Micronutrient Needs During Pregnancy and

Lactation

Nutrient requirements rise during pregnancy and lactation compared to

women who are not pregnant or breastfeeding. Energy requirements
increase by an estimated 300 kcal/day during the second and third
trimesters of pregnancy, and by 500 kcal/day during lactation, according
to mathematical models. In actuality, most women will only need about
200 more calories per day due to decreased physical activity during
pregnancy and greater lipolysis of fat stores during breast-feeding
[personal conversation with Dr. Berthold Koletzko]. Many micro-
nutrients (vitamins and nutritionally necessary minerals) requirements are
much higher during pregnancy and lactation, in comparison to the
increased energy demand; this page examines micro-nutrient needs
during these life stages.

Because of the physiologic changes in the woman and the metabolic

demands of the embryo/fetus, pregnancy is associated with higher dietary
needs. Proper maternal nutrition throughout pregnancy is so critical for
the health of both the mother and her child. Maternal malnutrition during
pregnancy has been linked to negative outcomes such as an increased risk
of maternal and child death, as well as low-birth-weight neonates (2,500
grams) — a metric that accounts for preterm birth and fetal growth
restriction. Deficiencies in certain nutrients have also been linked to
congenital abnormalities and birth problems.

The concept known as Barker's hypothesis, the thrifty phenotype

hypothesis, or the fetal origin of adult disease hypothesis has also been
linked to increased adult susceptibility to chronic disease in the offspring,
including type 2 diabetes, hypertension, coronary heart disease, and
stroke. Although micronutrient deficiencies are also a type of under-
nutrition, the term "maternal under-nutrition" is frequently used to
describe malnutrition brought on by inadequate calorie (energy) intake
from macro-nutrients (carbohydrates, proteins, and lipids) during
pregnancy. In pregnant women, several micronutrient deficits frequently
coexist.

Many micro-nutrients have higher daily requirements during pregnancy

to satisfy the physiologic changes and increased nutritional needs of
pregnancy. A healthy pregnancy also requires a good nutritional state
prior to conception. Folic acid supplementation, for example, reduces the
risk of catastrophic birth defects known as neural tube defects
significantly throughout the periconceptional period (approximately one
month before conception to the end of the first trimester) (see Folate
below). Folic acid supplementation (at least 400 g/day) is thus suggested
for all pregnant women (7-9). A well-balanced diet is required throughout
pregnancy to deliver micro-nutrients to the developing embryo/fetus. Iron
supplementation is often required in addition to folic acid
supplementation to address the increased demands for this mineral during
pregnancy.

NEXT (TABLE)
Vitamins

Biotin

Biotin is needed as a cofactor for carboxylase enzymes and for the

attachment of biotin to molecules, such as proteins, in a process known as
"biotinylation". Rapidly dividing cells of the developing fetus require
the vitamin for synthesis of essential carboxylase enzymes and
for histone biotinylation. Although maternal biotin deficiency in certain
strains of mice causes malformations in the offspring, namely cleft palate
and limb shortening, a link between biotin deficiency and birth defects in
humans has not been observed.

Experimentally induced, marginal biotin deficiency results in the

increased urinary excretion of 3-hydroxyisovaleric acid (3-HIA) and
decreased urinary excretion of biotin and the biotin catabolites,
bisnorbiotin (BNB) and biotin disulfoxide (BSO). Abnormally elevated
urinary excretion of 3-HIA and abnormally decreased urinary excretion
of biotin are the most extensively validated biomarkers of low biotin
status.

Two observational studies have reported that there is an increased urinary

excretion of 3-HIA during pregnancy, though other indices of biotin
status were not consistently altered. Similarly, a 2014 feeding study in
which all subjects consumed a mixed diet with a known amount of biotin
(average daily intake, 57 μg biotin/day), urinary 3-HIA excretion was
higher in pregnant compared to nonpregnant women, while urinary biotin
and BNB excretion did not differ between the groups. Supplementation
with biotin (300 μg/day for 14 days) reduced urinary 3-HIA and
increased urinary biotin excretion in pregnant women with elevated 3-
HIA; however, this intervention did the same for nonpregnant controls
considered to have normal biotin status.
Elevated urinary excretion of 3-HIA during pregnancy could be due to
several possibilities. Some suggest that it reflects marginal biotin
deficiency and the need for more biotin during pregnancy. Alternatively,
increased 3-HIA in isolation could reflect altered
leucine metabolism or renal handling of organic acids during pregnancy.

At this time, the AI for biotin (30 μg/day) is the same for pregnant and
nonpregnant women. Biotin is widespread in food, though its
concentration varies substantially (see the article on Biotin). Based on
dietary intake data from the National Health and Nutrition Examination
Survey (NHANES) II and the above-mentioned feeding study, a typical
mixed diet provides approximately 40 to 60 μg of biotin/day.

Folate

The terms folate and folic acid are often used interchangeably, but folic
acid is the synthetic form of the vitamin that is only found
in fortified food and supplements. Folic acid is more bioavailable than
folate from food (see the article on Folate); folic acid is converted to
biologically active forms of folate in the body. Folate is needed for amino
acid and nucleic acid (DNA and RNA) metabolism. Adequate
folate status is critical to embryonic and fetal growth — developmental
stages characterized by accelerated cell division. In particular, folate is
needed for closure of the neural tube early in pregnancy, and
periconceptional supplementation with folic acid has been shown to
dramatically reduce the incidence of neural tube defects (NTDs). NTDs
are devastating congenital malformations that can occur as
either anencephaly or spina bifida. Because these birth defects occur
between 21 to 27 days after conception, often before many women
recognize their pregnancy, it is recommended in the US that all women
capable of becoming pregnant take supplemental folic acid .

A recent systematic review of five trials, including 7,391 women, found

that periconceptional folic acid supplementation, alone or with other
micronutrients, was associated with a 69% lower risk of NTDs (risk ratio
(RR), 0.31; 95% confidence interval (CI), 0.17 to 0.58). The RDA for
pregnant women is 600 μg/day of dietary folate equivalents (DFE), which
is equivalent to 300 μg/day of synthetic folic acid on an empty stomach
or 353 μg/day of synthetic folic acid with a meal (see the article
on Folate). The US Preventive Services Task Force recommends a daily
supplement of 400-800 μg of folic acid, in addition to consuming food
folate from a varied diet, for all women planning or capable of pregnancy.
Supplemental folic acid use at the higher end of this suggested range has
been recommended by some, and 800 μg/day from supplements plus
dietary intake is safe for women of childbearing age.

Multivitamin/mineral supplements marketed in the US commonly contain

400 μg of folic acid, and many prenatal supplements marketed in the US
contain 800 μg of folic acid. Folic acid may also be present in the food
supply: several countries have programs of mandatory folic acid
fortification to help reduce the incidence of NTDs; for example, the US
FDA implemented legislation in 1998 requiring the fortification of all
enriched grain products with folic acid at a level of 140 μg folic acid/100
g of product. Mandatory fortification in the US has resulted in a 28
percent reduction (an estimated 1,326 births/year) in the prevalence of
NTDs.

Doses greater than 1 mg/day of folic acid are used pharmacologically to

treat hyperhomocysteinemia and to prevent reoccurrence of NTDs.
Women who have had a previous NTD-affected pregnancy may be
advised to consume up to 4 to 5 mg/day (4,000 to 5,000 μg/day) of folic
acid if they are planning a pregnancy, but this level of supplementation
should be prescribed by their medical provider (see the CDC
recommendations and the World Health Organization [WHO]
guidelines).

A new form of folate, 5-methyltetrahydrofolate (5-MTHF), has been

proposed as an alternative to folic acid. 5-MTHF is less likely to mask a
severe vitamin B12 deficiency, exhibits lower interaction potential with
antimalarial drugs, and may be preferable for women with an MTHFR
polymorphism. While the effect of 5-MTHF supplementation on NTDs
has not yet been evaluated, it is at least as effective as folic acid at raising
red blood cell folate status and reducing homocysteine concentrations in
nonpregnant healthy young women and lactating women.

Inadequate folate status may also be linked to other birth defects, such as
cleft lip, cleft palate, and limb malformations, but there are insufficient
data to evaluate the effect of folic acid supplementation on these
outcomes. However, results of some case-control studies and controlled
trials have suggested that periconceptional supplementation with a
multivitamin containing folic acid may protect against
congenital cardiovascular malformations, especially conotruncal (outflow
tract) and ventricular septal defects. A 2006 systematic review and meta-
analysis concluded that such supplementation was associated with a 22%
lower risk of cardiovascular defects in case-control studies and a 39%
lower risk in cohort studies and randomized controlled trials.

Impaired folate status during pregnancy may also be associated with other
adverse pregnancy outcomes. Elevated blood homocysteine
concentrations, considered an indicator of functional folate deficiency,
have been associated with increased risk of preeclampsia, premature
delivery, low placental weight, low birth weight, very low birth weight
(<1,500 grams), small for gestational age, neural tube defects (NTDs),
and stillbirth. Thus, it is reasonable to maintain folic acid
supplementation throughout pregnancy, even after closure of the neural
tube, in order to decrease the risk of other potential problems during
pregnancy.

Riboflavin

Riboflavin is a component of flavocoenzymes involved in

energy metabolism, as well as antioxidant functions. The Food and
Nutrition Board of the Institute of Medicine recommends that all pregnant
women consume 1.4 mg of riboflavin daily. Riboflavin deficiency has
been implicated in preeclampsia — a pregnancy-associated complication
characterized by elevated blood pressure, protein in the urine,
and edema (significant swelling). Preeclampsia is estimated to affect 2%-
8% of all pregnancies, and about 5% of women with preeclampsia
progress to eclampsia, a significant cause of maternal death. Eclampsia is
characterized by seizures, in addition to high blood pressure and
increased risk of hemorrhage (severe bleeding). Although the specific
causes of preeclampsia are not known, decreased intracellular
concentrations of flavocoenzymes could
cause mitochondrial dysfunction, increase oxidative stress, and interfere
with nitric oxide release and thus blood vessel dilation. All of these
changes have been associated with preeclampsia, but there have been few
studies on the association of riboflavin nutritional status and the
condition. A study in 154 pregnant women at high risk for preeclampsia
found that those who were riboflavin deficient were 4.7 times more likely
to develop preeclampsia than those who had adequate riboflavin
nutritional status. However, a small randomized, double-blind, placebo-
controlled trial in 450 pregnant women at high risk for preeclampsia
found that supplementation with 15 mg of riboflavin daily did not prevent
the condition.

Vitamin A

Adequate maternal status of vitamin A is critical for a healthy pregnancy.

Forms of the vitamin, known as retinoids, are involved in the regulation
of gene expression, cellular proliferation and differentiation, growth and
development, vision, and immunity (see the article on Vitamin A). The
retinoids, retinol and retinoic acid, are essential for embryonic and fetal
development; for example, retinoic acid functions in forming the heart,
eyes, ears, and limbs. Animal studies demonstrate that severe vitamin A
deficiency or excess during critical periods of development results in a
spectrum of malformations, especially affecting craniofacial structures,
limbs, and visceral organs.

Forms of vitamin A are also necessary for maternal health. Vitamin A

deficiency during pregnancy has been linked to impaired immunity,
increased susceptibility to infection, increased risk of maternal morbidity
and mortality, and night blindness. Vitamin A deficiency may exacerbate
iron-deficiency anemia (see section on Iron below); co-
supplementation with vitamin A and iron seems to ameliorate anemia
more effectively than either micronutrient supplement alone. Vitamin A
deficiency is a major public health problem in developing nations, where
availability of foods containing preformed vitamin A (retinol) and
provitamin A carotenoids is limited (for information on food sources of
vitamin A, see the article on Vitamin A). The RDA during pregnancy is
750 to 770 μg/day (2,500 to 2,567 IU/day) of preformed vitamin A.
Although normal embryonic and fetal development require sufficient
maternal vitamin A intake, consumption of excess preformed vitamin A
during pregnancy causes birth defects. An increased risk of vitamin A-
associated birth defects has not been observed at supplemental doses
below 3,000 μg (10,000 IU)/day of preformed vitamin. However, because
a number of foods in the US are fortified with preformed vitamin A, the
Linus Pauling Institute recommends that pregnant women avoid
multivitamin or prenatal supplements that contain more than 750 μg
(2,500 IU) of preformed vitamin A. Vitamin A from β-carotene is not
known to increase the risk of birth defects, although the safety of high-
dose β-carotene supplements in pregnancy has not been well studied.
Moreover, pharmacological use of retinoids by pregnant women causes
serious birth defects; thus, tretinate, isotretinoin (Accutane), and other
retinoids should not be used during pregnancy or if there is a possibility
of becoming pregnant. Use of tretinoin (Retin-A), a topically applied
retinoid, exhibits very low systemic absorption, but is not recommended
during pregnancy due to possible risks. It is important to note that
retinoids tend to be very long acting; birth defects have been reported to
occur months after discontinuing retinoid therapy. Retinoids are used
therapeutically to treat retinitis pigmentosa, acute promyelocytic
leukemia, various skin diseases, and other conditions.

Vitamin B6

Vitamin B6 has diverse roles in the body, including nervous system

function, red blood cell formation and
function, steroid hormone function, nucleic acid synthesis,
and niacin formation. Pyridoxal, pyridoxine, and pyridoxamine are three
forms of the vitamin. The RDA for vitamin B6 during pregnancy is 1.9
mg/day. Vitamin B6 has been used since the 1940s to treat nausea during
pregnancy. The results of two double-blind, placebo-controlled trials that
used 25 mg of pyridoxine every eight hours for three days or 10 mg of
pyridoxine every eight hours for five days suggest that vitamin B6 may
be beneficial in alleviating morning sickness. Each study found a slight
but significant reduction in nausea or vomiting in pregnant women.
A third randomized trial compared high-dose (10 mg/day) and low-dose
(1.28 mg/day) vitamin B6 in 60 pregnant women experiencing nausea
and/or vomiting prior to the twelfth week of gestation. After two weeks,
nausea and vomiting scores decreased to an equal extent in both
supplementation groups. A 2014 pooled analysis indicates
that supplemental vitamin B6 alone may be effective in alleviating
nausea, but not vomiting, during pregnancy. Vitamin B6 at the above-
mentioned dosages is considered safe during pregnancy, and the vitamin
has been used in pregnant women without any evidence of fetal harm.

Vitamin B6 was included in the medication Bendectin (a delayed-release

formulation of 10 mg doxylamine succinate [an antihistamine] and 10 mg
pyridoxine hydrochloride [vitamin B6]), which was prescribed for the
treatment of morning sickness and later withdrawn from the market in
1983 due to unproven concerns that it increased the risk of birth defects.
Since that time, several investigations have shown the combination of
doxylamine/pyridoxine to be both effective and safe, and in 2013, the US
Food and Drug Administration approved this same formulation for the
treatment of nausea and vomiting in pregnancy. The American and
Canadian Colleges of Obstetrics and Gynecology and the Association of
Professors of Gynecology and Obstetrics recommend the combination of
doxylamine/pyridoxine as first-line therapy for nausea and vomiting
during pregnancy.
The tolerable upper intake level (UL) for vitamin B6 during pregnancy is
80 to 100 mg/day.

Vitamin B12

In humans, vitamin B12 is needed as a cofactor for two enzymes. One

converts homocysteine to the amino acid, methionine. Methionine is
required for the synthesis of S-adenosylmethionine, a methyl group donor
used in many biological methylation reactions. DNA methylation that
occurs during embryonic and fetal development modulates gene
expression, cell differentiation, and the formation of organs. Thus,
adequate vitamin B12 status during pregnancy is critical.

Inadequate dietary intake of vitamin B12 causes elevated homocysteine

concentrations, which have been associated with adverse pregnancy
outcomes, including preeclampsia, premature delivery, low placental
weight, low birth weight, very low birth weight (<1,500 grams), small
for gestational age, neural tube defects (NTDs), and stillbirth.

Moreover, low serum concentrations of vitamin B12 during pregnancy

have been linked to an increased risk for NTDs, and there is concern that
folic acid supplementation during pregnancy may mask the clinical
diagnosis of vitamin B12 deficiency. For these reasons, adequate vitamin
B12 intake during pregnancy (RDA=2.6 μg/day) is important.

To ensure a daily intake of 6 to 30 μg of vitamin B12 in a form that is

easily absorbed, the Linus Pauling Institute recommends that women who
are planning a pregnancy take a daily multivitamin supplement or eat a
breakfast cereal fortified with vitamin B12 (for more information, see the
article on Vitamin B12).
Vitamin C and Vitamin E

Because oxidative stress has been implicated in the pathogenesis

of preeclampsia, nutritional status of the
two antioxidant vitamins, vitamin C and vitamin E, may be important in
preventing the condition. These vitamins have other biological functions;
for more information, see the separate articles on Vitamin C and Vitamin
E. Several trials have investigated whether supplementation with vitamins
C and E improves pregnancy-associated hypertension or preeclampsia,
but evidence supporting such an effect is largely lacking. An
early placebo-controlled trial found that supplementation with 1,000
mg/day of vitamin C and 400 mg of vitamin E (RRR-α-tocopherol) was
associated with a 61% reduction in the incidence of preeclampsia in
women at increased risk for the condition. However, more
recent randomized controlled trials have not found supplementation at
these dosages to be effective in preventing preeclampsia in high- or low-
risk women. Nevertheless, adequate intake of antioxidant vitamins is
important throughout pregnancy. According to data from the US National
Health and Nutrition Examination Survey (NHANES), 42%-46% and
85%-94% of US adults do not meet the estimated average requirement
(EAR) for vitamin C and vitamin E, respectively. The Linus Pauling
Institute’s recommends that adults, including pregnant women, reach
daily intakes of at least 400 mg of vitamin C and 15 mg (22.5 IU) of
vitamin E.

Vitamin D

In 2010, the FNB of the Institute of Medicine set the RDA for vitamin

D at 15 μg (600 IU)/day for all pregnant women. The FNB based this
recommendation on a limited number of studies using bone health as the
only indicator, assuming minimal sun exposure. Vitamin D, however, has
a number of other roles in disease prevention and health (see the article
on Vitamin D), and several vitamin D researchers believe that vitamin D
requirements for adults, including pregnant women, are higher than the
current RDA. Moreover, a number of studies indicate that vitamin D
deficiency and insufficiency are quite common among pregnant women.

Low vitamin D status in pregnancy has been associated with an

increased risk of adverse outcomes for both the mother and the infant. For
pregnant women, vitamin D deficiency (serum 25-hydroxyvitamin D less
than 50 nmol/L [20 ng/mL]) has been associated with an increased risk
of preeclampsia and gestational diabetes. For infants, low maternal
vitamin D status has been associated with an increased risk of preterm
birth (birth before 37 weeks of gestation) and low birth weight (a
newborn weighing less than 2,500 grams) (104-106). A pooled analysis
of 15 randomized controlled trials concluded that vitamin
D supplementation raises serum 25-hydroxyvitamin D during pregnancy
and may reduce the risk of preeclampsia, low birth weight, and preterm
birth; notably, combined supplementation of vitamin D and calcium may
increase the risk of preterm birth.

Vitamin D is found in very few foods, and prenatal supplements often

contain only 10 μg (400 IU) of vitamin D. Sunlight exposure is the main
source of the vitamin: vitamin D3 (cholecalciferol) is synthesized in skin
cells following exposure to ultraviolet-B radiation. However, the
contribution of sun exposure to vitamin D status depends on many
factors, including latitude, skin color, amount of skin exposed, duration of
exposure, and the use of sunscreens, which effectively block skin
production of vitamin D. Thus, vitamin D supplementation throughout
pregnancy is likely needed to achieve body concentrations thought to
benefit fetal and maternal health. The Linus Pauling Institute
recommends that generally healthy adults, including pregnant women,
take 2,000 IU (50 μg) of supplemental vitamin D daily. Because sun
exposure, diet, skin color, and obesity have variable, substantial impact
on body vitamin D concentrations, measuring serum concentrations of
25-hydroxyvitamin D — the clinical indicator of vitamin D status — is
important. The Linus Pauling Institute recommends aiming for a serum
25-hydroxyvitamin D level of at least 75 nmol/L (30 ng/mL).

Vitamin K

The adequate intake (AI) for vitamin K (90 μg/day for women aged 19-50
years and 75 μg/day for those aged 14-18 years) is not increased during
pregnancy, and a tolerable upper intake level (UL) has not been set for
vitamin K. However, if taken during pregnancy, a number of drugs,
including warfarin, rifampin, isoniazid, and anticonvulsants, may increase
the risk of neonatal vitamin K deficiency and hemorrhagic disease of the
newborn.

Placental transfer of vitamin K is low, thus all infants are born with low
concentrations of vitamin K. A small proportion of newborns (0.25 to
1.1%) does not have enough vitamin K to make their blood clot and may
develop vitamin K deficiency bleeding (VKDB). There are three
categories of VKDB depending on the age of onset: early (0-24 hours),
classic (one to seven days), and late (two to 12 weeks). Early VKDB is
seen mainly in infants of mothers taking drugs that inhibit vitamin K, as
listed above. Classic VKDB is more common and presents as
bruising, gastrointestinal blood loss, or bleeding from the umbilicus, skin,
or site of circumcision. Late VKDB is particularly concerning as it can
lead to life-threatening intracranial bleeding. Randomized controlled
trials have demonstrated that prophylactic intramuscular (IM) vitamin K
injection of the newborn raises plasma vitamin K concentration, reduces
PIVKA II (a marker of vitamin K deficiency), improves prothrombin
time, and decreases the risk of classic VKDB compared to placebo.
Administration of multiple oral doses of vitamin K can reduce PIVKA II
concentrations and raise plasma vitamin K concentration but is associated
with an increased incidence of late VKDB. The American Academy of
Pediatrics and several international professional organizations
recommend that all babies receive 0.5 to 1.0 mg intramuscular vitamin
K1 injection shortly after birth to prevent VKDB. 

Minerals

Calcium

Although 200 to 250 mg/day of calcium is transferred to the fetus,

primarily in the last trimester, dietary intake requirements of calcium are
not increased due to maternal physiological adaptations. In particular, the
efficiency of intestinal calcium absorption doubles during pregnancy, and
the mineral can also be transiently mobilized from maternal stores (i.e.,
the skeleton) to support fetal needs for calcium. Permanent
demineralization of bone during pregnancy has not been observed.
Moreover, there is no evidence from randomized controlled trials that
calcium supplementation during pregnancy confers any benefit to
maternal or fetal bone health. The RDA is 1,300 mg/day for women aged
14-18 years and 1,000 mg/day for women aged 19-50 years.   

Calcium intake during pregnancy, however, may influence the risk for

pregnancy-induced hypertension (PIH). PIH, which occurs in 10% of
pregnancies and is a major health risk for pregnant women and the fetus,
is a term that includes gestational hypertension, preeclampsia,
and eclampsia. Gestational hypertension is defined as an abnormally high
blood pressure that usually develops after the 20th week of pregnancy. In
addition to gestational hypertension, preeclampsia includes the
development of edema (severe swelling) and proteinuria (protein in the
urine). Preeclampsia may progress to eclampsia in which life-threatening
convulsions and coma may occur. Risk factors for PIH include first
pregnancies, multiple gestations (e.g., twins or triplets), chronic high
blood pressure, diabetes, and some autoimmune diseases. Although the
cause of PIH is not entirely understood, calcium metabolism appears to
play a role. Low calcium intake during pregnancy may: (1)
stimulate parathyroid hormone release, thereby increasing intracellular
calcium and vascular smooth muscle contractility; and/or (2) stimulate
renin release, leading to vasoconstriction and retention of sodium and
fluid. Data from observational studies suggest an inverse
relationship between dietary calcium intake and the incidence of PIH.
Additionally, a recent systematic review of randomized, placebo-
controlled trials (RCTs) reported that calcium supplementation during
pregnancy (≥1,000 mg/day) was associated with a 35% lower risk of high
blood pressure and a 55% lower risk of preeclampsia; the risk reduction
for preeclampsia was even stronger for women considered to be at high
risk for the condition (78% lower risk compared to placebo) and women
with low dietary intake of calcium (64% lower risk compared to placebo).
This analysis also found that calcium supplementation lowered the risk of
preterm birth by 24%, but no significant effect of calcium
supplementation was found regarding the risk of stillbirth, admission to
neonatal intensive care unit, or neonatal mortality before hospital
discharge. Of four RCTs that monitored maternal death or serious
morbidity, one RCT reported a 20% reduced risk for the "severe maternal
morbidity and mortality index" (a summary indicator defined as the
presence of at least one of the following outcomes: maternal admission to
intensive care or any special care unit, eclampsia, severe
preeclampsia, placental abruption, HELLP syndrome [hemolysis,
elevated liver enzymes, and low platelet count], renal failure, or death)
with calcium supplementation; no events occurred in the other three
RCTs.

Chromium

Chromium is known to enhance the action of insulin; therefore, several

studies have investigated the utility of chromium supplementation for the
control of blood glucose concentrations in type 2 diabetes (see the article
on Chromium). However, its use in gestational diabetes — a condition
that affects 4.6%-9.2% of all pregnancies in the US — has not been well
studied. Gestational diabetes is a glucose intolerance that usually appears
in the second or third trimester of pregnancy; blood glucose
concentrations must be tightly controlled to prevent adverse effects on the
developing fetus and other pregnancy complications. After delivery,
glucose tolerance generally reverts to normal, but women are at a
heightened risk of developing type 2 diabetes. In fact, a recent systematic
review and meta-analysis found that the risk of developing type 2
diabetes in women diagnosed with gestational diabetes is more than 7-
fold higher than women not diagnosed with gestational diabetes.
Gestational diabetes is also considered a risk factor for cardiovascular
disease. Two observational studies found that serum concentrations of
chromium in pregnant women were not associated with glucose
intolerance or gestational diabetes, although serum chromium
concentrations may not necessarily reflect tissue chromium
concentrations. An eight-week placebo-controlled trial in 24 women with
gestational diabetes found that supplementation in the form of chromium
picolinate (4 μg/day of chromium per kilogram of body weight) was
associated with lower fasting blood glucose and insulin concentrations.
However, it is important to note that insulin therapy was still required to
normalize the severely elevated blood glucose concentrations. Thus, more
research, especially from randomized controlled trials, is needed to
determine whether chromium supplementation has any utility in the
treatment of gestational diabetes. 

Iodine

Iodine requirements are increased by more than 45% during pregnancy:

the RDA for pregnant women is 220 μg/day compared to 150 μg/day for
women who are not pregnant. Adequate intake of this mineral is needed
for maternal thyroid hormone production, and thyroid hormone is needed
for myelination of the central nervous system and is thus essential for
normal fetal brain development. If iodine deficiency leads to inadequate
production of thyroid hormone during pregnancy, irreversible brain
damage in the fetus may occur. Severe maternal iodine deficiency has
also been associated with increased incidence of miscarriage, stillbirth,
and birth defects.

One of the most devastating effects of severe maternal iodine deficiency

is congenital hypothyroidism. A severe form of congenital
hypothyroidism may lead to a condition that is sometimes referred to
as cretinism and result in irreversible mental retardation. Cretinism occurs
in two forms, neurologic and myxedematous, although there is
considerable overlap between them. The neurologic form is characterized
by mental and physical retardation and deafness; it results from maternal
iodine deficiency that affects the fetus before its own thyroid is
functional. The myxedematous or hypothyroid form is characterized by
short stature and mental retardation. Severe maternal iodine deficiency
has also been linked to neurocognitive deficits in the offspring. In
severely iodine-deficient pregnant women,
iodine supplementation effectively reduces rates of cretinism, and
improves offspring cognitive function and survival. The timing of iodine
supplementation appears to be important: supplementation should be
initiated prior to conception and early in pregnancy (before the 10th week
of gestation) in order to see beneficial effects on offspring neurocognitive
outcomes.

Even mild forms of maternal iodine deficiency may have adverse effects
on cognitive development in the offspring, though this outcome is less
well studied. Randomized controlled trials conducted in moderately
iodine deficient pregnant women demonstrate that iodine
supplementation increases thyroid gland volume but has no effect on
thyroid hormone concentrations compared to placebo. The extent to
which supplementation in moderately iodine deficient pregnant women
affects neurocognitive outcomes in their offspring is currently under
investigation.

Iodine deficiency is now accepted as the most common cause of

preventable brain damage in the world. Thus, adequate intake of the
mineral throughout pregnancy is critical. A daily supplement providing
150 μg of iodine, as recommended by the American Thyroid Association,
will help to ensure that US pregnant women consume sufficient iodine.
However, it is important to note that several prenatal supplements and
some multivitamin/mineral supplements on the market in the US do not
contain iodine, presumably because manufacturers assume that women
receive sufficient iodine through iodized salt and other food sources. For
more information on iodine and iodine deficiency disorders, see the
article on Iodine.
Iron

Iron requirements are significantly increased during pregnancy:

the RDA is 27 mg/day for pregnant women of all ages compared to 15 to
18 mg/day for nonpregnant women. Many women have dietary iron
intakes below current recommendations. National surveys in the US
indicate that the average dietary iron intake is about 12 mg/day in
nonpregnant women and 15 mg/day in pregnant women. Iron is needed
for a number of biological functions (see the article on Iron), but during
pregnancy, the mineral is generally needed to support growth and
development of the fetus and placenta and to meet the increased demand
for red blood cells to transport oxygen. Intestinal absorption of dietary
iron increases during the second and third trimesters to accommodate for
expansion of red cell mass. Maternal blood volume expands by almost
50% during pregnancy, which results in a hemodilution of red blood
cells.

Despite maternal physiologic changes that enhance iron absorption, many

women develop iron-deficiency or iron-deficiency anemia during
pregnancy. The World Health Organization estimates that the
worldwide prevalence of anemia among pregnant women is 42%; the
prevalence of anemia is much higher in less developed nations compared
with industrialized nations, with almost 90% of these anemic women
living in Africa or Asia. In pregnant women in the US, the prevalence of
iron deficiency is 18%, and the prevalence of iron-deficiency anemia is
5%. Anemias can be caused by deficiencies in other micronutrients, such
as folate or vitamin B12, but iron deficiency is the primary cause of
anemia during pregnancy. Severe iron-deficiency anemia has been
associated with an increased risk of maternal death and with an increased
risk of low birth weight infants (<2,500 grams), premature delivery, and
perinatal mortality.

Two 2015 systematic reviews evaluated the effect of routine

iron supplementation compared to placebo or no treatment on maternal
and birth outcomes. Both reviews found that routine supplementation
with iron improved maternal iron status and decreased the risk of iron
deficiency and iron-deficiency anemia at term. There is some indication
that maternal iron supplementation could improve birth outcomes
(namely preterm birth and low birth weight) in developing countries, but
the evidence was deemed of low quality. Women taking higher doses of
iron (≥60 mg/day) tended to have abnormally high hemoglobin values at
term and were more likely to report side effects; side effects of high-dose
iron supplements include nausea, constipation, vomiting, and diarrhea.

Iron status of the woman at the time of conception is important for a

healthy pregnancy, to avoid postpartum anemia, and to provide the
breast-feeding infant with sufficient iron stores until six months of age,
when complementary feeding is recommended. Because of the increased
demands for the mineral during the second and third trimesters of
pregnancy, iron supplementation (30 mg/day) is usually recommended
beginning at 12 weeks’ gestation. Absorption of nonheme iron, which is
the form of iron found in supplements, is affected by a number of
enhancers (e.g., vitamin C) as well as inhibitors (e.g., polyphenols found
in tea and coffee). In general, iron supplements are better absorbed on an
empty stomach. High doses of iron supplements taken together
with zinc supplements on an empty stomach can inhibit the absorption of
zinc; supplemental iron at 38 to 65 mg/day of elemental iron may
decrease zinc absorption. For more information about dietary and
supplemental sources of iron, as well as the side effects and safety of
iron, see the article on Iron. 

Magnesium

The mineral magnesium plays a number of important roles in the

structure and the function of the human body (see the article
on Magnesium), and adequate intake of the mineral is needed for normal
embryonic and fetal development. National dietary surveys indicate that
magnesium insufficiency is relatively common in the US, with 56% of
American adults not meeting the EAR — the nutrient intake value that is
estimated to meet the requirement of half of the healthy individuals in a
particular life stage and gender group. Good sources of magnesium
include green leafy vegetables, whole grains, and nuts (see the article
on Magnesium). Several multivitamin/mineral and
prenatal supplements do not contain magnesium or contain no more than
100 mg of magnesium.

Preeclampsia-eclampsia is a disease that is unique to pregnancy and may

occur anytime after 20 weeks’ gestation. Preeclampsia is defined as the
presence of elevated blood pressure and protein in the urine; severe
swelling (edema) may also be present. Eclampsia occurs with the addition
of seizures to these symptoms. Approximately 5%-8% of women with
preeclampsia go on to develop eclampsia in developing countries, which
is a significant cause of maternal death.

A 2014 pooled analysis of randomized controlled trials concluded that

oral magnesium supplementation during pregnancy has no significant
effect on perinatal mortality, small-for-gestational age, or the risk of
preeclampsia. Intravenous administration of high-dose magnesium sulfate
has been the treatment of choice for preventing eclamptic seizures that
may occur in association with preeclampsia-eclampsia in late pregnancy
or during labor. Magnesium is believed to relieve cerebral blood vessel
spasm and promote peripheral vasodilation, thereby increasing blood
flow to the brain.

Zinc

The RDA for zinc is increased during pregnancy (from 8 mg/day-9

mg/day to 11 mg/day-12 mg/day), and pregnant women, especially
teenagers, are at increased risk of zinc deficiency. It has been estimated
that 82% of pregnant women in the world may have inadequate intake of
dietary zinc, leading to poor nutritional status of the mineral. Poor
nutritional status of zinc during pregnancy has been associated with a
number of adverse outcomes, including low birth weight (<2,500 grams),
premature delivery, labor and delivery complications, and congenital
anomalies. However, the results of maternal zinc supplementation trials
in the US and developing countries have been mixed. A 2014 systematic
review of 16 randomized controlled trials found that zinc
supplementation during pregnancy was associated with a 14% reduction
in premature deliveries; the lower incidence of preterm births was
observed mainly in low-income women. This analysis, however, did not
find zinc supplementation to benefit other indicators of maternal or infant
health.

It is important to note that supplemental levels of iron (38 to 65 mg/day

of elemental iron), but not dietary levels of iron, may decrease zinc
absorption. Because iron supplementation is often recommended during
pregnancy (see Iron above), pregnant women who take more than 60
mg/day of elemental iron may want to take a prenatal or multivitamin-
mineral supplement that also includes zinc.
Other Nutrients

Choline

Choline can be synthesized by the body in small amounts, but dietary

intake is needed to maintain health. Choline is essential for embryonic
and fetal brain development, liver function, and placental function. The
choline metabolite betaine is a source of methyl (CH3) groups required
for methylation reactions; DNA methylation that occurs during
embryonic and fetal development modulates gene expression,
cell differentiation, and the formation of organs. A mother delivers large
amounts of choline to the fetus across the placenta and to the infant via
breast milk, placing an increased demand on maternal stores of choline
during pregnancy and lactation. The induction of de novo choline
synthesis by the high levels of estrogen during pregnancy helps to meet
this increased demand. Additionally, pregnant women are encouraged to
consume choline-rich foods, such as eggs, meat, and seafood (for dietary
sources, see the article on Choline). The adequate intake (AI) for
pregnant women is 450 mg/day of choline, slightly higher than the 425
mg/day recommended for nonpregnant women.

Case-control studies have reported mixed results regarding the

relationship between dietary choline intake or blood choline
concentration and the risk of neural tube defects (NTDs). One case-
control study reported a lower risk of having an NTD-affected pregnancy
in those with the highest intake of betaine and choline combined, while
two other studies found no association between maternal choline intake
and NTD risk. Similarly, one case-control study found low serum choline
concentration was associated with a higher risk of NTDs, while another
study found no such association. Additionally, it is not known
if supplementation with choline or betaine, like supplementation with
folic acid (see Folate above), will lower the incidence of NTDs. More
research is needed to determine whether choline is involved in
the etiology of NTDs.

Maternal intake of choline during pregnancy could possibly

affect cognitive abilities of the offspring. Choline supplementation in
pregnant rats, as well as rat pups during the first month of life, leads to
improved performance in spatial memory tests months after choline
supplementation has been discontinued. A review by McCann et al.
discusses the experimental evidence from rodent studies regarding the
availability of choline during prenatal development and cognitive
function in the offspring. It is not clear whether findings in rodent studies
are applicable to humans. One randomized controlled trial demonstrated
that choline supplementation (750 mg/day of choline in the form of
phosphatidylcholine administered from week 18 of gestation through 90
days postpartum) in pregnant women consuming a moderate-choline diet
(approximately 360 mg/day) was safe but did not enhance infant
cognitive function at 10 or 12 months of age.

Finally, choline is important for homocysteine metabolism during

pregnancy. Methyl groups derived from choline may be used to convert
homocysteine to methionine. Elevated blood homocysteine
concentrations have been associated with increased risk of preeclampsia,
premature delivery, low placental weight, low birth weight (<2,500
grams), very low birth weight (<1,500 grams), small for gestational age,
NTDs, and stillbirth.
Essential fatty acids

Although not micronutrients, certain fatty acids are required in the

maternal diet during pregnancy and lactation; the US Institute of
Medicine’s adequate intake (AI) recommendations for omega-3 and
omega-6 fatty acids during pregnancy and lactation are listed in the
separate article on Essential Fatty Acids. For more information on the
importance of omega-3 fatty acids during these life stages, see two
sections in the separate article on essential fatty acids: Visual and
neurological development and Pregnancy and lactation. Information
about environmental contaminants in fish and supplements is included in
the sections, Contaminants in fish and Contaminants in supplements. 

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Maternal Micronutrient Requirements During Lactation

Breast-feeding confers health benefits to the child, as well as the
mother (175). Breast milk is the ideal source of nutrition for the infant
and also contains a number of bioactive compounds important in
immunity, such as antibodies, cytokines, antimicrobial agents, and
oligosaccharides. The American Academy of Pediatrics recommends
exclusive breast-feeding for the first six months of infancy, followed by
continued breast-feeding as complementary foods are introduced, with
continuation of breast-feeding until 12 months postpartum or longer as
mutually desired by the mother and child. The World Health
Organization recommends exclusive breast-feeding for the first six
months of life and continued breast-feeding, with complementary
feeding, up to two years or more postpartum. There are, however, a few
exceptions when breast-feeding is contraindicated, including those listed
on the CDC website.

Lactation is extremely energy expensive (exceeding pre-pregnancy

demands by approximately 500 kcal/day),
and macronutrient requirements for breast-feeding women are even
higher than during pregnancy. Likewise, the intake recommendations
(RDA or AI) for most micronutrients, which are based on amounts
secreted in breast milk, are higher for lactating women compared to
pregnant women. One notable exception is the RDA for iron, which is
significantly lower during lactation (9 to 10 mg/day) compared to
pregnancy (27 mg/day). Breast milk is considered to be low in iron;
however, the iron content of breast milk is not influenced by changes in
maternal iron status, such as through maternal supplementation. The
RDA for folate is also lower during lactation compared with pregnancy.
Dietary intake recommendations for calcium remain unchanged for
lactating women compared to recommendations for nonlactating women,
and calcium content in breast milk does not reflect maternal intake of
the mineral. Adequate calcium is maintained in breast milk because of
maternal physiological changes that involve transient bone resorption;
increased maternal intake of calcium through diet
and supplementation does not prevent maternal bone demineralization,
and studies have shown that maternal bone mineral content is restored
upon weaning.

In general, the amounts of water-soluble vitamins (B vitamins and

vitamin C) in breast milk reflect maternal intake from diet
and/or supplements. Thus, meeting daily intake recommendations for
these micronutrients is important for the health of the child. Maternal
vitamin deficiencies can negatively affect infant growth and
development; for instance, vitamin B12 deficiency during infancy can
impair brain development and cause neurological problems. Vitamin
B12 deficiency has been documented in nursing infants of mothers who
have untreated pernicious anemia and also in women who are strict
vegetarians (vegans). Vitamin B12 is found only in foods of animal origin
and fortified foods, and lactating women who follow vegetarian diets
should take supplemental vitamin B12. Vitamin B12 deficiency that
results from pernicious anemia can easily be corrected with high-dose
daily supplementation or with monthly intramuscular injections of the
vitamin (see the article on Vitamin B12). However, there has been
relatively little research on the effect of oral vitamin B12 supplementation
in lactating women, and it has been suggested that supplementation
during lactation may be too late to restore adequate milk concentrations
and infant status. Supplementation during pregnancy may more
effectively improve infant vitamin B12 status. For instance, oral daily
vitamin B12 supplementation (50 μg/day) administered from <14
weeks gestation through 6 weeks postpartum significantly increased
maternal plasma and breast milk concentrations of vitamin B12 and
improved infant vitamin B12 status. The concentrations of other water-
soluble vitamins in breast milk, including thiamin, riboflavin, and vitamin
B6, are also strongly dependent on maternal intake of these vitamins.
Likewise, vitamin C concentration in human milk varies with the vitamin
C status of the mother. Vitamin C supplementation can moderately
increase concentrations of the vitamin in breast milk, especially in
lactating women with poor vitamin C status, and maternal intakes of 100
mg/day maximize the amount of vitamin C in breast milk.
Compared to water-soluble vitamins, the concentrations of fat-soluble
vitamins (vitamins A, D, E, and K) in breast milk are less correlated with
maternal dietary intake. The RDA for vitamin A during lactation is 1,200
to 1,300 μg/day (4,000 to 4,333 IU/day). At such levels of maternal
intake, breast milk is a good source of vitamin A and provides the infant
with a sufficient amount of the vitamin. In contrast, breast milk is
considered to be low in vitamins D and K. Vitamin D concentrations in
human milk are dependent on maternal vitamin D status, which is
determined by the woman’s sun exposure and dietary and supplemental
intake. Vitamin D concentrations are low in breast milk, presumably
because many women have insufficient vitamin D status. Vitamin D
supplementation during lactation has been shown to improve vitamin D
status in the woman and the infant . The RDA for lactating women is 600
IU/day of vitamin D, but intake at this level in the absence of sun
exposure likely results in insufficient amounts for the infant. To prevent
vitamin D deficiency and rickets in infants, the American Academy of
Pediatrics recommends that all breast-fed and partially breast-fed infants
be given a vitamin D supplement of 400 IU/day. Liquid vitamin D
supplements are commercially available for infant supplementation. The
Linus Pauling Institute recommends that all adults take 2,000 IU/day of
supplemental vitamin D and aim for a serum 25-hydroxyvitamin D level
of at least 75 nmol/L (30 ng/mL). Human milk is also relatively low
in vitamin K. Thus, exclusively breast-fed newborns are at
increased risk for vitamin K deficiency. In general, newborns have low
vitamin K status for the following reasons: (1) vitamin K is not easily
transported across the placental barrier; (2) the newborn's intestines are
not yet colonized with bacteria that synthesize vitamin K; and (3) the
vitamin K cycle may not be fully functional in newborns, especially
premature infants. Vitamin K deficiency in newborns may result in a
bleeding disorder called vitamin K deficiency bleeding (VKDB). Because
VKDB is life-threatening and easily prevented, the American Academy
of Pediatrics and a number of similar international organizations
recommend that an injection of phylloquinone (vitamin K1) be
administered to all newborns shortly after birth. Additionally, the vitamin
E content in breast milk varies with maternal diet and vitamin E
supplement use. The RDA for vitamin E during lactation is 19 mg/day
(28.5 IU/day) of α-tocopherol. National surveys indicate that more than
90% of US adults have daily vitamin E intakes below 12 mg (18 IU). 

Maternal dietary intake recommendations for the 14 essential minerals

during lactation are shown in Table 3. The content of minerals in breast
milk does not correlate well with maternal intake or status, except
for iodine and selenium. Iodine requirements are increased during
lactation: breast-feeding women require 290 μg/day of iodine compared
to 220 μg/day for pregnant women and 150 μg/day for nonpregnant,
nonlactating women. Iodine-deficient women who are breast-feeding may
not be able to provide sufficient iodine to their infants who are
particularly vulnerable to the effects of iodine deficiency (see the article
on Iodine). A daily supplement providing 150 μg of iodine, as
recommended by the American Thyroid Association, will help to ensure
that US breast-feeding women consume sufficient iodine during these
critical periods. Additionally, the RDA for selenium is slightly higher for
lactating women (from 60 to 70 μg/day), and selenium content in breast
milk reflects maternal intake.

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