
importantly, it must be established that
the micronutrient deficiencies so
identified as requiring correction are
such that the correction cannot be
achieved through dietary diversification
using locally available foods.
These requirements have to be satisfied before
any pilot trials with multiple
micronutrient supplements are attempted.
A blunderbuss polypharmacy approach in
the absence of such data will amount to
exploitation of poor communities and
will be putting an unnecessary strain on
the already stretched resources of the
health systems of poor countries. The
fair name of the pharmaceutical industry
should not be allowed to be sullied by
overzealous promotion of untested
pharmaceutical solutions to basic public
health programmes of poor countries.
‘Supplements’ should not be promoted
as ‘substitutes’ for food.
The
Challenge
India is
no barren desert. It is a country which
can be rightly proud of its vast
biodiversity. The challenge before
Indian scientists is to investigate how
best the vast array of foods which are
available right at their own doorsteps
and which are rich in several
micronutrients, could be used optimally
in judicious combinations in order to
combat micronutrient deficiencies.
Diseases like beri-beri and pellagra,
which were once rampant in India, have
now totally disappeared as public health
problems. This was not brought about
through supplementation of thiamin or
niacin, but through all-round
socio-economic development and dietary
diversification. Classical kwashiorkar
was overcome not through the
distribution of ‘fish protein
concentrates’, vigorously advocated by
the bureaus of commercial fisheries of
powerful countries. Keratomalacia was
eliminated as a public health problem in
spite of the failure of the massive dose
vitamin A prophylaxis programme
initiated by the National Institute of
Nutrition in India over 25 years ago. As
one who has had a ringside view of the
changing nutrition scene in India for
over 50 years now, I can testify to
these developments.
Plant
foods which could provide several
nutrients are in plentiful supply in the
country (Table). Many of them are of low
cost. Traditionally, these foods had
been widely used in various combinations
during pregnancy, lactation and other
specific situations. Unfortunately, in
recent years these inexpensive foods and
food combinations have been largely
dismissed as folklore. It is time that
we return to take a good look at our
traditional heritage in order to see how
the micronutrient-rich foods, which are
available within our country, can be
combined in judicious combinations and
appropriately used. Women could be in
the forefront of such a programme,
because the technology that may be
needed for this purpose would not be
sophisticated and expensive.
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Table:
An Illustrative (not
exhaustive) List of Commonly
Available Micronutrient Rich
Foods
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Vegetables |
Rape
leaves, Cauliflower greens,
Amaranth, Curry leaves, Garden
cress, Drumstick (leaves),
Fenugreek leaves, Beet greens,
Spinach, Betel leaves,
Parsley, Turnip greens,
Parslane, Mint, Carrots, Lotus
stem, Tapioca chips, Colocasia,
Radish, Sweet potato, Yam. |
|
Condiments
& Spices |
Poppy,
Cumin, Coriander, Oregano,
Green chillies (fresh/dry),
Turmeric, Ginger, Fenugreek,
Pepper, Garlic, Mango powder. |
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Nuts
& Oilseeds |
Coconut
(deoiled/dry/milk), Groundnut,
Cashewnut, Pistachionut,
Gingelly seeds, Garden cress
seeds, Safflower seeds,
Mustard seeds, Niger seeds. |
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Fruits |
Indian
Gooseberry, Watermelon,
Custard Apple, Wood apple,
Tomato, Guava, Mango,
Pineapple, Orange, Papaya,
Grapes, Banana, Bael,
Pomegranate. |
Agricultural
scientists of India are currently
engaged in ambitious programmes for
augmentation of production of pulses and
GLVs, which are rich sources of
micronutrients. These programmes had
suffered relative neglect in the days of
the Green Revolution. These mistakes are
now being corrected. Health scientists
should join hands with agricultural food
scientists in promoting the production
and consumption of these foods in order
to achieve an improvement in the quality
of the habitual diets in poor
households. Emphasis should be on
food-based rather than drug-based
solutions. Food resources available
within the country should be put to
maximal use instead of resorting to
commercial pharmaceutical short cuts.
A
Meaningful Agenda
A
meaningful agenda for research on
micronutrients in pregnant Indian women
must include the following:
Assessing
present micronutrient status of Indian
women.
Investigating
the effect of pregnancy on micronutrient
status, and relationship of
micronutrient deficiency to actual
pregnancy outcome and low birth-weight.
(This information is, at present,
extremely scanty.)
Defining
micronutrient requirements in pregnancy
under Indian conditions.
Updating
information on the content of
micronutrients, bioactive phytochemicals
and antioxidants in locally available
low-cost foods using modern analytical
procedures; and identifying optimal ways
of using these foods singly or in
combination for combating micronutrient
malnutrition.
There is vast scope for Indo-US
cooperation with a research agenda as
proposed above. Such meaningful
cooperation could prove far more
rewarding from the point of view of
nutritional upliftment of poor
populations and would make far greater
contributions towards the advancement of
nutr-itional science, than would be the
case if the cooperation is limited to
the distribution of an arbitrary list of
multivitamin tablets at arbitrary
levels.
Excerpts
from the keynote address at the Indo-US
Workshop on Health and Nutrition in
Women, Infants and Children, held at
Hyderabad, on February 10-12, 2000. The
Workshop was attended by about 100
participants including 20 distinguished
scientists from the USA.
References
1. Human
Development Report, UNDP, Oxford
University Press, 1999.
2. The
State of the World’s children. UNICEF,
1999.
3.
National Family Health Survey (1992-93).
India: Summary Report. International
Institute for Population Sciences, 1995.
4. Ninth
Five Year Plan Report, Planning
Commission, Government of India, 1999.
5.
Ramakrishnan, U., Manjrekar, R., Rivera,
J., Gonzales-Cossio, T. and Martorell,
R.: Micronutrients in pregnancy outcome:
a review of the literature. Nutrition
Research, Vol 19: 103-159, 1999.
6.
Huffman, S.L., Baker, J., Shumann, J.
and Zehner, R.: The case for promoting
multiple vitamin and mineral supplements
for women of reproductive age in
developing countries. Food and Nutr
Bull Vol 20 (4): 379-394, 1999.
7. The
alpha-tocopherol beta-carotene Cancer
Prevention Study Group. The effect of
vitamin E and beta-carotene on the
incidence of lung cancer and other
cancers in male smokers. N Engl J Med,
330:1029-35,1994.
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