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The association between first-trimester omega-3 fatty acid supplementation and fetal growth trajectories

  • Yassaman Vafai
    Affiliations
    Epidemiology Branch, Division of Population Health Research, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD
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  • Edwina Yeung
    Affiliations
    Epidemiology Branch, Division of Population Health Research, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD
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  • Anindya Roy
    Affiliations
    University of Maryland Baltimore County, Baltimore, MD
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  • Dian He
    Affiliations
    Epidemiology Branch, Division of Population Health Research, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD

    The Prospective Group, Inc, Fairfax, VA
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  • Mengying Li
    Affiliations
    Epidemiology Branch, Division of Population Health Research, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD
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  • Stefanie N. Hinkle
    Affiliations
    Department of Biostatistics, Epidemiology and Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA
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  • William A. Grobman
    Affiliations
    Feinberg School of Medicine, Northwestern University, Chicago, IL
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  • Roger Newman
    Affiliations
    Department of Obstetrics and Gynecology, Medical University of South Carolina, Charleston, SC
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  • Jessica L. Gleason
    Affiliations
    Epidemiology Branch, Division of Population Health Research, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD
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  • Fasil Tekola-Ayele
    Affiliations
    Epidemiology Branch, Division of Population Health Research, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD
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  • Cuilin Zhang
    Affiliations
    Epidemiology Branch, Division of Population Health Research, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD

    Global Center for Asian Women’s Health, Bia-Echo Asia Centre for Reproductive Longevity & Equality, Yong Loo Lin School of Medicine, National University of Singapore, Singapore

    Department of Obstetrics and Gynaecology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore
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  • Katherine L. Grantz
    Correspondence
    Corresponding author: Katherine L. Grantz, MD, MS.
    Affiliations
    Epidemiology Branch, Division of Population Health Research, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD
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Published:August 08, 2022DOI:https://doi.org/10.1016/j.ajog.2022.08.007

      Background

      Prenatal omega-3 fatty acid supplementation, particularly docosahexaenoic acid and eicosapentaenoic acid, has been associated with greater birthweight in clinical trials; however, its effect on fetal growth throughout gestation is unknown.

      Objective

      This study aimed to examine the association between first-trimester docosahexaenoic acid and eicosapentaenoic acid supplementation and growth trajectories of estimated fetal weight and specific fetal biometrics measured longitudinally from the second trimester of pregnancy to delivery.

      Study Design

      In a multisite, prospective cohort of racially diverse, low-risk pregnant women, we used secondary data analysis to examine fetal growth trajectories in relation to self-reported (yes or no) first-trimester docosahexaenoic acid and eicosapentaenoic acid supplementation. Fetal ultrasonographic measurements, including abdominal circumference, biparietal diameter, femur length, head circumference, and humerus length, were measured at enrollment (8–13 weeks) and up to 5 follow-up visits. Estimated fetal weight and head circumference–to–abdominal circumference ratio (a measure of growth symmetry) were calculated. Fetal growth trajectories were modeled for each measure using a linear mixed model with cubic splines. If significant differences in fetal growth trajectories between groups were observed (global P<.05), weekly comparisons were performed to determine when in gestation these differences emerged. Analyses were adjusted for maternal sociodemographics, parity, infant sex, total energy consumption, and diet quality score. All analyses were repeated using dietary docosahexaenoic acid and eicosapentaenoic acid intake, dichotomized at the recommended cutoff for pregnant and lactating women (≥0.25 vs <0.25 g/d), among women who did not report supplement intake in the first trimester of pregnancy were repeated.

      Results

      Among 1535 women, 143 (9%) reported docosahexaenoic acid and eicosapentaenoic acid supplementation in the first trimester of pregnancy. Overall, first-trimester docosahexaenoic acid and eicosapentaenoic acid supplementation was associated with statistically significant differences (P-value <.05) in fetal growth trajectories during pregnancy. Specifically, estimated fetal weight was larger among women with docosahexaenoic acid and eicosapentaenoic acid supplementation than among those without supplementation (global P=.028) with significant weekly differences in median estimated fetal weight most apparent between 38 to 41 weeks of gestation (median estimated fetal weight difference at 40 weeks of gestation, 114 g). Differences in fetal growth trajectories for abdominal circumference (P=.003), head circumference (P=.003), and head circumference–to–abdominal circumference ratio (P=.0004) were also identified by supplementation status. In weekly comparisons, docosahexaenoic acid and eicosapentaenoic acid supplement use was associated with larger median abdominal circumference (changed from 2 to 9 mm) in midpregnancy onward (19 to 41 weeks), larger median head circumference between 30 to 33 weeks of gestation, and smaller median head circumference–to–abdominal circumference ratio in the second and third trimesters of pregnancy. There was no specific weekly difference in fetal femur length or humerus length by docosahexaenoic acid and eicosapentaenoic acid supplementation. First-trimester dietary sources of docosahexaenoic acid and eicosapentaenoic acid among women with no first-trimester docosahexaenoic acid and eicosapentaenoic acid supplementation (n=1392) were associated with differences in fetal biparietal diameter (P=.043), but not other metrics of fetal growth. At the recommended dietary docosahexaenoic acid and eicosapentaenoic acid levels compared with below-recommended levels, biparietal diameter was larger between 38 to 41 weeks of gestation.

      Conclusion

      In this racially diverse pregnancy cohort, first-trimester docosahexaenoic acid and eicosapentaenoic acid supplementation was associated with significant increases in fetal growth, specifically greater estimated fetal abdominal circumference in the second and third trimesters of pregnancy.

      Key words

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      References

        • Thompson M.
        • Hein N.
        • Hanson C.
        • et al.
        Omega-3 fatty acid intake by age, gender, and pregnancy status in the United States: national health and nutrition examination survey 2003-2014.
        Nutrients. 2019; 11: 177
        • U.S. Department of Health and Human Services
        Office of Disease Prevention and Health Promotion.
        2015–2020 dietary guidelines. health.gov. 2021; (Available at:)
        • Taylor C.M.
        • Emmett P.M.
        • Emond A.M.
        • Golding J.
        A review of guidance on fish consumption in pregnancy: is it fit for purpose?.
        Public Health Nutr. 2018; 21: 2149-2159
        • Oken E.
        • Radesky J.S.
        • Wright R.O.
        • et al.
        Maternal fish intake during pregnancy, blood mercury levels, and child cognition at age 3 years in a US cohort.
        Am J Epidemiol. 2008; 167: 1171-1181
        • Halldorsson T.I.
        • Thorsdottir I.
        • Meltzer H.M.
        • Nielsen F.
        • Olsen S.F.
        Linking exposure to polychlorinated biphenyls with fatty fish consumption and reduced fetal growth among Danish pregnant women: a cause for concern?.
        Am J Epidemiol. 2008; 168: 958-965
        • Conway M.C.
        • Mulhern M.S.
        • McSorley E.M.
        • et al.
        Dietary determinants of polyunsaturated fatty acid (PUFA) status in a high fish-eating cohort during pregnancy.
        Nutrients. 2018; 10: 927
        • Middleton P.
        • Gomersall J.C.
        • Gould J.F.
        • Shepherd E.
        • Olsen S.F.
        • Makrides M.
        Omega-3 fatty acid addition during pregnancy.
        Cochrane Database Syst Rev. 2018; 11: CD003402
        • Grootendorst-van Mil N.H.
        • Tiemeier H.
        • Steenweg-de Graaff J.
        • et al.
        Maternal plasma n-3 and n-6 polyunsaturated fatty acids during pregnancy and features of fetal health: fetal growth velocity, birth weight and duration of pregnancy.
        Clin Nutr. 2018; 37: 1367-1374
        • Vinding R.K.
        • Stokholm J.
        • Sevelsted A.
        • et al.
        Fish oil supplementation in pregnancy increases gestational age, size for gestational age, and birth weight in infants: a randomized controlled trial.
        J Nutr. 2019; 149: 628-634
        • Carlsen K.
        • Pedersen L.
        • Bønnelykke K.
        • Stark K.D.
        • Lauritzen L.
        • Bisgaard H.
        Association between whole-blood polyunsaturated fatty acids in pregnant women and early fetal weight.
        Eur J Clin Nutr. 2013; 67: 978-983
        • Heppe D.H.
        • Steegers E.A.
        • Timmermans S.
        • et al.
        Maternal fish consumption, fetal growth and the risks of neonatal complications: the Generation R Study.
        Br J Nutr. 2011; 105: 938-949
        • Buck Louis G.M.
        • Grewal J.
        • Albert P.S.
        • et al.
        Racial/ethnic standards for fetal growth: the NICHD Fetal Growth Studies.
        Am J Obstet Gynecol. 2015; 213 (e1–41): 449
        • Grewal J.
        • Grantz K.L.
        • Zhang C.
        • et al.
        Cohort profile: NICHD Fetal Growth Studies-Singletons and Twins.
        Int J Epidemiol. 2018; 47 (25–25l)
        • Hinkle S.N.
        • Zhang C.
        • Grantz K.L.
        • et al.
        Nutrition during pregnancy: findings from the National Institute of Child Health and Human Development (NICHD) Fetal Growth Studies-Singleton cohort.
        Curr Dev Nutr. 2020; 5: nzaa182
        • Radesky J.S.
        • Oken E.
        • Rifas-Shiman S.L.
        • Kleinman K.P.
        • Rich-Edwards J.W.
        • Gillman M.W.
        Diet during early pregnancy and development of gestational diabetes.
        Paediatr Perinat Epidemiol. 2008; 22: 47-59
        • Hediger M.L.
        • Fuchs K.M.
        • Grantz K.L.
        • et al.
        Ultrasound quality assurance for singletons in the National Institute of Child Health and Human Development Fetal Growth Studies.
        J Ultrasound Med. 2016; 35: 1725-1733
        • Hadlock F.P.
        • Harrist R.B.
        • Sharman R.S.
        • Deter R.L.
        • Park S.K.
        Estimation of fetal weight with the use of head, body, and femur measurements--a prospective study.
        Am J Obstet Gynecol. 1985; 151: 333-337
        • Hammoud N.M.
        • Visser G.H.
        • Peters S.A.
        • Graatsma E.M.
        • Pistorius L.
        • de Valk H.W.
        Fetal growth profiles of macrosomic and non-macrosomic infants of women with pregestational or gestational diabetes.
        Ultrasound Obstet Gynecol. 2013; 41: 390-397
        • Crane J.P.
        • Kopta M.M.
        Prediction of intrauterine growth retardation via ultrasonically measured head/abdominal circumference ratios.
        Obstet Gynecol. 1979; 54: 597-601
        • Rosso P.
        • Winick M.
        Intrauterine growth retardation. A new systematic approach based on the clinical and biochemical characteristics of this condition.
        J Perinat Med. 1974; 2: 147-160
        • Duryea E.L.
        • Hawkins J.S.
        • McIntire D.D.
        • Casey B.M.
        • Leveno K.J.
        A revised birth weight reference for the United States.
        Obstet Gynecol. 2014; 124: 16-22
        • Kelley K.E.
        • Kelley T.P.
        • Kaufman D.W.
        • Mitchell A.A.
        The Slone Drug Dictionary: a research driven pharmacoepidemiology tool.
        Pharmacoepidemiol Drug Saf. 2003; 12: 168-169
        • National Cancer Institute, Division of Cancer Control & Population Science
        Diet History Questionnaire II (DHQ II) for U.S. and Canada.
        (Available at:)
        https://epi.grants.cancer.gov/dhq2/
        Date: 2010
        Date accessed: January 20, 2020
        • Zhang Z.
        • Fulgoni V.L.
        • Kris-Etherton P.M.
        • Mitmesser S.H.
        Dietary intakes of EPA and DHA omega-3 fatty acids among US childbearing-age and pregnant women: an analysis of NHANES 2001-2014.
        Nutrients. 2018; 10: 416
        • U.S. Department of Health and Human Services, U.S. Department of Agriculture
        2015–2020 Dietary Guidelines for Americans.
        8th Edition. 2015 (Available at)
        • Guenther P.M.
        • Kirkpatrick S.I.
        • Reedy J.
        • et al.
        The Healthy Eating Index-2010 is a valid and reliable measure of diet quality according to the 2010 Dietary Guidelines for Americans.
        J Nutr. 2014; 144: 399-407
        • Benjamini Y.
        • Yekutieli D.
        The control of the false discovery rate in multiple testing under dependency.
        Ann Statist. 2001; 29: 1165-1188
        • Leventakou V.
        • Roumeliotaki T.
        • Martinez D.
        • et al.
        Fish intake during pregnancy, fetal growth, and gestational length in 19 European birth cohort studies.
        Am J Clin Nutr. 2014; 99: 506-516
        • Makrides M.
        • Best K.
        • Yelland L.
        • et al.
        A randomized trial of prenatal n-3 fatty acid supplementation and preterm delivery.
        N Engl J Med. 2019; 381: 1035-1045
        • Nykjaer C.
        • Higgs C.
        • Greenwood D.C.
        • Simpson N.A.B.
        • Cade J.E.
        • Alwan N.A.
        Maternal fatty fish intake prior to and during pregnancy and risks of adverse birth outcomes: findings from a British cohort.
        Nutrients. 2019; 11: 643
        • Gonzalez-Casanova I.
        • Stein A.D.
        • Hao W.
        • et al.
        Prenatal supplementation with docosahexaenoic acid has no effect on growth through 60 months of age.
        J Nutr. 2015; 145: 1330-1334
        • Dilli D.
        • Doğan N.N.
        • İpek M.Ş.
        • et al.
        MaFOS-GDM trial: maternal fish oil supplementation in women with gestational diabetes and cord blood DNA methylation at insulin like growth factor-1 (IGF-1) gene.
        Clin Nutr ESPEN. 2018; 23: 73-78
        • Carlson S.E.
        • Colombo J.
        • Gajewski B.J.
        • et al.
        DHA supplementation and pregnancy outcomes.
        Am J Clin Nutr. 2013; 97: 808-815
        • Ostadrahimi A.
        • Mohammad-Alizadeh S.
        • Mirghafourvand M.
        • Farshbaf-Khalili S.
        • Jafarilar-Agdam N.
        • Farshbaf-Khalili A.
        The effect of fish oil supplementation on maternal and neonatal outcomes: a triple-blind, randomized controlled trial.
        J Perinat Med. 2017; 45: 1069-1077
        • Lucia Bergmann R.
        • Bergmann K.E.
        • Haschke-Becher E.
        • et al.
        Does maternal docosahexaenoic acid supplementation during pregnancy and lactation lower BMI in late infancy?.
        J Perinat Med. 2007; 35: 295-300
        • Ramakrishnan U.
        • Stein A.D.
        • Parra-Cabrera S.
        • et al.
        Effects of docosahexaenoic acid supplementation during pregnancy on gestational age and size at birth: randomized, double-blind, placebo-controlled trial in Mexico.
        Food Nutr Bull. 2010; 31: S108-S116
        • Harris M.A.
        • Reece M.S.
        • McGregor J.A.
        • et al.
        The Effect of Omega-3 docosahexaenoic acid supplementation on gestational length: randomized trial of supplementation compared to nutrition education for increasing n-3 intake from foods.
        BioMed Res Int. 2015; 2015123078
        • Min Y.
        • Djahanbakhch O.
        • Hutchinson J.
        • et al.
        Effect of docosahexaenoic acid-enriched fish oil supplementation in pregnant women with type 2 diabetes on membrane fatty acids and fetal body composition--double-blinded randomized placebo-controlled trial.
        Diabet Med. 2014; 31: 1331-1340
        • Olsen S.F.
        • Østerdal M.L.
        • Salvig J.D.
        • Weber T.
        • Tabor A.
        • Secher N.J.
        Duration of pregnancy in relation to fish oil supplementation and habitual fish intake: a randomised clinical trial with fish oil.
        Eur J Clin Nutr. 2007; 61: 976-985
        • Keenan K.
        • Hipwell A.
        • McAloon R.
        • Hoffmann A.
        • Mohanty A.
        • Magee K.
        The effect of prenatal docosahexaenoic acid supplementation on infant outcomes in African American women living in low-income environments: a randomized, controlled trial.
        Psychoneuroendocrinology. 2016; 71: 170-175