Headnote
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 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. J. Nutr. 133: 1997S-2002S, 2003.
KEY WORDS: * pregnancy * lactation * nutritional requirements * dietary supplements
The health of mothers and their infants is a priority in the United
States, and Healthy People 2010, our nationwide health promotion and
disease prevention agenda, identifies measurable objectives for
improvement (1). Many of these objectives are based on nutrition
research that offers promise for enhancing reproductive outcomes.
Accumulating evidence from evaluation of public health nutrition
programs and nutrient-specific intervention trials indicates that
maternal nutritional modifications can and do produce desirable health
advantages (2-4).
During
pregnancy
and lactation, nutritional requirements increase to support fetal and
infant growth and development as well as maternal metabolism and tissue
development specific to reproduction. Total nutrient requirements are
not necessarily the simple sum of those accumulated in maternal tissues,
products of
pregnancy
and lactation and those attributable to maintenance of nonreproducing
women even though this process of summation is sometimes used to derive
estimates of recommended nutrient intakes.
Pregnancy
and lactation are anabolic states that are orchestrated via hormones to
produce a redirection of nutrients to highly specialized maternal
tissues characteristic of reproduction (i.e., placenta and mammary
gland) and their transfer to the developing fetus or infant. In this
article the physiological adjustments and nutritional requirements of
pregnant and lactating women and the possible role of dietary
supplementation in meeting requirements for nutrients likely to be
limiting in the diet are discussed.
Physiological adjustments of
pregnancy
Hormonal changes during
pregnancy.
Plasma levels of human chorionic gonadotropin increase immediately upon
implantation of the ovum; the hormone is detectable in urine within 2
wk of implantation. It reaches a peak at [approximate]=8 wk of
gestation
and then declines to a stable plateau until birth. Human chorionic
gonadotropin maintains corpus luteum function for 8-10 wk. Human
placental lactogen (also called human chorionic somatomammotropin) has a
structure that closely resembles growth hormone, and its rate of
secretion appears to parallel placental growth and may be used as a
measure of placental function. At its peak, the rate of secretion of
placental lactogen is 1-2 g/d, far in excess of the production of any
other hormones. Placental lactogen stimulates lipolysis, antagonizes
insulin actions and may be important in maintaining a flow of
energy-yielding substrates to the fetus. Placental lactogen along with
prolactin from the pituitary may promote mammary gland growth. After
delivery, placental lactogen rapidly disappears from the circulation.
The placenta becomes the main source of steroid hormones at weeks 8-10 of
gestation.
Before then, progesterone and estrogens are synthesized in the maternal
corpus luteum. These hormones play essential roles in maintaining the
early uterine environment and development of the placenta. The placenta
takes over progesterone production, which increases throughout
pregnancy. Progesterone, known as the hormone of
pregnancy,
stimulates maternal respiration; relaxes smooth muscle, notably in the
uterus and gastrointestinal tract; and may act as an immunosuppressant
in the placenta, where its concentration can be 50 times greater than in
plasma. Progesterone may promote lobular development in the breast and
is responsible for the inhibition of milk secretion during
pregnancy.
The secretion of estrogens from the placenta is complex (5). Estradiol
and estrone are synthesized from the precursor dehydroepiandrosterone
sulfate (DHEA-S), which is derived from both maternal and fetal blood.
The synthesis of estriol is from fetal
16-a-hydroxy-dehydroepiandrosterone sulfate (16-OH-DHEA-S). The fetus is
unable to synthesize pregnenolone, the precursor of DHEA-S and
16-OH-DHEA-S, and must get the precursor from the placenta. The
placental secretion of estrogens also increases manyfold with the
progression of
pregnancy. The functions of high estrogen levels in
pregnancy
include stimulation of uterine growth, enhancement of uterine blood
flow and possibly promotion of breast development. Because estrogen
precursors originate in the fetus, maternal estrogen levels can be used
as a measure of fetal viability.
The increased amount of estrogens during
pregnancy
also stimulates a population of cells (somatotrophs) in the maternal
pituitary to become mammotrophs, or prolactin-secreting cells. The
increased prolactin secretion probably helps promote mammary
development. In addition, the increased number of pituitary mammotrophs
at the end of
pregnancy provides the large amounts of prolactin necessary to initiate and maintain lactation.
Blood volume and composition. During
pregnancy
there is an increase in blood volume of [approximate]=35-40%, expressed
as a percentage of the nonpregnant value, that results principally from
the expansion of plasma volume by [approximate]=45-50% and of red cell
mass by [approximate]15-20% as measured in the third trimester. Because
the expansion of red cell mass is proportionally less than the expansion
of plasma, hemoglobin concentration and hematocrit values fall in
parallel with red cell volume. Hemoglobin and hematocrit values are at
their lowest in the second trimester of
pregnancy
and rise again in the third trimester. For these reasons,
trimester-specific values for hemoglobin and hematocrit are proposed for
screening for anemia in pregnant women (6).
Total plasma protein concentration falls from [approximate]=70 to 60 g/L
largely because of a fall in albumin concentration from [approximate]=4
to 2.5 g/100 mL near term. Plasma concentrations of [alpha]1-,
[alpha]2-and [beta]-globulins increase by [approximate]=60%, 50% and
35%, respectively, whereas the [gamma]-globulin fraction decreases by
13% (7). Estrogens are responsible for these changes in plasma proteins,
which can be reproduced by administration of estradiol to nonpregnant
women. Plasma levels of most lipid fractions, including triacylglycerol,
VLDL, LDL and HDL, increase during
pregnancy.
Recommended weight gain. The average weight gained by healthy
primigravidae eating without restriction is 12.5 kg (27.5 lb) (5). This
weight gain represents two major components: 1) the products of
conception: fetus, amniotic fluid and the placenta and 2) maternal
accretion of tissues: expansion of blood and extracellular fluid,
enlargement of uterus and mammary glands and maternal stores (adipose
tissue).
Low weight gain is associated with
increased risk of intrauterine growth retardation and perinatal
mortality. High weight gain is associated with high birth weight and
secondarily with increased risk of complications related to fetopelvic
disproportion. A large body of epidemiologic evidence now shows
convincingly that maternal prepregnancy weight-for-height is a
determinant of fetal growth above and beyond gestational weight gain. At
the same gestational weight gain, thin women give birth to infants
smaller than those born to heavier women. Because higher birth weights
present lower risk for infants, current recommendations for weight gain
during
pregnancy
are higher for thin women than for women of normal weight and lower for
short overweight and obese women (7). These recommendations are
summarized below (Table 1).
Recommendations for weight gain during
pregnancy
were formulated in recognition of the need to balance the benefits of
increased fetal growth against the risks of labor and delivery
complications and of postpartum maternal weight retention. The target
range for desirable weight gain in each prepregnancy weight-for-height
category is that associated with delivery of a full-term infant weighing
between 3 and 4 kg. Recent evidence indicates that <50% of 622 women
sampled in upstate New York gained weight within the ranges recommended
and that weight gain greater than these recommended amounts placed them
at risk for major weight gain 1 y post-delivery (8).
Nutritional needs during
pregnancy
Determination of nutrient needs during
pregnancy
is complicated because nutrient levels in tissues and fluids available
for evaluation and interpretation are normally altered by
hormone-induced changes in metabolism, shifts in plasma volume and
changes in renal function and patterns of urinary excretion. Nutrient
concentrations in blood and plasma are often decreased because of
expanding plasma volume, although total circulating quantities can be
greatly increased. Individual profiles vary widely, but in general,
water-soluble nutrients and metabolites are present in lower
concentrations in pregnant than in nonpregnant women whereas fat-soluble
nutrients and metabolites are present in similar or higher
concentrations. Homeostatic control mechanisms are not well understood
and abnormal alterations are ill-defined.
Dietary Reference Intakes for pregnant and lactating women in
comparison with those of adult, nonreproducing women are presented in
Table 2. Also presented in Table 2 are comparative cumulative energy and
nutrient expenditures of adult, pregnant and lactating women. The
recommended intakes for pregnant adolescents generally would be
increased by an amount proportional to the incomplete maternal growth at
conception. The percentage increase in estimated energy requirement is
small relative to the estimated increased need for most other nutrients.
Accordingly, pregnant women must select foods with enhanced nutrient
density or risk nutritional inadequacy.
Energy. Energy needs during
pregnancy
are currently estimated to be the sum of total energy expenditure of a
nonpregnant woman plus the median change in total energy expenditure of 8
kcal/gestational week plus the energy deposition during
pregnancy
of 180 kcal/d (13). Because total energy expenditure does not change
greatly and weight gain is minimal in the first trimester, additional
energy intake is recommended only in the second and third trimesters.
Approximately an additional 340 and 450 kcal are recommended during the
second and third trimesters, respectively.
Protein. Additional protein is needed during
pregnancy
to cover the estimated 21 g/d deposited in fetal, placental and
maternal tissues during the second and third trimesters (13). Women of
reproductive age select diets containing average protein intakes of
[approximate]70 g/d (14), a value very close to the theoretical need of
71 g during
pregnancy.
Vitamins and minerals. The assessment of vitamin and mineral status during
pregnancy is difficult because there is a general lack of
pregnancy-specific
laboratory indexes for nutritional evaluation. Plasma concentrations of
many vitamins and minerals show a slow, steady decrease with the
advance of
gestation, which may be due to hemodilution; however, other vitamins and minerals can be unaffected or increased because of
pregnancy-induced
changes in levels of carrier molecules (15). When these patterns are
unaltered by elevated maternal intakes, it is easy to conclude that they
represent a normal physiological adjustment to
pregnancy
rather than increased needs or deficient intakes. Even when enhanced
maternal intake does induce a change in an observed pattern,
interpretation of such a change is difficult unless it can be related to
some functional consequence (15). For these reasons, much of our
knowledge is based on observational studies and intervention trials in
which low or high maternal intakes are associated with adverse or
favorable
pregnancy outcomes. Available data on vitamin and mineral metabolism and requirements during
pregnancy
are fragmentary at best, and it is exceedingly difficult to determine
consequences of seemingly deficient or excessive intakes in human
populations. However, animal data show convincingly that maternal
vitamin and mineral deficiencies can cause fetal growth retardation and
congenital anomalies. Similar associations in humans are rare. Selected
vitamins and minerals that are likely to be limiting or excessive in the
diets of pregnant women and their association with
pregnancy outcome are briefly discussed.
Placental transport of vitamin A between mother and fetus is
substantial, and recommended intakes are increased by [approximate]10%
(12). Low maternal vitamin A status is inconsistently associated with
intrauterine growth retardation in communities at risk for vitamin A
deficiency. Dietary supplementation with vitamin A or [beta]-carotene is
reported to reduce maternal mortality by 40% but to not affect fetal
loss or infant mortality rates (16,17). Overt vitamin A deficiency is
not apparent in the United States; instead, the concern during
pregnancy is about excess (18).
The main circulating form of vitamin D in plasma,
25-hydroxycholecalciferol, is responsive to increased maternal intake
and falls with maternal deficiency. The biologically active form of the
vitamin, 1,25-dihydroxycholecalciferol, circulates in bound and free
forms and both are elevated in
pregnancy (19). All forms of vitamin D are transported across the placenta to the fetus. Vitamin D deficiency during
pregnancy
is associated with several disorders of calcium metabolism in both the
mother and her infant, including neonatal hypocalcemia and tetany,
infant hypoplasia of tooth enamel and maternal osteomalacia (20).
Supplementation of 10 [mu]g (400 IU)/d in affected women lowered the
incidence of neonatal hypocalcemia and tetany and maternal osteomalacia
whereas higher amounts (25 [mu]g/d) increased weight and length gains in
infants postnatally (21). The prevalence of vitamin D deficiency is
high in pregnant Asian women in England and in pregnant women in other
European countries at northern latitudes, where the amount of
ultraviolet light reaching the earth's surface is not sufficient for
synthesis of vitamin D in the skin during winter months. Food sources of
vitamin D are few and no increase in vitamin D intake during
pregnancy
is recommended (9). However, recent data from the third National Health
and Nutrition Examination Survey indicate that [approximate]=42%) of
African American women and 4% of white women show biochemical evidence
of vitamin D insufficiency (22). Research is needed to assess vitamin D
requirements of women of reproductive age, the extent to which the diet
or light exposure can furnish needed amounts and the possible benefit of
supplemental quantities before and during
pregnancy.
Compromised maternal folate intake or status is associated with several negative
pregnancy
outcomes including low birth weight, abruptio placentae, risk for
spontaneous abortions and neural tube defects (23). Folic acid
supplementation prevents both the occurrence and recurrence of neural
tube defects (24) and significantly reduces the incidence of low birth
weight (25). Previously, folic acid supplementation was started
relatively late in
pregnancy
but now in the United States, the Food and Drug Administration requires
folic acid fortification of most grain products, and intakes have
dramatically increased. The recommended intake for folate during
pregnancy
is 600 [mu]g/d (10). It will be important to evaluate the extent to
which folic acid fortification increases intake of reproducing women,
decreases neural tube defects and affects growth and development of the
fetus.
The total iron cost of
pregnancy
is estimated at 1040 mg, of which 200 mg are retained by the woman when
blood volume decreases after delivery and 840 mg are permanently lost.
Iron is transferred to the fetus ([approximate]300 mg) and used for the
formation of the placenta (50-75 mg), expansion of red cell mass
([approximate]450 mg) and blood loss during delivery ([approximate]200
mg). Hemoglobin concentration declines during
pregnancy
along with serum iron, percentage saturation of transferrin and serum
ferritin. Although these decreases reflect hemodilution to a large
extent, transferrin levels actually increase from mean nonpregnant
values of 3 mg/L to 5 mg/L in the last trimester of
pregnancy,
perhaps to facilitate iron transfer to the fetus. Enhanced intestinal
iron absorption (two- to threefold) is an important physiological
adjustment that assists pregnant women in meeting the requirement for
absorbed iron, which is estimated to be [approximate]3 mg/d. Maternal
anemia is associated with perinatal maternal and infant mortality and
premature delivery. To preserve maternal stores and to prevent the
development of iron deficiency, the recommended iron intake during
pregnancy
is increased by 9 mg to a total of 27 mg/d (12). This level cannot
normally be obtained from foods, and supplementation is required to
achieve recommended intakes. The routine use of iron supplements during
pregnancy,
however, is not universally endorsed. Another paper in this publication
provides recent evidence supporting iron supplementation during
pregnancy (26).
Maternal iodine deficiency leading to fetal hypothyroidism results in
cretinism, characterized by severe mental retardation (3). Thyroid
hormones are critical for normal brain development and maturation.
Manifestation of other features of cretinism (deafmutism, short stature
and spasticity) depends on the stage of
pregnancy when hypothyroidism develops. When it develops late in
pregnancy, the neurological damage is not as severe as when it exists early in
pregnancy. Cretinism is prevented by correcting maternal iodine deficiency before or during the first 3 mo of
pregnancy.
The World Health Organization estimates that 20 million people
worldwide have brain damage resulting from maternal iodine deficiency
that could be prevented by iodine supplementation (27). The recommended
iodine intake is 220 [mu]g/d during
pregnancy (12). The mean intake of U.S. women of childbearing age is [approximate]170 [mu]g/d, excluding iodine from iodized salt (5).
Endocrine regulation of lactation
The establishment and maintenance of human lactation are under the
influence of complex neuroendocrine control mechanisms (28). After
parturition, elevated levels of prolactin and withdrawal of estrogens
and progesterone results in the onset of milk secretion (lactogenesis).
The breasts must have undergone appropriate growth and development
beginning in puberty and completed during
pregnancy
for milk secretion to occur. The initiation of lactogenesis does not
require infant sucking but lactation cannot be maintained unless the
infant is put to the breast by 3 or 4 d postpartum. For the first 3-5 d
postpartum the mammary secretion is termed "colostrum." This early milk
is thick and straw-colored, rich in minerals and immune factors (i.e.,
lactoferrin and secretory immunoglobulin A) and low in lactose and total
protein. The concentration of lactose increases and that of sodium and
chloride decrease as milk secretion is enhanced. The characteristics of
mature milk are evident by day 10 of lactation.
With established lactation, prolactin is required for maintenance of
milk production. Prolactin release into the circulation from mammotrophs
in the anterior pituitary is in response to sucking. Prolactin
secretion is mediated by a transient decline in the secretion of
dopamine from the hypothalamus, which normally inhibits its secretion.
Milk secretion continues as long as the infant continues to nurse more
than once a day. The daily milk volume transferred to the infant
increases from [asymptotically =]50 mL on day 1 to 500 mL by day 5,
[asymptotically =]650 mL by 1 mo and 750 mL at 3 mo of lactation. Most
women can secrete considerably more milk than needed by a single infant.
Milk secretion is continuous and the quantity produced is principally
regulated by infant demand. Oxytocin release from the posterior
pituitary results from neural impulses reaching the hypothalamus caused
by sucking of the nursing infant. Circulating oxytocin causes
contraction of myoepithelial cells that surround mammary alveoli and
ducts, forcing milk into ducts of the nipple so that it can be removed
by the infant. This response is termed "milk ejection" or "let-down" and
can be initiated by the mere sight of the infant or by hearing the
infant cry. Continuation of lactation and associated hyperprolactinemia
inhibit ovarian activity by suppressing the pulsatile release of
luteinizing hormone and by interfering with the secretion of
gonadotropin-releasing hormone. This provides 98% protection from
pregnancy
during the first 6 mo of lactation if the nursing mother continues to
be amenorrheic (29). Milk secretion ceases in 1 or 2 d when infant
sucking or milk removal is terminated.
Nutritional needs during lactation
The nutritive demands of lactation are considerably greater than those of
pregnancy. In the first 4-6 mo of the postpartum period, infants double their birth weight accumulated during the 9 mo of
pregnancy. The milk secreted in 4 mo represents an amount of energy roughly equivalent to the total energy cost of
pregnancy. However, some of the energy and many of the nutrients stored during
pregnancy
are available to support milk production. The recommended intakes for
energy and specific nutrients during lactation are summarized in Table
2. Most of these recommended intakes are based on our knowledge of the
amount of milk produced during lactation, its energy and nutrient
contents and the amounts of maternal energy and nutrient reserves.
Recommended intakes during lactation are based on even less quantitative
data than recommendations during
pregnancy.
Lactation is viewed as successful when the fully breast-fed infant is
growing well and maintaining appropriate biochemical indexes of
nutritional status. The quantity of milk consumed by the infant and the
nutrient content of human milk under these circumstances are often used
as proxies to assess maternal nutritional adequacy during lactation. In
very few studies have specific measures of nutritional status been
applied to the lactating mother.
Human milk
feeding is adequate as the sole source of nutrition for up to age 6 mo
providing that the maternal diet and reserves are adequate and a
sufficient quantity is transferred to the infant. The composition of
human milk is exceedingly variable; nonetheless, such variance is
compatible with successful lactation. The Handbook of Milk Composition
provides comprehensive data on human milk composition and factors
capable of altering it (30). During lactation the mammary gland exhibits
metabolic priority for nutrients, often at the expense of maternal
reserves (31). Measurable differences in milk nutrient content due to
dietary intake can and do occur, most notably in the vitamin
constituents (32).
The recommended energy intake
during the first 6 mo of lactation is an additional 500 kcal under the
assumption that 170 kcal/d will be mobilized from energy stores
accumulated in
pregnancy. The energy demands of comparable periods of full lactation (780 mL/d) greatly exceed those of
pregnancy.
The recommended energy intake after 6 mo is reduced to an additional
400 kcal/d because milk production rates decrease to 600 mL/d. Few
studies have evaluated maternal nutrient adequacy, milk content and
infant nutrient indicators in the second half of the first year of
infancy and lactation.
As with energy, recommended intakes for several vitamins and minerals are similarly higher in lactation than in
pregnancy
(Table 2) with the notable exception of iron (12). The recommended iron
intake for women of reproductive age is 18 mg/d. Recommended iron
intakes for nonreproducing women were estimated based on basal losses
and menstrual losses. For lactating women, estimations were based on
basal losses, with the assumption that menstruation resumes at 6 mo,
plus the quantity secreted in milk. It is difficult to reconcile that
iron needs during lactation would be less than those of the
nonreproducing women considering that 16% of women of childbearing age
enter
pregnancy
with biochemical evidence of iron deficiency (ferritin concentration
<15 [mu]g/L) (12) and that in 1996, 29% of low income women were
anemic (hemoglobin concentration < 110 g/L), a prevalence rate that
has not changed since 1979 (32). Moreover, national data indicate that
one-fourth of all females of childbearing age failed to meet the
previous recommended intake of 15 mg/d, 2.5% less than the current
recommended amount (33). It may be prudent to factor in recovery of iron
stores and mitigation of iron deficiency after
pregnancy in formulating recommended iron intakes during lactation.
Available information on nutrients in milk that can be influenced by
maternal nutrition as well as nutrients associated with recognizable
deficiencies in breast-fed infants are summarized elsewhere (30,34). At
present our information about the role of dietary supplementation in
lactation, is limited. The available information, in large part, is from
studies conducted in early lactation. The nutritional demands of
lactation are directly proportional to intensity and duration, and
evaluation in early lactation may not bear on circumstances in late
lactation (>6 mo). The need for continued study is paramount now that
evidence exists that the initiation of breast-feeding and
breast-feeding to 6 mo in the United States have reached their highest
levels to date, 69.5% and 32.5%, respectively (35).
As is the case during
pregnancy,
nutrient density of the maternal diet assumes great importance during
lactation because the estimated increase in energy needs is less than
estimated increases in needs for other nutrients. At energy intakes less
than recommended, maternal intakes of calcium, magnesium, zinc, vitamin
B-6 and folate may be correspondingly low (30). The extent to which low
intakes of these and other nutrients affect the success of lactation
and long-term maternal and infant health has not been examined except
when a distinct nutritional deficiency is evident in the nursing infant,
for example, in vitamins D and B-12. A supplement of vitamin D (10
[mu]g/d) is recommended for women who avoid milk and other foods
fortified with vitamin D. Similarly, a supplement of vitamin B-12 (2.6
[mu]g/d) is recommended for lactating women who are complete vegetarians
(30). In addition, most studies have considered a single nutrient in
isolation. It is possible that limitations in one nutrient may be a
marker for other nutrient inadequacies (e.g., iron and folate
deficiencies often coexist) and focusing on one nutrient may limit our
understanding of nutrient-nutrient interaction.
Summary
Our knowledge of the effect of maternal dietary adequacy on the success
of reproduction is far from complete as is the role that dietary
supplement may play. Although few scientific studies furnish clear links
between maternal nutrient intakes from foods and supplements and
reproductive outcomes, there are indications that maternal nutritional
adequacy does influence performance indexes both in
pregnancy
and lactation. Birth weight and infant growth measures are the
principal indicators of reproductive success used in scientific studies
and these markers may not provide the needed sensitivity to assess the
influence of maternal nutrition. Moreover, the health and nutritional
status of the mother should be evaluated. Research is needed to identify
sensitive, noninvasive and specific biomarkers of functional
reproductive outcomes. This understanding is essential for the
development of meaningful public heath policies and recommendations
directed at reproducing women for ensuring appropriate nutrient intakes
from food and the safe and effective use of dietary supplements for
nutrients that are limited in the maternal diet.
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