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Nutrition and Multiple Gestation

Barbara Luke, ScD, MPH, RD

Multiple pregnancy represents a state of magnified nutritional requirements, resulting in a


greater nutrient drain on maternal resources and an accelerated depletion of nutritional
reserves. The accelerated starvation which occurs in pregnancy is exaggerated with a
multiple gestation, particularly during the second half of pregnancy, with more rapid
depletion of glycogen stores and resultant metabolism of fat between meals and during an
overnight fast. A reduced glucose stream from mother to fetus results in slower fetal
growth, smaller birth size, as well as a higher risk of preterm labor and preterm birth. For
this reason, diet therapy with a diabetic regimen of 20% of calories from protein, 40% of
calories from carbohydrate, and 40% of calories from fat may be particularly useful.
Iron-deficiency anemia has also been linked to preterm delivery and other adverse preg-
nancy outcomes. Mobilization of maternal iron stores, in addition to an adequate amount
and pattern of gestational weight gain (including BMI-specific weight gain goals by 20 and
28 weeks gestation), has been associated with significantly better fetal growth and longer
gestations in twin pregnancies. Supplementation with calcium, magnesium, and zinc, as
well as multivitamins and essential fatty acids may also reduce pregnancy complications
and improve postnatal health for infants born from a multiple gestation. Diet therapy for
women pregnant with multiples is an important component of effective prenatal care.
Semin Perinatol 29:349-354 © 2005 Elsevier Inc. All rights reserved.

KEYWORDS multiple pregnancy, diabetic diets, targeted supplementation

M ultiple pregnancy represents a state of magnified nutri-


tional requirements, resulting in a greater nutrient
drain on maternal resources and an accelerated depletion of
a physiologic perspective, the special nutritional demands of
a multiple pregnancy have important implications for the
mother’s future health. For example, when a woman has a
nutritional reserves. The majority of studies to date have multiple pregnancy in her 40s or 50s, she may be within only
evaluated the effects of nutritional factors on the course and a few years of menopause, and the substantial calcium drain
outcome of singleton pregnancies; the body of literature on may increase her risk for osteoporosis.1 The following chap-
multiple gestations is growing, but there are still many gaps ter summarizes current research on maternal pregravid
in our knowledge of normal and abnormal physiologic weight, gestational weight gain, carbohydrate metabolism,
changes and effective interventions. The population of iron status, and vitamin and mineral intake on fetal growth
women pregnant with multiple gestations is distinctly differ- and length of gestation in singletons, and when known, in
ent than the average pregnant woman in the United States twin and triplet gestations.
(Table 1). Over the past 20 years there has been a growing
trend in delaying pregnancy—this pattern is magnified
among women pregnant with multiples. Whereas the percent Carbohydrate Metabolism
of women ages 35 and older having a singleton baby has
increased threefold since 1980, the percent having twins has Pregnancy is a state of accelerated starvation, resulting in
increased nearly fourfold, and those having triplets or higher lower fasting glucose levels and an exaggeration of the
order births nearly sixfold. Although older maternal age may insulin response to eating. In twin pregnancies, these
be associated with better financial and social resources, from changes are magnified, particularly during the second half
of pregnancy, with significantly lower maternal serum glu-
cose and insulin concentrations, and higher plasma con-
University of Miami, School of Nursing and Health Studies, Coral Gables, centrations of ␤-hydroxybutyrate compared with maternal
FL.
Address reprint requests to Barbara Luke, ScD, MPH, RD, University of
concentrations in singleton pregnancies, indicating more
Miami, School of Nursing and Health Studies, 5801 Red Road, Coral rapid depletion of glycogen stores and resultant metabo-
Gables, FL 33143-3850. E-mail: BLuke@med.miami.edu lism of fat between meals and during an overnight fast.2

0146-0005/05/$-see front matter © 2005 Elsevier Inc. All rights reserved. 349
doi:10.1053/j.semperi.2005.08.004
350 B. Luke

Table 1 Live Births by Maternal Age, Birth Order, and Plurality, United States, 1980, 1990, and 2002
Percent of Births
by Maternal Age
Birth Order Number of Births by Maternal Age (years) (year)
and Year All Ages <20 20-24 25-29 30-34 35-39 >40 >30 >35 >40
First births
1980 1,545,604 435,333 605,183 371,859 112,964 18,241 2,024 8.6 1.3 0.1
1990 1,689,118 401,900 515,455 465,458 230,612 66,541 9,152 18.1 4.5 0.5
2002 1,594,921 343,210 472,976 378,647 276,110 102,180 21,798 25.1 7.8 1.4
All births
1980 3,612,258 562,330 1,226,200 1,108,291 550,354 140,793 24,290 19.8 4.6 0.7
1990 4,158,212 533,483 1,093,730 1,277,108 886,063 317,583 50,245 30.2 8.8 1.2
2002 4,021,726 432,808 1,022,106 1,060,391 951,219 453,927 101,275 37.5 13.8 2.5
Plurality
and Year
Singletons
1980 3,478,715 545,958 1,184,408 1,064,764 526,049 134,294 23,242 19.7 4.5 0.7
1990 4,061,319 525,793 1,072,431 1,246,144 860,478 307,498 48,975 30.0 8.8 1.2
2002 3,889,191 425,880 998,739 1,028,038 911,431 430,447 94,656 36.9 13.5 2.4
Twins
1980 68,339 7,212 21,374 22,712 12,944 3,559 538 24.9 6.0 0.8
1990 93,865 7,605 20,945 30,020 24,466 9,587 1,242 37.6 11.5 1.3
2002 125,134 6,835 22,856 30,725 36,956 21,637 6,125 51.7 22.2 4.9
Triplets and more
1980 1,337 83 385 474 321 67 7 29.5 5.5 0.5
1990 3,028 85 354 944 1,119 498 28 54.3 17.4 0.9
2002 7,401 93 511 1,628 2,832 1,843 494 69.8 31.6 6.7
All multiples
1980 69,676 7,295 21,759 23,186 13,265 3,626 545 25.0 6.0 0.8
1990 96,893 7,690 21,299 30,964 25,585 10,085 1,270 38.1 11.7 1.3
2002 132,535 7,771 23,367 32,353 39,788 23,480 6,619 52.7 22.7 5.0

Both fasting and ketonuria have been linked to an increase Table 2). We have found in studies with both twins and
in preterm labor and preterm delivery, a phenomenon triplets5,6 that diet therapy with 20% of calories from pro-
termed the “Yom Kippur effect.”3 A reduced glucose tein, but a lower percentage of calories from carbohydrate
stream from mother to fetus results in slower fetal growth, (40%) for better glycemic control, and a higher percentage
smaller birth size, and an increased risk of fetal growth of calories from fat (40%), to provide additional calories
restriction.4 The diet therapy we have used successfully in with less bulk, are most effective. The emphasis is also on
both twin and triplet pregnancies5,6 is based on the dia- the use of low glycemic index carbohydrates to prevent
betic regimen of three meals and three snacks per day (see wide fluctuations in blood glucose concentrations.

Table 2 BMI-Specific Dietary Recommendations for Twin Gestations*


BMI Group Underweight Normal Weight Overweight Obese
BMI Range <19.8 19.8-26.0 26.1-29.0 >29.0
Calories 4,000 3,500 3,250 3,000
Protein (20% of calories) 200 g 175 g 163 g 150 g
Carbohydrate (40% of calories) 400 g 350 g 325 g 300 g
Fat (40% of calories) 178 g 156 g 144 g 133 g
Exchanges (Servings) per day
Dairy 10 8 8 8
Grains 12 10 8 8
Meat & meat equivalents 10 10 8 6
Eggs 2 2 2 2
Vegetables 5 4 4 4
Fruits 8 7 6 6
Fats & oils 7 6 5 5
*Adapted from Luke et al.5
Nutrition and multiple gestation 351

Iron Status demands of pregnancy may exceed one gram, with nearly
half this amount in the red cell mass increase in blood vol-
Iron-deficiency anemia is also significantly associated with ume, the maternal preconceptional and early pregnancy iron
preterm delivery.7-9 Serum ferritin levels, which are lowered status are extremely important. Severe maternal iron-defi-
with iron-deficiency and elevated in the presence of infec- ciency anemia leads to placental adaptive hypertrophy, a fall
tion, have also been linked to prematurity. Extremes of ma- in the cortisol metabolizing system, and increased suscepti-
ternal serum ferritin levels measured early in the second tri- bility to hypertension in later life.
mester (15-17 weeks), as well as elevated levels at 24, 26, or
28 weeks, have been associated with preterm birth.10,11 It has
been shown that, when elevated third trimester serum ferritin Calcium, Magnesium,
levels reflect a failure to decline from entry to care, they are and Zinc Supplementation
significantly associated with preterm and very preterm birth,
with iron-deficiency anemia and poor maternal nutritional Calcium, magnesium, and zinc have been identified by the
status underlying the relationship.11 Dietary sources of iron World Health Organization as having the most potential for
are preferable, particularly heme-iron-rich sources such as reducing pregnancy complications and improving out-
red meat, pork, poultry, fish, and eggs, because of better comes.16,17 Results of calcium supplementation trials among
absorption and utilization, their positive effect on nonheme high-risk women have been promising, with significant re-
iron bioavailability, and their high quality and quantity of ductions in preterm deliveries among teenagers and women
protein and other nutrients. The inclusion of nonheme-iron with low calcium diets.18,19 Other studies have shown incon-
sources is encouraged as well, such as iron-fortified breads sistent results in lowering the rates of pregnancy-induced
and grains, vegetables, and nuts. hypertension, and no effect on preterm delivery and small-
The few studies that have evaluated iron status in multiple for-gestational age births.20,21 The ability of supplemental cal-
pregnancies have reported lower hemoglobin levels in the cium to decrease the risk of preterm delivery may be confined
first and second trimesters, higher rates of iron-deficiency to high-risk populations where there is either a severe dietary
anemia, and even residual iron-deficiency anemia in the in- restriction of calcium or, as in the case of adolescents and
fants, up to 6 months of age.12-14 Hediger and Luke15 evalu- multiple gestations, an increased physiologic demand for cal-
ated the hemodynamics during twin pregnancy and the as- cium. Similar inconsistent results have also been reported in
sociation of hemoglobin (Hgb) and hematocrit (Hct) levels studies of magnesium supplementation, which may have
with maternal nutritional status and twin outcome. Serial been due to differences in study design, study populations,
measures of iron status (Hgb, Hct) and measures of maternal and the concurrent use of other medications. Magnesium,
nutritional status, including weight gain, were collected for though, may have a neuroprotective role, particularly for the
293 twin pregnancies. As in singleton pregnancies, levels of premature infant, in addition to being an effective therapy for
Hgb and Hct declined through the first trimester to a nadir at preeclampsia. Although maternal zinc nutriture has been sig-
20 to 24 weeks. Consistent with greater volume expansion in nificantly related to length of gestation, infection, and risk of
twin pregnancies, the levels were even lower in the second premature rupture of membranes,22,23 clinical trials of zinc
trimester than for singleton pregnancies. By the third trimes- supplementation have yielded equivocal results.24 A trial that
ter, lower levels of serum ferritin (indicating better volume randomly supplemented only women with plasma zinc levels
expansion) were associated with pregravid BMI (⫺0.50 ⫾ below the median reported an increase in length of gestation
0.21 ␮g/L per kg gain, P ⫽ 0.02) and rate of weight gain to 20 of approximately 0.5 week and an increase in birth weight
weeks (⫺11.6 ⫾ 5.0 ␮g/L per kg weight gain, P ⫽ 0.02). As (about half of which was explained by the longer duration of
shown in prior studies, both maternal pregravid BMI and rate gestation).25 To date, there have been no mineral supplemen-
of weight gain before 20 weeks are consistently strong pre- tation trials with twin pregnancies. Scholl, Hediger, and co-
dictors of twin birth weight outcomes. Mean levels by trimes- workers26 reported that a low dietary zinc intake during sin-
ter are shown in Table 3. gleton pregnancy (ⱕ6 mg/d or ⬍40% of the RDA for
Iron status during pregnancy has also been linked to fetal pregnancy) was associated with an increased incidence of
programming and the development of chronic disease. Low iron-deficiency anemia at entry to care, a lower use of prena-
maternal hemoglobin is strongly related to the development tal supplements during pregnancy, and a higher incidence of
of a large placenta and high placental/birth weight ratio, inadequate weight gain during pregnancy and an increased
which is seen as predictive of long-term programming of risk of LBW, preterm delivery, and early preterm delivery.
hypertension and cardiovascular disease. Because the iron The joint effect of iron-deficiency anemia at entry to care and
a low dietary zinc intake during pregnancy increased risk of
preterm delivery fivefold.
Table 3 Changes in Maternal Iron Status in Twin Pregnancy
First Second Third
Trimester Trimester Trimester Multivitamin and
Hemoglobin 12.8 g/dL 11.3 g/dL 11.0 g/dL Multimineral Supplementation
Hematocrit 37.3% 32.8% 32.0% Ideally, pregnant women should get the level and range of
Ferritin 56.6 ␮g/L 34.3 ␮g/L 12.2 ␮g/L
required nutrients through a balanced diet. Recent national
352 B. Luke

dietary surveys indicate, though, that adult women fail to Maternal Weight Gain
meet the RDAs for five nutrients: calcium, magnesium, zinc,
and vitamins E and B6.27 In addition, prenatal use of vitamin- The pattern of maternal weight gain has been shown to be as
mineral supplements among low-income women has been important as total weight gain in its effect on birth weight in
both singleton and twin pregnancies. Although the increase
shown to reduce the risks of preterm delivery and low birth
in fetal weight is greatest during the third trimester (after 28
weight, particularly if initiated during the first trimester.28
weeks), gains during mid-gestation (either second trimester
Supplementation in excess of twice the recommended dietary
or 20-28 weeks) have the strongest association with birth
allowance (RDA) should be avoided, due to the potential for
weight. In singletons, Abrams and Selvin33 demonstrated that
birth defects. The fat-soluble vitamins, particularly vitamins birth weight increased in each trimester by 18 g, 33 g, and
A and D, are the most potentially toxic during pregnancy. 17 g, respectively, per kilogram per week of maternal weight
The pediatric and obstetric literature includes case reports of gain. Scholl, Hediger and coworkers34 reported that weight
kidney malformations in children whose mothers took be- gains to 20 weeks and to 28 weeks were most strongly related
tween 40,000 and 50,000 IU of vitamin A during pregnancy. to birth weight, contributing 22 to 24 g to birth weight per
Even at lower doses, excessive amounts of vitamin A may kilogram per week of maternal weight gain. In addition, a low
cause subtle damage to the developing nervous system, re- rate of weight gain or a poor pattern of weight gain is associ-
sulting in serious behavioral and learning disabilities in later ated with an increased risk of preterm birth. Studies in twins
life. The margin of safety for vitamin D is smaller for this by our research team have shown similar results, with low
vitamin than for any other. Birth defects of the heart, partic- weight gains consistently associated with reduced birth-
ularly aortic stenosis, have been reported in both humans weights. Early- and mid-gestation weight gains seem to exert
and experimental animals with doses as low as 4000 IU, an even greater effect on twin birthweights, with gains to 20
which is 10 times the RDA (Recommended Dietary Allow- weeks, between 20 to 28 weeks, and from 28 weeks to birth
ance) during pregnancy. increasing birthweights by 65 g, 37 g, and 16 g, respectively,
per kilogram per week of maternal weight gain.35-37
BMI-specific weight gain guidelines are associated with the
best intrauterine growth and subsequent birthweights, and
Essential Fatty longer length of gestation.38,39 Advice regarding weight gain
Acid Requirements and target weight gain goals is important underlying factors
There is an established maternal drain of the essential fatty strongly associated with actual weight gain. But studies
among women pregnant with singletons40,41 and twins42 have
acids during pregnancy, particularly during multiple gesta-
reported that more than one-fourth of women receive no
tion.29,30 Additional supplementation with omega-3 fatty ac-
advice regarding weight gain. Among women who do receive
ids, which are vital for neurological and retinal development,
guidance, for more than one-third of women, the advice they
may be particularly beneficial during pregnancy for both the
receive is inappropriate.40 In a study by our research team of
mother and her developing baby. Because many of the food 928 women who had been delivered of twins,42 those women
sources of omega-3 fatty acids may be contaminated with who received nutrition advice from a registered dietitian were
environmental pollutants such as lead or mercury, supple- the most likely to have the highest weight gains (60% gained
ments may be a safer alternative. Populations with a higher ⱖ40 lbs, with an average gain of 46.3 lbs) and the lowest
intake of omega-3 fatty acids have significantly lower rates of proportion of very low birth weight infants (2% versus 12%
preterm delivery and low birth weight.31 Infants whose for women not receiving any advice). We have developed
mothers had higher omega-3 fatty acid levels at birth dem- BMI-specific guidelines for twins based on optimal rates of
onstrated better cognitive development.32 Many prenatal fetal growth birthweights between the singleton 50th percen-
supplements are now incorporating omega-3 fatty acids in tile and twin 90th percentile at 36 to 38 weeks (2700-2800
their formulation. g)43 (Table 4).

Table 4 Optimal Rates of Maternal Weight Gain and Cumulative Gain by Pregravid BMI Status*
Rates of Weight Gain (lbs/week) Cumulative Weight Gain (lbs)
0-20 20-28 28 weeks- to to to
Pregravid BMI weeks weeks delivery 20 weeks 28 weeks 36-38 weeks
Underweight (BMI <19.8) 1.25-1.75 1.50-1.75 1.25 25-35 37-49 50-62
Normal Weight (BMI 19.8-26.0) 1.0-1.50 1.25-1.75 1.0 20-30 30-44 40-54
Overweight (BMI 26.1-29.0) 1.0-1.25 1.0-1.50 1.0 20-25 28-37 38-47
Obese (BMI >29.0) 0.75-1.0 0.75-1.25 0.75 15-20 21-30 29-38
*Adapted from Luke et al.43
BMI, body mass index.
Results are from models controlling for diabetes and gestational diabetes, preeclampsia, smoking during pregnancy, parity, placental
membranes, and fetal growth before 20 weeks.
Nutrition and multiple gestation 353

and extended overnight fast in twin gestation. Am J Obstet Gynecol


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