optimal nutrition for improved twin pregnancy outcome · optimal nutrition for improved twin...

Clinical Expert Series

Continuing medical education is available online at www.greenjournal.org

Optimal Nutrition for Improved TwinPregnancy OutcomeWilliam 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 ofincreased risks of low birth weight and prematurity. Although the cause of the morbidity ismultifactorial, attention to twin-specific maternal nutrition may be beneficial in achieving optimalfetal 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, andcarbohydrate-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 usualprenatal vitamin. Daily supplementation of docosahexaenoic acid and vitamin D should also beconsidered. Multiple gestation-specific prenatal care settings with a focus on nutritional interventionsimprove birth weight and length of gestation and should be considered for the care of womencarrying multiples. Antepartum lactation consultation can also improve the rate of postpartumbreastfeeding in twin pregnancies. Twin gestation-specific nutritional interventions seem effective inimproving the outcome of these pregnancies and should be emphasized in the antepartum care ofmultiple gestations. This review examines the available evidence and offers recommendations fortwin pregnancy-specific nutritional interventions.(Obstet Gynecol 2009;114:1121–34)

The increasing rate of twin gestations is well docu-mented. Twin gestations account for a dispropor-

tionate share of neonatal morbidity, with increased

risks of preterm birth, low birth weight, and intrauter-ine growth restriction. Infants of multiple births rep-resent 3% of all deliveries but account for 15% ofpreterm birth, 20% low birth weight (LBW; less than2,500 g), and 19–24% of very low birth weight (lessthan 1,500 g) neonates born in the United States.Optimal twin survival has been demonstrated to beassociated with birth weights more than 2,850 g anddelivery after 36 weeks gestational age.1–3 Unfortu-nately, twins often deliver with average birth weightsbetween 2,300 g and 2,600 g at a mean gestational ageof 35 weeks to 36 weeks. Impaired fetal growth is alsoassociated with long-term complications, including anincreased lifetime risk of cardiovascular disease andobesity. Neonatal body composition in appropriatelygrown twin gestations is similar to singleton neonates,whereas small for gestational age twins have a lowerlean body mass, a lower fat mass, and a trend to lowerbone density compared with small for gestational agesingleton neonates.4

From the Departments of Obstetrics and Gynecology, Division of Maternal–FetalMedicine, University of North Carolina at Chapel Hill, Chapel Hill, NorthCarolina; and Medical University of South Carolina, Charleston, South Carolina.

The practice of medicine continues to evolve and individual circumstances willvary. This opinion reflects information available at the time of its acceptance forpublication, and is neither designed nor intended to establish an exclusivestandard of care. This publication is not expected to reflect the opinions of allmembers 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 ofObstetrics and Gynecology, Division of Maternal–Fetal Medicine, University ofNorth Carolina at Chapel Hill, 3010 Old Clinic Building/CB# 7516; ChapelHill, NC 27599-7516; e-mail: [email protected].

Financial DisclosureThe authors did not report any potential conflicts of interest.

© 2009 by The American College of Obstetricians and Gynecologists. Publishedby Lippincott Williams & Wilkins.ISSN: 0029-7844/09

VOL. 114, NO. 5, NOVEMBER 2009 OBSTETRICS & GYNECOLOGY 1121

Maternal pregestational and gestational nutri-tional status in singleton pregnancies without questionis associated with pregnancy outcome. The nutritionaldemands of pregnancy are magnified by the presenceof multiple fetuses, and the potential beneficial impactof optimal nutrition on pregnancy outcomes shouldnot be underestimated. Thus, the nutritional recom-mendations for singleton pregnancy require specificadaptation for a multifetal gestation. The nutritionalcompetition engendered by the presence of multiplefetuses results in the accelerated depletion of maternalnutritional reserves.5 Although monochorionic twinpregnancies carry a greater risk of the above adversepregnancy outcomes than dichorionic twins, there aresimilar rates of selective intrauterine growth restric-tion between monochorionic and dichorionic twins.6

The overall risk of fetal growth restriction in twinpregnancies creates a situation where modification ofnutritional intake has a greater opportunity to posi-tively influence the outcome for twins compared withsingleton gestations. This article will suggest specificmaternal nutritional recommendations for twin preg-nancy based on available scientific evidence.

The goals for optimization of maternal nutritionin multiple gestations therefore include

1. optimizing fetal growth and development,2. reducing incidence of obstetric complications,3. increasing gestational age at delivery, and4. avoiding excess maternal weight gain that could

result in unnecessary postpartum weight retention.

PHYSIOLOGIC ADAPTATIONS TO TWINPREGNANCYMultifetal gestations undergo significant maternalphysiologic adaptations beyond the usual pregnancychanges, including increased plasma volume, in-creased basal metabolic rate, and increased resistanceto carbohydrate metabolism. The blood volume in atwin gestation increases by 50–70% by 20 weeks ofgestation, with only a 25% increase in erythrocytes.7

This plasma volume expansion results in decreasedconcentrations of hemoglobin, albumin, and water-soluble vitamins, whereas increases in fat-soluble vi-tamins, triglycerides, cholesterol, and free fatty acidshave been demonstrated.7 The relatively greater in-crease in plasma volume in a twin pregnancy alsoresults in a dilutional effect on red blood cells in thesecond and third trimesters of pregnancy.8

The resting energy expenditure is an indicator ofmaternal basal metabolic rate that can be used toestimate energy requirements. The maternal resting

energy expenditure increases each trimester in bothsingleton and multiple gestations.9 Singagawa et al9

demonstrated that compared with singleton pregnan-cies, maternal resting energy expenditure increasedby 10% in twin pregnancies, independent of changes inminute ventilation. The increase in resting energy ex-penditure can also be seen as a result of the increasedmass of maternal tissues, including the breast, uterus,body fat, and muscle as well as the increase in bloodvolume. Such an increase in resting energy expenditurecan result in a 40% increase in caloric requirements fortwin gestations.

The relatively larger placental mass in multiplegestations results in an increase in placental steroidand hormone production.7 As a result, multifetalgestation has been described as a state of “acceleratedstarvation,” in which the development of starvationketosis occurs at a more rapid rate in twin gestationsthan in a singleton pregnancy. These hormonallydriven metabolic changes result in remarkable mater-nal carbohydrate use, resulting in a greater propensityfor depletion of maternal hepatic glycogen stores andthe development of maternal ketonemia. Casele etal10 demonstrated that women with twin gestations feda diet of 40 kcal/kg ideal body weight, divided intothree meals, are more susceptible to the developmentof ketosis after fasting, as evidenced by elevated�-hydroxybutyrate serum levels after an evening fastcompared with singleton gestations. Classically, theUnited States Department of Agriculture (USDA),Institute of Medicine (IOM), and American DieteticAssociation (ADA) recommendations for reproduc-tive age women suggest that 45–65% of calories dailybe derived from carbohydrates,11 a diet that has beensuggested to result in poor glycemic control andexcess weight gain in twin gestations.12 Luke et al12

demonstrated that a diet composed of 40% carbohy-drates and a greater percentage of fats and proteinwith an appropriate caloric intake (3,000–4,000kcal/d in underweight to normal weight women)achieved a greater degree of euglycemia during preg-nancy. Other limited trials also suggest that a lowerproportion of carbohydrates in the diet in women withgestational diabetes is associated with improved glyce-mic control, as evidenced by lower insulin utilization.

DIETARY COMPOSITIONAlthough no established nutritional guidelines exist,an estimate of individual macronutrient requirementsfor twins is described in Table 1. These recommen-dations are based on extrapolation of the singletonrecommended dietary allowances (RDA) published

1122 Goodnight and Newman Twin Nutrition OBSTETRICS & GYNECOLOGY

by the Food and Nutrition Board of the NationalResearch Council and body mass index (BMI)-spe-cific recommendations for twin gestations publishedby Luke and coworkers. Luke et al12 have proposed adietary composition for twins in which energy intakeis derived 20% from protein, 40% from low-glycemicindex carbohydrates, and 40% from fat (Table 1). Dueto the increased nutritional demands of the fetus andmaternal metabolism, these recommendations equateto a daily intake of 3,500 calories, composed of a dietwith 175 g protein, 350 g of carbohydrate, and 156 gof fat per day for women of normal prepregnancyBMI. Adequate protein intake is essential to normalfetal growth in twin gestations. In singleton pregnan-cies, the protein storage during pregnancy has beenestimated to be 925 g, distributed as 400 g to the fetus,100 g to the placenta, and 425 g additional stored inthe mother.7 Inadequate protein intake can occursecondary to insufficient dietary intake, intake of poorquality protein (high fat meats), or inadequate caloricintake, which results in dietary protein being divertedto meet maternal energy requirements.12 Reducedamino acid availability to the fetus not only affects fetalgrowth but may also restrict placental growth, furthercompounding the effect of protein deficiency.12 Addi-tionally, Moore et al13 evaluated maternal diet compo-sition and the effect on neonatal weight and ponderalindex. The percentage of energy from protein (14.4–18.1% in this study) in early pregnancy had the bestpositive association with neonatal weight, whereas thepercentage of energy from carbohydrates (45.3–53.2%in this sample) was inversely proportional to the pon-

deral index (increased carbohydrates resulted in neo-natal thinness).13 Ideal protein sources include leanmeat, fish, and skin-free poultry, eggs, dried beans,peas, and tofu. An emphasis on low to mediumglycemic 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 forwide serum glucose fluctuations. To gain the neces-sary calories, the proportion of caloric rich fats issubstituted for carbohydrates.14 Table 2 suggests thenumber of serving suggestions daily to achieve thisdiet composition and caloric requirements.14 Thisdietary intake should be divided into three mainmeals with three smaller snacks interposed in theusual meal schedule to help reduce the developmentof hypoglycemia and transient ketosis.14 In under-weight women (BMI less than 19.8 kg/m2) and thosewith poor weight gain in pregnancy, addition ofhigher fat, calorie-rich foods, including nutritionalsupplement drinks, whole or 2% milk, fruit juices, andthe change to five balanced meals per day can achievethe necessary weight gain. Similarly, excessive weightgain in pregnancy should lead to a reduction in thesehigh fat, calorie-dense foods.

WEIGHT GAINTotal maternal weight gain and the timing of weightgain are crucial to optimal fetal growth in twingestations. The preponderance of the evidence insingleton gestations is that there is a relationshipbetween increasing maternal weight gain and in-

Table 1. Suggested Daily Diet Composition for Twin Gestation by Maternal Prepregnancy Body MassIndex14

Underweight Normal Weight Overweight Obese

Calories (kcal) 4,000 3,000–3,500 3,250 2,700–3,000Protein (g)* 200 175 163 150Carbohydrate (g)* 400 350 325 300Fat (g)† 178 156 144 133

* 4 kcal/g.† 9 kcal/g.

Table 2. 2002 American Dietetic Association Serving Suggestions for Multiple Pregnancy of Normal BodyMass Index

Milk/Yogurt/Cheese

Meat/Poultry/Fish/Eggs Vegetable Fruit

Bread/Cereal/Rice/Pasta

Dailyservings

3 3 3 2 6

Servingsuggestion

1 cup milk; 1oz cheese

2–3 oz lean meat,fish, poultry;1 egg

1 cup raw/cookedvegetables; 2 cups rawgreen leafy vegetables

1 cup fruit; cupdried fruit

1 slice bread; 1 cup readyto eat cereal; cupcooked rice/pasta

VOL. 114, NO. 5, NOVEMBER 2009 Goodnight and Newman Twin Nutrition 1123

creases in birth weight, with a corresponding reduc-tion in the incidence of low birth weight. The pub-lished literature also suggests that low maternalweight gain superimposed on a low maternal pre-gravid weight compounds the adverse affects of each,resulting in high rates of both low birth weightdelivery and premature birth. The effect of lowmaternal weight gain is diminished in women withhigher pregravid weights. Historically, weight gainrecommendations were made to reduce the risk ofLBW, with contemporary recommendations made toachieve optimal fetal growth without excess maternalweight gain. Early retrospective studies attempted todefine the appropriate maternal weight gain for twingestations based on optimal neonatal outcomes. Ped-erson et al15 demonstrated that optimal twin preg-nancy outcome, defined as two living infants, eachmore than 2,500 g, born after 37 weeks estimatedgestational age, and 5-minute Apgar score more than7 was associated with a maternal weight gain of 20 kg(44 lb). Less than optimal outcomes were seen withmaternal weight gains less than 16.8 kg (37 lb).15 Thetiming and the rate of maternal weight gain also affectboth birth weight and prematurity. Midgestationalmaternal weight gains seem to have the greatest effecton fetal growth and ultimate birth weight.16,17 Optimaltwin outcomes (birth weight more than 2,500 g) havebeen associated with maternal weight gain of 24 lb by24 weeks of gestation.16,18 Even when there is appro-priate catch-up maternal weight gain after 24 weeks, alow rate of weight gain before 24 weeks (less than 0.85lb/wk) was strongly associated with poor intrauterinegrowth and earlier delivery.16,18,19 In studies makinguse of serial ultrasonographic measures of fetalgrowth in relation to maternal weight gain, it has beendemonstrated that early maternal weight gain (lessthan 20 weeks) and midpregnancy weight gain (20–28weeks) significantly enhanced the rates of fetal growthbetween 20 weeks and 28 weeks and from 28 weeksuntil birth.20 As noted in singleton gestations, thisinfluence of early maternal weight gain on subsequentfetal growth was most pronounced in underweightwomen. Physiologically, this relationship suggests thatearly weight gain results in improved maternal nutrientstores that become important later in pregnancy as anutrient reserve when fetal demands begin to increase.Adequate early maternal weight gain may also enhanceplacental growth, which helps to sustain an adequatenutrient supply to the twins later in pregnancy.

Luke et al21 suggested weight gain goals for twinpregnancy based on maternal prepregnancy BMI.Optimal maternal weight gain and timing of weightgain were modeled based on ideal fetal growth and

newborn birth weights determined to be between thesingleton 50th and twin 90th percentiles by 38 weeksof gestation. Among twins achieving these optimalfetal growth and birth weights, the associated mater-nal BMI-specific weight gains were found to bedescribed by the maternal weight gain curves noted inFigure 1.21 In a follow-up study of the effects of usingthese BMI-specific weight gain recommendations,twin gestations that failed to achieve BMI-specificweight gain goals demonstrated a lower birth weightby nearly 200 g (P�.001) and a 1.04-week shorterlength of gestation (P�.02) (Goodnight W, Hill E,Newman R, Rowland A. Achieving maternal BMI-specific weight gain goals improves birthweight andgestational age at delivery in twin pregnancies [ab-stract]. Am J Obstet Gynecol 2006;195:S121). Basedin part on this new data, the 2009 IOM guidelines forweight gain in twin pregnancy now recommend BMI-specific weight gains for normal weight women of17–25 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 ondifferent BMI categories used in the IOM recommen-dations. In practice, we continue to use the graphscreated by Luke et al to track and recommendmaternal weight gain during pregnancy.

Determinants of maternal weight gain in preg-nancy have not been extensively studied in multiplegestations but are likely influenced by multiple bio-logic, behavioral, cultural, and psychosocial factors.Wells et al23 demonstrated in a retrospective analysisthat maternal obesity and hypertension are associatedwith a greater risk for weight gain above the IOMrecommended weight gains, whereas diabetes was notassociated with excessive or below IOM weight gaingoals, and prior live births was associated with lowerrisk of excessive maternal weight gain in pregnancy.Initial physician counseling is thus necessary to deter-mine maternal perceptions of weight gain goals, re-view potential maternal risk factors for excessive orpoor weight gain, and provide education and supportto achieve optimal weight gain goals.

Although it is well established that increased mater-nal weight gain in pregnancy increases birth weight intwins, the long-term effects of retained maternal weightafter delivery remains of concern. Although not exten-sively evaluated in multiple gestations, excessive mater-nal weight gain in pregnancy may be associated withincreased risks of gestational hypertension, cesareandelivery, and birthweight more than 4,000 g (rare intwins).24 The weight gain recommendations for twinpregnancy have been criticized for potentially contrib-uting to the risk of maternal obesity through postpartum


retention of the weight gain. Luke et al (Luke B, HedigerML, Min L, Nugent C, Newman RB, Hankins GD, et al.The effect of weight gain by 20 weeks’ gestation on twinbirthweight and maternal postpartum weight [abstract].Am J Obstet Gynecol 2006;195:S85), however, demon-strated that the mean weight retention for those whogained within the recommended BMI specific weightgain goals was only 1.5 lb at 6 weeks postpartum,minimally above the 0.9 lb weight retention seen inthose with maternal weight gain below the BMI-specificweight gain goals. In singleton pregnancy, long-termmaternal weight (15 years postpartum) was equivalentamong women who gained below or within IOMrecommendations, with excessive maternal weight gainin pregnancy associated with higher long-term weightgain.25 Thus, in the multiple gestation clinical situation,attention should be given to both achievement of therecommended maternal weight gain goals and serial

assessment of weight gain and equal intervention toprevent or slow excessive weight gain.

MICRONUTRIENTSRecommendations for micronutrient intake are deter-mined by the Food and Nutrition Board of theInstitute of Medicine. Dietary Reference Intakes havereplaced the RDA estimates. The RDA recommen-dations were determined to estimate the intakeneeded to meet the needs of 97–98% of the popula-tion, whereas an Adequate Intake is estimated tocover the needs for all individuals in a specific group.These estimates are supplemented by the TolerableUpper Intake Levels, an estimate of the maximalintake level that should not cause harm. Nutrientssuch as magnesium, calcium, and zinc are oftenlacking in women’s diets and may have effects on fetalgrowth and preterm delivery. In a randomized, pla-

Gestational age (weeks)

11.3 (25 lb)

28.1 (62 lb)

22.7 (50 lb)

22.2 (49 lb)

16.8 (37 lb)

15.9 (35 lb)

A382820

30

25

20

15

10

5

0

Wei

ght g

ain

(kilo

gram

s)

13.6 (30 lb) 18.1 (40 lb)

24.5 (54 lb)

13.6 (30 lb)

20.0 (44 lb)

9.1 (20 lb)

Gestational age (weeks) B382820

30

25

20

15

10

5

0

Wei

ght g

ain

(kilo

gram

s)11.3 (25 lb) 17.2 (38 lb)

21.3 (47 lb)

12.7 (28 lb)

16.8 (37 lb)

9.1 (20 lb)

Gestational age (weeks) C382820

30

25

20

15

10

5

0

Wei

ght g

ain

(kilo

gram

s)

9.1 (20 lb) 13.2 (29 lb)

17.2 (38 lb)

13.6 (30 lb)

9.5 (21 lb)

6.8 (15 lb)

Gestational age (weeks) D382820

30

25

20

15

10

5

0

Wei

ght g

ain

(kilo

gram

s)

Fig. 1. Body mass index-specific weight gain goals. A. Maternal weight gain in kilograms for underweight prepregnancybody mass index (BMI) (BMI less than 19.8 kg/m2). B. Maternal weight gain in kilograms for normal prepregnancy BMI (BMI19.8–26 kg/m2). C. Maternal weight gain in kilograms for overweight prepregnancy BMI (BMI 26.1–29 kg/m2). D. Maternalweight gain in kilograms for obese prepregnancy BMI (BMI more than 29 kg/m2). Modified from Luke B, Hediger ML, NugentC, Newman RB, Mauldin JG, Witter FR, et al. Body mass index-specific weight gains associated with optimal birth weightsin twin pregnancies. J Reprod Med 2003;48:217–24.Goodnight. Twin Nutrition. Obstet Gynecol 2009.


cebo controlled clinical trial in 2004, Hininger et al26

demonstrated that micronutrient supplementation (vi-tamin 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 87.5mg, and calcium carbonate 100 mg) in pregnancyresulted 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 amongsingleton pregnancies. There are fewer data availableon micronutrient supplementation in twin pregnan-cies. However, the expectation would be that similaror greater benefits may be expected because micro-nutrient needs are greater and deficiencies may bemore common in multiple gestations. Because twingestations are at increased risk for poor fetal growthand preterm birth, small improvements from benigninterventions such as micronutrient supplementationmay have significant benefits.

Although the majority of micronutrient supple-ments have a wide safety margin, notable potentiallyadverse complications may arise from excessive mi-cronutrient supplementation. Excessive doses of vita-min A (at least more than 10,000 international units/dand probably more than 25,000 international units/d)in pregnancy have been associated with fetal anoma-lies, including anomalies of the cardiovascular system,face and palate, ears, and genitourinary tract; thus, themaximal recommended vitamin A supplement inpregnancy is 8,000 international units/d. Excessivesupplementation of most other vitamins can result ingastrointestinal disturbances but seem without terato-genic effect.

CALCIUM AND VITAMIN DDuring in utero life, the fetus accumulates 25–30 g ofcalcium, the majority of which occurs in the thirdtrimester.27 Calcium is made available to the fetus byextraction from maternal bone mass and throughincreased maternal intestinal absorption.27 Maternalcalcium is also lost in pregnancy because of anincrease in urinary calcium excretion.28 An estimated200–300 mg/d increase in calcium intake aboveprepregnancy requirements is thus required to meetthe fetal demands and maintain maternal calciumhomeostasis.28 During lactation, there is a reduction inurinary calcium excretion.28 However, the majority ofpregnant women do not consume diets with an ade-quate calcium intake. Food sources for calcium areprimarily milk and dairy products, with some calciumin green leafy vegetables such as kale and turnipgreens, with approximately one third of ingested

calcium being absorbed. The IOM recommends acalcium intake in pregnancy of 1,000–1,300 mg daily(Tolerable Upper Intake Levels 2,500 mg). A Co-chrane review of calcium supplementation of at least1,000 mg daily in pregnancy, not specifically describ-ing twin gestations, demonstrated significant reduc-tions in the risks of hypertension (relative risk [RR]0.7, 95% confidence interval [CI] 0.57–0.86) andpreeclampsia (RR 0.48, 95% CI 0.33–0.69) in bothlow- and high-risk populations.29 The effects of cal-cium supplementation were most beneficial in high-risk women and in those with low dietary calciumintake.30 These findings are likely applicable to twinpregnancies because of the increased fetal demandsfor calcium and the increased baseline risk of pre-eclampsia in these gestations. Calcium supplementa-tion may also have fetal programming effects thatpersist into childhood. In a trial by Belizan et al,31

children of mothers who received calcium supple-ment in pregnancy had lower rates of hypertension(RR 0.59, 95% CI 0.39–0.9). The presence of mater-nal contraindications to calcium supplementation (eg,nephrolithiasis) may require reductions in the dailysupplement.

Vitamin D is also necessary for the appropriatemetabolism of calcium, and deficiency is common inpregnancy.32 Fetal vitamin D is dependent on mater-nal vitamin D levels, and low maternal vitamin D isthe dominant risk factor for neonatal rickets. Theactive metabolite of vitamin D is 1,25-dihydroxyvita-min D [1,25 (OH)2D], which facilitates intestinalcalcium absorption and calcium mobilization frombone, and decreases renal calcium excretion.33 Theserum 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�83pmol/L), compared with the nonpregnant state(100�32 pmol/L).28,33 The current Dietary ReferenceIntake recommendation for vitamin D is 400 interna-tional units/d based on estimated adequate intakes;however, supplementation at this dose in adults doesnot result in increased circulating 25(OH)D levels.34

Adults require sun exposure daily for conversion ofvitamin D to 1,25 (OH)2D, with whites requiring 0.5hours per day and African Americans requiring 5times this amount.34 For those with minimal sunexposure, supplementation during pregnancy shouldapproach 1,000 international units/d. Wagner andGreer35 report that vitamin D supplementation oflevels more than 1,000 international units/d are nec-essary to achieve normal vitamin D levels (more than50 nmol/L 25-OH-D). This supplement, plus appro-priate sun exposure, will not result in high levels


associated with hypervitaminosis D (hypercalciuria,hypercalcemia, and extraskeletal calcifications withsymptoms of nausea and vomiting and arthralgias),but will provide adequate vitamin D levels for mater-nal and fetal development.34 Vitamin D supplemen-tation during pregnancy has been associated with anincrease in birth weight as well as an increase innewborn weight gain,34 whereas deficiency has beenassociated with an increased risk of preeclampsia.36

Thus, vitamin D supplementation may be beneficialin twin gestations. The Dietary Reference Intakes/Tolerable Upper Intake Levels for calcium and Vita-min D are 1,300 mg/2,500 mg and 200 internationalunits/2,000 international units daily, thus the dietrecommendation for twin gestations includes 2,000–2,500 mg/d of calcium and 1,000 international unitsof vitamin D daily. Due to the variations in sunexposure and vitamin D levels, assessment of mater-nal vitamin D levels in twins should be considered infirst and early third trimester to allow alterations inthe supplement dosage. Attention to vitamin D sup-plement is especially important given the frequentoccurrence of complications resulting in bedrest intwin pregnancy.

ANTIOXIDANTS, VITAMIN C AND EThe role of antioxidant supplements to reduce the riskof preeclampsia and preterm birth has been investi-gated in pregnancy. Early studies demonstrated areduction in the recurrence of preeclampsia and animprovement in the plasminogen-activator inhibitorPAI-1 to PAI-2 ratio (favorable antioxidant measure)with vitamin C (1,000 mg) and vitamin E (400 micro-grams) supplementation during pregnancy.37,38 TheVIP trial,39 however, did not reveal any reduction inpreeclampsia either in the overall at-risk populationor in a subgroup of twin gestations. Nevertheless,analysis of serum vitamin C levels was noted to belower in the supplemented group who developedpreeclampsia compared with those who did not re-ceive supplementation. The VIP trial, however, dem-onstrated an increased risk of LBW in those withvitamin C and E supplementation (RR 1.15, 95% CI1.02–1.30, P�.02). Vitamin C has also been suggestedto provide protection against preterm premature rup-ture of membranes in singleton pregnancy.40 Antiox-idant trials to date have examined primarily singletongestations and demonstrate the most significant ben-efit in pregnancies with nutritional deficiencies. Thecurrent Dietary Reference Intakes/Tolerable UpperIntake Levels for vitamin C and E, respectively, are80/1,800 mg/d and 15/800 micrograms/d,41 makingsuggested intakes of 500–1,000 mg/400 micro-

grams/d vitamin C/vitamin E reasonable for twingestations, whereas specific trials in twin pregnancyawait. Vitamin C and E have not been associated withtoxicities at very high doses, with the exception ofgastrointestinal disturbances, and no adverse fetaleffects have been noted. Vegetable oils are the pri-mary source of vitamin E, whereas vitamin C is foundin citrus fruit and green vegetables.

ZINC AND MAGNESIUMZinc is necessary in several biologic systems, includ-ing protein synthesis and nucleic acid metabolism aswell as prevention of free radical formation. Meats,seafood, and eggs provide the optimal dietary sourcesof zinc. Zinc deficiency, although rare, may be asso-ciated with fetal neurologic malformations andgrowth restriction, and late pregnancy deficiency mayalso be associated with impaired brain function andbehavior abnormalities due to abnormal neuronalgrowth.42 Zinc supplementation in pregnancy mayimprove several pregnancy outcomes, including re-ducing preeclampsia and preterm birth, and result inimproved birth weight in deficient populations. Hin-niger et al26 demonstrated that maternal zinc levelswere not different between supplemented or placebogroups in a multinutrient supplement trial, but zinclevels did correlate well with neonatal length (r 0.58,P�.03). Although there are few data in twin gesta-tions, a systematic review of zinc supplementation of15–44 mg daily in pregnancy was associated with a14% reduction in preterm birth (RR 0.86, 95% CI0.76–0.98), with the majority of the effect seen innutritionally deficient populations.43 However, no ef-fect on birth weight was seen. Although zinc metab-olism has not been systematically studied in multiplegestations, zinc supplementation could theoreticallybe beneficial in this population at high risk forpreterm birth and LBW. The Dietary ReferenceIntakes/Tolerable Upper Intake Levels for zinc is 12mg/40 mg/d respectively.41 Zinc is not stored in thebody and virtually nontoxic; rare cases of leukopeniaand anemia have been reported with prolonged in-take of more than 50–300 mg/d. Based on NationalHealth and Nutrition Examination Survey III data,44

59% of pregnant women achieve adequate intake(supplement and diet) of zinc, with a mean dietaryintake of 9.2 (�2.1) mg. Thus achievement of dailyintake of zinc of 14–45 mg/d is recommended fortwin gestations, often requiring supplement.

Although individual trials of variable quality anddesign demonstrate conflicting results regarding theeffects of magnesium supplementation on pretermbirth and fetal growth, a systematic review by


Makrides and Crowther45 in singleton pregnanciesdemonstrated a reduction in preterm birth more than37 weeks (RR 0.73, 95% CI 0.57–0.94) and LBW (RR0.67, 95% CI 0.46–0.96). The authors of this analysissummarized that no conclusions about the beneficialeffects of magnesium supplementation on pregnancyoutcome could be made due to the poor quality of theincluded trials, and twin data remain lacking. TheDietary Reference Intake for magnesium in pregnancyis 350–460 mg/d and supplementation of up to 1,000mg daily has been suggested for twin gestations.14

ANEMIA AND IRON REQUIREMENTSIron deficiency is the most common nutritional defi-ciency worldwide, and has been associated with pre-term birth and low birth weight. In the United States,estimates of iron deficiency anemia in pregnancyrange from 5–17%, whereas estimates of low maternalferritin (less than 15 micrograms/L) with normalhemoglobin are seen in up to 20% of pregnantwomen. Fetal and neonatal iron deficiency, as mea-sured by cord blood ferritin level less than 30 micro-grams/L is associated with severe maternal anemia(hemoglobin less than 6.0 g/dL).46 Both mild maternalanemia (hemoglobin less than 8.5 g/dL) and a mater-nal ferritin level less than 12 micrograms/L are asso-ciated with poor fetal iron supply.46 Scholl et al47

demonstrated an association between iron deficiencyand poor maternal weight gain (adjusted odds ratio[AOR] 2.67, 95% CI 1.13–6.3). Additionally, irondeficiency anemia was also associated with an in-creased risk of preterm birth (AOR 2.66, 95% CI1.15–6.17) and LBW (AOR 3.10, 95% CI 1.16–4.39).47 Cogswell et al48 demonstrated that iron sup-plementation with 30 mg elemental iron daily re-sulted in a significant increase in birth weight (200 g)compared with placebo even in the presence ofnormal serum ferritin levels in the first trimester.

Twin pregnancies have lower maternal hemoglo-bin levels in the first and second trimesters and higherrates of iron deficiency anemia, and the resultinginfants have increased risk of residual iron deficiencyanemia for up to 6 months of age. The rate of irondeficiency anemia is 2.4–4 times higher than insingleton pregnancies. The iron requirement for twinpregnancy is estimated to be nearly twofold that of asingleton pregnancy.7 Rosello-Soberon et al7 reportedan estimated 869 mg elemental iron requirement fortwins compared with 476 mg for singleton pregnan-cies. Iron supplementation during the first and secondtrimesters has been associated with reductions in bothpreterm birth and LBW.49 In women with iron defi-ciency (serum ferritin less than 15 micrograms/L),

daily replacement with 60–120 mg of elemental ironwill increase the hemoglobin concentration by 1g/dLover 4 weeks.

The ideal source of iron supplementation is froman adequate diet that includes heme iron–rich foodsources such as red meat, pork, fish, and eggs. Thesesources of dietary iron are ideal in that they not onlyprovide iron that is more easily absorbed but alsorepresent a higher quality and quantity of protein.Nonheme iron sources, such as iron fortified bread,leafy green vegetables, and nuts, should also beencouraged both for their iron content as well as forthe presence of folate. The Dietary Reference Intake/Tolerable Upper Intake Levels for iron are 27 mg/45mg daily, respectively.41 Supplementation of nonane-mic twin gestations of 30 mg daily of elemental ironwould be appropriate to meet the increased maternaland fetal needs of the pregnancy.

Folic acid is also an important micronutrient inpregnancy because it is essential in DNA synthesisand cell division. Folate is required for the increase inmaternal red blood cells as well as for the growth ofthe fetus. Hyperhomocysteinemia is associated withdeficiency in folate and has been associated withintrauterine growth restriction, preeclampsia, and pla-cental abruption through vascular endothelial injury.Anemia due to folate deficiency is eight times morecommon in twins than in singleton pregnancy.7 Trialsof folic acid supplement in pregnancy have not dem-onstrated consistent improvements in pregnancy out-come, with one meta-analysis demonstrating a reduc-tion in the risk of low birthweight (RR 0.73, 95% CI0.53–0.99)50 and a retrospective review demonstrat-ing a reduction in the risk of preterm birth withpreconception folic acid supplementation.51 The cur-rent recommendation for folic acid in the preconcep-tion period and during pregnancy include 400 micro-grams/d, whereas the Dietary Reference Intake/Tolerable Upper Intake Levels for folate are 600micrograms/1,000 micrograms daily.41 Based onthese recommendations, 1mg daily folic acid is sug-gested for twin gestations.

OMEGA-3-FATTY ACIDSEssential fatty acids (EFA) are lipids that cannot besynthesized in the body and thus require appropriatedietary intake. Essential fatty acids are involved inmany metabolic processes, including energy storage,cell membrane function (including neuronal develop-ment), control of inflammation, and control of throm-bosis.52 Two groups of EFA exist: omega-6 (�-6FA:linoleic acid, derived from cereals, grains, processedfoods, meat, milk, eggs, and oils, including corn,


sunflower, safflower, and sesame) and omega-3 (�-3FA: �-linolenic acid, only found in selected seeds,nuts, and fish oils).52 Because plant sources may notcontain the necessary docosahexaenoic acid (DHA)component of �-3FA, the optimal nutritional source isfish oils. Optimal homeostatic inflammatory andthrombotic states have been theorized to result from abalance between �-3FA and �-6FA, with ideal dietshaving a ratio of �-6 to �-3 of 1–2:1.52 A deficiency in�-3 results in a prothrombotic and proinflammatorystate that has been associated with an increased risk ofcardiovascular and inflammatory diseases.52 A typicalWestern diet currently has an �-6 to �-3 ratio of16:1.52

In comparison with singleton pregnancies, neo-nates born of twin pregnancies have lower levels of�-3FA in the walls of their umbilical veins andarteries, indicating an inadequate dietary supply.53 Anin vitro trial of singleton and twin pregnancies dem-onstrated that DHA concentration in fetal erythrocytemembrane was directly related to maternal concen-tration and that lower concentration of �-3FA wasassociated with increased membrane rigidity and in-creased resistance to flow.54 In this study, the meanerythrocyte DHA concentration was significantly lowerin twin gestations, leading the authors to conclude thatfetal demand for DHA in multiple pregnancies may notbe satisfied by typical dietary intake.54

Epidemiologic data from the Faroe Islands,where diets are rich in marine oils, suggest that dietswith a more favorable �-6 to �-3 ratio increase birthweight through either prolongation of pregnancy orby optimizing the fetal growth rate.55 In prospectivetrials, fish oil supplementation of 2.7g of �-3FA dailyhas been shown to prevent recurrent preterm birth insingleton pregnancies (OR 0.54, 95% CI 0.3–0.98),with a trend toward a reduction in preterm birthamong twins.56 Smuts et al57 also demonstrated anincrease in length of gestation by 6.0�2.3 days amongsingleton gestations randomized to receive supple-mental DHA (133 mg daily) in the third trimester.Trends for increased neonatal length and head cir-cumference were also noted.57

Controversy exists as to the risk of contaminants,notably methyl mercury (MeHg) and polychlorinatedbiphenyls, found in fish that are rich in �-3FA.Exposure to extremely high levels of MeHg is asso-ciated with microcephaly, seizures, cerebral palsy,and learning deficiency. Such exposures have oc-curred as a result of toxic environmental spills anddeliberate poisoning. However, epidemiologic studiesfrom the Seychelles, in which 85% of the populationconsume ocean fish containing MeHg levels compa-

rable to fish consumed in the United States (0.05–0.25ppm methylmercury) on a daily basis, have notdemonstrated adverse neurodevelopmental delay inthe offspring to 66 months of life.58 Maternal con-sumption of seafood in a large epidemiologic study inEngland demonstrated that low maternal consump-tion (less than 340 g/wk) was associated with anincreased risk of their children being in the lowestquartile for verbal IQ, as well as more commonsuboptimal social behaviors, fine motor and commu-nication skills, and social development scores,59 sug-gesting low �-3FA exposure being associated with anincreased risk of adverse neurologic development.

The World Health Organization currently recom-mends 300–500 mg per day of �-3FA (such as DHAand eicosapentaenoic acid) in an effort to promotefetal and early childhood mental development. Con-sumption of at least two meals (12 oz total) weekly oflow-mercury–containing fish (eg, shrimp, cannedlight tuna, salmon, pollock, and catfish) by pregnantwomen, those planning pregnancy, or breastfeedingwomen, contributes to an adequate �-3FA intake foroptimal fetal neurodevelopmental and obstetric out-comes. It remains wise to follow the U.S. Environ-mental Protection Agency recommendations to avoidhighly contaminated fish (eg. shark, swordfish, kingmackerel, tilefish) during pregnancy. Purified nutri-tional supplements of fish oil can be used to achievethe goal of 300–500 mg daily of DHA. Other sourcesof �-3FA include sunflower, safflower, corn, andsoybean oil, as well as egg yolk, meat, and spinach.

Although most nutritional supplement trials inpregnancy have shown modest effects on the rates ofpreeclampsia and preterm birth, at best, these out-comes have usually been improved when deficientpopulations received supplementation. These find-ings are likely applicable to twin pregnancy, in whichthe added demands are typically not met by routinedietary intake. Even among middle- to upper-incomewomen with advanced education, Turner et al60 dem-onstrated that pregnant women (singleton gestations)remain at risk for suboptimal intake of some micro-nutrients. In this study, the probability of intake lessthan the estimated average requirement for iron was91%, zinc 31%, magnesium 53%, and vitamin B621%.59 Given the likelihood of increased micronutri-ent requirements in twin gestations, high risk ofmicronutrient deficiency, and the potential benefit ofmicronutrient supplementation in deficiency states,our practice is to recommend the supplement de-scribed in this review for twin pregnancies.


SPECIALIZED TWIN NUTRITIONALPROGRAMS AND PROVIDERINTERVENTIONSGiven the importance of attention to nutrition inmultifetal gestations, consultation with a registereddietitian is encouraged if available. The constraintsassociated with traditional prenatal care visits usuallydo not allow adequate time for in-depth counselingand education regarding the importance of diet andadequate nutrition. Nutritional consultation can alsoresult in the development of individualized BMI-specific weight gain recommendations, ongoing track-ing of maternal weight gain, and interventions tomodify maternal diet when women either exceed orfail to meet their recommended weight gain goals.Surveys of women carrying twins reveal that morethan 25% receive no advice at all regarding weightgain and that among those who do receive nutritionalcounseling, the guidance is often incorrect.61 Clinicalstudies have suggested that prenatal care for twinpregnancies provided through specialized, multidisci-plinary multiple-gestation programs or clinics resultsin improved maternal and neonatal outcomes.62–64 Amainstay of these interventions is the grouping ofwomen with multiple gestations into specialty clinicsthat have a strong emphasis on nutritional evaluationand education in addition to the provision of prenatalcare.

In the Michigan Multiples Clinic, women withmultiple gestations received prenatal care in a settingthat provides twice monthly dietitian and nurse prac-titioner visits for dietary counseling, along with phy-sician-directed prenatal care visits. Nutritional modi-fications emphasized in this program includedmultimineral supplementation with daily calcium car-bonate (3 g), magnesium oxide (1.2 g), zinc oxide (45mg) in addition to a multivitamin with 100% RDA fornonpregnant recommendations (increased to 200%RDA at 20 weeks).63 The recommended diet compo-sition included 3,000–4,000 kcal/d, composed of 20%protein, 40% carbohydrates, and 40% fat, divided intothree meals and three snacks daily. Compared withnonparticipants, Nutritional Intervention Programmothers were more likely to meet weight gain goals at20 and 28 weeks and had fewer pregnancy complica-tions (Fig. 2). Program participants also demonstratedan increase in the length of gestation (13.1 daysP�.001), increased birth weight (435 g, P�.001), 7.4fewer hospital admission days (P�.001), and reducedrates of preterm labor and LBW.62 These reductionsin adverse pregnancy outcomes resulted in a costsavings of $52,553 in hospital charges per twin pair.63

Follow up of the twins at 8, 18, and 36 monthsdemonstrated that children of program nonpartici-pants were more likely to have lagging growth (AOR1.76, 95%CI 1.26–2.45) and more likely to be classi-fied as developmentally delayed (AOR 1.55, 95% CI1.04–2.31).63

A similar program was conducted as part of theHiggins Nutritional Intervention Program conductedby the Montreal Diet Dispensary, emphasizing indi-vidualized nutrition assessment and similar diet rec-ommendations as the Michigan Multiples Clinic. TheHiggins Program demonstrated a 27% reduction inLBW (OR 0.73, 95% CI 0.54–0.99) along with areduction in early pregnancy low weight gain (OR0.49, 95% CI 0.26–0.93) in those receiving the inter-vention compared with a matched control popula-tion.62 Similar trends toward a reduction in very lowbirth weight and preterm birth were also noted in theintervention group. Although these studies lacked arandomized prospective design, they suggest that estab-lishment of twin pregnancy–specific nutritional recom-mendations, together with intensive education and con-tinued maternal assessment and counseling, canimprove birth weights and prolong the length of gesta-tion in twin pregnancies in a cost-effective manner.

Finally, does physician input into nutritional ed-ucation influence the patient’s attention to proper

Fig. 2. University of Michigan Nutrition Intervention Pro-gram rates of twin pregnancy outcomes (all differencesP�.01). Major morbidity defined as any of retinopathy ofprematurity, necrotizing enterocolitis, ventilator support, orintraventricular hemorrhage. Very low birth weight, lessthan 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 out-comes in twin pregnancy. Am J Obstet Gynecol 2003;189:934–8.)Goodnight. Twin Nutrition. Obstet Gynecol 2009.


nutrition? Although evaluated in few clinical trials intwin gestations, several clinical trials demonstrate thatprovider input into nutritional education is able toaffect maternal weight gain and nutritional status inpregnancy,65,66 and antenatal consultation improvesinitiation of lactation in twin pregnancy.67 Tools avail-able for provider counseling include individual coun-seling at prenatal care visits, nutrition or dietitianreferrals, placement and serial review of maternalweight gain graphs during the pregnancy in theobstetric record, and review of dietary recall surveys,which are commercially available.

POSTPARTUM AND BREASTFEEDINGThe importance of nutrition for twin gestations doesnot end after delivery, because proper nutrition isnecessary to support breastfeeding. Rates of initiationof breastfeeding in twins can range from 40–90%,with wide population variation.68 Complications suchas prematurity, low birth weight, and neonatal sepsiscan adversely affect rates of twin breastfeeding. Thereare few evidence-based recommendations for specific

diet modifications for breastfeeding twins; however,some suggestions may be beneficial. Milk productionmay be 1.2–2 L per day by the second month of lifeand require an excess maternal caloric intake of1,200–1,500 kcal/d.68 A diet similar to that duringpregnancy is recommended (20% of calories fromprotein, 40% from carbohydrates, and 40% from fat),and continuation of a prenatal vitamin supplement,including DHA is recommended.68 Diets with totaldaily caloric intake during lactation of less than 2,700cal/d may also be at risk for micronutrient deficiencyin calcium, magnesium, zinc, vitamin B6, and folate.Until further specific research is completed, continu-ation of micronutrient supplementation as in theantenatal care of twins into the lactation period isreasonable to prevent such micronutrient limitations.

FUTURE RESEARCHSeveral unanswered questions remain regarding therole of maternal nutrition in improving outcomes intwin gestation. The effects of specific diet compositionon maternal weight gain and neonatal birth weight

Table 3. Twin Pregnancy Nutritional Recommendations

Intervention First Trimester Second Trimester Third Trimester

Maternal weight/weight gain Assess maternal pregravidBMI, determine BMI-specific weight gain goals

Assess/counsel re: maternalBMI-specific weight gain (eachprenatal care visit)

Assess/counsel re: maternalBMI-specific weight gain (eachprenatal care visit)

Caloric requirements (kcal·kg–1·d–1)

Normal BMI 40–45 Alter as necessary for weightgain goal

Alter as necessary for weightgain goal

Underweight 42–50Overweight 30–35

Micronutrient Supplement(daily total intake)

MVI with iron (30 mgelemental tablets)

1 2 2

Calcium (mg) 1,500 2,500 2,500Vitamin D (international

units)1,000 1,000 1,000

Magnesium (mg) 400 800 800Zinc (mg) 15 30 30DHA/EPA (mg) 300–500 300–500 300–500Folic Acid (mg) 1 1 1Vitamin C/E (mg/

international units)500–1,000/400 500–1,000/400 500–1,000/400

Nutritional consultation Yes Repeat if not at weight gaingoal, anemia, GDM

Repeat if not at weight gaingoal, anemia, GDM

Laboratory nutritionalassessment

Hemoglobin ferritin folate/B12 early screen for GDM(risk factors) vitamin D

Follow up abnormalities fromfirst trimester

Hemoglobin ferritin GDM screenwith or without vitamin D

Risk Factor appropriateexercise or reductionin activity

Screen Screen Screen

BMI, body mass index; MVI, multivitamin; DHA, docosahexaenoic acid; EPA, eicosapentaenoic acid; GDM, gestational diabetes mellitus.


and body composition can be explored. Systematicreviews of nutrient use throughout the twin gestationare lacking. Research into the maternal nutrient levelsassociated with optimal fetal growth in early and latepregnancy may determine baseline values for screen-ing and supplementation as necessary. Evaluation ofthe effect of supplements such as zinc, magnesium,and �-3FA on neurodevelopmental outcomes are alsoneeded. Further evaluation of maternal calcium ho-meostasis and vitamin D metabolism in multiplepregnancies and the effect on bone mineral density ofthe offspring are also warranted. If optimal nutritioncan result in increases in twin birth weights, modestprolongations of pregnancy, or neurobehavioral ben-efits as has been suggested in retrospective trials, thenfuture prospective controlled trials of nutritional in-terventions in twin pregnancies are needed.

CONCLUSIONWe have discussed the nutritional recommendationsand evaluation used in our institutions for twin preg-nancies, summarized in Table 3. The current litera-ture supports the benefits of BMI-specific weight gainguidelines specific for twin gestations for improvedtwin birth weight. Thus our practice is to trackmaternal weight gain through the pregnancy andprovide nutrition consultation to achieve these goals.Twin pregnancy is also at risk for micronutrientdeficiency and thus supplementation with iron, cal-cium, and folate, beyond a typical prenatal vitamin, isrecommended. Finally, �-3FA dietary intake or sup-plementation is also encouraged for potential neuro-developmental benefits. Although nutritional inter-vention may not reduce all perinatal morbidityassociated with twin pregnancy, increased attention tospecific nutritional needs in twin-specific prenatalcare settings have been associated with improvedneonatal outcomes and should be incorporated intothe prenatal care of twins.

REFERENCES1. Luke B. Reducing fetal deaths in multiple births: optimal

birthweights and gestational ages for infants of twin and tripletbirths. Acta Genet Med Gemellol (Roma) 1996;45:333–48.

2. Luke B, Minogue J. The contribution of gestational age andbirthweight to perinatal viability in singleton versus twins.J Matern Fetal Med 1994;3:263–74.

3. Papiernik E, Keith L, Oleszczuk JJ, Cervantes A. What inter-ventions are useful in reducing the rate of preterm delivery intwins? Clin Obstet Gynecol 1998;41:12–23.

4. Demarini S, Koo W, Hockman E. Bone, lean and fat mass ofnewborn twins versus singletons. Acta Paediatr 2006;95:594–9.

5. Yildiz A, Balikci E, Gurdogan F. Serum mineral levels atpregnancy and postpartum in single and twin pregnant sheep.Biol Trace Elem Res 2005;107:247–54.

6. Acosta-Rojas R, Becker J, Munoz-Abellana B, Ruiz C, CarrerasE, Gratacos E, et al. Twin chorionicity and the risk of adverseperinatal outcome. Int J Gynaecol Obstet 2007;96:98–102.

7. Rosello-Soberon M, Fuentes-Chaparro L, Casanueva E. Twinpregnancies: eating for three? Maternal nutrition update. NutrRev 2005;63:295–302.

8. Krafft A, Breymann C, Streich J, Huch R, Huch A. Hemoglo-bin concentration in multiple versus singleton pregnancies—retrospective evidence for physiology not pathology. Eur JObstet Gynecol Reprod Biol 2001;99:184–7.

9. Shinagawa S, Suzuki S, Chihara H, Otsubo Y, Takeshita T,Araki T. Maternal basal metabolic rate in twin pregnancy.Gynecol Obstet Invest 2005;60:145–8.

10. Casele H, Dooley S, Metzger BE. Metabolic response to mealeating and extended overnight fast in twin gestation. Am JObstet Gynecol 1996;175:917–21.

11. Dietary guidelines for Americans 2005. Available at:www.healthierus.gov/dietaryguidelines. Retrieved June 18,2008.

12. Luke B. Improving multiple pregnancy outcomes with nutri-tional interventions. Clin Obstet Gynecol 2004;47:146–62.

13. Moore V, Davies M, Willson K, Worsley A, Robinson J.Dietary composition of pregnant women is related to size of thebaby at birth. J Nutr 2004;134:1820–6.

14. Luke B. Nutrition and multiple gestation. Semin Perinatol2005;29:349–54.

15. Pederson A, Worthington-Roberts B, Hickok DE. Weight gainpatterns during twin gestation. J Am Diet Assoc 1989;89:642–6.

16. Luke B, Gillespie B, Min SJ, Avni M, Witter FR, O’SullivanMJ. Critical periods of maternal weight gain: effect on twinbirth weight. Am J Obstet Gynecol 1997;177:1055–62.

17. Lantz M, Chez RA, Rodriguez A, Porter KB. Maternal weightgain patterns and birth weight outcome in twin gestation.Obstet Gynecol 1996;87:551–6.

18. Luke B, Minogue J, Witter FR, Keith LG, Johnson TR. Theideal twin pregnancy: patterns of weight gain, discordancy andlength of gestation. Am J Obstet Gynecol 1993;169:588–97.

19. Luke B. The evidence linking maternal nutrition and prema-turity. J Perinat Med 2005;33:500–5.

20. Luke B. What is the influence of maternal weight gain on thefetal growth of twins. Clin Obstet Gynecol 1998;41:57–64.

21. Luke B, Hediger ML, Nugent C, Newman RB, Mauldin JG,Witter FR, et al. Body mass index–specific weight gainsassociated with optimal birth weights in twin pregnancies.J Reprod Med 2003;48:217–24.

22. Institute of Medicine. Weight gain during pregnancy: reexam-ining the guidelines. Washington (DC): The National Acade-mies Press; 2009.

23. Wells C, Schwalberg R, Noonan G, Gabor V. Factors influ-encing inadequate and excessive weight gain in pregnancy:Colorado, 2000–2002. Matern Child Health J 2006;10:55–62.

24. Viswanathan M, Siega-Riz A, Moos MK, Deierlein S, Mum-ford S, Knaack, TP, Lux LJ, Lohr KN. Outcomes of maternalweight gain, evidence reports/technology assessment no. 168.AHRQ Publication Number 08-E-09. Rockville (MD): Agencyfor Healthcare Research and Quality; 2008.

25. Amorim A, Rossner S, Neovius M, Lourenco PM, Linne Y.Does excessive pregnancy weight gain constitute a major riskfor increasing long-term BMI. Obesity (Silver Spring) 2007;15:1278–86.

26. Hininger I, Favier M, Arnaud J, Faure H, Thoulon JM,Hariveau E, et al. Effects of a combined micronutrient supple-


mentation on maternal biological status and newborn anthro-pometrics measurements: a randomized double-blind, place-bo-controlled trial in apparently healthy pregnant women. EurJ Clin Nutr 2004;58:52–9.

27. Thomas M, Weisman SM. Calcium supplementation duringpregnancy and lactation: effects on the mother and the fetus.Am J Obstet Gynecol 2006;194:937–45.

28. Ritchie L, Fung E, Halloran B, Turnlund JR, Van Loan MD,Cann CE, et al. A longitudinal study of calcium homeostasisduring human pregnancy and lactation and after resumptionof menses. Am J Clin Nutr 1998;67:693–701.

29. Hofmeyr G, Atallah AN, Duley L. Calcium supplementationduring pregnancy for preventing hypertensive disorders andrelated problems. The Cochrane Database of SystematicReviews 2006, Issue 3. Art. No.: CD001059. DOI: 10.1002/14651858.CD001059.pub2.

30. Hofmeyr GJ, Duley L, Atallah A. Dietary calcium supple-mentation for prevention of pre-eclampsia and related prob-lems: a systematic review and commentary. BJOG 2007;114:933–43.

31. Belizan J, Villar J, Bergel E, del Pino A, Di Fulvio S, GallianoSV, et al. Long-term effect of calcium supplementation duringpregnancy in the blood pressure of offspring: follow up of arandomized controlled trial. BMJ 1997;315:281–5.

32. Bodnar L, Simhan H, Powers R, Frank M, Cooperstein E,Roberts J. High prevalence of vitamin D insufficiency in blackand white pregnant women residing in the Northern UnitedStated and their neonates. J Nutr 2007;137:447–52.

33. Specker B. Vitamin D requirements during pregnancy. AmJ Clin Nutr 2004;80:1740S–7S.

34. Hollis B, Wagner C. Assessment of dietary vitamin D require-ments during pregnancy and lactation. Am J Clin Nutr 2004;79:717–26.

35. Wagner C, Greer F, American Academy of PediatricsSection on Breastfeeding, American Academy of PediatricsCommittee on Nutrition. Prevention of rickets and vitaminD deficiency in infants, children, and adolescents [publishederratum in Pediatrics 2009;123:197]. Pediatrics 2008;122:1142–52.

36. Bodnar L, Catov JM, Simhan H, Holick M, Powers R, RobertsJ. Maternal vitamin D deficiency increases the risk of pre-eclampsia. J Clin Endocrinol Metab 2007;92:3517–22.

37. Chappell L, Seed PT, Briley AL, Kelly FJ, Lee R, Hunt BJ, etal. Effect of antioxidants on the occurrence of pre-eclampsia inwomen at increased risk: a randomised trial. Lancet 1999;354:810–6.

38. Chappell L, Seed PT, Kelly FJ, Briley A, Hunt BJ, Charnock-Jones DS, et al. Vitamin C and E supplementation in womenat risk of preeclampsia is associated with changes in indices ofoxidative stress and placental function. Am J Obstet Gynecol2002;187:777–84.

39. Poston L, Briley AL, Seed PT, Kelly FJ, Shennan AH, Vita-mins in Pre-eclampsia (VIP) Trial Consortium. Vitamin C andvitamin E in pregnant women at risk for pre-eclampsia (VIPtrial): randomised placebo-controlled trial. Lancet 2006;367:1145–54.

40. Casanueva E, Ripoll C, Tolentino M, Morales RM, Pfeffer F,Vilchis P, et al. Vitamin C supplementation to prevent prema-ture rupture of the chorioamnionic membranes: a randomizedtrial. Am J Clin Nutr 2005;81:859–63.

41. Dietary Reference Intakes. 2007 [cited 2007; Available from:http://www.nap.edu.

42. Black R. Micronutrients in pregnancy. Br J Nutr 2001;85:S193–7.

43. Mahomed K, Bhutta Z, Middleton P. Zinc supplementation forimproving pregnancy and infant outcomes. The CochraneDatabase of Systematic Reviews 2007, Issue 3. Art. No.:CD000230. DOI: 10.1002/14651858.CD000230.pub3.

44. Briefel RR, Bialostosky K, Kennedy-Stephenson J, McDowellMA, Ervin RB, Wright JD. Zinc intake of the U.S. popula-tion: findings from the third National Health and Nutri-tion Examination Survey, 1988 –1994. J Nutr 2000;130:1367S–73S.

45. Makrides M, Crowther CA. Magnesium supplementationin pregnancy. The Cochrane Database of SystematicReviews 2001, Issue 4. Art. No.: CD000937. DOI: 10.1002/14651858.CD000937.

46. Rao R, Georgieff M. Iron in fetal and neonatal nutrition. SeminFetal Neonatal Med 2007;12:54–63.

47. Scholl T, Hediger ML, Fischer RL, Shearer JW. Anemia vsiron deficiency: increased risk of preterm delivery in a pro-spective study. Am J Clin Nutr 1992;55:985–8.

48. Cogswell M, Parvanta I, Ickes L, Yip R, Brittenham GM.Iron supplement during pregnancy, anemia, and birthweight: a randomized controlled trial. Am J Clin Nutr2003;78:773–81.

49. Jackson A, Bhutta ZA, Lumbiganon P. Nutrition as a preven-tative strategy against adverse pregnancy outcomes. Introduc-tion. J Nutr 2003;133:1589S–91S.

50. Charles D, Ness A, Campbell D, Smith GD, Whitley E, HallM. Folic acid supplements in pregnancy and birth outcome:re-analysis of a large randomized controlled trial and updateof Cochrane review. Paediatr Perinat Epidemiol 2005;19:112–24.

51. Bukowski R, Malone FD, Porter FT, Nyberg DA, ComstockCH, Hankins GD, et al. Preconceptional folate supplementa-tion and the risk of spontaneous preterm birth: a cohort study.PLoS Med 2009;6:e1000061.

52. Genuis S, Schwalfenberg GK. Time for an oil check: the role ofessential omega-3 fatty acids in maternal and pediatric health.J Perinatol 2006;26:359–65.

53. Foreman-van Drongelen M, Zeijdner E, van Houwelingen A,Kester A, Al M, Hasaart T, et al. Essential fatty acid statusmeasured in umbilical vessel walls of infants born after amultiple pregnancy. Early Hum Dev 1996;46:205–15.

54. McFadyen M, Farquharson J, Cockburn F. Maternal andumbilical cord erythrocyte omega-3 and omega-6 fatty acidsand haemorheology in singleton and twin pregnancies. ArchDis Child Fetal Neonatal Ed 2003;88:F134–8.

55. Olsen S, Hansen HS, Sorensen TI, Jensen B, Secher NJ,Sommer S, et al. Intake of marine fat, rich in (n-3)-polyunsat-urated fatty acids, may increase birthweight by prolonginggestation. Lancet 1986;22:367–9.

56. Olsen S, Secher N, Tabor A, Weber T, Walker JJ, Gluud C.Randomised clinical trials of fish oil supplementation in highrisk pregnancies. Fish Oil Trials In Pregnancy (FOTIP) Team.BJOG 2000;107:382–95.

57. Smuts C, Huang M, Mundy D, Plasse T, Major S, Carlson SE.A randomized trial of docosahexaenoic acid supplementationduring the third trimester of pregnancy. Obstet Gynecol2003;101:469–79.

58. Davidson P, Myers G, Cox C, Axtell C, Axtell C, Shamlaye C,Sloane-Reeves J, et al. Effects of prenatal and postnatal meth-ylmercury exposure from fish consumption on neurodevelop-ment: outcomes at 66 months of age in the Seychelles ChildDevelopment Study. JAMA 1998;280:701–7.

59. Hibbeln J, Davis JM, Steer C, Emmett P, Rogers I, Williams C,et al. Maternal seafood consumption in pregnancy andneurodevelopmental outcomes in childhood (ALSPAC


study): an observational cohort study. Lancet 2007;369:578–85.

60. Turner R, Langkamp-Henken B, Littell R, Lukowski M, SuarezM. Comparing nutrient intake from food to the estimatedaverage requirements shows middle- to upper-income preg-nant women lack iron and possibly magnesium. J Am DietAssoc 2003;103:461–6.

61. Cogswell M, Scanlon KS, Fein SB, Schieve LA. Medicallyadvised, mother’s personal target, and actual weight gainduring pregnancy. Obstet Gynecol 1999;94:616–22.

62. Dubois S, Dougherty C, Duquette M, Hanley J, Moutquin J.Twin pregnancy: the impact of the Higgins Nutrition Interven-tion Program on maternal and neonatal outcomes. Am J ClinNutr 1991;53:1397–403.

63. Luke B, Brown MB, Misiunas R, Anderson E, Nugent C, vande Ven C, et al. Specialized prenatal care and maternal andinfant outcomes in twin pregnancy. Am J Obstet Gynecol2003;189:934–8.

64. Ellings J, Newman RB, Hulsey TC, Bivins HA Jr, Keenan A.Reduction in very low birth weight deliveries and perinatalmortality in a specialized, multidisciplinary twin clinic. ObstetGynecol 1993;81:387–91.

65. Piirainen T, Isolauri E, Lagstrom H, Laitinen K. Impactof dietary counseling on nutrient intake during pre-gnancy: a prospective cohort study. Br J Nutr 2006;96:1095–104.

66. Asbee S, Jenkins TR, Butler JR, White J, Elliot M, Rutledge A.Preventing excessive weight gain during pregnancy throughdietary and lifestyle counseling: a randomized controlled trial.Obstet Gynecol 2009;113:305–12.

67. Friedman S, Flidel-Rimon O, Lavie E, Shinwell ES. The effect ofprenatal consultation with a neonatologist on human milk feedingin preterm infants. Acta Paediatr 2004;93:775–8.

68. Flidel-Rimon O, Shinwell ES. Breast feeding twins and highmultiples. Arch Dis Child Fetal Neonatal Ed 2006;91:F377–80.


optimal nutrition for improved twin pregnancy outcome · optimal nutrition for improved twin...

Documents