Clinical Expert Series
Continuing medical education is available online at www.greenjournal.org
Optimal Nutrition for Improved Twin
Pregnancy Outcome
William Goodnight,
MD, MSCR,
and Roger Newman,
MD,
for the Society of Maternal–Fetal Medicine
Twin pregnancies contribute a disproportionate degree to perinatal morbidity, partly because of
increased risks of low birth weight and prematurity. Although the cause of the morbidity is
multifactorial, attention to twin-specific maternal nutrition may be beneficial in achieving optimal
fetal growth and birth weight. Achievement of body mass index (BMI)-specific weight gain goals,
micronutrient and macronutrient supplementation specific to the physiology of twin gestations, and
carbohydrate-controlled diets are recommended for optimal twin growth and pregnancy outcomes.
The daily recommended caloric intake for normal-BMI women with twins is 40 – 45 kcal/kg each day,
and iron, folate, calcium, magnesium, and zinc supplementation is recommended beyond a usual
prenatal vitamin. Daily supplementation of docosahexaenoic acid and vitamin D should also be
considered. Multiple gestation-specific prenatal care settings with a focus on nutritional interventions
improve birth weight and length of gestation and should be considered for the care of women
carrying multiples. Antepartum lactation consultation can also improve the rate of postpartum
breastfeeding in twin pregnancies. Twin gestation-specific nutritional interventions seem effective in
improving the outcome of these pregnancies and should be emphasized in the antepartum care of
multiple gestations. This review examines the available evidence and offers recommendations for
twin pregnancy-specific nutritional interventions.
(Obstet Gynecol 2009;114:1121–34)
T
he increasing rate of twin gestations is well documented. Twin gestations account for a disproportionate share of neonatal morbidity, with increased
From the Departments of Obstetrics and Gynecology, Division of Maternal–Fetal
Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North
Carolina; and Medical University of South Carolina, Charleston, South Carolina.
The practice of medicine continues to evolve and individual circumstances will
vary. This opinion reflects information available at the time of its acceptance for
publication, and is neither designed nor intended to establish an exclusive
standard of care. This publication is not expected to reflect the opinions of all
members of the Society for Maternal–Fetal Medicine.
Continuing medical education for this article is available at http://links.lww.
com/AOG/A130.
Corresponding author: William Goodnight, MD, MSCR, Department of
Obstetrics and Gynecology, Division of Maternal–Fetal Medicine, University of
North Carolina at Chapel Hill, 3010 Old Clinic Building/CB# 7516; Chapel
Hill, NC 27599-7516; e-mail: [email protected].
Financial Disclosure
The authors did not report any potential conflicts of interest.
© 2009 by The American College of Obstetricians and Gynecologists. Published
by Lippincott Williams & Wilkins.
ISSN: 0029-7844/09
VOL. 114, NO. 5, NOVEMBER 2009
risks of preterm birth, low birth weight, and intrauterine growth restriction. Infants of multiple births represent 3% of all deliveries but account for 15% of
preterm birth, 20% low birth weight (LBW; less than
2,500 g), and 19 –24% of very low birth weight (less
than 1,500 g) neonates born in the United States.
Optimal twin survival has been demonstrated to be
associated with birth weights more than 2,850 g and
delivery after 36 weeks gestational age.1–3 Unfortunately, twins often deliver with average birth weights
between 2,300 g and 2,600 g at a mean gestational age
of 35 weeks to 36 weeks. Impaired fetal growth is also
associated with long-term complications, including an
increased lifetime risk of cardiovascular disease and
obesity. Neonatal body composition in appropriately
grown twin gestations is similar to singleton neonates,
whereas small for gestational age twins have a lower
lean body mass, a lower fat mass, and a trend to lower
bone density compared with small for gestational age
singleton neonates.4
OBSTETRICS & GYNECOLOGY
1121
Maternal pregestational and gestational nutritional status in singleton pregnancies without question
is associated with pregnancy outcome. The nutritional
demands of pregnancy are magnified by the presence
of multiple fetuses, and the potential beneficial impact
of optimal nutrition on pregnancy outcomes should
not be underestimated. Thus, the nutritional recommendations for singleton pregnancy require specific
adaptation for a multifetal gestation. The nutritional
competition engendered by the presence of multiple
fetuses results in the accelerated depletion of maternal
nutritional reserves.5 Although monochorionic twin
pregnancies carry a greater risk of the above adverse
pregnancy outcomes than dichorionic twins, there are
similar rates of selective intrauterine growth restriction between monochorionic and dichorionic twins.6
The overall risk of fetal growth restriction in twin
pregnancies creates a situation where modification of
nutritional intake has a greater opportunity to positively influence the outcome for twins compared with
singleton gestations. This article will suggest specific
maternal nutritional recommendations for twin pregnancy based on available scientific evidence.
The goals for optimization of maternal nutrition
in multiple gestations therefore include
1.
2.
3.
4.
optimizing fetal growth and development,
reducing incidence of obstetric complications,
increasing gestational age at delivery, and
avoiding excess maternal weight gain that could
result in unnecessary postpartum weight retention.
PHYSIOLOGIC ADAPTATIONS TO TWIN
PREGNANCY
Multifetal gestations undergo significant maternal
physiologic adaptations beyond the usual pregnancy
changes, including increased plasma volume, increased basal metabolic rate, and increased resistance
to carbohydrate metabolism. The blood volume in a
twin gestation increases by 50 –70% by 20 weeks of
gestation, with only a 25% increase in erythrocytes.7
This plasma volume expansion results in decreased
concentrations of hemoglobin, albumin, and watersoluble vitamins, whereas increases in fat-soluble vitamins, triglycerides, cholesterol, and free fatty acids
have been demonstrated.7 The relatively greater increase in plasma volume in a twin pregnancy also
results in a dilutional effect on red blood cells in the
second and third trimesters of pregnancy.8
The resting energy expenditure is an indicator of
maternal basal metabolic rate that can be used to
estimate energy requirements. The maternal resting
1122
Goodnight and Newman
Twin Nutrition
energy expenditure increases each trimester in both
singleton and multiple gestations.9 Singagawa et al9
demonstrated that compared with singleton pregnancies, maternal resting energy expenditure increased
by 10% in twin pregnancies, independent of changes in
minute ventilation. The increase in resting energy expenditure can also be seen as a result of the increased
mass of maternal tissues, including the breast, uterus,
body fat, and muscle as well as the increase in blood
volume. Such an increase in resting energy expenditure
can result in a 40% increase in caloric requirements for
twin gestations.
The relatively larger placental mass in multiple
gestations results in an increase in placental steroid
and hormone production.7 As a result, multifetal
gestation has been described as a state of “accelerated
starvation,” in which the development of starvation
ketosis occurs at a more rapid rate in twin gestations
than in a singleton pregnancy. These hormonally
driven metabolic changes result in remarkable maternal carbohydrate use, resulting in a greater propensity
for depletion of maternal hepatic glycogen stores and
the development of maternal ketonemia. Casele et
al10 demonstrated that women with twin gestations fed
a diet of 40 kcal/kg ideal body weight, divided into
three meals, are more susceptible to the development
of ketosis after fasting, as evidenced by elevated
␤-hydroxybutyrate serum levels after an evening fast
compared with singleton gestations. Classically, the
United States Department of Agriculture (USDA),
Institute of Medicine (IOM), and American Dietetic
Association (ADA) recommendations for reproductive age women suggest that 45– 65% of calories daily
be derived from carbohydrates,11 a diet that has been
suggested to result in poor glycemic control and
excess weight gain in twin gestations.12 Luke et al12
demonstrated that a diet composed of 40% carbohydrates and a greater percentage of fats and protein
with an appropriate caloric intake (3,000 – 4,000
kcal/d in underweight to normal weight women)
achieved a greater degree of euglycemia during pregnancy. Other limited trials also suggest that a lower
proportion of carbohydrates in the diet in women with
gestational diabetes is associated with improved glycemic control, as evidenced by lower insulin utilization.
DIETARY COMPOSITION
Although no established nutritional guidelines exist,
an estimate of individual macronutrient requirements
for twins is described in Table 1. These recommendations are based on extrapolation of the singleton
recommended dietary allowances (RDA) published
OBSTETRICS & GYNECOLOGY
Table 1. Suggested Daily Diet Composition for Twin Gestation by Maternal Prepregnancy Body Mass
Index14
Calories (kcal)
Protein (g)*
Carbohydrate (g)*
Fat (g)†
Underweight
Normal Weight
Overweight
Obese
4,000
200
400
178
3,000–3,500
175
350
156
3,250
163
325
144
2,700–3,000
150
300
133
* 4 kcal/g.
†
9 kcal/g.
by the Food and Nutrition Board of the National
Research Council and body mass index (BMI)-specific recommendations for twin gestations published
by Luke and coworkers. Luke et al12 have proposed a
dietary composition for twins in which energy intake
is derived 20% from protein, 40% from low-glycemic
index carbohydrates, and 40% from fat (Table 1). Due
to the increased nutritional demands of the fetus and
maternal metabolism, these recommendations equate
to a daily intake of 3,500 calories, composed of a diet
with 175 g protein, 350 g of carbohydrate, and 156 g
of fat per day for women of normal prepregnancy
BMI. Adequate protein intake is essential to normal
fetal growth in twin gestations. In singleton pregnancies, the protein storage during pregnancy has been
estimated to be 925 g, distributed as 400 g to the fetus,
100 g to the placenta, and 425 g additional stored in
the mother.7 Inadequate protein intake can occur
secondary to insufficient dietary intake, intake of poor
quality protein (high fat meats), or inadequate caloric
intake, which results in dietary protein being diverted
to meet maternal energy requirements.12 Reduced
amino acid availability to the fetus not only affects fetal
growth but may also restrict placental growth, further
compounding the effect of protein deficiency.12 Additionally, Moore et al13 evaluated maternal diet composition and the effect on neonatal weight and ponderal
index. The percentage of energy from protein (14.4 –
18.1% in this study) in early pregnancy had the best
positive association with neonatal weight, whereas the
percentage of energy from carbohydrates (45.3–53.2%
in this sample) was inversely proportional to the pon-
deral index (increased carbohydrates resulted in neonatal thinness).13 Ideal protein sources include lean
meat, fish, and skin-free poultry, eggs, dried beans,
peas, and tofu. An emphasis on low to medium
glycemic index carbohydrates (such as brown rice,
whole wheat/multigrain bakery products and pastas,
boiled potatoes, green vegetables, beans, and lentils)
is also suggested to further reduce the potential for
wide serum glucose fluctuations. To gain the necessary calories, the proportion of caloric rich fats is
substituted for carbohydrates.14 Table 2 suggests the
number of serving suggestions daily to achieve this
diet composition and caloric requirements.14 This
dietary intake should be divided into three main
meals with three smaller snacks interposed in the
usual meal schedule to help reduce the development
of hypoglycemia and transient ketosis.14 In underweight women (BMI less than 19.8 kg/m2) and those
with poor weight gain in pregnancy, addition of
higher fat, calorie-rich foods, including nutritional
supplement drinks, whole or 2% milk, fruit juices, and
the change to five balanced meals per day can achieve
the necessary weight gain. Similarly, excessive weight
gain in pregnancy should lead to a reduction in these
high fat, calorie-dense foods.
WEIGHT GAIN
Total maternal weight gain and the timing of weight
gain are crucial to optimal fetal growth in twin
gestations. The preponderance of the evidence in
singleton gestations is that there is a relationship
between increasing maternal weight gain and in-
Table 2. 2002 American Dietetic Association Serving Suggestions for Multiple Pregnancy of Normal Body
Mass Index
Daily
servings
Serving
suggestion
Milk/Yogurt/
Cheese
Meat/Poultry/
Fish/Eggs
Vegetable
Fruit
Bread/Cereal/
Rice/Pasta
3
3
3
2
6
2–3 oz lean meat,
fish, poultry;
1 egg
1 cup raw/cooked
vegetables; 2 cups raw
green leafy vegetables
1 cup fruit; cup
dried fruit
1 slice bread; 1 cup ready
to eat cereal; cup
cooked rice/pasta
1 cup milk; 1
oz cheese
VOL. 114, NO. 5, NOVEMBER 2009
Goodnight and Newman
Twin Nutrition
1123
creases in birth weight, with a corresponding reduction in the incidence of low birth weight. The published literature also suggests that low maternal
weight gain superimposed on a low maternal pregravid weight compounds the adverse affects of each,
resulting in high rates of both low birth weight
delivery and premature birth. The effect of low
maternal weight gain is diminished in women with
higher pregravid weights. Historically, weight gain
recommendations were made to reduce the risk of
LBW, with contemporary recommendations made to
achieve optimal fetal growth without excess maternal
weight gain. Early retrospective studies attempted to
define the appropriate maternal weight gain for twin
gestations based on optimal neonatal outcomes. Pederson et al15 demonstrated that optimal twin pregnancy outcome, defined as two living infants, each
more than 2,500 g, born after 37 weeks estimated
gestational age, and 5-minute Apgar score more than
7 was associated with a maternal weight gain of 20 kg
(44 lb). Less than optimal outcomes were seen with
maternal weight gains less than 16.8 kg (37 lb).15 The
timing and the rate of maternal weight gain also affect
both birth weight and prematurity. Midgestational
maternal weight gains seem to have the greatest effect
on fetal growth and ultimate birth weight.16,17 Optimal
twin outcomes (birth weight more than 2,500 g) have
been associated with maternal weight gain of 24 lb by
24 weeks of gestation.16,18 Even when there is appropriate catch-up maternal weight gain after 24 weeks, a
low rate of weight gain before 24 weeks (less than 0.85
lb/wk) was strongly associated with poor intrauterine
growth and earlier delivery.16,18,19 In studies making
use of serial ultrasonographic measures of fetal
growth in relation to maternal weight gain, it has been
demonstrated that early maternal weight gain (less
than 20 weeks) and midpregnancy weight gain (20 –28
weeks) significantly enhanced the rates of fetal growth
between 20 weeks and 28 weeks and from 28 weeks
until birth.20 As noted in singleton gestations, this
influence of early maternal weight gain on subsequent
fetal growth was most pronounced in underweight
women. Physiologically, this relationship suggests that
early weight gain results in improved maternal nutrient
stores that become important later in pregnancy as a
nutrient reserve when fetal demands begin to increase.
Adequate early maternal weight gain may also enhance
placental growth, which helps to sustain an adequate
nutrient supply to the twins later in pregnancy.
Luke et al21 suggested weight gain goals for twin
pregnancy based on maternal prepregnancy BMI.
Optimal maternal weight gain and timing of weight
gain were modeled based on ideal fetal growth and
1124
Goodnight and Newman
Twin Nutrition
newborn birth weights determined to be between the
singleton 50th and twin 90th percentiles by 38 weeks
of gestation. Among twins achieving these optimal
fetal growth and birth weights, the associated maternal BMI-specific weight gains were found to be
described by the maternal weight gain curves noted in
Figure 1.21 In a follow-up study of the effects of using
these BMI-specific weight gain recommendations,
twin gestations that failed to achieve BMI-specific
weight gain goals demonstrated a lower birth weight
by nearly 200 g (P⬍.001) and a 1.04-week shorter
length of gestation (P⫽.02) (Goodnight W, Hill E,
Newman R, Rowland A. Achieving maternal BMIspecific weight gain goals improves birthweight and
gestational age at delivery in twin pregnancies [abstract]. Am J Obstet Gynecol 2006;195:S121). Based
in part on this new data, the 2009 IOM guidelines for
weight gain in twin pregnancy now recommend BMIspecific weight gains for normal weight women of
17–25 kg (37–54 lb), overweight women, 14 –23 kg
(31–50 lb), and obese women, 11–19 kg (25– 42 lb).22
The small differences from Luke et al are based on
different BMI categories used in the IOM recommendations. In practice, we continue to use the graphs
created by Luke et al to track and recommend
maternal weight gain during pregnancy.
Determinants of maternal weight gain in pregnancy have not been extensively studied in multiple
gestations but are likely influenced by multiple biologic, behavioral, cultural, and psychosocial factors.
Wells et al23 demonstrated in a retrospective analysis
that maternal obesity and hypertension are associated
with a greater risk for weight gain above the IOM
recommended weight gains, whereas diabetes was not
associated with excessive or below IOM weight gain
goals, and prior live births was associated with lower
risk of excessive maternal weight gain in pregnancy.
Initial physician counseling is thus necessary to determine maternal perceptions of weight gain goals, review potential maternal risk factors for excessive or
poor weight gain, and provide education and support
to achieve optimal weight gain goals.
Although it is well established that increased maternal weight gain in pregnancy increases birth weight in
twins, the long-term effects of retained maternal weight
after delivery remains of concern. Although not extensively evaluated in multiple gestations, excessive maternal weight gain in pregnancy may be associated with
increased risks of gestational hypertension, cesarean
delivery, and birthweight more than 4,000 g (rare in
twins).24 The weight gain recommendations for twin
pregnancy have been criticized for potentially contributing to the risk of maternal obesity through postpartum
OBSTETRICS & GYNECOLOGY
30
28.1 (62 lb)
30
22.2 (49 lb)
20
22.7 (50 lb)
15.9 (35 lb)
15
10
16.8 (37 lb)
11.3 (25 lb)
5
0
A
38
13.6 (30 lb)
13.6 (30 lb)
10
5
18.1 (40 lb)
9.1 (20 lb)
20
28
Gestational age (weeks)
38
16.8 (37 lb)
15
17.2 (38 lb)
11.3 (25 lb)
12.7 (28 lb)
10
9.1 (20 lb)
Weight gain (kilograms)
25
20
C
15
30
21.3 (47 lb)
0
20
B
25
5
20.0 (44 lb)
0
20
28
Gestational age (weeks)
30
Weight gain (kilograms)
24.5 (54 lb)
25
Weight gain (kilograms)
Weight gain (kilograms)
25
20
10
5
38
9.1 (20 lb)
13.2 (29 lb)
9.5 (21 lb)
0
20
28
Gestational age (weeks)
17.2 (38 lb)
13.6 (30 lb)
15
D
6.8 (15 lb)
20
28
Gestational age (weeks)
38
Fig. 1. Body mass index-specific weight gain goals. A. Maternal weight gain in kilograms for underweight prepregnancy
body mass index (BMI) (BMI less than 19.8 kg/m2). B. Maternal weight gain in kilograms for normal prepregnancy BMI (BMI
19.8 –26 kg/m2). C. Maternal weight gain in kilograms for overweight prepregnancy BMI (BMI 26.1–29 kg/m2). D. Maternal
weight gain in kilograms for obese prepregnancy BMI (BMI more than 29 kg/m2). Modified from Luke B, Hediger ML, Nugent
C, Newman RB, Mauldin JG, Witter FR, et al. Body mass index-specific weight gains associated with optimal birth weights
in twin pregnancies. J Reprod Med 2003;48:217–24.
Goodnight. Twin Nutrition. Obstet Gynecol 2009.
retention of the weight gain. Luke et al (Luke B, Hediger
ML, Min L, Nugent C, Newman RB, Hankins GD, et al.
The effect of weight gain by 20 weeks’ gestation on twin
birthweight and maternal postpartum weight [abstract].
Am J Obstet Gynecol 2006;195:S85), however, demonstrated that the mean weight retention for those who
gained within the recommended BMI specific weight
gain goals was only 1.5 lb at 6 weeks postpartum,
minimally above the 0.9 lb weight retention seen in
those with maternal weight gain below the BMI-specific
weight gain goals. In singleton pregnancy, long-term
maternal weight (15 years postpartum) was equivalent
among women who gained below or within IOM
recommendations, with excessive maternal weight gain
in pregnancy associated with higher long-term weight
gain.25 Thus, in the multiple gestation clinical situation,
attention should be given to both achievement of the
recommended maternal weight gain goals and serial
VOL. 114, NO. 5, NOVEMBER 2009
assessment of weight gain and equal intervention to
prevent or slow excessive weight gain.
MICRONUTRIENTS
Recommendations for micronutrient intake are determined by the Food and Nutrition Board of the
Institute of Medicine. Dietary Reference Intakes have
replaced the RDA estimates. The RDA recommendations were determined to estimate the intake
needed to meet the needs of 97–98% of the population, whereas an Adequate Intake is estimated to
cover the needs for all individuals in a specific group.
These estimates are supplemented by the Tolerable
Upper Intake Levels, an estimate of the maximal
intake level that should not cause harm. Nutrients
such as magnesium, calcium, and zinc are often
lacking in women’s diets and may have effects on fetal
growth and preterm delivery. In a randomized, pla-
Goodnight and Newman
Twin Nutrition
1125
cebo controlled clinical trial in 2004, Hininger et al26
demonstrated that micronutrient supplementation (vitamin C 60 mg, B-carotene 4.8 mg, vitamin E 10 mg,
thiamin 1.4 mg, riboflavin 1.6 mg, niacin 15 mg,
pantothenic acid 6 mg, folic acid 200 microgram,
cobalamin 1 microgram, zinc 15 mg, magnesium 87.5
mg, and calcium carbonate 100 mg) in pregnancy
resulted in a 10% improvement in birth weight
(3,300⫾474 g compared with 3,049⫾460 g, P⫽.03)
and a reduction in birth weight below 2,700 g among
singleton pregnancies. There are fewer data available
on micronutrient supplementation in twin pregnancies. However, the expectation would be that similar
or greater benefits may be expected because micronutrient needs are greater and deficiencies may be
more common in multiple gestations. Because twin
gestations are at increased risk for poor fetal growth
and preterm birth, small improvements from benign
interventions such as micronutrient supplementation
may have significant benefits.
Although the majority of micronutrient supplements have a wide safety margin, notable potentially
adverse complications may arise from excessive micronutrient supplementation. Excessive doses of vitamin A (at least more than 10,000 international units/d
and probably more than 25,000 international units/d)
in pregnancy have been associated with fetal anomalies, including anomalies of the cardiovascular system,
face and palate, ears, and genitourinary tract; thus, the
maximal recommended vitamin A supplement in
pregnancy is 8,000 international units/d. Excessive
supplementation of most other vitamins can result in
gastrointestinal disturbances but seem without teratogenic effect.
CALCIUM AND VITAMIN D
During in utero life, the fetus accumulates 25–30 g of
calcium, the majority of which occurs in the third
trimester.27 Calcium is made available to the fetus by
extraction from maternal bone mass and through
increased maternal intestinal absorption.27 Maternal
calcium is also lost in pregnancy because of an
increase in urinary calcium excretion.28 An estimated
200 –300 mg/d increase in calcium intake above
prepregnancy requirements is thus required to meet
the fetal demands and maintain maternal calcium
homeostasis.28 During lactation, there is a reduction in
urinary calcium excretion.28 However, the majority of
pregnant women do not consume diets with an adequate calcium intake. Food sources for calcium are
primarily milk and dairy products, with some calcium
in green leafy vegetables such as kale and turnip
greens, with approximately one third of ingested
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Goodnight and Newman
Twin Nutrition
calcium being absorbed. The IOM recommends a
calcium intake in pregnancy of 1,000 –1,300 mg daily
(Tolerable Upper Intake Levels 2,500 mg). A Cochrane review of calcium supplementation of at least
1,000 mg daily in pregnancy, not specifically describing twin gestations, demonstrated significant reductions in the risks of hypertension (relative risk [RR]
0.7, 95% confidence interval [CI] 0.57– 0.86) and
preeclampsia (RR 0.48, 95% CI 0.33– 0.69) in both
low- and high-risk populations.29 The effects of calcium supplementation were most beneficial in highrisk women and in those with low dietary calcium
intake.30 These findings are likely applicable to twin
pregnancies because of the increased fetal demands
for calcium and the increased baseline risk of preeclampsia in these gestations. Calcium supplementation may also have fetal programming effects that
persist into childhood. In a trial by Belizan et al,31
children of mothers who received calcium supplement in pregnancy had lower rates of hypertension
(RR 0.59, 95% CI 0.39 – 0.9). The presence of maternal contraindications to calcium supplementation (eg,
nephrolithiasis) may require reductions in the daily
supplement.
Vitamin D is also necessary for the appropriate
metabolism of calcium, and deficiency is common in
pregnancy.32 Fetal vitamin D is dependent on maternal vitamin D levels, and low maternal vitamin D is
the dominant risk factor for neonatal rickets. The
active metabolite of vitamin D is 1,25-dihydroxyvitamin D [1,25 (OH)2D], which facilitates intestinal
calcium absorption and calcium mobilization from
bone, and decreases renal calcium excretion.33 The
serum concentration of 1,25 (OH)2D increases 50 –
75% in the second trimester (mean 176⫾36 pmol/L)
and doubles by the third trimester (mean 212⫾83
pmol/L), compared with the nonpregnant state
(100⫾32 pmol/L).28,33 The current Dietary Reference
Intake recommendation for vitamin D is 400 international units/d based on estimated adequate intakes;
however, supplementation at this dose in adults does
not result in increased circulating 25(OH)D levels.34
Adults require sun exposure daily for conversion of
vitamin D to 1,25 (OH)2D, with whites requiring 0.5
hours per day and African Americans requiring 5
times this amount.34 For those with minimal sun
exposure, supplementation during pregnancy should
approach 1,000 international units/d. Wagner and
Greer35 report that vitamin D supplementation of
levels more than 1,000 international units/d are necessary to achieve normal vitamin D levels (more than
50 nmol/L 25-OH-D). This supplement, plus appropriate sun exposure, will not result in high levels
OBSTETRICS & GYNECOLOGY
associated with hypervitaminosis D (hypercalciuria,
hypercalcemia, and extraskeletal calcifications with
symptoms of nausea and vomiting and arthralgias),
but will provide adequate vitamin D levels for maternal and fetal development.34 Vitamin D supplementation during pregnancy has been associated with an
increase in birth weight as well as an increase in
newborn weight gain,34 whereas deficiency has been
associated with an increased risk of preeclampsia.36
Thus, vitamin D supplementation may be beneficial
in twin gestations. The Dietary Reference Intakes/
Tolerable Upper Intake Levels for calcium and Vitamin D are 1,300 mg/2,500 mg and 200 international
units/2,000 international units daily, thus the diet
recommendation for twin gestations includes 2,000 –
2,500 mg/d of calcium and 1,000 international units
of vitamin D daily. Due to the variations in sun
exposure and vitamin D levels, assessment of maternal vitamin D levels in twins should be considered in
first and early third trimester to allow alterations in
the supplement dosage. Attention to vitamin D supplement is especially important given the frequent
occurrence of complications resulting in bedrest in
twin pregnancy.
ANTIOXIDANTS, VITAMIN C AND E
The role of antioxidant supplements to reduce the risk
of preeclampsia and preterm birth has been investigated in pregnancy. Early studies demonstrated a
reduction in the recurrence of preeclampsia and an
improvement in the plasminogen-activator inhibitor
PAI-1 to PAI-2 ratio (favorable antioxidant measure)
with vitamin C (1,000 mg) and vitamin E (400 micrograms) supplementation during pregnancy.37,38 The
VIP trial,39 however, did not reveal any reduction in
preeclampsia either in the overall at-risk population
or in a subgroup of twin gestations. Nevertheless,
analysis of serum vitamin C levels was noted to be
lower in the supplemented group who developed
preeclampsia compared with those who did not receive supplementation. The VIP trial, however, demonstrated an increased risk of LBW in those with
vitamin C and E supplementation (RR 1.15, 95% CI
1.02–1.30, P⫽.02). Vitamin C has also been suggested
to provide protection against preterm premature rupture of membranes in singleton pregnancy.40 Antioxidant trials to date have examined primarily singleton
gestations and demonstrate the most significant benefit in pregnancies with nutritional deficiencies. The
current Dietary Reference Intakes/Tolerable Upper
Intake Levels for vitamin C and E, respectively, are
80/1,800 mg/d and 15/800 micrograms/d,41 making
suggested intakes of 500 –1,000 mg/400 micro-
VOL. 114, NO. 5, NOVEMBER 2009
grams/d vitamin C/vitamin E reasonable for twin
gestations, whereas specific trials in twin pregnancy
await. Vitamin C and E have not been associated with
toxicities at very high doses, with the exception of
gastrointestinal disturbances, and no adverse fetal
effects have been noted. Vegetable oils are the primary source of vitamin E, whereas vitamin C is found
in citrus fruit and green vegetables.
ZINC AND MAGNESIUM
Zinc is necessary in several biologic systems, including protein synthesis and nucleic acid metabolism as
well as prevention of free radical formation. Meats,
seafood, and eggs provide the optimal dietary sources
of zinc. Zinc deficiency, although rare, may be associated with fetal neurologic malformations and
growth restriction, and late pregnancy deficiency may
also be associated with impaired brain function and
behavior abnormalities due to abnormal neuronal
growth.42 Zinc supplementation in pregnancy may
improve several pregnancy outcomes, including reducing preeclampsia and preterm birth, and result in
improved birth weight in deficient populations. Hinniger et al26 demonstrated that maternal zinc levels
were not different between supplemented or placebo
groups in a multinutrient supplement trial, but zinc
levels did correlate well with neonatal length (r 0.58,
P⫽.03). Although there are few data in twin gestations, a systematic review of zinc supplementation of
15– 44 mg daily in pregnancy was associated with a
14% reduction in preterm birth (RR 0.86, 95% CI
0.76 – 0.98), with the majority of the effect seen in
nutritionally deficient populations.43 However, no effect on birth weight was seen. Although zinc metabolism has not been systematically studied in multiple
gestations, zinc supplementation could theoretically
be beneficial in this population at high risk for
preterm birth and LBW. The Dietary Reference
Intakes/Tolerable Upper Intake Levels for zinc is 12
mg/40 mg/d respectively.41 Zinc is not stored in the
body and virtually nontoxic; rare cases of leukopenia
and anemia have been reported with prolonged intake of more than 50 –300 mg/d. Based on National
Health and Nutrition Examination Survey III data,44
59% of pregnant women achieve adequate intake
(supplement and diet) of zinc, with a mean dietary
intake of 9.2 (⫾2.1) mg. Thus achievement of daily
intake of zinc of 14 – 45 mg/d is recommended for
twin gestations, often requiring supplement.
Although individual trials of variable quality and
design demonstrate conflicting results regarding the
effects of magnesium supplementation on preterm
birth and fetal growth, a systematic review by
Goodnight and Newman
Twin Nutrition
1127
Makrides and Crowther45 in singleton pregnancies
demonstrated a reduction in preterm birth more than
37 weeks (RR 0.73, 95% CI 0.57– 0.94) and LBW (RR
0.67, 95% CI 0.46 – 0.96). The authors of this analysis
summarized that no conclusions about the beneficial
effects of magnesium supplementation on pregnancy
outcome could be made due to the poor quality of the
included trials, and twin data remain lacking. The
Dietary Reference Intake for magnesium in pregnancy
is 350 – 460 mg/d and supplementation of up to 1,000
mg daily has been suggested for twin gestations.14
ANEMIA AND IRON REQUIREMENTS
Iron deficiency is the most common nutritional deficiency worldwide, and has been associated with preterm birth and low birth weight. In the United States,
estimates of iron deficiency anemia in pregnancy
range from 5–17%, whereas estimates of low maternal
ferritin (less than 15 micrograms/L) with normal
hemoglobin are seen in up to 20% of pregnant
women. Fetal and neonatal iron deficiency, as measured by cord blood ferritin level less than 30 micrograms/L is associated with severe maternal anemia
(hemoglobin less than 6.0 g/dL).46 Both mild maternal
anemia (hemoglobin less than 8.5 g/dL) and a maternal ferritin level less than 12 micrograms/L are associated with poor fetal iron supply.46 Scholl et al47
demonstrated an association between iron deficiency
and poor maternal weight gain (adjusted odds ratio
[AOR] 2.67, 95% CI 1.13– 6.3). Additionally, iron
deficiency anemia was also associated with an increased risk of preterm birth (AOR 2.66, 95% CI
1.15– 6.17) and LBW (AOR 3.10, 95% CI 1.16 –
4.39).47 Cogswell et al48 demonstrated that iron supplementation with 30 mg elemental iron daily resulted in a significant increase in birth weight (200 g)
compared with placebo even in the presence of
normal serum ferritin levels in the first trimester.
Twin pregnancies have lower maternal hemoglobin levels in the first and second trimesters and higher
rates of iron deficiency anemia, and the resulting
infants have increased risk of residual iron deficiency
anemia for up to 6 months of age. The rate of iron
deficiency anemia is 2.4 – 4 times higher than in
singleton pregnancies. The iron requirement for twin
pregnancy is estimated to be nearly twofold that of a
singleton pregnancy.7 Rosello-Soberon et al7 reported
an estimated 869 mg elemental iron requirement for
twins compared with 476 mg for singleton pregnancies. Iron supplementation during the first and second
trimesters has been associated with reductions in both
preterm birth and LBW.49 In women with iron deficiency (serum ferritin less than 15 micrograms/L),
1128
Goodnight and Newman
Twin Nutrition
daily replacement with 60 –120 mg of elemental iron
will increase the hemoglobin concentration by 1g/dL
over 4 weeks.
The ideal source of iron supplementation is from
an adequate diet that includes heme iron–rich food
sources such as red meat, pork, fish, and eggs. These
sources of dietary iron are ideal in that they not only
provide iron that is more easily absorbed but also
represent a higher quality and quantity of protein.
Nonheme iron sources, such as iron fortified bread,
leafy green vegetables, and nuts, should also be
encouraged both for their iron content as well as for
the presence of folate. The Dietary Reference Intake/
Tolerable Upper Intake Levels for iron are 27 mg/45
mg daily, respectively.41 Supplementation of nonanemic twin gestations of 30 mg daily of elemental iron
would be appropriate to meet the increased maternal
and fetal needs of the pregnancy.
Folic acid is also an important micronutrient in
pregnancy because it is essential in DNA synthesis
and cell division. Folate is required for the increase in
maternal red blood cells as well as for the growth of
the fetus. Hyperhomocysteinemia is associated with
deficiency in folate and has been associated with
intrauterine growth restriction, preeclampsia, and placental abruption through vascular endothelial injury.
Anemia due to folate deficiency is eight times more
common in twins than in singleton pregnancy.7 Trials
of folic acid supplement in pregnancy have not demonstrated consistent improvements in pregnancy outcome, with one meta-analysis demonstrating a reduction in the risk of low birthweight (RR 0.73, 95% CI
0.53– 0.99)50 and a retrospective review demonstrating a reduction in the risk of preterm birth with
preconception folic acid supplementation.51 The current recommendation for folic acid in the preconception period and during pregnancy include 400 micrograms/d, whereas the Dietary Reference Intake/
Tolerable Upper Intake Levels for folate are 600
micrograms/1,000 micrograms daily.41 Based on
these recommendations, 1mg daily folic acid is suggested for twin gestations.
OMEGA-3-FATTY ACIDS
Essential fatty acids (EFA) are lipids that cannot be
synthesized in the body and thus require appropriate
dietary intake. Essential fatty acids are involved in
many metabolic processes, including energy storage,
cell membrane function (including neuronal development), control of inflammation, and control of thrombosis.52 Two groups of EFA exist: omega-6 (␻-6FA:
linoleic acid, derived from cereals, grains, processed
foods, meat, milk, eggs, and oils, including corn,
OBSTETRICS & GYNECOLOGY
sunflower, safflower, and sesame) and omega-3 (␻3FA: ␣-linolenic acid, only found in selected seeds,
nuts, and fish oils).52 Because plant sources may not
contain the necessary docosahexaenoic acid (DHA)
component of ␻-3FA, the optimal nutritional source is
fish oils. Optimal homeostatic inflammatory and
thrombotic states have been theorized to result from a
balance between ␻-3FA and ␻-6FA, with ideal diets
having a ratio of ␻-6 to ␻-3 of 1–2:1.52 A deficiency in
␻-3 results in a prothrombotic and proinflammatory
state that has been associated with an increased risk of
cardiovascular and inflammatory diseases.52 A typical
Western diet currently has an ␻-6 to ␻-3 ratio of
16:1.52
In comparison with singleton pregnancies, neonates born of twin pregnancies have lower levels of
␻-3FA in the walls of their umbilical veins and
arteries, indicating an inadequate dietary supply.53 An
in vitro trial of singleton and twin pregnancies demonstrated that DHA concentration in fetal erythrocyte
membrane was directly related to maternal concentration and that lower concentration of ␻-3FA was
associated with increased membrane rigidity and increased resistance to flow.54 In this study, the mean
erythrocyte DHA concentration was significantly lower
in twin gestations, leading the authors to conclude that
fetal demand for DHA in multiple pregnancies may not
be satisfied by typical dietary intake.54
Epidemiologic data from the Faroe Islands,
where diets are rich in marine oils, suggest that diets
with a more favorable ␻-6 to ␻-3 ratio increase birth
weight through either prolongation of pregnancy or
by optimizing the fetal growth rate.55 In prospective
trials, fish oil supplementation of 2.7g of ␻-3FA daily
has been shown to prevent recurrent preterm birth in
singleton pregnancies (OR 0.54, 95% CI 0.3– 0.98),
with a trend toward a reduction in preterm birth
among twins.56 Smuts et al57 also demonstrated an
increase in length of gestation by 6.0⫾2.3 days among
singleton gestations randomized to receive supplemental DHA (133 mg daily) in the third trimester.
Trends for increased neonatal length and head circumference were also noted.57
Controversy exists as to the risk of contaminants,
notably methyl mercury (MeHg) and polychlorinated
biphenyls, found in fish that are rich in ␻-3FA.
Exposure to extremely high levels of MeHg is associated with microcephaly, seizures, cerebral palsy,
and learning deficiency. Such exposures have occurred as a result of toxic environmental spills and
deliberate poisoning. However, epidemiologic studies
from the Seychelles, in which 85% of the population
consume ocean fish containing MeHg levels compa-
VOL. 114, NO. 5, NOVEMBER 2009
rable to fish consumed in the United States (0.05– 0.25
ppm methylmercury) on a daily basis, have not
demonstrated adverse neurodevelopmental delay in
the offspring to 66 months of life.58 Maternal consumption of seafood in a large epidemiologic study in
England demonstrated that low maternal consumption (less than 340 g/wk) was associated with an
increased risk of their children being in the lowest
quartile for verbal IQ, as well as more common
suboptimal social behaviors, fine motor and communication skills, and social development scores,59 suggesting low ␻-3FA exposure being associated with an
increased risk of adverse neurologic development.
The World Health Organization currently recommends 300 –500 mg per day of ␻-3FA (such as DHA
and eicosapentaenoic acid) in an effort to promote
fetal and early childhood mental development. Consumption of at least two meals (12 oz total) weekly of
low-mercury– containing fish (eg, shrimp, canned
light tuna, salmon, pollock, and catfish) by pregnant
women, those planning pregnancy, or breastfeeding
women, contributes to an adequate ␻-3FA intake for
optimal fetal neurodevelopmental and obstetric outcomes. It remains wise to follow the U.S. Environmental Protection Agency recommendations to avoid
highly contaminated fish (eg. shark, swordfish, king
mackerel, tilefish) during pregnancy. Purified nutritional supplements of fish oil can be used to achieve
the goal of 300 –500 mg daily of DHA. Other sources
of ␻-3FA include sunflower, safflower, corn, and
soybean oil, as well as egg yolk, meat, and spinach.
Although most nutritional supplement trials in
pregnancy have shown modest effects on the rates of
preeclampsia and preterm birth, at best, these outcomes have usually been improved when deficient
populations received supplementation. These findings are likely applicable to twin pregnancy, in which
the added demands are typically not met by routine
dietary intake. Even among middle- to upper-income
women with advanced education, Turner et al60 demonstrated that pregnant women (singleton gestations)
remain at risk for suboptimal intake of some micronutrients. In this study, the probability of intake less
than the estimated average requirement for iron was
91%, zinc 31%, magnesium 53%, and vitamin B6
21%.59 Given the likelihood of increased micronutrient requirements in twin gestations, high risk of
micronutrient deficiency, and the potential benefit of
micronutrient supplementation in deficiency states,
our practice is to recommend the supplement described in this review for twin pregnancies.
Goodnight and Newman
Twin Nutrition
1129
SPECIALIZED TWIN NUTRITIONAL
PROGRAMS AND PROVIDER
INTERVENTIONS
Given the importance of attention to nutrition in
multifetal gestations, consultation with a registered
dietitian is encouraged if available. The constraints
associated with traditional prenatal care visits usually
do not allow adequate time for in-depth counseling
and education regarding the importance of diet and
adequate nutrition. Nutritional consultation can also
result in the development of individualized BMIspecific weight gain recommendations, ongoing tracking of maternal weight gain, and interventions to
modify maternal diet when women either exceed or
fail to meet their recommended weight gain goals.
Surveys of women carrying twins reveal that more
than 25% receive no advice at all regarding weight
gain and that among those who do receive nutritional
counseling, the guidance is often incorrect.61 Clinical
studies have suggested that prenatal care for twin
pregnancies provided through specialized, multidisciplinary multiple-gestation programs or clinics results
in improved maternal and neonatal outcomes.62– 64 A
mainstay of these interventions is the grouping of
women with multiple gestations into specialty clinics
that have a strong emphasis on nutritional evaluation
and education in addition to the provision of prenatal
care.
In the Michigan Multiples Clinic, women with
multiple gestations received prenatal care in a setting
that provides twice monthly dietitian and nurse practitioner visits for dietary counseling, along with physician-directed prenatal care visits. Nutritional modifications emphasized in this program included
multimineral supplementation with daily calcium carbonate (3 g), magnesium oxide (1.2 g), zinc oxide (45
mg) in addition to a multivitamin with 100% RDA for
nonpregnant recommendations (increased to 200%
RDA at 20 weeks).63 The recommended diet composition included 3,000 – 4,000 kcal/d, composed of 20%
protein, 40% carbohydrates, and 40% fat, divided into
three meals and three snacks daily. Compared with
nonparticipants, Nutritional Intervention Program
mothers were more likely to meet weight gain goals at
20 and 28 weeks and had fewer pregnancy complications (Fig. 2). Program participants also demonstrated
an increase in the length of gestation (13.1 days
P⬍.001), increased birth weight (435 g, P⬍.001), 7.4
fewer hospital admission days (P⬍.001), and reduced
rates of preterm labor and LBW.62 These reductions
in adverse pregnancy outcomes resulted in a cost
savings of $52,553 in hospital charges per twin pair.63
1130
Goodnight and Newman
Twin Nutrition
Fig. 2. University of Michigan Nutrition Intervention Program rates of twin pregnancy outcomes (all differences
P⬍.01). Major morbidity defined as any of retinopathy of
prematurity, necrotizing enterocolitis, ventilator support, or
intraventricular hemorrhage. Very low birth weight, less
than 1,500 g; low birth weight, less than 2,500 g. NICU,
neonatal intensive care unit. (Data from Luke B, Brown MB,
Misiunas R, Anderson E, Nugent C, van de Ven C, et al.
Specialized prenatal care and maternal and infant outcomes in twin pregnancy. Am J Obstet Gynecol 2003;189:
934 – 8.)
Goodnight. Twin Nutrition. Obstet Gynecol 2009.
Follow up of the twins at 8, 18, and 36 months
demonstrated that children of program nonparticipants were more likely to have lagging growth (AOR
1.76, 95%CI 1.26 –2.45) and more likely to be classified as developmentally delayed (AOR 1.55, 95% CI
1.04 –2.31).63
A similar program was conducted as part of the
Higgins Nutritional Intervention Program conducted
by the Montreal Diet Dispensary, emphasizing individualized nutrition assessment and similar diet recommendations as the Michigan Multiples Clinic. The
Higgins Program demonstrated a 27% reduction in
LBW (OR 0.73, 95% CI 0.54 – 0.99) along with a
reduction in early pregnancy low weight gain (OR
0.49, 95% CI 0.26 – 0.93) in those receiving the intervention compared with a matched control population.62 Similar trends toward a reduction in very low
birth weight and preterm birth were also noted in the
intervention group. Although these studies lacked a
randomized prospective design, they suggest that establishment of twin pregnancy–specific nutritional recommendations, together with intensive education and continued maternal assessment and counseling, can
improve birth weights and prolong the length of gestation in twin pregnancies in a cost-effective manner.
Finally, does physician input into nutritional education influence the patient’s attention to proper
OBSTETRICS & GYNECOLOGY
nutrition? Although evaluated in few clinical trials in
twin gestations, several clinical trials demonstrate that
provider input into nutritional education is able to
affect maternal weight gain and nutritional status in
pregnancy,65,66 and antenatal consultation improves
initiation of lactation in twin pregnancy.67 Tools available for provider counseling include individual counseling at prenatal care visits, nutrition or dietitian
referrals, placement and serial review of maternal
weight gain graphs during the pregnancy in the
obstetric record, and review of dietary recall surveys,
which are commercially available.
POSTPARTUM AND BREASTFEEDING
The importance of nutrition for twin gestations does
not end after delivery, because proper nutrition is
necessary to support breastfeeding. Rates of initiation
of breastfeeding in twins can range from 40 –90%,
with wide population variation.68 Complications such
as prematurity, low birth weight, and neonatal sepsis
can adversely affect rates of twin breastfeeding. There
are few evidence-based recommendations for specific
diet modifications for breastfeeding twins; however,
some suggestions may be beneficial. Milk production
may be 1.2–2 L per day by the second month of life
and require an excess maternal caloric intake of
1,200 –1,500 kcal/d.68 A diet similar to that during
pregnancy is recommended (20% of calories from
protein, 40% from carbohydrates, and 40% from fat),
and continuation of a prenatal vitamin supplement,
including DHA is recommended.68 Diets with total
daily caloric intake during lactation of less than 2,700
cal/d may also be at risk for micronutrient deficiency
in calcium, magnesium, zinc, vitamin B6, and folate.
Until further specific research is completed, continuation of micronutrient supplementation as in the
antenatal care of twins into the lactation period is
reasonable to prevent such micronutrient limitations.
FUTURE RESEARCH
Several unanswered questions remain regarding the
role of maternal nutrition in improving outcomes in
twin gestation. The effects of specific diet composition
on maternal weight gain and neonatal birth weight
Table 3. Twin Pregnancy Nutritional Recommendations
Intervention
First Trimester
Maternal weight/weight gain Assess maternal pregravid
BMI, determine BMIspecific weight gain goals
Caloric requirements (kcal·
kg–1·d–1)
Normal BMI
40–45
Underweight
Overweight
Micronutrient Supplement
(daily total intake)
MVI with iron (30 mg
elemental tablets)
Calcium (mg)
Vitamin D (international
units)
Magnesium (mg)
Zinc (mg)
DHA/EPA (mg)
Folic Acid (mg)
Vitamin C/E (mg/
international units)
Nutritional consultation
Yes
Laboratory nutritional
assessment
Risk Factor appropriate
exercise or reduction
in activity
Second Trimester
Third Trimester
Assess/counsel re: maternal
Assess/counsel re: maternal
BMI-specific weight gain (each
BMI-specific weight gain (each
prenatal care visit)
prenatal care visit)
Alter as necessary for weight
gain goal
Alter as necessary for weight
gain goal
42–50
30–35
1
2
2
1,500
1,000
2,500
1,000
2,500
1,000
400
15
300–500
1
500–1,000/400
800
30
300–500
1
500–1,000/400
800
30
300–500
1
500–1,000/400
Repeat if not at weight gain
goal, anemia, GDM
Hemoglobin ferritin folate/ Follow up abnormalities from
B12 early screen for GDM
first trimester
(risk factors) vitamin D
Screen
Screen
Repeat if not at weight gain
goal, anemia, GDM
Hemoglobin ferritin GDM screen
with or without vitamin D
Screen
BMI, body mass index; MVI, multivitamin; DHA, docosahexaenoic acid; EPA, eicosapentaenoic acid; GDM, gestational diabetes mellitus.
VOL. 114, NO. 5, NOVEMBER 2009
Goodnight and Newman
Twin Nutrition
1131
and body composition can be explored. Systematic
reviews of nutrient use throughout the twin gestation
are lacking. Research into the maternal nutrient levels
associated with optimal fetal growth in early and late
pregnancy may determine baseline values for screening and supplementation as necessary. Evaluation of
the effect of supplements such as zinc, magnesium,
and ␻-3FA on neurodevelopmental outcomes are also
needed. Further evaluation of maternal calcium homeostasis and vitamin D metabolism in multiple
pregnancies and the effect on bone mineral density of
the offspring are also warranted. If optimal nutrition
can result in increases in twin birth weights, modest
prolongations of pregnancy, or neurobehavioral benefits as has been suggested in retrospective trials, then
future prospective controlled trials of nutritional interventions in twin pregnancies are needed.
CONCLUSION
We have discussed the nutritional recommendations
and evaluation used in our institutions for twin pregnancies, summarized in Table 3. The current literature supports the benefits of BMI-specific weight gain
guidelines specific for twin gestations for improved
twin birth weight. Thus our practice is to track
maternal weight gain through the pregnancy and
provide nutrition consultation to achieve these goals.
Twin pregnancy is also at risk for micronutrient
deficiency and thus supplementation with iron, calcium, and folate, beyond a typical prenatal vitamin, is
recommended. Finally, ␻-3FA dietary intake or supplementation is also encouraged for potential neurodevelopmental benefits. Although nutritional intervention may not reduce all perinatal morbidity
associated with twin pregnancy, increased attention to
specific nutritional needs in twin-specific prenatal
care settings have been associated with improved
neonatal outcomes and should be incorporated into
the prenatal care of twins.
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