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Role of Nutrition in pregnancy
Micronutrients in pregnancy
British Journal of Nutrition (2001), 85, Suppl. 2, S193±S197
Abstract
Vitamins and minerals, referred to collectively as micronutrients, have important influences on the
health of pregnant women and the growing fetus. Iron deficiency results in anemia which may increase
the risk of death from hemorrhage during delivery, but its effects on fetal development and birth
outcomes is still unclear. Folic acid deficiency can lead to hematological consequences, pregnancy
complications and congenital malformations, but again the association with other birth outcomes is
equivocal. Zinc deficiency has been associated in some, but not all studies with complications of
pregnancy and delivery, as well as with growth retardation,congenital abnormalities and retarded
neurobehavioral and immunological development in the fetus. Iodine deficiency during pregnancy
results in cretinism and possible fetal wastage and preterm delivery. Deficiency of other minerals such as
magnesium, selenium, copper, and calcium has also been associated with complications of pregnancy,
childbirth or fetal development. Deficiencies of vitamins other than folate may likewise be related to
such complications; and vitamin A or b-carotene supplements in pregnancy reduced maternal mortality
by 50 % in a controlled trial in Nepal. Additional research is need on the prevalence of such deficiencies
and their consequences and on cost-effective public health interventions for their control.

Complied By : Asma Saleem
Pregnancy and Lactation: Physiological Adjustments,
Nutritional Requirements and the Role of Dietary
Supplements
American Society for Nutritional Sciences 133:1997S-2002S, June 2003
ABSTRACT
Nutritional needs are increased during pregnancy and lactation for support of fetal and infant growth
and development along with alterations in maternal tissues and metabolism. Total nutrient needs are not
necessarily the sum of those accumulated in maternal tissues, products of pregnancy and lactation and
those attributable to the maintenance of nonreproducing women. Maternal metabolism is adjusted
through the elaboration of hormones that serve as mediators, redirecting nutrients to highly specialized
maternal tissues specific to reproduction (i.e., placenta and mammary gland). It is most unlikely that the
heightened nutrient needs for successful reproduction can always be met from the maternal diet.
Requirements for energy-yielding macronutrients increase modestly compared with several
micronutrients that are unevenly distributed among foods. Altered nutrient utilization and mobilization
of reserves often offset enhanced needs but sometimes nutrient deficiencies are precipitated by

Complied By : Asma Saleem
reproduction. There are only limited data from well-controlled intervention studies with dietary
supplements and with few exceptions (iron during pregnancy and folate during the periconceptional
period), the evidence is not strong that nutrient supplements confer measurable benefit. More research is
needed and in future studies attention must be given to subject characteristics that may influence ability
to meet maternal and infant demands (genetic and environmental), nutrient-nutrient interactions,
sensitivity and selectivity of measured outcomes and proper use of proxy measures. Consideration of
these factors in future studies of pregnancy and lactation are necessary to provide an understanding of
the links among maternal diet; nutritional supplementation; and fetal, infant and maternal health.

Dietary calcium and pregnancy-induced
hypertension: is there a relation?
American Journal of Clinical Nutrition, Vol. 71, No. 5, 1371S-1374s, May 2000
Abstract
The evidence that calcium plays a role in the etiology, prevention, and treatment of pregnancy-induced
hypertension (PIH) is reviewed. The precise factors involved in the pathogenesis of PIH are unclear, but
several alterations in calcium metabolism have been identified. Epidemiologic data suggest an inverse
correlation between dietary calcium intake and incidence of PIH. Although evidence suggests a possible
beneficial effect of supplemental calcium, contradictions persist in clinical trials of pregnant women.

Complied By : Asma Saleem
Presently, there is insufficient evidence to support routine calcium supplementation of all pregnant
women. However, high-risk groups, such as pregnant teens, populations with inadequate calcium
intake, and women at risk of developing PIH, may benefit from consuming additional dietary calcium.

Pregnancy-induced hypertension and low
birth weight: the role of calcium
American Journal of Clinical Nutrition, Vol 54, 237S-241S, 1991
Abstract
Considerable interest has developed regarding the role of calcium in the regulation of blood pressure.
Epidemiologic investigations, laboratory evaluations, and clinical trials all confirm that the relationship
between calcium and blood pressure extends to include the pregnant state. On the basis of current
information it is clear that calcium supplementation during pregnancy lowers blood pressure.
Additionally, the effect of calcium on blood pressure may influence the incidence and/or gestational age
of development of preeclampsia. Additionally, the effect on smooth-muscle relaxation detected in
calcium-supplemented patients may affect the incidence of prematurity. Although the mechanism for
these effects has not been entirely elucidated, calcium supplementation appears to affect circulating

Complied By : Asma Saleem
concentrations of parathyroid hormone and renin, which may modulate intracellular ionized calcium,
resulting in the observed effect on smooth-muscle relaxation. This effect may also be responsible for
reduced uterine activity and for a lowering of the incidence of prematurity.

Iron:
Iron is a key mineral for human metabolism. The healthy human body contains between 2.5 g (40
mg/kg: menstruating woman) and 4.0 g (50 mg/kg: adult male) iron. About 60% is found in the
haemoglobin of the red blood cells, and 15% in myoglobin (in muscles) and various enzymes.
Haemoglobin and myoglobin are proteins specialized in the transport and storage of oxygen. About 25%
of body iron is stored (as ferritin or haemosiderin) mainly in the liver, spleen and bone marrow. Iron
turnover is normally small. In the absence of bleeding (including menstruation) or pregnancy, about 1
mg iron is lost daily. During menstruation and lactation, iron loss may be twice as high. Iron
requirements are also increased during pregnancy (5-6 mg daily in the second and third trimesters) to
meet the needs of the foetus and the increased blood volume.

Importance for health:
Iron is required for a number of vital functions, including growth, reproduction, wound healing, and
immune function. The main role of iron is to carry oxygen to the tissues where it is needed. Iron is also

Complied By : Asma Saleem
essential for the proper functioning of numerous enzymes involved in DNA synthesis2, energy
metabolism, and protection against microbes and free radicals. Iron deficiency affects about 30% of the
world population, and is one of the main deficiency disorders in Europe People with iron deficiency
may get short of breath and tire quickly; they have a lower resistance to infection, and may develop
sores at the corner of the mouth, on the tongue and in the stomach. Severe iron deficiency results in
anemia associated with adverse pregnancy outcomes, and impaired mental and physical performance

Folic Acid, Iron during Pregnancy Improves
Children's Skills
American Journal of Clinical Nutrition 2010; 91:1035-43
Researchers found that children whose mothers took prenatal folic acid, iron, and vitamin A have better
working memory, inhibitory control, and fine motor functioning than children whose mothers took
vitamin A alone.

Complied By : Asma Saleem
Getting bone health right from the start!
Pregnancy, lactation and weaning
Journal of Family Health Care 2008; 18(4): 137-141
ABSTRACT
Maximizing bone health begins with maternal health and nutrition, which influences skeletal mass and
bone density in the fetus. Maternal health and nutrition, as well as the baby’s intake of Vitamin D and
calcium during breastfeeding and weaning, may have a long-lasting effect on the baby’s future health.
Vitamin D and calcium (alongside physical activity) play key roles in bone health for both mother and
baby.

Iron Deficiency Anemia
American Journal of Clinical Nutrition May 2000
Low levels of iron in the mother can lead to poor iron transfer to the fetus and lowers the amount
available for the mother even more. Iron deficiency can increase the risk for maternal mortality and is

Complied By : Asma Saleem
associated with low birth weight and low infant Apgar scores, which indicate infant health at the time of
birth.

Anemia and iron deficiency: effects on
pregnancy outcome
American Journal of Clinical Nutrition, Vol. 71, No. 5, 1280S-1284s, May 2000
ABSTRACT
This article reviews current knowledge of the effects of maternal anemia and iron deficiency on
pregnancy outcome. A considerable amount of information remains to be learned about the benefits of
maternal iron supplementation on the health and iron status of the mother and her child during
pregnancy and postpartum. Current knowledge indicates that iron deficiency anemia in pregnancy is a
risk factor for preterm delivery and subsequent low birth weight, and possibly for inferior neonatal
health. Data are inadequate to determine the extent to which maternal anemia might contribute to
maternal mortality. Even for women who enter pregnancy with reasonable iron stores, iron supplements
improve iron status during pregnancy and for a considerable length of time postpartum, thus providing
some protection against iron deficiency in the subsequent pregnancy. Mounting evidence indicates that
maternal iron deficiency in pregnancy reduces fetal iron stores, perhaps well into the first year of life.

Complied By : Asma Saleem
This deserves further exploration because of the tendency of infants to develop iron deficiency anemia
and because of the documented adverse consequences of this condition on infant development. The
weight of evidence supports the advisability of routine iron supplementation during pregnancy.
Key Words: Anemia • iron deficiency • pregnancy • maternal mortality • birth weight • preterm
delivery • infants

Serum calcium level as a marker of
pregnancy-induced hypertension
American Journal of Clinical Nutrition 2006; 83(3): 657-666
Abstract
Background: Regulation of intracellular calcium plays a key role in hypertension. Hypertension has
been estimated to complicate 5% of all pregnancies and 11% of first pregnancies. Half of the pregnant
women with hypertension have pre-eclampsia. Hypertensive disorders account for up to 40 000
maternal deaths annually.
Objective: To compare total serum calcium levels in pregnant women complicated with pre-eclampsia
with those in normotensive control.
Patients and Methods: This is a case-control hospital based study carried out at Omdurman Maternity
Hospital, Khartoum Teaching Hospital, and Khartoum North Teaching Hospital in Khartoum State,

Complied By : Asma Saleem
Sudan in the period from October 2006 to June 2007. One hundred thirty-five women were enrolled in
this study. 90 women with pregnancy - induced hypertension (PIH) admitted after 20th week of
pregnancy represented the study group. Forty five women with normal pregnancy, at same age; same
gestational age were selected as control group.
Results: The mean (±SD) serum calcium of the study group was 8.38±1.04 mg/dl, while that of the
control group was 9.04±1.13mg/dl (P= 0.001).
Conclusion: Low level of maternal total calcium may have a role in the development PIH. Therefore
calcium consumption in pregnancy should be encouraged. Calcium supplement is recommended for
women who live in places of low socioeconomic status as well as for women who prefer to skip milk and
milk products due to personal preference.

Complied By : Asma Saleem
Iron status at 9 months of infants with low
iron stores at birth
The Journal of Pediatrics
Volume 141, Issue 3 , Pages 405-409, September 2002
Abstract
Objective: To determine the 9-month follow-up iron status of infants born with abnormally low serum
ferritin concentrations.
Study design: Ten infants of >34 weeks' gestation with cord serum ferritin concentrations <5th
percentile at birth (<70 μg/L) and 12 control infants with cord serum ferritin concentrations >80 μg/L
had follow-up serum ferritin concentrations measured at 9 ± 1 month of age. The mean follow-up
ferritins, incidences of iron deficiency and iron-deficiency anemia, and growth rates from 0 to 12 months
were compared between the two groups.
Results: At follow-up, the low birth ferritin group had a lower mean ferritin than the control group (30
± 17 vs 57 ± 33 μg/L; P = .03), but no infant in either group had iron deficiency (serum ferritin <10 μg/L)
or iron-deficiency anemia. Both groups grew equally well, but more rapid growth rates were associated

Complied By : Asma Saleem
with lower follow-up ferritin concentrations only in the low birth ferritin group (r = −0.52; P = .05). Both
groups were predominantly breast-fed without iron supplementation before 6 months.
Conclusions: Infants born with serum ferritin concentrations <5th percentile continue to have
significantly lower ferritin concentrations at 9 months of age compared with infants born with normal
iron status, potentially conferring a greater risk of later onset iron deficiency in the second postnatal year

Worldwide prevalence of anemia, WHO Vitamin and Mineral Nutrition
Information System, 1993-2005.
Public Health Nutr. 2009 Apr;12(4):444-54. Epub 2008 May 23
Objective: To provide current global and regional estimates of anemia prevalence and number of
persons affected in the total population and by population subgroup.
Setting and design: We used anemia prevalence data from the WHO Vitamin and Mineral Nutrition
Information System for 1993-2005 to generate anemia prevalence estimates for countries with data
representative at the national level or at the first administrative level that is below the national level. For
countries without eligible data, we employed regression-based estimates, which used the UN Human
Development Index (HDI) and other health indicators. We combined country estimates, weighted by

Complied By : Asma Saleem
their population, to estimate anemia prevalence at the global level, by UN Regions and by category of
human development.
Results: Survey data covered 48.8 % of the global population, 76.1 % of preschool-aged children, 69.0 %
of pregnant women and 73.5 % of non-pregnant women. The estimated global anemia prevalence is 24.8
% (95 % CI 22.9, 26.7 %), affecting 1.62 billion people (95 % CI 1.50, 1.74 billion). Estimated anemia
prevalence is 47.4 % (95 % CI 45.7, 49.1 %) in preschool-aged children, 41.8 % (95 % CI 39.9, 43.8 %) in
pregnant women and 30.2 % (95 % CI 28.7, 31.6 %) in non-pregnant women. In numbers, 293 million (95
% CI 282, 303 million) preschool-aged children, 56 million (95 % CI 54, 59 million) pregnant women and
468 million (95 % CI 446, 491 million) non-pregnant women are affected.
Conclusion: Anemia affects one-quarter of the world's population and is concentrated in preschool-aged
children and women, making it a global public health problem. Data on relative contributions of causal
factors are lacking, however, which makes it difficult to effectively address the problem

Complied By : Asma Saleem
DHA supplementation During Pregnancy
Am J Clin Nutr 2007;85:1572-1577.
New research reaffirms that DHA supplementation during pregnancy improves cognitive function in
infants and children. A study published this month in the American Journal of Clinical Nutrition
showed that infants born to mothers who consumed DHA from fish oil (300 mg/day) demonstrated
better problem solving abilities than those who consumed a corn oil placebo. This data supports earlier
work published in 2003 that showed children born to mothers who supplemented with 2 tsp Cod Liver
Oil daily during pregnancy and lactation had higher IQs at age four when compared to children of
mothers who consumed placebo. Maternal DHA intake during pregnancy is far below the currently
recommended amount (minimum of 300 mg/day), which may be contributing to the unprecedented
incidence of neurological and behavioural problems that face children today. During the last trimester
of pregnancy, mothers selectively transfer DHA to the foetus to support the growth of the brain, eyes,
and nervous system. Without sufficient intake, mothers become depleted of DHA and increase their risk
of suffering major depressive symptoms in the postpartum period. In fact, population studies have
shown that lower intakes of DHA are associated with higher rates of postpartum depression4. It is well
established that the essential fatty acid, DHA, is a critical component to a healthy pregnancy. However, a
recent survey of expecting mothers showed that in 68% of the women surveyed, their doctor never
mentioned DHA, and half of the women surveyed had never heard of it.

Complied By : Asma Saleem
Position of the American Dietetic Association: nutrition
and lifestyle for a healthy pregnancy outcome.
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J Am Diet Assoc. 2010 Jan;110(1):141.
J Am Diet Assoc. 2009 Jul;109(7):1296.

Abstract
It is the position of the American Dietetic Association that women of child-bearing ages should maintain
good nutritional status through a lifestyle that optimizes maternal health and reduces the risk of birth
defects, suboptimal fetal growth and development, and chronic health problems in their children. The
key components of a health-promoting lifestyle during pregnancy include appropriate weight gain;
appropriate physical activity; consumption of a variety of foods in accordance with the Dietary
Guidelines for Americans 2005; appropriate and timely vitamin and mineral supplementation;
avoidance of alcohol, tobacco, and other harmful substances; and safe food handling. Pregnant women
with inappropriate weight gain, hyperemesis, poor dietary patterns, phenylketonuria, certain chronic
health problems, or a history of substance abuse should be referred to a registered dietitian for medical
nutrition therapy. Prenatal weight gain within the Institute of Medicine recommended ranges has been
associated with better pregnancy outcomes. Most pregnant women need 2,200 to 2,900 kcal a day, but
prepregnancy body mass index, rate of weight gain, maternal age, and appetite must be considered

Complied By : Asma Saleem
when tailoring this recommendation to the individual. The consumption of more food to meet energy
needs, and the increased absorption and efficiency of nutrient utilization that occurs in pregnancy, are
generally adequate to meet the needs for most nutrients. However, vitamin and mineral
supplementation is appropriate for some nutrients and situations. This position paper also includes
recommendations pertaining to use of alcohol, tobacco, caffeine, and illicit drugs.

Effect of supplementing pregnant and lactating mothers with n-3 very-long-chain
fatty acids on children's IQ and body mass index at 7 years of age.
Pediatrics. 2008 Aug;122(2):e472Abstract
OBJECTIVES: Arachidonic acid (20:4n-6) and docosahexaenoic acid (22:6n-3) are essential for brain
growth and cognitive development. We have reported that supplementing pregnant and lactating
women with n-3 very-long-chain polyunsaturated fatty acids promotes higher IQ scores at 4 years of age
as compared with maternal supplementation with n-6 polyunsaturated fatty acids. In our present study,
the children were examined at 7 years of age with the same cognitive tests as at 4 years of age. We also
examined the relation between plasma fatty acid pattern and BMI in children, because an association
between arachidonic acid and adipose tissue size has been suggested.

Complied By : Asma Saleem
METHODS: The study was randomized and double-blinded. The mothers took 10 mL of cod liver oil or
corn oil from week 18 of pregnancy until 3 months after delivery. Their children were tested with the
Kaufman Assessment Battery for Children at 7 years of age, and their height and weight were measured.
RESULTS: We did not find any significant differences in scores on the Kaufman Assessment Battery for
Children test at 7 years of age between children whose mothers had taken cod liver oil (n = 82) or corn
oil (n = 61). We observed, however, that maternal plasma phospholipid concentrations of alpha-linolenic
acid (18:3n-3) and docosahexaenoic acid during pregnancy were correlated to sequential processing at 7
years of age. We observed no correlation between fatty acid status at birth or during the first 3 months of
life and BMI at 7 years of age.
CONCLUSION: This study suggests that maternal concentration of n-3 very-long-chain
polyunsaturated fatty acids during pregnancy might be of importance for later cognitive function, such
as sequential processing, although we observed no significant effect of n-3 fatty acid intervention on
global IQs. Neonatal fatty acid status had no influence on BMI at 7 years of age.

DHA:
DHA (docosahexaenoic acid) is an essential fatty acid (EFA). EFAs are called “essential” because very
little can be synthesized by the body—we must obtain them from our diet. DHA is one of the omega-3
fatty acids, whose best-known source is perhaps fish oil.

Complied By : Asma Saleem
EFAs are necessary for good health, and DHA is well-known as one of the keys to a healthy nervous
system. DHA is the building block of human brain tissue—60 percent of the brain is fat, and DHA is the
most abundant fat in the brain, as well as in the retina of the eye. DHA is essential in communication
between the brain and nervous system—it plays a role in the cell membrane, where the electrical
impulses that are the basis of communication within the nervous system are generated. Without DHA
and other fatty acids, communication within this system can break down or become less effective.
The importance of DHA to the brain and nervous system is seen early in our development. In the first
few weeks of embryonic development, the mother’s blood supplies the fetus with large amounts of
DHA. In the last trimester of a pregnancy, the DHA content of the brain’s cerebrum and cerebellum—
which contains centers for speech and abstract thought—increases threefold.
DHA is recognized as extremely important—so much so that the World Health Organization has
recommended that DHA be added to infant formulas. Many health practitioners also recommend it for
pregnant women and nursing mothers.
DHA supplementation may be especially important as we grow older. The body’s ability to synthesize
DHA, which is limited in all people, may decline even further with age. This is compounded by the
small amounts of DHA we get in our diet, especially those who strive for a vegetarian diet—the richest
sources of DHA are red meats, animal organs, and eggs.

Complied By : Asma Saleem
Research indicates that low levels of DHA may be involved in a number of health problems relating to
the nervous system.

Depression:
Depression is on the rise in North America. This is often attributed to the ups and downs of our lives
and is often seen among the aging population. However, recent research indicates that there may be a
physiological aspect to depression that relates to nutrition.
A study published in the American Journal of Clinical Nutrition (62 (July 1995): 1-9) presents research
indicating that omega-3 fatty acids, specifically DHA, may reduce the risk of depression. The authors
associate the increase in depression in North America in the past century with the decline in
consumption of DHA during the same period. To lend support to this idea, the authors also note that
there are lower rates of major depression in those societies that consume large amounts of fish, a key
dietary source of DHA.

Complied By : Asma Saleem
Dementia and Alzheimer’s disease
DHA is also being considered as a factor in dementia and Alzheimer’s disease. In 1997, a link between
low levels of DHA and Alzheimer’s disease and memory loss was the subject of a conference at The New
York Hospital Cornell Medical Center’s Nutrition Information Center. Among the finding discussed at
the conference was that a low level of DHA is a significant risk factor for dementia, including
Alzheimer’s disease. Further support for this comes from Australia. In a letter published in the Medical
Journal of Australia (153 (November 5, 1990): 563-64), Dr. Robert Peers suggests that an imbalance
between an excessive intake of omega-6 fatty acids (from vegetable oils and margarine) and a deficient
intake of omega-3 fatty acids may be a factor in Alzheimer’s disease.
The Japan Functional Food Research Association has also investigated DHA and dementia. The
association notes that those with senile dementia achieved positive results when taking DHA: in 10 of 13
cerebral vascular dementia cases and five of five senile dementia cases, the patients showed more than
slight improvements in psychiatric symptoms such as communication, will power, motivation, delirium,
the tendency to wander, emotional disorders, and mental depression

Complied By : Asma Saleem
Vision

:

DHA is also the major fat in retinal tissue. It plays a strong role in the photoreceptor cells of the retina,
suggesting an essential role for DHA in vision. DHA deficiency in laboratory animals shows a marked
decrease in proper functioning of the visual cycle.
In a recent study looking at fish oil, which contains DHA, and macular degeneration, researchers found
that more frequent consumption of fish appears to protect against late age-related macular degeneration.
Only a moderate intake of fish was necessary for the protective effect (Archives of Ophthalmology 118
(March 2000): 401-404).

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The importance of DHA during pregnancy and breastfeeding
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A 2003 study published in the journal Pediatrics showed children whose mothers took a DHA
supplement during pregnancy scored higher on intelligence tests at four years of age than children
of mothers not taking DHA supplements.
A 2004 study published in Child Development found that babies whose mothers had high blood
levels of DHA at delivery had advanced attention spans into their second year of life. During the
first six months of life these infants were two months ahead of babies whose mothers had lower
DHA levels.
Other research studies suggest breastfed babies have IQs of six to 10 points higher than formula-fed
babies. Medical and nutritional experts attribute this difference to the DHA infants receive while
nursing.
In a trial of women receiving DHA supplementation during the third trimester, the average length
of gestation increased six days (Obstetrics & Gynecology, 2003).
Research has found low levels of DHA in mother's milk and in the red blood cells of women with
postpartum depression. (Journal of Affective Disorders, 2002). Some scientists believe increasing
levels of maternal DHA may reduce the risk of postpartum depression.

Complied By : Asma Saleem
Omega-3 Fatty Acid Supplementation during Pregnancy
Rev Obstet Gynecol. 2008 Fall; 1(4): 162–169.
Abstract
Omega-3 fatty acids are essential and can only be obtained from the diet. The requirements during
pregnancy have not been established, but likely exceed that of a nonpregnant state. Omega-3 fatty acids
are critical for fetal neurodevelopment and may be important for the timing of gestation and birth
weight as well. Most pregnant women likely do not get enough omega-3 fatty acids because the major
dietary source, seafood, is restricted to 2 servings a week. For pregnant women to obtain adequate
omega-3 fatty acids, a variety of sources should be consumed: vegetable oils, 2 low-mercury fish
servings a week, and supplements (fish oil or algae-based docosahexaenoic acid).

Complied By : Asma Saleem
Vitamin D requirements during pregnancy
American Journal of Clinical Nutrition, Vol. 80, No. 6, 1740S-1747S, December 2004
ABSTRACT
Adequate vitamin D concentrations during pregnancy are necessary to ensure appropriate maternal
responses to the calcium demands of the fetus and neonatal handling of calcium. The purpose of this
report is to review studies that investigated maternal and neonatal outcomes of vitamin D deficiency or
supplementation during pregnancy. Most studies reported included women at high risk of vitamin D
deficiency, because of low vitamin D and calcium intake or decreased ability to synthesize endogenous
vitamin D (attributable to lack of sun exposure or to heavily pigmented skin). Overall, vitamin D
supplementation in these populations leads to improved neonatal handling of calcium. Results
concerning benefits for fetal growth and bone development are inconclusive. There is no evidence of a
benefit of supplementation during pregnancy above amounts routinely required to prevent vitamin D
deficiency.

Complied By : Asma Saleem
Vitamin D for the Prevention of Preeclampsia
Nutrition Reviews
Volume 63, Issue 7, pages 225–232, July 2005
Abstract:
Preeclampsia has been suggested to result from a partial breakdown of tolerance to the developing
fetus after maternal immune maladaptation. Several of the proposed immunomodulatory
properties of the hormonal vitamin D system could potentially have beneficial effects for successful
maintenance of pregnancy. Preeclampsia is characterized by marked changes in vitamin D
metabolism. This paper reviews the evidence suggesting that the immunomodulatory properties of
1,25(OH)2D may play a key role in maintaining immunological tolerance in pregnancy, and
proposes that ensuring adequate vitamin D status/intake may help in the prevention and
management of preeclampsia

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Low vitamin D during pregnancy linked to pre-eclampsia
Journal of Clinical Endocrinology and Metabolism. September 7, 2007
“Vitamin D deficiency early in pregnancy is associated with a five-fold increased risk of
preeclampsia”.
“Our results showed that maternal vitamin D deficiency early in pregnancy is a strong, independent risk
factor for preeclampsia,” said Lisa M. Bodnar, Ph.D., M.P.H., R.D., assistant professor of epidemiology at
the University of Pittsburgh Graduate School of Public Health (GSPH) and lead author of the study.
“Women who developed preeclampsia had vitamin D concentrations that were significantly lower early
in pregnancy compared to women whose pregnancies were normal. And even though vitamin D
deficiency was common in both groups, the deficiency was more prevalent among those who went on to
develop preeclampsia.”
“Even a small decline in vitamin D concentration more than doubled the risk of preeclampsia,” noted
James M. Roberts, M.D., senior author of the study and MWRI founding director. “And since newborn’s

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vitamin D stores are completely reliant on vitamin D from the mother, low vitamin levels also were
observed in the umbilical cord blood of newborns from mothers with preeclampsia.”

Low vitamin D during pregnancy linked
to pre-eclampsia
American Journal of Obstetrics & Gynecology
Volume 203, Issue 4 , Pages 366.e1-366.e6, October 2010
Objective
Vitamin D deficiency has been linked to adverse pregnancy outcomes. The purpose of this investigation
was to assess total 25-hydroxyvitamin D (25-OH-D) levels at diagnosis of early-onset severe
preeclampsia (EOSPE).
Study Design
After institutional review board approval, we enrolled subjects with EOSPE (<34 weeks' gestation with
severe preeclampsia) in this case-control investigation in a 1:2 ratio with gestation-matched,

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contemporaneous control subjects. Demographic and outcome information was collected for each
subject. Plasma total 25-OH-D levels were determined by radioimmunoassay and reported in
nanograms per milliliter. Results were analyzed by Mann-Whitney U and multivariable regression.
Results
Subjects with EOSPE (n = 50) were noted to have decreased total 25-OH-D levels relative to healthy
control subjects (n = 100; P < .001). This difference in total 25-OH-D remained significant after control for
potential confounders.
Conclusion
Total 25-OH-D is decreased at diagnosis of EOSPE. Further study is needed to understand the impact of
vitamin D deficiency on pregnancy outcomes.

Complied By : Asma Saleem
Maternal fatty acid status during pregnancy
and lactation and relation to newborn and
infant statusmcn_3


Maternal and Child Nutrition (2011), 7 (Suppl. 2), pp. 41–5803 41..58

Abstract
The present review of determinants of infant fatty acid status was undertaken as part of a
conference on ‘Fatty acid status in early life in low-income countries: determinants and
consequences’. Emphasis is placed on the essential fatty acids, and particularly the physiologically
important long chain polyunsaturated fatty acids (LCPUFAs) of 20 and 22 carbons.We are unaware
of any studies of determinants of infant fatty acid status in populations with a cultural dietary
pattern with low amounts of linoleic acid (LA, 18:2n-6) and a-linolenic acid
(ALA,18:3n-3). Many reports suggest that there may be adverse health effects related to the
increased proportion of LA in relation to ALA, which have occurred worldwide due to the
increased availability of vegetable oils high in LA. The issue of dietary n-6 to n-3 balance may apply
to infant fatty acid status both during fetal and post-natal life; however, this review focuses on the
n-3 and n-6 LCPUFA, in particular, docosahexaenoic acid (DHA, 22:6n-3) and arachidonic acid (AA,
20:4n-6), which are the predominant n-3 and n-6 LCPUFA found in cell membranes. The evidence
that these fatty acids are preferentially transferred from maternal to fetal circulation across the

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placenta, and the sources and mechanisms for this transfer, are reviewed.We also addressthe
sources of DHA andAA for the newborn including human milk DHA andAA and the factors that
influence maternal DHA status and consequently the amount of DHA available for transfer to the
fetus and infant via human milk.

Implications of vitamin D deficiency In pregnancy and lactation
Am J Obstet Gynecol 2010;202:429.

Vitamin D is an essential fat soluble vitamin and a key modulator of calcium metabolism inchildren and
adults. Because calcium demands increase in the third trimester of pregnancy, vitamin D status becomes
crucial for maternal health, fetal skeletal growth, and optimal maternal and fetal outcomes. Vitamin D
deficiency is common in pregnant women (5-50%) and in breastfed infants (10-56%), despite the
widespread use of prenatal vitamins, because these are inadequate to maintain normal vitamin D levels
(_32 ng/mL). Adverse health outcomes such as preeclampsia, low birthweight, neonatal hypocalcemia,
poor postnatal growth, bone fragility, and increased incidence of autoimmune diseases have been linked
to low vitamin D levels during pregnancy and infancy. Studies are underway to establish the
recommended daily doses of vitamin D in pregnant women. This review discusses vitamin D
metabolism and the implications of vitamin D deficiency in pregnancy and lactation.

Complied By : Asma Saleem
Vitamin D and pregnancy: An old problem revisited
Research Clinical Endocrinology & Metabolism 24 (2010) 527–539
Vitamin D has historically been considered to play a role solely in bone and calcium metabolism. Human
disease associations and basic physiological studies suggest that vitamin D deficiency is plausibly
implicated in adverse health outcomes including
mortality, malignancy, cardiovascular disease, immune functioning and glucose metabolism. There is
considerable evidence that low maternal levels of 25 hydroxyvitamin D are associated with adverse
outcomes for both mother and fetus in pregnancy as well as the neonate and child. Vitamin D deficiency
during pregnancy
has been linked with a number of maternal problems including infertility, preeclampsia, gestational
diabetes and an increased rate of caesarean section. Likewise, for the child, there is an association with
small size, impaired growth and skeletal problems in infancy, neonatal hypocalcaemia and seizures, and
an increased risk of HIV transmission. Other childhood disease associations include type 1 diabetes and
effects on immune tolerance. The optimal concentration of 25 hydroxyvitamin D is unknown and
compounded by difficulties in defining the normal range. Whilst there is suggestive
physiological evidence to support a causal role for many of the associations, whether vitamin D
deficiency is a marker of poor health or the underlying a etiological problem is unclear. Randomized

Complied By : Asma Saleem
controlled trials of vitamin D supplementation with an appropriate assessment of a variety of health
outcomes are required.

Vitamin B6 may boost conception
American Journal of Epidemiology
Volume 166, Number 3, Pages 304-312
A study, published in the American Journal of Epidemiology, may see vitamin B6 become as important
as the current "Big 3" of pregnancy nutrition: folic acid, calcium with vitamin D, and omega-3 fatty acids.
Researchers in China looked at blood levels of homocysteine, folate, and vitamins B6 and B12 in over 350
women to see if there was a link between B vitamin status and ease of conception. The women had an
average age of 25 years and had all conceived at least once between 1996-8. Daily urine samples were
taken for 12 months and tested for human chorionic gonadatropin (hCG) to detect conception and early
pregnancy loss.
It was found that women with an adequate vitamin B6 status (>30nm/l) had a 40% better chance of
conception and a 30% lower risk of miscarriage early in pregnancy compared with women with a low
vitamin B6 status. Having high vitamin B6 levels in the blood improved these chances further with a

Complied By : Asma Saleem
120% increased chance of conception at 38nm/l and a 50% lower risk of early pregnancy loss at 46nm/l.
The results suggest that increasing vitamin B6 levels prior to conception could boost conception rates
and decrease the risk of early miscarraige.

Drug therapy during pregnancy
Curr Opin Obstet Gynecol (UNITED STATES) Feb 1992, 4 (1) p43-7
A randomized prospective trial has shown that folic acid started before conception and continued for the
first trimester reduces the risk of recurrence of neural tube defects by 72% in women with a previously
affected child. Carbamazepine exposure in utero is associated with a 1% risk of spina bifida. Long-term
follow-up of antenatal exposure to phenobarbital and carbamazepine in two groups of infants shows no
neurologic differences between the two groups. Magnesium sulfate is more effective in prevention of
recurrent eclamptic seizures than phenytoin. During pregnancy, the need for thyroxine increases in
many women. Vitamin B6 and ginger are both effective for nausea and vomiting in early pregnancy.
Low-dose aspirin does not change the course of preeclampsia when it is started after the diagnosis is
made. Angiotensin-converting enzyme inhibitors cause significant disturbances of fetal and neonatal
renal function. Prophylactic beta-adrenergic agents fail to prevent prematurity in twins. Oral tocolysis
with magnesium chloride or ritodrine is no more effective than observation alone. The risk of primary
pulmonary hypertension in the newborn after indomethacin tocolysis is increased with prolonged
therapy. Lithium causes polyhydramnios from fetal diabetes insipidus in utero. Treatment of

Complied By : Asma Saleem
Ureaplasma urealyticum infection with erythromycin during pregnancy does not eliminate the organism
from the lower genital tract and does not improve perinatal outcome.

Multivitamins Improve the Chances of a Full-Term
Pregnancy
American Journal of Epidemiology 1997 Jul 15;146(2):134-41.
Abstract
The objective of this study was to examine the association of prenatal multivitamin/mineral supplement
use during the first and second trimesters of pregnancy by low income, urban women in the Camden
Study (1985-1995, n = 1,430) and preterm delivery (< 37 completed weeks) and infant low birth weight (<
2,500 g). Prenatal supplement use was corroborated by assay of circulating micronutrients at entry to
care (no differences) and week 28 gestation (increased concentrations of folate and ferritin for
supplement users). Compared with women who entered care during the first or second trimester but did
not use prenatal supplements, supplement use starting in the first or second trimester was associated
with approximately a twofold reduction in risk of preterm delivery. After controlling for potential
confounding variables, risk of very preterm delivery (< 33 weeks' gestation) was reduced more than
fourfold for first trimester users and approximately twofold when use dated from the second trimester.
Infant low birth weight and very low birth weight (< 1,500 g) risks were also reduced. Risk of low birth

Complied By : Asma Saleem
weight was reduced approximately twofold with supplement use during the first and second trimester.
Diminution in risk was greater for very low birth weight infants, amounting to a sevenfold reduction in
risk of very low birth weight with first trimester supplementation and a greater than six-fold reduction
when supplement use started in the second trimester. Thus, in low income, urban women, use of
prenatal multivitamin/mineral supplements may have the potential to diminish infant morbidity and
mortality.

Effects of vitamin A deficiency during
pregnancy on maternal and child health.
British Journal of Gynecology 2002 Jun;109(6):689-93.
Abstract
OBJECTIVE: To examine the association between biochemical vitamin A deficiency in pregnancy and
maternal and fetal health.
DESIGN: A cross sectional clinical study.
SETTING: Antenatal clinic of nutrition unit of Niloufer Hospital catering for a low socio-economic
population, and a private nursing home (Swapna nursing home) catering for a high socio-economic
population.

Complied By : Asma Saleem
POPULATION: 736 pregnant women in their third trimester of pregnancy belonging to low (n = 522)
and high socio-economic groups (n = 214).
METHODS: All the women were subjected to a detailed clinical, anthropometric and obstetric
examination. Night blindness was assessed by administering the standard WHO questionnaire.
Birthweight and gestational age of the infants, maternal anaemia and development of pregnancyinduced hypertension in the mother were recorded. Haemoglobin and serum retinol were estimated at
the time of recruitment to the study.
MAIN OUTCOME MEASURES: Serum retinol levels, anaemia, pregnancy-induced hypertension, birth
weight and gestational age of the infant.
RESULTS: Night blindness was observed in 2.9% of the women and subclincal vitamin A deficiency
(serum retinol <20 microg/dL with no clinical signs) in 27% of the women. Moderate to severe anaemia
was observed in 41.2% of the women, and 15.8% of the women developed pregnancy-induced
hypertension. Sixty-one (9.4%) women delivered preterm. Univariate analysis identified a significant
association between serum retinol <20 microg/dL and preterm delivery (OR = 1.74, 95% CI 1.03-2.96),
maternal anaemia (OR = 1.82, 95% CI 1.28-2.60) and pregnancy-induced hypertension (OR = 1.56, 95% CI
1.02-2.83). After adjusting for the confounding variables (body mass index, parity, age and socioeconomic status) in a multivariate analysis, the significant associations between serum retinol <20
microg/dL and preterm delivery (P = 0.02) and anaemia (P = 0.003) persisted, while that for pregnancyinduced hypertension disappeared (P = 0.71).

Complied By : Asma Saleem
CONCLUSION: The study suggests that subclinical vitamin A deficiency is a problem during the third
trimester of pregnancy. Serum concentration of retinol <20 microg/dL appears to indicate a deficient
status, and is associated with an increased risk of preterm delivery and maternal anaemia.

Vitamin D Supplementation during Pregnancy Part 2
NICHD/CTSA Randomized Clinical Trial (RCT):
Pediatric Academic Societies Meeting, May 1, 2010 Abstract 1665.6

Abstract
BACKGROUND: Vitamin D (vitD) deficiency during pregnancy is a serious public health issue,
affecting mother and fetus. Establishing optimal vitD requirements of pregnant women is vital in
preventing vitD deficiency and its health-associated comorbidities.
OBJECTIVE: Evaluate the effectiveness of high dose vitD supplementation in decreasing pregnancy
comorbidity risks.
DESIGN/METHODS: Following their consent, pregnant women 12-16 wks' gestation were randomized
into 1 of 3 tx grps stratified by race: 400, 2000 or 4000 IU vitD3/day until delivery. Women were
evaluated for safety (Abstr#750939), efficacy and effectiveness with monthly 25(OH)D; 1,25(OH)2D;
serum Ca, Cr, phos, and urinary Ca/Cr levels, all measured using standardized methodology.
Comorbidities of pregnancy (preeclampsia, gest diabetes, any infection, preterm labor (PTL)/preterm

Complied By : Asma Saleem
birth (PTB)<37 wks GA) were recorded prospectively for each subject. Investigators and health team
were blinded to tx grp.
RESULTS: Of the 494 women who enrolled in the study, 350 women continued until delivery: 98
African American (AA), 137 Hispanic (Hisp) and 115 Caucasian (Cauc) women; with 111 controls, 122 in
2000 IU and 117 in 4000 IU groups. There were no differences in baseline vitD status between dose
groups. The mean 25(OH)D by dose group at delivery, as chronic level, and 1-month before delivery
were significantly different between control and 2000, control and 4000, and 2000 vs. 4000 (p<0.0001).
25(OH)D had a direct influence on 1,25(OH)2D levels throughout pregnancy (p<0.0001) with 25(OH)D
of 40 ng/mL required to obtain maximum 1,25(OH)2D production. In bivariate analyses controlling for
race, PTL/PTB and infection were inversely related to 25(OH)D and were lowest in the 4000 IU grp
(p<0.0001). In logistic regression, comparing 400 vs. 4000 IU and controlling for race, the risk of
comorbidities were 0.50 (CI 0.27-0.95; p=0.03) among those in the 4000 IU grp. Using least sq means,
when adjusting for race, 25(OH)D of women with comorbidities was 33.4 ng/mL compared to 39.0
ng/mL in those women without (p<0.008).
CONCLUSIONS: VitD sufficiency was strongly associated with decreased risk for PTL/PTB and
infection during pregnancy and co-morbidities of pregnancy, with the greatest effect with 4000 IU
vitamin D/day regimen. Therefore, to attain a minimal 25(OH)D level of 40 ng/mL, we recommend
4000 IU/day for all pregnant women.

Complied By : Asma Saleem
Vitamin C intake and the risk of pre-term delivery
American Journal of Obstetrics and Gynecology August 2003;189(2):519-525.
Abstract
OBJECTIVE: Ascorbic acid deficiency may lead to premature rupture of the membranes.
STUDY DESIGN: The study included a prospective cohort of pregnant women, aged ?16 years, with
singleton gestations who received care at one of four prenatal clinics in central North Carolina from 1995
through 1998. Vitamin C intake pre-conceptionally and during the second trimester was examined for its
association with preterm delivery and subsets of preterm labor, premature rupture of the membranes,
and medical induction in 2064 women.
RESULTS: Women who had total vitamin C intakes of <10th percentile pre-conceptionally had twice the
risk of preterm delivery because of premature rupture of the membranes (relative risk, 2.2; 95% CI, 1.1,
4.5). This risk was attenuated slightly for second-trimester intake (relative risk, 1.7; 95% CI, 0.8, 3.5). The
elevated risk of preterm premature rupture of the membranes was greatest for women with a low
vitamin C intake during both time periods.
CONCLUSION: Because diet and supplement use are modifiable behaviors, corroboration of these
findings would suggest a possible intervention strategy.

Complied By : Asma Saleem
Folic acid at 1,000 mcg/day improves chances of healthy birth weight.
Epigenetics 6:1, 86-94; January 2011

Abstract
Supplementation with folic acid during pregnancy is known to reduce the risk of neural tube defects and
low birth weight. It is thought that folate and other one-carbon intermediates might secure these clinical
effects via DNA methylation. We examined the effects of folate on the human methylome using
quantitative interrogation of 27,578 CpG loci associated with 14,496 genes at single-nucleotide resolution
across 12 fetal cord blood samples. Consistent with previous studies, the majority of CpG dinucleotides
located within CpG islands exhibited hypo-methylation while those outside CpG islands showed midhigh methylation. However, for the first time in human samples, unbiased analysis of methylation across
samples revealed a significant correlation of methylation patterns with plasma homocysteine, LINE-1
methylation and birth weight centile. Additionally, CpG methylation significantly correlated with either
birth weight or LINE-1 methylation were predominantly located in CpG islands. These data indicate that
levels of folate-associated intermediates in cord blood reflect their influence and consequences for the
fetal epigenome and potentially on pregnancy outcome. In these cases, their influence might be exerted
during late gestation or reflect those present during the peri-conceptual period.

Complied By : Asma Saleem
Iron supplementation during pregnancy, anemia, and
birth weight
American Journal of Clinical Nutrition, Vol. 78, No. 4, 773-781, October 2003.

Abstract
BACKGROUND: The need for prophylactic iron during pregnancy is uncertain.
OBJECTIVE: We tested the hypothesis that administration of a daily iron supplement from enrollment to
28 wk of gestation to initially iron-replete, nonanemic pregnant women would reduce the prevalence of
anemia at 28 wk and increase birth weight.
DESIGN: Between June 1995 and September 1998, 513 low-income pregnant women in Cleveland were
enrolled in the study before 20 wk of gestation. Of these, 275 had a hemoglobin concentration ≥ 110 g/L
and a ferritin concentration ≥ 20 µg/L and were randomly assigned to receive a monthly supply of
capsules containing either 30 mg Fe as ferrous sulfate or placebo until 28 wk of gestation. At 28 and 38
wk of gestation, women with a ferritin concentration of 12 to < 20 µg/L or < 12 µg/L received 30 and 60
mg Fe/d, respectively, regardless of initial assignment. Almost all the women received some
supplemental iron during pregnancy. We obtained infant birth weight and gestational age at delivery for
117 and 96 of the 146 and 129 women randomly assigned to receive iron and placebo, respectively.

Complied By : Asma Saleem
RESULTS: Compared with placebo, iron supplementation from enrollment to 28 wk of gestation did not
significantly affect the overall prevalence of anemia or the incidence of preterm births but led to a
significantly higher mean (± SD) birth weight (206 ± 565 g; P = 0.010), a significantly lower incidence of
low-birth-weight infants (4% compared with 17%; P = 0.003), and a significantly lower incidence of
preterm low-birth-weight infants (3% compared with 10%; P = 0.017).
Conclusion: Prenatal prophylactic iron supplementation deserves further examination as a measure to
improve birth weight and potentially reduce health care costs.

Zinc Improves the Chances of Full Birth Weight
American Medical Association. 1995;274(6):463-468.

Abstract
Objective:To evaluate whether zinc supplementation during pregnancy is associated with an increase in
birth weight.
Design: A randomized double-blind placebo-controlled trial.
Setting:Outpatient clinic and delivery service at the University of Alabama at Birmingham.
Patients:Five hundred eighty medically indigent but otherwise healthy African-American pregnant
women with plasma zinc levels below the median at enrollment in prenatal care, randomized at 19

Complied By : Asma Saleem
weeks' gestational age. Women were subdivided by the population median body mass index of 26
kg/m2 into two groups for additional analyses.
Intervention:Women who were taking a non—zinc-containing prenatal multivitamin/mineral tablet
were randomized to receive either a daily dose of 25 mg of zinc or a placebo until delivery.
Main Outcome Measures:Birth weight, gestational age at birth, and head circumference at birth.
Results:In all women, infants in the zinc supplement group had a significantly greater birth weight (126
g, P=.03) and head circumference (0.4 cm, P=.02) than infants in the placebo group. In women with a
body mass index less than 26 kg/m2, zinc supplementation was associated with a 248-g higher infant
birth weight (P=.005) and a 0.7-cm larger infant head circumference (P=.007). Plasma zinc concentrations
were significantly higher in the zinc supplement group.
Conclusions:Daily zinc supplementation in women with relatively low plasma zinc concentrations in
early pregnancy is associated with greater infant birth weights and head circumferences, with the effect
occurring predominantly in women with a body mass index less than 26 kg/m2.

Complied By : Asma Saleem
Use of folic acid in the prevention of neural tube defect
Genecology Obstetriciade Mexico 1996 Sep;64:418-21
Abstract
The incidence of neural tube defects (NTDs) is about 1.3 cases per 1000 live births. The higher incidence
of NTDs occurs among certain ethnic groups, and geographic areas. The fetal morbimortality is high and
the treatment for those babies who live is expensive with poor quality of live. It is unclear what
biochemical mechanism involving folate explains the relationship of this vitamin to the pathogenesis of
NTDs. However elevated concentrations of homocysteine or decreased methionine concentrations could
be interfere with closure of the neural tube. The pharmacologic periconceptional intake of 0.4-4.0
mg/day of folic acid reduces the risk of occurrent NTDs by approximately 40-75%. A relatively high
dietary intake of folate may also reduce the risk.

Complied By : Asma Saleem
Calcium improves chances of healthy baby’s bones.
Obstetrics and Gynecololgy. 1999 Oct;94(4):577-82.
OBJECTIVES: To determine the effect of maternal calcium supplementation during pregnancy on fetal
bone mineralization.
METHODS: Healthy mothers with early ultrasound confirmation of dates and singleton pregnancies
were enrolled in a double-masked study and randomized before 22 weeks' gestation to 2 g/day of
elemental calcium or placebo until delivery. Maternal dietary intake at randomization and at 32-33
weeks' gestation was recorded with 24-hour dietary recalls. Dual-energy x-ray absorptiometry
measurements of the whole body and lumbar spine of the neonates were performed before hospital
discharge.
RESULTS: The infants of 256 women (128 per group) had dual-energy x-ray absorptiometry
measurements during the first week of life. There were no significant differences between treatment
groups in gestational age, birth weight, or length of the infants, or in the total-body or lumbar spine bone
mineral content. However, when bone mineral content was analyzed by treatment group within
quintiles of maternal dietary calcium intake, total body bone mineral content (mean +/- standard error
of the mean) was significantly greater in infants born to calcium-supplemented mothers (64.1+/-3.2
versus 55.7+/-2.7 g in the placebo group) in the lowest quintile of dietary calcium intake (less than 600
mg/day). The effect of calcium supplementation remained significant after adjustment for maternal age
and maternal body mass index and after normalization for skeletal area and body length of the infant.

Complied By : Asma Saleem
CONCLUSION: Maternal calcium supplementation of up to 2 g/day during the second and third
trimesters can increase fetal bone mineralization in women with low dietary calcium intake. However,
calcium supplementation in pregnant women with adequate dietary calcium intake is unlikely to result
in major improvement in fetal bone mineralization.

Effects of vitamin A deficiency during pregnancy on maternal and child health.
British Journal of Gynecology 2002 Jun;109(6):689-93.
Abstract
OBJECTIVE: To examine the association between biochemical vitamin A deficiency in pregnancy and
maternal and fetal health.
DESIGN: A cross sectional clinical study.
SETTING:Antenatal clinic of nutrition unit of Niloufer Hospital catering for a low socio-economic
population, and a private nursing home (Swapna nursing home) catering for a high socio-economic
population.
POPULATION:736 pregnant women in their third trimester of pregnancy belonging to low (n = 522)
and high socio-economic groups (n = 214).
METHODS:All the women were subjected to a detailed clinical, anthropometric and obstetric
examination. Night blindness was assessed by administering the standard WHO questionnaire.

Complied By : Asma Saleem
Birthweight and gestational age of the infants, maternal anaemia and development of pregnancyinduced hypertension in the mother were recorded. Haemoglobin and serum retinol were estimated at
the time of recruitment to the study.
MAIN OUTCOME MEASURES:Serum retinol levels, anaemia, pregnancy-induced hypertension, birth
weight and gestational age of the infant.
RESULTS: Night blindness was observed in 2.9% of the women and subclincal vitamin A deficiency
(serum retinol <20 microg/dL with no clinical signs) in 27% of the women. Moderate to severe anaemia
was observed in 41.2% of the women, and 15.8% of the women developed pregnancy-induced
hypertension. Sixty-one (9.4%) women delivered preterm. Univariate analysis identified a significant
association between serum retinol <20 microg/dL and preterm delivery (OR = 1.74, 95% CI 1.03-2.96),
maternal anaemia (OR = 1.82, 95% CI 1.28-2.60) and pregnancy-induced hypertension (OR = 1.56, 95% CI
1.02-2.83). After adjusting for the confounding variables (body mass index, parity, age and socioeconomic status) in a multivariate analysis, the significant associations between serum retinol <20
microg/dL and preterm delivery (P = 0.02) and anaemia (P = 0.003) persisted, while that for pregnancyinduced hypertension disappeared (P = 0.71).
CONCLUSION:The study suggests that subclinical vitamin A deficiency is a problem during the third
trimester of pregnancy. Serum concentration of retinol <20 microg/dL appears to indicate a deficient
status, and is associated with an increased risk of preterm delivery and maternal anaemia.

Complied By : Asma Saleem
Vitamin D Supplementation during Pregnancy Part 2
NICHD/CTSA Randomized Clinical Trial (RCT): Outcomes.
Pediatric Academic Societies Meeting, May 1, 2010
Abstract
BACKGROUND:Vitamin D (vitD) deficiency during pregnancy is a serious public health issue,
affecting mother and fetus. Establishing optimal vitD requirements of pregnant women is vital in
preventing vitD deficiency and its health-associated comorbidities.
OBJECTIVE:Evaluate the effectiveness of high dose vitD supplementation in decreasing pregnancy
comorbidity risks.
DESIGN/METHODS:Following their consent, pregnant women 12-16 wks' gestation were randomized
into 1 of 3 tx grps stratified by race: 400, 2000 or 4000 IU vitD3/day until delivery. Women were
evaluated for safety (Abstr#750939), efficacy and effectiveness with monthly 25(OH)D; 1,25(OH)2D;
serum Ca, Cr, phos, and urinary Ca/Cr levels, all measured using standardized methodology.
Comorbidities of pregnancy (preeclampsia, gest diabetes, any infection, preterm labor (PTL)/preterm
birth (PTB)<37 wks GA) were recorded prospectively for each subject. Investigators and health team
were blinded to tx grp.
RESULTS: Of the 494 women who enrolled in the study, 350 women continued until delivery: 98
African American (AA), 137 Hispanic (Hisp) and 115 Caucasian (Cauc) women; with 111 controls, 122 in
2000 IU and 117 in 4000 IU groups. There were no differences in baseline vitD status between dose

Complied By : Asma Saleem
groups. The mean 25(OH)D by dose group at delivery, as chronic level, and 1-month before delivery
were significantly different between control and 2000, control and 4000, and 2000 vs. 4000 (p<0.0001).
25(OH)D had a direct influence on 1,25(OH)2D levels throughout pregnancy (p<0.0001) with 25(OH)D
of 40 ng/mL required to obtain maximum 1,25(OH)2D production. In bivariate analyses controlling for
race, PTL/PTB and infection were inversely related to 25(OH)D and were lowest in the 4000 IU grp
(p<0.0001). In logistic regression, comparing 400 vs. 4000 IU and controlling for race, the risk of
comorbidities were 0.50 (CI 0.27-0.95; p=0.03) among those in the 4000 IU grp. Using least sq means,
when adjusting for race, 25(OH)D of women with comorbidities was 33.4 ng/mL compared to 39.0
ng/mL in those women without (p<0.008).
CONCLUSIONS:VitD sufficiency was strongly associated with decreased risk for PTL/PTB and
infection during pregnancy and co-morbidities of pregnancy, with the greatest effect with 4000 IU
vitamin D/day regimen. Therefore, to attain a minimal 25(OH)D level of 40 ng/mL, we recommend
4000 IU/day for all pregnant women.

Complied By : Asma Saleem
Vitamin C supplementation to prevent premature rupture of the
chorioamniotic membranes: a randomized trial
American Journal of Clinical Nutrition, Vol. 81, April 2005, pp. 859-86.
ABSTRACT
Background: Vitamin C is involved in the synthesis and degradation of collagen and is important for
maintenance of the chorioamniotic membranes. Inadequate availability of ascorbic acid during
pregnancy has been proposed as a risk factor for premature rupture of the chorioamniotic membranes
(PROM).
Objective: The objective of the study was to evaluate the effectiveness of 100 mg vitamin C/d in
preventing PROM.
Design: A controlled double-blind trial was performed. Pregnant women (n = 126) in their 20th wk of
gestation were invited; 120 accepted and were randomly assigned to 2 groups (100 mg vitamin C/d or
placebo). Every 4 wk, plasma and leukocyte vitamin C concentrations were measured, and each subject
was evaluated for cervicovaginal infection. The incidence of PROM was recorded for each group as an
indicator of the protective effect of vitamin C supplementation.

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Results: One hundred nine patients finished the study. Mean plasma vitamin C concentrations
decreased significantly throughout the pregnancy in both groups (P = 0.001), and there were no
significant differences between groups. Between weeks 20 and 36, mean leukocyte vitamin C
concentrations decreased from 17.5 to 15.23 µg/108 cells in the placebo group and increased from 17.26
to 22.17 µg/108 cells in the supplemented group (within- and between-group differences: P = 0.001). The
incidence of PROM was 14 per 57 pregnancies (24.5%) in the placebo group and 4 per 52 pregnancies
(7.69%) in the supplemented group (relative risk: 0.26; 95% CI: 0.078, 0.837).
Conclusion: Daily supplementation with 100 mg vitamin C after 20 wk of gestation effectively lessens
the incidence of PROM.
Key Words: Vitamin C • ascorbic acid • pregnancy • premature rupture of the chorioamniotic
membranes • preterm labor • dietary reference intakes • DRIs • Mexico

Complied By : Asma Saleem
Evidence for the role of zinc in childhood survival
Journal of Pediatrics, 135: 208-217 (1999)1
Science, 27: 1081-1085 (1996).2
American Journal of Clinical Nutrition, 68 (Suppl.): 447S-4463S (1998).3
Journal of Paediatric Gastroenterology and Nutrition, 15: 289-296 (1992).4
Gut, 35: 1707-1711 (1994).5
Journal of Pediatrics, 135: 689-697 (1999).6
Although the theoretical basis for a potential role of zinc has been postulated for quite some time, convincing evidence
for its importance in child health has come only recently from randomized controlled trials of zinc supplementation.
Episodes of childhood diarrhoea that last 14 days or more are associated with increased morbidity and growth
retardation. Children who experience such episodes are more likely to have other serious infections and to die (1).
Zinc is essential for many cellular functions, including transcription of DNA and cell division (2) and is required for
normal immune function (3). It has been shown to hasten mucosal recovery after diarrhoea. Zinc deficiency, as
indicated by low plasma zinc concentrations, is associated with both an increased risk of diarrhoeal episodes and
greater severity of these illnesses (4, 5).
The data from 10 trials evaluating preventive effects of zinc supplementation; three trials evaluating the therapeutic
effects on acute diarrhoea; and four trials in therapy of persistent diarrhoea have now been subjected to a pooled

Complied By : Asma Saleem
analysis (6). This evaluation assessed studies carried out on the effects of zinc supplementation in the prevention of
diarrhoea and pneumonia. Trials included those that provided oral supplements containing at least one half of the
United States Recommended Daily Allowance of zinc in children under 5 years of age and evaluated the prevention of
serious infectious morbidity. The effects of supplements on diarrhoea and pneumonia were analysed overall and in
subgroups, defined by age, baseline plasma zinc concentration, nutritional status, and sex. The analysis used random
effects hierarchical models to calculate odds ratios and confidence interval.
This analysis indicated that there is significant homogeneity in the results across the studies conducted throughout 10
developing countries. Zinc supplementation in these children in developing countries is associated with substantial
reductions in the rates of diarrhoea and pneumonia, the two leading causes of death in these settings. These studies also
provide by far the best evidence of widespread prevalence of zinc deficiency among preschool children.
However, although the available evidence is promising, it is still insufficient to formulate public health policies.
Extrapolation of mortality impact from morbidity trial data is fraught with problems of both underestimating and
overestimating the impact. Therefore, given its substantial potential to become a powerful intervention to promote
child survival, the World Health Organization, in collaboration with UNICEF backed by funding from the United
Nations Foundation, has initiated two large studies to determine whether zinc supplementation truly has an important
role in decreasing child mortality and morbidity. These studies should provide conclusive new evidence on which to
base interventions within the next 30 months and allow recommendations concerning the benefit of zinc
supplementation in young children to be made.

Complied By : Asma Saleem
The effect of calcium supplementation during pregnancy on the birth
weight

J Reprod Infertil. 2003;4(3):184-191.

Nutritional status during pregnancy and intake of essential nutrients affect pregnancy outcome and child health. In
most previous studies, high doses of calcium supplements were used during pregnancy to evaluate the effect of calcium
intake on pregnancy outcome and their results showed no consistency. In addition, those studies have been mainly
carried out to determine the effect of calcium supplementation on relative risk of preeclampsia. The aim of this double
blind, placebo controlled, randomized clinical trial on healthy pregnant women during the third trimester of pregnancy
was to determine the effect of calcium supplementation (1 g/day, as two 500 mg calcium carbonate capsules) on
pregnancy outcome. Participants were 68 healthy pregnant women, allocated randomly into "Calcium Supplement"
(n=33) or "Placebo" (n=35) groups from the 28th -30th weeks of gestation through delivery. Factors such as blood
pressure, weight, height and BMI were analyzed in both groups. Hemoglobin and blood glucose concentration were
determined on the basis of patients’ records and dietary calcium intake was estimated by FFQ. Anthropometric
parameters of neonates including weight, head circumference and length were recorded. Student t. test and c2 were
used for analyses of the continuous quantitative and qualitative variables, respectively and p-value <0.05 was
considered as statistically significant. There was no difference between our 2 groups regarding such factors as age,
parity, height, weight, pre-pregnancy body mass index (BMI), blood pressure, and dietary calcium intake. Compliance
was >80% in both groups and there was no significant and meaningful difference between them regarding this factor.
As compared to the placebo, calcium supplementation increased the mean birth weight in the "Calcium Supplement"

Complied By : Asma Saleem
group (P<0.05). The observed effect remained unchanged after removing four neonates born before the 37th week of
gestation (251 g, P<0.05). It is concluded that calcium supplementation in healthy pregnant mothers may increase birth
weight independent of gestational age.

Complied By : Asma Saleem

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Nutrition references

  • 1. Role of Nutrition in pregnancy Micronutrients in pregnancy British Journal of Nutrition (2001), 85, Suppl. 2, S193±S197 Abstract Vitamins and minerals, referred to collectively as micronutrients, have important influences on the health of pregnant women and the growing fetus. Iron deficiency results in anemia which may increase the risk of death from hemorrhage during delivery, but its effects on fetal development and birth outcomes is still unclear. Folic acid deficiency can lead to hematological consequences, pregnancy complications and congenital malformations, but again the association with other birth outcomes is equivocal. Zinc deficiency has been associated in some, but not all studies with complications of pregnancy and delivery, as well as with growth retardation,congenital abnormalities and retarded neurobehavioral and immunological development in the fetus. Iodine deficiency during pregnancy results in cretinism and possible fetal wastage and preterm delivery. Deficiency of other minerals such as magnesium, selenium, copper, and calcium has also been associated with complications of pregnancy, childbirth or fetal development. Deficiencies of vitamins other than folate may likewise be related to such complications; and vitamin A or b-carotene supplements in pregnancy reduced maternal mortality by 50 % in a controlled trial in Nepal. Additional research is need on the prevalence of such deficiencies and their consequences and on cost-effective public health interventions for their control. Complied By : Asma Saleem
  • 2. Pregnancy and Lactation: Physiological Adjustments, Nutritional Requirements and the Role of Dietary Supplements American Society for Nutritional Sciences 133:1997S-2002S, June 2003 ABSTRACT Nutritional needs are increased during pregnancy and lactation for support of fetal and infant growth and development along with alterations in maternal tissues and metabolism. Total nutrient needs are not necessarily the sum of those accumulated in maternal tissues, products of pregnancy and lactation and those attributable to the maintenance of nonreproducing women. Maternal metabolism is adjusted through the elaboration of hormones that serve as mediators, redirecting nutrients to highly specialized maternal tissues specific to reproduction (i.e., placenta and mammary gland). It is most unlikely that the heightened nutrient needs for successful reproduction can always be met from the maternal diet. Requirements for energy-yielding macronutrients increase modestly compared with several micronutrients that are unevenly distributed among foods. Altered nutrient utilization and mobilization of reserves often offset enhanced needs but sometimes nutrient deficiencies are precipitated by Complied By : Asma Saleem
  • 3. reproduction. There are only limited data from well-controlled intervention studies with dietary supplements and with few exceptions (iron during pregnancy and folate during the periconceptional period), the evidence is not strong that nutrient supplements confer measurable benefit. More research is needed and in future studies attention must be given to subject characteristics that may influence ability to meet maternal and infant demands (genetic and environmental), nutrient-nutrient interactions, sensitivity and selectivity of measured outcomes and proper use of proxy measures. Consideration of these factors in future studies of pregnancy and lactation are necessary to provide an understanding of the links among maternal diet; nutritional supplementation; and fetal, infant and maternal health. Dietary calcium and pregnancy-induced hypertension: is there a relation? American Journal of Clinical Nutrition, Vol. 71, No. 5, 1371S-1374s, May 2000 Abstract The evidence that calcium plays a role in the etiology, prevention, and treatment of pregnancy-induced hypertension (PIH) is reviewed. The precise factors involved in the pathogenesis of PIH are unclear, but several alterations in calcium metabolism have been identified. Epidemiologic data suggest an inverse correlation between dietary calcium intake and incidence of PIH. Although evidence suggests a possible beneficial effect of supplemental calcium, contradictions persist in clinical trials of pregnant women. Complied By : Asma Saleem
  • 4. Presently, there is insufficient evidence to support routine calcium supplementation of all pregnant women. However, high-risk groups, such as pregnant teens, populations with inadequate calcium intake, and women at risk of developing PIH, may benefit from consuming additional dietary calcium. Pregnancy-induced hypertension and low birth weight: the role of calcium American Journal of Clinical Nutrition, Vol 54, 237S-241S, 1991 Abstract Considerable interest has developed regarding the role of calcium in the regulation of blood pressure. Epidemiologic investigations, laboratory evaluations, and clinical trials all confirm that the relationship between calcium and blood pressure extends to include the pregnant state. On the basis of current information it is clear that calcium supplementation during pregnancy lowers blood pressure. Additionally, the effect of calcium on blood pressure may influence the incidence and/or gestational age of development of preeclampsia. Additionally, the effect on smooth-muscle relaxation detected in calcium-supplemented patients may affect the incidence of prematurity. Although the mechanism for these effects has not been entirely elucidated, calcium supplementation appears to affect circulating Complied By : Asma Saleem
  • 5. concentrations of parathyroid hormone and renin, which may modulate intracellular ionized calcium, resulting in the observed effect on smooth-muscle relaxation. This effect may also be responsible for reduced uterine activity and for a lowering of the incidence of prematurity. Iron: Iron is a key mineral for human metabolism. The healthy human body contains between 2.5 g (40 mg/kg: menstruating woman) and 4.0 g (50 mg/kg: adult male) iron. About 60% is found in the haemoglobin of the red blood cells, and 15% in myoglobin (in muscles) and various enzymes. Haemoglobin and myoglobin are proteins specialized in the transport and storage of oxygen. About 25% of body iron is stored (as ferritin or haemosiderin) mainly in the liver, spleen and bone marrow. Iron turnover is normally small. In the absence of bleeding (including menstruation) or pregnancy, about 1 mg iron is lost daily. During menstruation and lactation, iron loss may be twice as high. Iron requirements are also increased during pregnancy (5-6 mg daily in the second and third trimesters) to meet the needs of the foetus and the increased blood volume. Importance for health: Iron is required for a number of vital functions, including growth, reproduction, wound healing, and immune function. The main role of iron is to carry oxygen to the tissues where it is needed. Iron is also Complied By : Asma Saleem
  • 6. essential for the proper functioning of numerous enzymes involved in DNA synthesis2, energy metabolism, and protection against microbes and free radicals. Iron deficiency affects about 30% of the world population, and is one of the main deficiency disorders in Europe People with iron deficiency may get short of breath and tire quickly; they have a lower resistance to infection, and may develop sores at the corner of the mouth, on the tongue and in the stomach. Severe iron deficiency results in anemia associated with adverse pregnancy outcomes, and impaired mental and physical performance Folic Acid, Iron during Pregnancy Improves Children's Skills American Journal of Clinical Nutrition 2010; 91:1035-43 Researchers found that children whose mothers took prenatal folic acid, iron, and vitamin A have better working memory, inhibitory control, and fine motor functioning than children whose mothers took vitamin A alone. Complied By : Asma Saleem
  • 7. Getting bone health right from the start! Pregnancy, lactation and weaning Journal of Family Health Care 2008; 18(4): 137-141 ABSTRACT Maximizing bone health begins with maternal health and nutrition, which influences skeletal mass and bone density in the fetus. Maternal health and nutrition, as well as the baby’s intake of Vitamin D and calcium during breastfeeding and weaning, may have a long-lasting effect on the baby’s future health. Vitamin D and calcium (alongside physical activity) play key roles in bone health for both mother and baby. Iron Deficiency Anemia American Journal of Clinical Nutrition May 2000 Low levels of iron in the mother can lead to poor iron transfer to the fetus and lowers the amount available for the mother even more. Iron deficiency can increase the risk for maternal mortality and is Complied By : Asma Saleem
  • 8. associated with low birth weight and low infant Apgar scores, which indicate infant health at the time of birth. Anemia and iron deficiency: effects on pregnancy outcome American Journal of Clinical Nutrition, Vol. 71, No. 5, 1280S-1284s, May 2000 ABSTRACT This article reviews current knowledge of the effects of maternal anemia and iron deficiency on pregnancy outcome. A considerable amount of information remains to be learned about the benefits of maternal iron supplementation on the health and iron status of the mother and her child during pregnancy and postpartum. Current knowledge indicates that iron deficiency anemia in pregnancy is a risk factor for preterm delivery and subsequent low birth weight, and possibly for inferior neonatal health. Data are inadequate to determine the extent to which maternal anemia might contribute to maternal mortality. Even for women who enter pregnancy with reasonable iron stores, iron supplements improve iron status during pregnancy and for a considerable length of time postpartum, thus providing some protection against iron deficiency in the subsequent pregnancy. Mounting evidence indicates that maternal iron deficiency in pregnancy reduces fetal iron stores, perhaps well into the first year of life. Complied By : Asma Saleem
  • 9. This deserves further exploration because of the tendency of infants to develop iron deficiency anemia and because of the documented adverse consequences of this condition on infant development. The weight of evidence supports the advisability of routine iron supplementation during pregnancy. Key Words: Anemia • iron deficiency • pregnancy • maternal mortality • birth weight • preterm delivery • infants Serum calcium level as a marker of pregnancy-induced hypertension American Journal of Clinical Nutrition 2006; 83(3): 657-666 Abstract Background: Regulation of intracellular calcium plays a key role in hypertension. Hypertension has been estimated to complicate 5% of all pregnancies and 11% of first pregnancies. Half of the pregnant women with hypertension have pre-eclampsia. Hypertensive disorders account for up to 40 000 maternal deaths annually. Objective: To compare total serum calcium levels in pregnant women complicated with pre-eclampsia with those in normotensive control. Patients and Methods: This is a case-control hospital based study carried out at Omdurman Maternity Hospital, Khartoum Teaching Hospital, and Khartoum North Teaching Hospital in Khartoum State, Complied By : Asma Saleem
  • 10. Sudan in the period from October 2006 to June 2007. One hundred thirty-five women were enrolled in this study. 90 women with pregnancy - induced hypertension (PIH) admitted after 20th week of pregnancy represented the study group. Forty five women with normal pregnancy, at same age; same gestational age were selected as control group. Results: The mean (±SD) serum calcium of the study group was 8.38±1.04 mg/dl, while that of the control group was 9.04±1.13mg/dl (P= 0.001). Conclusion: Low level of maternal total calcium may have a role in the development PIH. Therefore calcium consumption in pregnancy should be encouraged. Calcium supplement is recommended for women who live in places of low socioeconomic status as well as for women who prefer to skip milk and milk products due to personal preference. Complied By : Asma Saleem
  • 11. Iron status at 9 months of infants with low iron stores at birth The Journal of Pediatrics Volume 141, Issue 3 , Pages 405-409, September 2002 Abstract Objective: To determine the 9-month follow-up iron status of infants born with abnormally low serum ferritin concentrations. Study design: Ten infants of >34 weeks' gestation with cord serum ferritin concentrations <5th percentile at birth (<70 μg/L) and 12 control infants with cord serum ferritin concentrations >80 μg/L had follow-up serum ferritin concentrations measured at 9 ± 1 month of age. The mean follow-up ferritins, incidences of iron deficiency and iron-deficiency anemia, and growth rates from 0 to 12 months were compared between the two groups. Results: At follow-up, the low birth ferritin group had a lower mean ferritin than the control group (30 ± 17 vs 57 ± 33 μg/L; P = .03), but no infant in either group had iron deficiency (serum ferritin <10 μg/L) or iron-deficiency anemia. Both groups grew equally well, but more rapid growth rates were associated Complied By : Asma Saleem
  • 12. with lower follow-up ferritin concentrations only in the low birth ferritin group (r = −0.52; P = .05). Both groups were predominantly breast-fed without iron supplementation before 6 months. Conclusions: Infants born with serum ferritin concentrations <5th percentile continue to have significantly lower ferritin concentrations at 9 months of age compared with infants born with normal iron status, potentially conferring a greater risk of later onset iron deficiency in the second postnatal year Worldwide prevalence of anemia, WHO Vitamin and Mineral Nutrition Information System, 1993-2005. Public Health Nutr. 2009 Apr;12(4):444-54. Epub 2008 May 23 Objective: To provide current global and regional estimates of anemia prevalence and number of persons affected in the total population and by population subgroup. Setting and design: We used anemia prevalence data from the WHO Vitamin and Mineral Nutrition Information System for 1993-2005 to generate anemia prevalence estimates for countries with data representative at the national level or at the first administrative level that is below the national level. For countries without eligible data, we employed regression-based estimates, which used the UN Human Development Index (HDI) and other health indicators. We combined country estimates, weighted by Complied By : Asma Saleem
  • 13. their population, to estimate anemia prevalence at the global level, by UN Regions and by category of human development. Results: Survey data covered 48.8 % of the global population, 76.1 % of preschool-aged children, 69.0 % of pregnant women and 73.5 % of non-pregnant women. The estimated global anemia prevalence is 24.8 % (95 % CI 22.9, 26.7 %), affecting 1.62 billion people (95 % CI 1.50, 1.74 billion). Estimated anemia prevalence is 47.4 % (95 % CI 45.7, 49.1 %) in preschool-aged children, 41.8 % (95 % CI 39.9, 43.8 %) in pregnant women and 30.2 % (95 % CI 28.7, 31.6 %) in non-pregnant women. In numbers, 293 million (95 % CI 282, 303 million) preschool-aged children, 56 million (95 % CI 54, 59 million) pregnant women and 468 million (95 % CI 446, 491 million) non-pregnant women are affected. Conclusion: Anemia affects one-quarter of the world's population and is concentrated in preschool-aged children and women, making it a global public health problem. Data on relative contributions of causal factors are lacking, however, which makes it difficult to effectively address the problem Complied By : Asma Saleem
  • 14. DHA supplementation During Pregnancy Am J Clin Nutr 2007;85:1572-1577. New research reaffirms that DHA supplementation during pregnancy improves cognitive function in infants and children. A study published this month in the American Journal of Clinical Nutrition showed that infants born to mothers who consumed DHA from fish oil (300 mg/day) demonstrated better problem solving abilities than those who consumed a corn oil placebo. This data supports earlier work published in 2003 that showed children born to mothers who supplemented with 2 tsp Cod Liver Oil daily during pregnancy and lactation had higher IQs at age four when compared to children of mothers who consumed placebo. Maternal DHA intake during pregnancy is far below the currently recommended amount (minimum of 300 mg/day), which may be contributing to the unprecedented incidence of neurological and behavioural problems that face children today. During the last trimester of pregnancy, mothers selectively transfer DHA to the foetus to support the growth of the brain, eyes, and nervous system. Without sufficient intake, mothers become depleted of DHA and increase their risk of suffering major depressive symptoms in the postpartum period. In fact, population studies have shown that lower intakes of DHA are associated with higher rates of postpartum depression4. It is well established that the essential fatty acid, DHA, is a critical component to a healthy pregnancy. However, a recent survey of expecting mothers showed that in 68% of the women surveyed, their doctor never mentioned DHA, and half of the women surveyed had never heard of it. Complied By : Asma Saleem
  • 15. Position of the American Dietetic Association: nutrition and lifestyle for a healthy pregnancy outcome.   J Am Diet Assoc. 2010 Jan;110(1):141. J Am Diet Assoc. 2009 Jul;109(7):1296. Abstract It is the position of the American Dietetic Association that women of child-bearing ages should maintain good nutritional status through a lifestyle that optimizes maternal health and reduces the risk of birth defects, suboptimal fetal growth and development, and chronic health problems in their children. The key components of a health-promoting lifestyle during pregnancy include appropriate weight gain; appropriate physical activity; consumption of a variety of foods in accordance with the Dietary Guidelines for Americans 2005; appropriate and timely vitamin and mineral supplementation; avoidance of alcohol, tobacco, and other harmful substances; and safe food handling. Pregnant women with inappropriate weight gain, hyperemesis, poor dietary patterns, phenylketonuria, certain chronic health problems, or a history of substance abuse should be referred to a registered dietitian for medical nutrition therapy. Prenatal weight gain within the Institute of Medicine recommended ranges has been associated with better pregnancy outcomes. Most pregnant women need 2,200 to 2,900 kcal a day, but prepregnancy body mass index, rate of weight gain, maternal age, and appetite must be considered Complied By : Asma Saleem
  • 16. when tailoring this recommendation to the individual. The consumption of more food to meet energy needs, and the increased absorption and efficiency of nutrient utilization that occurs in pregnancy, are generally adequate to meet the needs for most nutrients. However, vitamin and mineral supplementation is appropriate for some nutrients and situations. This position paper also includes recommendations pertaining to use of alcohol, tobacco, caffeine, and illicit drugs. Effect of supplementing pregnant and lactating mothers with n-3 very-long-chain fatty acids on children's IQ and body mass index at 7 years of age. Pediatrics. 2008 Aug;122(2):e472Abstract OBJECTIVES: Arachidonic acid (20:4n-6) and docosahexaenoic acid (22:6n-3) are essential for brain growth and cognitive development. We have reported that supplementing pregnant and lactating women with n-3 very-long-chain polyunsaturated fatty acids promotes higher IQ scores at 4 years of age as compared with maternal supplementation with n-6 polyunsaturated fatty acids. In our present study, the children were examined at 7 years of age with the same cognitive tests as at 4 years of age. We also examined the relation between plasma fatty acid pattern and BMI in children, because an association between arachidonic acid and adipose tissue size has been suggested. Complied By : Asma Saleem
  • 17. METHODS: The study was randomized and double-blinded. The mothers took 10 mL of cod liver oil or corn oil from week 18 of pregnancy until 3 months after delivery. Their children were tested with the Kaufman Assessment Battery for Children at 7 years of age, and their height and weight were measured. RESULTS: We did not find any significant differences in scores on the Kaufman Assessment Battery for Children test at 7 years of age between children whose mothers had taken cod liver oil (n = 82) or corn oil (n = 61). We observed, however, that maternal plasma phospholipid concentrations of alpha-linolenic acid (18:3n-3) and docosahexaenoic acid during pregnancy were correlated to sequential processing at 7 years of age. We observed no correlation between fatty acid status at birth or during the first 3 months of life and BMI at 7 years of age. CONCLUSION: This study suggests that maternal concentration of n-3 very-long-chain polyunsaturated fatty acids during pregnancy might be of importance for later cognitive function, such as sequential processing, although we observed no significant effect of n-3 fatty acid intervention on global IQs. Neonatal fatty acid status had no influence on BMI at 7 years of age. DHA: DHA (docosahexaenoic acid) is an essential fatty acid (EFA). EFAs are called “essential” because very little can be synthesized by the body—we must obtain them from our diet. DHA is one of the omega-3 fatty acids, whose best-known source is perhaps fish oil. Complied By : Asma Saleem
  • 18. EFAs are necessary for good health, and DHA is well-known as one of the keys to a healthy nervous system. DHA is the building block of human brain tissue—60 percent of the brain is fat, and DHA is the most abundant fat in the brain, as well as in the retina of the eye. DHA is essential in communication between the brain and nervous system—it plays a role in the cell membrane, where the electrical impulses that are the basis of communication within the nervous system are generated. Without DHA and other fatty acids, communication within this system can break down or become less effective. The importance of DHA to the brain and nervous system is seen early in our development. In the first few weeks of embryonic development, the mother’s blood supplies the fetus with large amounts of DHA. In the last trimester of a pregnancy, the DHA content of the brain’s cerebrum and cerebellum— which contains centers for speech and abstract thought—increases threefold. DHA is recognized as extremely important—so much so that the World Health Organization has recommended that DHA be added to infant formulas. Many health practitioners also recommend it for pregnant women and nursing mothers. DHA supplementation may be especially important as we grow older. The body’s ability to synthesize DHA, which is limited in all people, may decline even further with age. This is compounded by the small amounts of DHA we get in our diet, especially those who strive for a vegetarian diet—the richest sources of DHA are red meats, animal organs, and eggs. Complied By : Asma Saleem
  • 19. Research indicates that low levels of DHA may be involved in a number of health problems relating to the nervous system. Depression: Depression is on the rise in North America. This is often attributed to the ups and downs of our lives and is often seen among the aging population. However, recent research indicates that there may be a physiological aspect to depression that relates to nutrition. A study published in the American Journal of Clinical Nutrition (62 (July 1995): 1-9) presents research indicating that omega-3 fatty acids, specifically DHA, may reduce the risk of depression. The authors associate the increase in depression in North America in the past century with the decline in consumption of DHA during the same period. To lend support to this idea, the authors also note that there are lower rates of major depression in those societies that consume large amounts of fish, a key dietary source of DHA. Complied By : Asma Saleem
  • 20. Dementia and Alzheimer’s disease DHA is also being considered as a factor in dementia and Alzheimer’s disease. In 1997, a link between low levels of DHA and Alzheimer’s disease and memory loss was the subject of a conference at The New York Hospital Cornell Medical Center’s Nutrition Information Center. Among the finding discussed at the conference was that a low level of DHA is a significant risk factor for dementia, including Alzheimer’s disease. Further support for this comes from Australia. In a letter published in the Medical Journal of Australia (153 (November 5, 1990): 563-64), Dr. Robert Peers suggests that an imbalance between an excessive intake of omega-6 fatty acids (from vegetable oils and margarine) and a deficient intake of omega-3 fatty acids may be a factor in Alzheimer’s disease. The Japan Functional Food Research Association has also investigated DHA and dementia. The association notes that those with senile dementia achieved positive results when taking DHA: in 10 of 13 cerebral vascular dementia cases and five of five senile dementia cases, the patients showed more than slight improvements in psychiatric symptoms such as communication, will power, motivation, delirium, the tendency to wander, emotional disorders, and mental depression Complied By : Asma Saleem
  • 21. Vision : DHA is also the major fat in retinal tissue. It plays a strong role in the photoreceptor cells of the retina, suggesting an essential role for DHA in vision. DHA deficiency in laboratory animals shows a marked decrease in proper functioning of the visual cycle. In a recent study looking at fish oil, which contains DHA, and macular degeneration, researchers found that more frequent consumption of fish appears to protect against late age-related macular degeneration. Only a moderate intake of fish was necessary for the protective effect (Archives of Ophthalmology 118 (March 2000): 401-404). Complied By : Asma Saleem
  • 22. The importance of DHA during pregnancy and breastfeeding      A 2003 study published in the journal Pediatrics showed children whose mothers took a DHA supplement during pregnancy scored higher on intelligence tests at four years of age than children of mothers not taking DHA supplements. A 2004 study published in Child Development found that babies whose mothers had high blood levels of DHA at delivery had advanced attention spans into their second year of life. During the first six months of life these infants were two months ahead of babies whose mothers had lower DHA levels. Other research studies suggest breastfed babies have IQs of six to 10 points higher than formula-fed babies. Medical and nutritional experts attribute this difference to the DHA infants receive while nursing. In a trial of women receiving DHA supplementation during the third trimester, the average length of gestation increased six days (Obstetrics & Gynecology, 2003). Research has found low levels of DHA in mother's milk and in the red blood cells of women with postpartum depression. (Journal of Affective Disorders, 2002). Some scientists believe increasing levels of maternal DHA may reduce the risk of postpartum depression. Complied By : Asma Saleem
  • 23. Omega-3 Fatty Acid Supplementation during Pregnancy Rev Obstet Gynecol. 2008 Fall; 1(4): 162–169. Abstract Omega-3 fatty acids are essential and can only be obtained from the diet. The requirements during pregnancy have not been established, but likely exceed that of a nonpregnant state. Omega-3 fatty acids are critical for fetal neurodevelopment and may be important for the timing of gestation and birth weight as well. Most pregnant women likely do not get enough omega-3 fatty acids because the major dietary source, seafood, is restricted to 2 servings a week. For pregnant women to obtain adequate omega-3 fatty acids, a variety of sources should be consumed: vegetable oils, 2 low-mercury fish servings a week, and supplements (fish oil or algae-based docosahexaenoic acid). Complied By : Asma Saleem
  • 24. Vitamin D requirements during pregnancy American Journal of Clinical Nutrition, Vol. 80, No. 6, 1740S-1747S, December 2004 ABSTRACT Adequate vitamin D concentrations during pregnancy are necessary to ensure appropriate maternal responses to the calcium demands of the fetus and neonatal handling of calcium. The purpose of this report is to review studies that investigated maternal and neonatal outcomes of vitamin D deficiency or supplementation during pregnancy. Most studies reported included women at high risk of vitamin D deficiency, because of low vitamin D and calcium intake or decreased ability to synthesize endogenous vitamin D (attributable to lack of sun exposure or to heavily pigmented skin). Overall, vitamin D supplementation in these populations leads to improved neonatal handling of calcium. Results concerning benefits for fetal growth and bone development are inconclusive. There is no evidence of a benefit of supplementation during pregnancy above amounts routinely required to prevent vitamin D deficiency. Complied By : Asma Saleem
  • 25. Vitamin D for the Prevention of Preeclampsia Nutrition Reviews Volume 63, Issue 7, pages 225–232, July 2005 Abstract: Preeclampsia has been suggested to result from a partial breakdown of tolerance to the developing fetus after maternal immune maladaptation. Several of the proposed immunomodulatory properties of the hormonal vitamin D system could potentially have beneficial effects for successful maintenance of pregnancy. Preeclampsia is characterized by marked changes in vitamin D metabolism. This paper reviews the evidence suggesting that the immunomodulatory properties of 1,25(OH)2D may play a key role in maintaining immunological tolerance in pregnancy, and proposes that ensuring adequate vitamin D status/intake may help in the prevention and management of preeclampsia Complied By : Asma Saleem
  • 26. Low vitamin D during pregnancy linked to pre-eclampsia Journal of Clinical Endocrinology and Metabolism. September 7, 2007 “Vitamin D deficiency early in pregnancy is associated with a five-fold increased risk of preeclampsia”. “Our results showed that maternal vitamin D deficiency early in pregnancy is a strong, independent risk factor for preeclampsia,” said Lisa M. Bodnar, Ph.D., M.P.H., R.D., assistant professor of epidemiology at the University of Pittsburgh Graduate School of Public Health (GSPH) and lead author of the study. “Women who developed preeclampsia had vitamin D concentrations that were significantly lower early in pregnancy compared to women whose pregnancies were normal. And even though vitamin D deficiency was common in both groups, the deficiency was more prevalent among those who went on to develop preeclampsia.” “Even a small decline in vitamin D concentration more than doubled the risk of preeclampsia,” noted James M. Roberts, M.D., senior author of the study and MWRI founding director. “And since newborn’s Complied By : Asma Saleem
  • 27. vitamin D stores are completely reliant on vitamin D from the mother, low vitamin levels also were observed in the umbilical cord blood of newborns from mothers with preeclampsia.” Low vitamin D during pregnancy linked to pre-eclampsia American Journal of Obstetrics & Gynecology Volume 203, Issue 4 , Pages 366.e1-366.e6, October 2010 Objective Vitamin D deficiency has been linked to adverse pregnancy outcomes. The purpose of this investigation was to assess total 25-hydroxyvitamin D (25-OH-D) levels at diagnosis of early-onset severe preeclampsia (EOSPE). Study Design After institutional review board approval, we enrolled subjects with EOSPE (<34 weeks' gestation with severe preeclampsia) in this case-control investigation in a 1:2 ratio with gestation-matched, Complied By : Asma Saleem
  • 28. contemporaneous control subjects. Demographic and outcome information was collected for each subject. Plasma total 25-OH-D levels were determined by radioimmunoassay and reported in nanograms per milliliter. Results were analyzed by Mann-Whitney U and multivariable regression. Results Subjects with EOSPE (n = 50) were noted to have decreased total 25-OH-D levels relative to healthy control subjects (n = 100; P < .001). This difference in total 25-OH-D remained significant after control for potential confounders. Conclusion Total 25-OH-D is decreased at diagnosis of EOSPE. Further study is needed to understand the impact of vitamin D deficiency on pregnancy outcomes. Complied By : Asma Saleem
  • 29. Maternal fatty acid status during pregnancy and lactation and relation to newborn and infant statusmcn_3  Maternal and Child Nutrition (2011), 7 (Suppl. 2), pp. 41–5803 41..58 Abstract The present review of determinants of infant fatty acid status was undertaken as part of a conference on ‘Fatty acid status in early life in low-income countries: determinants and consequences’. Emphasis is placed on the essential fatty acids, and particularly the physiologically important long chain polyunsaturated fatty acids (LCPUFAs) of 20 and 22 carbons.We are unaware of any studies of determinants of infant fatty acid status in populations with a cultural dietary pattern with low amounts of linoleic acid (LA, 18:2n-6) and a-linolenic acid (ALA,18:3n-3). Many reports suggest that there may be adverse health effects related to the increased proportion of LA in relation to ALA, which have occurred worldwide due to the increased availability of vegetable oils high in LA. The issue of dietary n-6 to n-3 balance may apply to infant fatty acid status both during fetal and post-natal life; however, this review focuses on the n-3 and n-6 LCPUFA, in particular, docosahexaenoic acid (DHA, 22:6n-3) and arachidonic acid (AA, 20:4n-6), which are the predominant n-3 and n-6 LCPUFA found in cell membranes. The evidence that these fatty acids are preferentially transferred from maternal to fetal circulation across the Complied By : Asma Saleem
  • 30. placenta, and the sources and mechanisms for this transfer, are reviewed.We also addressthe sources of DHA andAA for the newborn including human milk DHA andAA and the factors that influence maternal DHA status and consequently the amount of DHA available for transfer to the fetus and infant via human milk. Implications of vitamin D deficiency In pregnancy and lactation Am J Obstet Gynecol 2010;202:429. Vitamin D is an essential fat soluble vitamin and a key modulator of calcium metabolism inchildren and adults. Because calcium demands increase in the third trimester of pregnancy, vitamin D status becomes crucial for maternal health, fetal skeletal growth, and optimal maternal and fetal outcomes. Vitamin D deficiency is common in pregnant women (5-50%) and in breastfed infants (10-56%), despite the widespread use of prenatal vitamins, because these are inadequate to maintain normal vitamin D levels (_32 ng/mL). Adverse health outcomes such as preeclampsia, low birthweight, neonatal hypocalcemia, poor postnatal growth, bone fragility, and increased incidence of autoimmune diseases have been linked to low vitamin D levels during pregnancy and infancy. Studies are underway to establish the recommended daily doses of vitamin D in pregnant women. This review discusses vitamin D metabolism and the implications of vitamin D deficiency in pregnancy and lactation. Complied By : Asma Saleem
  • 31. Vitamin D and pregnancy: An old problem revisited Research Clinical Endocrinology & Metabolism 24 (2010) 527–539 Vitamin D has historically been considered to play a role solely in bone and calcium metabolism. Human disease associations and basic physiological studies suggest that vitamin D deficiency is plausibly implicated in adverse health outcomes including mortality, malignancy, cardiovascular disease, immune functioning and glucose metabolism. There is considerable evidence that low maternal levels of 25 hydroxyvitamin D are associated with adverse outcomes for both mother and fetus in pregnancy as well as the neonate and child. Vitamin D deficiency during pregnancy has been linked with a number of maternal problems including infertility, preeclampsia, gestational diabetes and an increased rate of caesarean section. Likewise, for the child, there is an association with small size, impaired growth and skeletal problems in infancy, neonatal hypocalcaemia and seizures, and an increased risk of HIV transmission. Other childhood disease associations include type 1 diabetes and effects on immune tolerance. The optimal concentration of 25 hydroxyvitamin D is unknown and compounded by difficulties in defining the normal range. Whilst there is suggestive physiological evidence to support a causal role for many of the associations, whether vitamin D deficiency is a marker of poor health or the underlying a etiological problem is unclear. Randomized Complied By : Asma Saleem
  • 32. controlled trials of vitamin D supplementation with an appropriate assessment of a variety of health outcomes are required. Vitamin B6 may boost conception American Journal of Epidemiology Volume 166, Number 3, Pages 304-312 A study, published in the American Journal of Epidemiology, may see vitamin B6 become as important as the current "Big 3" of pregnancy nutrition: folic acid, calcium with vitamin D, and omega-3 fatty acids. Researchers in China looked at blood levels of homocysteine, folate, and vitamins B6 and B12 in over 350 women to see if there was a link between B vitamin status and ease of conception. The women had an average age of 25 years and had all conceived at least once between 1996-8. Daily urine samples were taken for 12 months and tested for human chorionic gonadatropin (hCG) to detect conception and early pregnancy loss. It was found that women with an adequate vitamin B6 status (>30nm/l) had a 40% better chance of conception and a 30% lower risk of miscarriage early in pregnancy compared with women with a low vitamin B6 status. Having high vitamin B6 levels in the blood improved these chances further with a Complied By : Asma Saleem
  • 33. 120% increased chance of conception at 38nm/l and a 50% lower risk of early pregnancy loss at 46nm/l. The results suggest that increasing vitamin B6 levels prior to conception could boost conception rates and decrease the risk of early miscarraige. Drug therapy during pregnancy Curr Opin Obstet Gynecol (UNITED STATES) Feb 1992, 4 (1) p43-7 A randomized prospective trial has shown that folic acid started before conception and continued for the first trimester reduces the risk of recurrence of neural tube defects by 72% in women with a previously affected child. Carbamazepine exposure in utero is associated with a 1% risk of spina bifida. Long-term follow-up of antenatal exposure to phenobarbital and carbamazepine in two groups of infants shows no neurologic differences between the two groups. Magnesium sulfate is more effective in prevention of recurrent eclamptic seizures than phenytoin. During pregnancy, the need for thyroxine increases in many women. Vitamin B6 and ginger are both effective for nausea and vomiting in early pregnancy. Low-dose aspirin does not change the course of preeclampsia when it is started after the diagnosis is made. Angiotensin-converting enzyme inhibitors cause significant disturbances of fetal and neonatal renal function. Prophylactic beta-adrenergic agents fail to prevent prematurity in twins. Oral tocolysis with magnesium chloride or ritodrine is no more effective than observation alone. The risk of primary pulmonary hypertension in the newborn after indomethacin tocolysis is increased with prolonged therapy. Lithium causes polyhydramnios from fetal diabetes insipidus in utero. Treatment of Complied By : Asma Saleem
  • 34. Ureaplasma urealyticum infection with erythromycin during pregnancy does not eliminate the organism from the lower genital tract and does not improve perinatal outcome. Multivitamins Improve the Chances of a Full-Term Pregnancy American Journal of Epidemiology 1997 Jul 15;146(2):134-41. Abstract The objective of this study was to examine the association of prenatal multivitamin/mineral supplement use during the first and second trimesters of pregnancy by low income, urban women in the Camden Study (1985-1995, n = 1,430) and preterm delivery (< 37 completed weeks) and infant low birth weight (< 2,500 g). Prenatal supplement use was corroborated by assay of circulating micronutrients at entry to care (no differences) and week 28 gestation (increased concentrations of folate and ferritin for supplement users). Compared with women who entered care during the first or second trimester but did not use prenatal supplements, supplement use starting in the first or second trimester was associated with approximately a twofold reduction in risk of preterm delivery. After controlling for potential confounding variables, risk of very preterm delivery (< 33 weeks' gestation) was reduced more than fourfold for first trimester users and approximately twofold when use dated from the second trimester. Infant low birth weight and very low birth weight (< 1,500 g) risks were also reduced. Risk of low birth Complied By : Asma Saleem
  • 35. weight was reduced approximately twofold with supplement use during the first and second trimester. Diminution in risk was greater for very low birth weight infants, amounting to a sevenfold reduction in risk of very low birth weight with first trimester supplementation and a greater than six-fold reduction when supplement use started in the second trimester. Thus, in low income, urban women, use of prenatal multivitamin/mineral supplements may have the potential to diminish infant morbidity and mortality. Effects of vitamin A deficiency during pregnancy on maternal and child health. British Journal of Gynecology 2002 Jun;109(6):689-93. Abstract OBJECTIVE: To examine the association between biochemical vitamin A deficiency in pregnancy and maternal and fetal health. DESIGN: A cross sectional clinical study. SETTING: Antenatal clinic of nutrition unit of Niloufer Hospital catering for a low socio-economic population, and a private nursing home (Swapna nursing home) catering for a high socio-economic population. Complied By : Asma Saleem
  • 36. POPULATION: 736 pregnant women in their third trimester of pregnancy belonging to low (n = 522) and high socio-economic groups (n = 214). METHODS: All the women were subjected to a detailed clinical, anthropometric and obstetric examination. Night blindness was assessed by administering the standard WHO questionnaire. Birthweight and gestational age of the infants, maternal anaemia and development of pregnancyinduced hypertension in the mother were recorded. Haemoglobin and serum retinol were estimated at the time of recruitment to the study. MAIN OUTCOME MEASURES: Serum retinol levels, anaemia, pregnancy-induced hypertension, birth weight and gestational age of the infant. RESULTS: Night blindness was observed in 2.9% of the women and subclincal vitamin A deficiency (serum retinol <20 microg/dL with no clinical signs) in 27% of the women. Moderate to severe anaemia was observed in 41.2% of the women, and 15.8% of the women developed pregnancy-induced hypertension. Sixty-one (9.4%) women delivered preterm. Univariate analysis identified a significant association between serum retinol <20 microg/dL and preterm delivery (OR = 1.74, 95% CI 1.03-2.96), maternal anaemia (OR = 1.82, 95% CI 1.28-2.60) and pregnancy-induced hypertension (OR = 1.56, 95% CI 1.02-2.83). After adjusting for the confounding variables (body mass index, parity, age and socioeconomic status) in a multivariate analysis, the significant associations between serum retinol <20 microg/dL and preterm delivery (P = 0.02) and anaemia (P = 0.003) persisted, while that for pregnancyinduced hypertension disappeared (P = 0.71). Complied By : Asma Saleem
  • 37. CONCLUSION: The study suggests that subclinical vitamin A deficiency is a problem during the third trimester of pregnancy. Serum concentration of retinol <20 microg/dL appears to indicate a deficient status, and is associated with an increased risk of preterm delivery and maternal anaemia. Vitamin D Supplementation during Pregnancy Part 2 NICHD/CTSA Randomized Clinical Trial (RCT): Pediatric Academic Societies Meeting, May 1, 2010 Abstract 1665.6 Abstract BACKGROUND: Vitamin D (vitD) deficiency during pregnancy is a serious public health issue, affecting mother and fetus. Establishing optimal vitD requirements of pregnant women is vital in preventing vitD deficiency and its health-associated comorbidities. OBJECTIVE: Evaluate the effectiveness of high dose vitD supplementation in decreasing pregnancy comorbidity risks. DESIGN/METHODS: Following their consent, pregnant women 12-16 wks' gestation were randomized into 1 of 3 tx grps stratified by race: 400, 2000 or 4000 IU vitD3/day until delivery. Women were evaluated for safety (Abstr#750939), efficacy and effectiveness with monthly 25(OH)D; 1,25(OH)2D; serum Ca, Cr, phos, and urinary Ca/Cr levels, all measured using standardized methodology. Comorbidities of pregnancy (preeclampsia, gest diabetes, any infection, preterm labor (PTL)/preterm Complied By : Asma Saleem
  • 38. birth (PTB)<37 wks GA) were recorded prospectively for each subject. Investigators and health team were blinded to tx grp. RESULTS: Of the 494 women who enrolled in the study, 350 women continued until delivery: 98 African American (AA), 137 Hispanic (Hisp) and 115 Caucasian (Cauc) women; with 111 controls, 122 in 2000 IU and 117 in 4000 IU groups. There were no differences in baseline vitD status between dose groups. The mean 25(OH)D by dose group at delivery, as chronic level, and 1-month before delivery were significantly different between control and 2000, control and 4000, and 2000 vs. 4000 (p<0.0001). 25(OH)D had a direct influence on 1,25(OH)2D levels throughout pregnancy (p<0.0001) with 25(OH)D of 40 ng/mL required to obtain maximum 1,25(OH)2D production. In bivariate analyses controlling for race, PTL/PTB and infection were inversely related to 25(OH)D and were lowest in the 4000 IU grp (p<0.0001). In logistic regression, comparing 400 vs. 4000 IU and controlling for race, the risk of comorbidities were 0.50 (CI 0.27-0.95; p=0.03) among those in the 4000 IU grp. Using least sq means, when adjusting for race, 25(OH)D of women with comorbidities was 33.4 ng/mL compared to 39.0 ng/mL in those women without (p<0.008). CONCLUSIONS: VitD sufficiency was strongly associated with decreased risk for PTL/PTB and infection during pregnancy and co-morbidities of pregnancy, with the greatest effect with 4000 IU vitamin D/day regimen. Therefore, to attain a minimal 25(OH)D level of 40 ng/mL, we recommend 4000 IU/day for all pregnant women. Complied By : Asma Saleem
  • 39. Vitamin C intake and the risk of pre-term delivery American Journal of Obstetrics and Gynecology August 2003;189(2):519-525. Abstract OBJECTIVE: Ascorbic acid deficiency may lead to premature rupture of the membranes. STUDY DESIGN: The study included a prospective cohort of pregnant women, aged ?16 years, with singleton gestations who received care at one of four prenatal clinics in central North Carolina from 1995 through 1998. Vitamin C intake pre-conceptionally and during the second trimester was examined for its association with preterm delivery and subsets of preterm labor, premature rupture of the membranes, and medical induction in 2064 women. RESULTS: Women who had total vitamin C intakes of <10th percentile pre-conceptionally had twice the risk of preterm delivery because of premature rupture of the membranes (relative risk, 2.2; 95% CI, 1.1, 4.5). This risk was attenuated slightly for second-trimester intake (relative risk, 1.7; 95% CI, 0.8, 3.5). The elevated risk of preterm premature rupture of the membranes was greatest for women with a low vitamin C intake during both time periods. CONCLUSION: Because diet and supplement use are modifiable behaviors, corroboration of these findings would suggest a possible intervention strategy. Complied By : Asma Saleem
  • 40. Folic acid at 1,000 mcg/day improves chances of healthy birth weight. Epigenetics 6:1, 86-94; January 2011 Abstract Supplementation with folic acid during pregnancy is known to reduce the risk of neural tube defects and low birth weight. It is thought that folate and other one-carbon intermediates might secure these clinical effects via DNA methylation. We examined the effects of folate on the human methylome using quantitative interrogation of 27,578 CpG loci associated with 14,496 genes at single-nucleotide resolution across 12 fetal cord blood samples. Consistent with previous studies, the majority of CpG dinucleotides located within CpG islands exhibited hypo-methylation while those outside CpG islands showed midhigh methylation. However, for the first time in human samples, unbiased analysis of methylation across samples revealed a significant correlation of methylation patterns with plasma homocysteine, LINE-1 methylation and birth weight centile. Additionally, CpG methylation significantly correlated with either birth weight or LINE-1 methylation were predominantly located in CpG islands. These data indicate that levels of folate-associated intermediates in cord blood reflect their influence and consequences for the fetal epigenome and potentially on pregnancy outcome. In these cases, their influence might be exerted during late gestation or reflect those present during the peri-conceptual period. Complied By : Asma Saleem
  • 41. Iron supplementation during pregnancy, anemia, and birth weight American Journal of Clinical Nutrition, Vol. 78, No. 4, 773-781, October 2003. Abstract BACKGROUND: The need for prophylactic iron during pregnancy is uncertain. OBJECTIVE: We tested the hypothesis that administration of a daily iron supplement from enrollment to 28 wk of gestation to initially iron-replete, nonanemic pregnant women would reduce the prevalence of anemia at 28 wk and increase birth weight. DESIGN: Between June 1995 and September 1998, 513 low-income pregnant women in Cleveland were enrolled in the study before 20 wk of gestation. Of these, 275 had a hemoglobin concentration ≥ 110 g/L and a ferritin concentration ≥ 20 µg/L and were randomly assigned to receive a monthly supply of capsules containing either 30 mg Fe as ferrous sulfate or placebo until 28 wk of gestation. At 28 and 38 wk of gestation, women with a ferritin concentration of 12 to < 20 µg/L or < 12 µg/L received 30 and 60 mg Fe/d, respectively, regardless of initial assignment. Almost all the women received some supplemental iron during pregnancy. We obtained infant birth weight and gestational age at delivery for 117 and 96 of the 146 and 129 women randomly assigned to receive iron and placebo, respectively. Complied By : Asma Saleem
  • 42. RESULTS: Compared with placebo, iron supplementation from enrollment to 28 wk of gestation did not significantly affect the overall prevalence of anemia or the incidence of preterm births but led to a significantly higher mean (± SD) birth weight (206 ± 565 g; P = 0.010), a significantly lower incidence of low-birth-weight infants (4% compared with 17%; P = 0.003), and a significantly lower incidence of preterm low-birth-weight infants (3% compared with 10%; P = 0.017). Conclusion: Prenatal prophylactic iron supplementation deserves further examination as a measure to improve birth weight and potentially reduce health care costs. Zinc Improves the Chances of Full Birth Weight American Medical Association. 1995;274(6):463-468. Abstract Objective:To evaluate whether zinc supplementation during pregnancy is associated with an increase in birth weight. Design: A randomized double-blind placebo-controlled trial. Setting:Outpatient clinic and delivery service at the University of Alabama at Birmingham. Patients:Five hundred eighty medically indigent but otherwise healthy African-American pregnant women with plasma zinc levels below the median at enrollment in prenatal care, randomized at 19 Complied By : Asma Saleem
  • 43. weeks' gestational age. Women were subdivided by the population median body mass index of 26 kg/m2 into two groups for additional analyses. Intervention:Women who were taking a non—zinc-containing prenatal multivitamin/mineral tablet were randomized to receive either a daily dose of 25 mg of zinc or a placebo until delivery. Main Outcome Measures:Birth weight, gestational age at birth, and head circumference at birth. Results:In all women, infants in the zinc supplement group had a significantly greater birth weight (126 g, P=.03) and head circumference (0.4 cm, P=.02) than infants in the placebo group. In women with a body mass index less than 26 kg/m2, zinc supplementation was associated with a 248-g higher infant birth weight (P=.005) and a 0.7-cm larger infant head circumference (P=.007). Plasma zinc concentrations were significantly higher in the zinc supplement group. Conclusions:Daily zinc supplementation in women with relatively low plasma zinc concentrations in early pregnancy is associated with greater infant birth weights and head circumferences, with the effect occurring predominantly in women with a body mass index less than 26 kg/m2. Complied By : Asma Saleem
  • 44. Use of folic acid in the prevention of neural tube defect Genecology Obstetriciade Mexico 1996 Sep;64:418-21 Abstract The incidence of neural tube defects (NTDs) is about 1.3 cases per 1000 live births. The higher incidence of NTDs occurs among certain ethnic groups, and geographic areas. The fetal morbimortality is high and the treatment for those babies who live is expensive with poor quality of live. It is unclear what biochemical mechanism involving folate explains the relationship of this vitamin to the pathogenesis of NTDs. However elevated concentrations of homocysteine or decreased methionine concentrations could be interfere with closure of the neural tube. The pharmacologic periconceptional intake of 0.4-4.0 mg/day of folic acid reduces the risk of occurrent NTDs by approximately 40-75%. A relatively high dietary intake of folate may also reduce the risk. Complied By : Asma Saleem
  • 45. Calcium improves chances of healthy baby’s bones. Obstetrics and Gynecololgy. 1999 Oct;94(4):577-82. OBJECTIVES: To determine the effect of maternal calcium supplementation during pregnancy on fetal bone mineralization. METHODS: Healthy mothers with early ultrasound confirmation of dates and singleton pregnancies were enrolled in a double-masked study and randomized before 22 weeks' gestation to 2 g/day of elemental calcium or placebo until delivery. Maternal dietary intake at randomization and at 32-33 weeks' gestation was recorded with 24-hour dietary recalls. Dual-energy x-ray absorptiometry measurements of the whole body and lumbar spine of the neonates were performed before hospital discharge. RESULTS: The infants of 256 women (128 per group) had dual-energy x-ray absorptiometry measurements during the first week of life. There were no significant differences between treatment groups in gestational age, birth weight, or length of the infants, or in the total-body or lumbar spine bone mineral content. However, when bone mineral content was analyzed by treatment group within quintiles of maternal dietary calcium intake, total body bone mineral content (mean +/- standard error of the mean) was significantly greater in infants born to calcium-supplemented mothers (64.1+/-3.2 versus 55.7+/-2.7 g in the placebo group) in the lowest quintile of dietary calcium intake (less than 600 mg/day). The effect of calcium supplementation remained significant after adjustment for maternal age and maternal body mass index and after normalization for skeletal area and body length of the infant. Complied By : Asma Saleem
  • 46. CONCLUSION: Maternal calcium supplementation of up to 2 g/day during the second and third trimesters can increase fetal bone mineralization in women with low dietary calcium intake. However, calcium supplementation in pregnant women with adequate dietary calcium intake is unlikely to result in major improvement in fetal bone mineralization. Effects of vitamin A deficiency during pregnancy on maternal and child health. British Journal of Gynecology 2002 Jun;109(6):689-93. Abstract OBJECTIVE: To examine the association between biochemical vitamin A deficiency in pregnancy and maternal and fetal health. DESIGN: A cross sectional clinical study. SETTING:Antenatal clinic of nutrition unit of Niloufer Hospital catering for a low socio-economic population, and a private nursing home (Swapna nursing home) catering for a high socio-economic population. POPULATION:736 pregnant women in their third trimester of pregnancy belonging to low (n = 522) and high socio-economic groups (n = 214). METHODS:All the women were subjected to a detailed clinical, anthropometric and obstetric examination. Night blindness was assessed by administering the standard WHO questionnaire. Complied By : Asma Saleem
  • 47. Birthweight and gestational age of the infants, maternal anaemia and development of pregnancyinduced hypertension in the mother were recorded. Haemoglobin and serum retinol were estimated at the time of recruitment to the study. MAIN OUTCOME MEASURES:Serum retinol levels, anaemia, pregnancy-induced hypertension, birth weight and gestational age of the infant. RESULTS: Night blindness was observed in 2.9% of the women and subclincal vitamin A deficiency (serum retinol <20 microg/dL with no clinical signs) in 27% of the women. Moderate to severe anaemia was observed in 41.2% of the women, and 15.8% of the women developed pregnancy-induced hypertension. Sixty-one (9.4%) women delivered preterm. Univariate analysis identified a significant association between serum retinol <20 microg/dL and preterm delivery (OR = 1.74, 95% CI 1.03-2.96), maternal anaemia (OR = 1.82, 95% CI 1.28-2.60) and pregnancy-induced hypertension (OR = 1.56, 95% CI 1.02-2.83). After adjusting for the confounding variables (body mass index, parity, age and socioeconomic status) in a multivariate analysis, the significant associations between serum retinol <20 microg/dL and preterm delivery (P = 0.02) and anaemia (P = 0.003) persisted, while that for pregnancyinduced hypertension disappeared (P = 0.71). CONCLUSION:The study suggests that subclinical vitamin A deficiency is a problem during the third trimester of pregnancy. Serum concentration of retinol <20 microg/dL appears to indicate a deficient status, and is associated with an increased risk of preterm delivery and maternal anaemia. Complied By : Asma Saleem
  • 48. Vitamin D Supplementation during Pregnancy Part 2 NICHD/CTSA Randomized Clinical Trial (RCT): Outcomes. Pediatric Academic Societies Meeting, May 1, 2010 Abstract BACKGROUND:Vitamin D (vitD) deficiency during pregnancy is a serious public health issue, affecting mother and fetus. Establishing optimal vitD requirements of pregnant women is vital in preventing vitD deficiency and its health-associated comorbidities. OBJECTIVE:Evaluate the effectiveness of high dose vitD supplementation in decreasing pregnancy comorbidity risks. DESIGN/METHODS:Following their consent, pregnant women 12-16 wks' gestation were randomized into 1 of 3 tx grps stratified by race: 400, 2000 or 4000 IU vitD3/day until delivery. Women were evaluated for safety (Abstr#750939), efficacy and effectiveness with monthly 25(OH)D; 1,25(OH)2D; serum Ca, Cr, phos, and urinary Ca/Cr levels, all measured using standardized methodology. Comorbidities of pregnancy (preeclampsia, gest diabetes, any infection, preterm labor (PTL)/preterm birth (PTB)<37 wks GA) were recorded prospectively for each subject. Investigators and health team were blinded to tx grp. RESULTS: Of the 494 women who enrolled in the study, 350 women continued until delivery: 98 African American (AA), 137 Hispanic (Hisp) and 115 Caucasian (Cauc) women; with 111 controls, 122 in 2000 IU and 117 in 4000 IU groups. There were no differences in baseline vitD status between dose Complied By : Asma Saleem
  • 49. groups. The mean 25(OH)D by dose group at delivery, as chronic level, and 1-month before delivery were significantly different between control and 2000, control and 4000, and 2000 vs. 4000 (p<0.0001). 25(OH)D had a direct influence on 1,25(OH)2D levels throughout pregnancy (p<0.0001) with 25(OH)D of 40 ng/mL required to obtain maximum 1,25(OH)2D production. In bivariate analyses controlling for race, PTL/PTB and infection were inversely related to 25(OH)D and were lowest in the 4000 IU grp (p<0.0001). In logistic regression, comparing 400 vs. 4000 IU and controlling for race, the risk of comorbidities were 0.50 (CI 0.27-0.95; p=0.03) among those in the 4000 IU grp. Using least sq means, when adjusting for race, 25(OH)D of women with comorbidities was 33.4 ng/mL compared to 39.0 ng/mL in those women without (p<0.008). CONCLUSIONS:VitD sufficiency was strongly associated with decreased risk for PTL/PTB and infection during pregnancy and co-morbidities of pregnancy, with the greatest effect with 4000 IU vitamin D/day regimen. Therefore, to attain a minimal 25(OH)D level of 40 ng/mL, we recommend 4000 IU/day for all pregnant women. Complied By : Asma Saleem
  • 50. Vitamin C supplementation to prevent premature rupture of the chorioamniotic membranes: a randomized trial American Journal of Clinical Nutrition, Vol. 81, April 2005, pp. 859-86. ABSTRACT Background: Vitamin C is involved in the synthesis and degradation of collagen and is important for maintenance of the chorioamniotic membranes. Inadequate availability of ascorbic acid during pregnancy has been proposed as a risk factor for premature rupture of the chorioamniotic membranes (PROM). Objective: The objective of the study was to evaluate the effectiveness of 100 mg vitamin C/d in preventing PROM. Design: A controlled double-blind trial was performed. Pregnant women (n = 126) in their 20th wk of gestation were invited; 120 accepted and were randomly assigned to 2 groups (100 mg vitamin C/d or placebo). Every 4 wk, plasma and leukocyte vitamin C concentrations were measured, and each subject was evaluated for cervicovaginal infection. The incidence of PROM was recorded for each group as an indicator of the protective effect of vitamin C supplementation. Complied By : Asma Saleem
  • 51. Results: One hundred nine patients finished the study. Mean plasma vitamin C concentrations decreased significantly throughout the pregnancy in both groups (P = 0.001), and there were no significant differences between groups. Between weeks 20 and 36, mean leukocyte vitamin C concentrations decreased from 17.5 to 15.23 µg/108 cells in the placebo group and increased from 17.26 to 22.17 µg/108 cells in the supplemented group (within- and between-group differences: P = 0.001). The incidence of PROM was 14 per 57 pregnancies (24.5%) in the placebo group and 4 per 52 pregnancies (7.69%) in the supplemented group (relative risk: 0.26; 95% CI: 0.078, 0.837). Conclusion: Daily supplementation with 100 mg vitamin C after 20 wk of gestation effectively lessens the incidence of PROM. Key Words: Vitamin C • ascorbic acid • pregnancy • premature rupture of the chorioamniotic membranes • preterm labor • dietary reference intakes • DRIs • Mexico Complied By : Asma Saleem
  • 52. Evidence for the role of zinc in childhood survival Journal of Pediatrics, 135: 208-217 (1999)1 Science, 27: 1081-1085 (1996).2 American Journal of Clinical Nutrition, 68 (Suppl.): 447S-4463S (1998).3 Journal of Paediatric Gastroenterology and Nutrition, 15: 289-296 (1992).4 Gut, 35: 1707-1711 (1994).5 Journal of Pediatrics, 135: 689-697 (1999).6 Although the theoretical basis for a potential role of zinc has been postulated for quite some time, convincing evidence for its importance in child health has come only recently from randomized controlled trials of zinc supplementation. Episodes of childhood diarrhoea that last 14 days or more are associated with increased morbidity and growth retardation. Children who experience such episodes are more likely to have other serious infections and to die (1). Zinc is essential for many cellular functions, including transcription of DNA and cell division (2) and is required for normal immune function (3). It has been shown to hasten mucosal recovery after diarrhoea. Zinc deficiency, as indicated by low plasma zinc concentrations, is associated with both an increased risk of diarrhoeal episodes and greater severity of these illnesses (4, 5). The data from 10 trials evaluating preventive effects of zinc supplementation; three trials evaluating the therapeutic effects on acute diarrhoea; and four trials in therapy of persistent diarrhoea have now been subjected to a pooled Complied By : Asma Saleem
  • 53. analysis (6). This evaluation assessed studies carried out on the effects of zinc supplementation in the prevention of diarrhoea and pneumonia. Trials included those that provided oral supplements containing at least one half of the United States Recommended Daily Allowance of zinc in children under 5 years of age and evaluated the prevention of serious infectious morbidity. The effects of supplements on diarrhoea and pneumonia were analysed overall and in subgroups, defined by age, baseline plasma zinc concentration, nutritional status, and sex. The analysis used random effects hierarchical models to calculate odds ratios and confidence interval. This analysis indicated that there is significant homogeneity in the results across the studies conducted throughout 10 developing countries. Zinc supplementation in these children in developing countries is associated with substantial reductions in the rates of diarrhoea and pneumonia, the two leading causes of death in these settings. These studies also provide by far the best evidence of widespread prevalence of zinc deficiency among preschool children. However, although the available evidence is promising, it is still insufficient to formulate public health policies. Extrapolation of mortality impact from morbidity trial data is fraught with problems of both underestimating and overestimating the impact. Therefore, given its substantial potential to become a powerful intervention to promote child survival, the World Health Organization, in collaboration with UNICEF backed by funding from the United Nations Foundation, has initiated two large studies to determine whether zinc supplementation truly has an important role in decreasing child mortality and morbidity. These studies should provide conclusive new evidence on which to base interventions within the next 30 months and allow recommendations concerning the benefit of zinc supplementation in young children to be made. Complied By : Asma Saleem
  • 54. The effect of calcium supplementation during pregnancy on the birth weight J Reprod Infertil. 2003;4(3):184-191. Nutritional status during pregnancy and intake of essential nutrients affect pregnancy outcome and child health. In most previous studies, high doses of calcium supplements were used during pregnancy to evaluate the effect of calcium intake on pregnancy outcome and their results showed no consistency. In addition, those studies have been mainly carried out to determine the effect of calcium supplementation on relative risk of preeclampsia. The aim of this double blind, placebo controlled, randomized clinical trial on healthy pregnant women during the third trimester of pregnancy was to determine the effect of calcium supplementation (1 g/day, as two 500 mg calcium carbonate capsules) on pregnancy outcome. Participants were 68 healthy pregnant women, allocated randomly into "Calcium Supplement" (n=33) or "Placebo" (n=35) groups from the 28th -30th weeks of gestation through delivery. Factors such as blood pressure, weight, height and BMI were analyzed in both groups. Hemoglobin and blood glucose concentration were determined on the basis of patients’ records and dietary calcium intake was estimated by FFQ. Anthropometric parameters of neonates including weight, head circumference and length were recorded. Student t. test and c2 were used for analyses of the continuous quantitative and qualitative variables, respectively and p-value <0.05 was considered as statistically significant. There was no difference between our 2 groups regarding such factors as age, parity, height, weight, pre-pregnancy body mass index (BMI), blood pressure, and dietary calcium intake. Compliance was >80% in both groups and there was no significant and meaningful difference between them regarding this factor. As compared to the placebo, calcium supplementation increased the mean birth weight in the "Calcium Supplement" Complied By : Asma Saleem
  • 55. group (P<0.05). The observed effect remained unchanged after removing four neonates born before the 37th week of gestation (251 g, P<0.05). It is concluded that calcium supplementation in healthy pregnant mothers may increase birth weight independent of gestational age. Complied By : Asma Saleem