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Clinical Trial
. 2023 Nov;42(11):2229-2240.
doi: 10.1016/j.clnu.2023.09.005. Epub 2023 Sep 20.

DHA, nutrient intake, and maternal characteristics as predictors of pregnancy outcomes in a randomised clinical trial of DHA supplementation

Yu Wang  1 , Byron J Gajewski  1 , Christina J Valentine  2 , Sarah A Crawford  3 , Alexandra R Brown  1 , Dinesh Pal Mudaranthakam  1 , Juliana Teruel Camargo  3 , Susan E Carlson  4
Affiliations
Clinical Trial

DHA, nutrient intake, and maternal characteristics as predictors of pregnancy outcomes in a randomised clinical trial of DHA supplementation

Yu Wang et al. Clin Nutr. 2023 Nov.

Abstract

Purpose: To investigate the relationships among docosahexaenoic acid (DHA) intake, nutrient intake, and maternal characteristics on pregnancy outcomes in a phase III randomised clinical trial designed to determine the effect of a DHA dose of 1000 mg/day compared to 200 mg/day on early preterm birth (<34 weeks gestation).

Methods: A secondary aim of the phase III randomised trial was to explore the relationships among pregnancy outcomes (maternal red blood cell phospholipid (RBC-PL) DHA at delivery, preterm birth, gestational age at delivery, labor type, birth anthropometric measures, low birth weight, gestational diabetes, pre-eclampsia, and admission to a neonatal intensive care unit) in participants (n = 1100). We used Bayesian multiple imputation and linear and logistic regression models to conduct an analysis of five general classes of predictor variables collected during the trial: a) DHA intake, b) nutrient intake from food and supplements, c) environmental exposure to tobacco and alcohol, d) maternal demographics, and e) maternal medical history.

Results: DHA supplementation lowered the risk of preterm birth and NICU admission, and increased gestation and birth weight as observed in the primary analysis. Higher maternal RBC-PL-DHA at delivery was associated with DHA supplementation and formal education of a bachelor's degree or higher. DHA supplementation and maternal age were associated with a higher risk of gestational diabetes. Total vitamin A intake was associated with longer gestation, while fructose and intake of the long chain omega-6 fatty acid, arachidonic acid, were associated with shorter gestation. Risk of preterm birth was associated with a history of low birth weight, preterm birth, pre-eclampsia, and NICU admission.

Conclusion: Bayesian models provide a comprehensive approach to relationships among DHA intake, nutrient intake, maternal characteristics, and pregnancy outcomes. We observed previously unreported relationships between gestation duration and fructose, vitamin A, and arachidonic acid that could be the basis for future research.

Trial registration number and date: ClinicalTrials.gov (NCT02626299); December 10, 2015.

Keywords: Arachidonic acid; DHA; Fructose; Pregnancy; Preterm birth; Vitamin A.

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Conflict of interest statement

Conflicts of interest CJV, BJG and SEC were the principal investigators for the primary clinical trial. SEC has collaborated with DSM, the company that donated the capsules for the primary clinical trial but has no other conflicts of interest. All other authors have no conflicts of interest. YW conducted the Bayesian analysis as partial fulfillment for her PhD dissertation in the Department of Biostatistics and Data Science. She also wrote the manuscript with the assistance of SEC and BJG.

Figures

Figure 1.
Figure 1.
Forest Plot of Significant Predictors for Maternal RBC-PL DHA at Delivery
Figure 2.
Figure 2.
Forest Plot of Significant Predictors for Gestational Age
Figure 3.
Figure 3.
Forest Plot of Significant Predictors for Birth Weight
Figure 4.
Figure 4.
Forest Plot of Significant Predictors for Birth Length
Figure 5.
Figure 5.
Forest Plot of Significant Predictors for Birth Head Circumference
Figure 6.
Figure 6.
Forest Plot of Significant Predictors for Low Birth Weight (<2500 g)
Figure 7.
Figure 7.
Forest Plot of Significant Predictors for Preterm Birth (< 37 weeks)
Figure 8.
Figure 8.
Forest Plot of Significant Predictors for Gestational Diabetes
Figure 9.
Figure 9.
Forest Plot of Significant Predictors for Pre-eclampsia
Figure 10.
Figure 10.
Forest Plot of Significant Predictors for Neonatal ICU Admission
Figure 11.
Figure 11.
Forest Plot of Significant Predictors for Spontaneous Labor
See this image and copyright information in PMC

References

    1. Unterscheider J, O’Donoghue K, Daly S, Geary MP, Kennelly MM, McAuliffe FM, et al. Fetal growth restriction and the risk of perinatal mortality–case studies from the multicentre PORTO study. BMC Pregnancy and Childbirth. 2014;14(1):63. - PMC - PubMed
    1. Carlson SE, Gajewski BJ, Valentine CJ, Rogers LK, Weiner CP, Defranco EA, et al. Assessment of DHA on reducing early preterm birth: the ADORE randomized controlled trial protocol. BMC Pregnancy and Childbirth. 2017;17(1). - PMC - PubMed
    1. Carlson SE, Gajewski BJ, Valentine CJ, Kerling EH, Weiner CP, Cackovic M, et al. Higher dose docosahexaenoic acid supplementation during pregnancy and early preterm birth: A randomised, double-blind, adaptive-design superiority trial. EClinicalMedicine. 2021;36:100905. - PMC - PubMed
    1. Carlson SE, Gajewski BJ, Valentine CJ, Sands SA, Brown AR, Kerling EH, et al. Early and late preterm birth rates in participants adherent to randomly assigned high dose docosahexaenoic acid (DHA) supplementation in pregnancy. Clin Nutr. 2023;42(2):235–43. - PMC - PubMed
    1. National Institutes of Health EaGRP, National Cancer Institute. Diet History Questionnaire 2020.

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