Abstract
Introduction
Maternal–infant equilibrium occurs when cord blood docosahexaenoic acid (DHA) is less than or equal to maternal DHA at delivery. Equilibrium may be an indicator of sufficient DHA for optimal fetal and infant neurodevelopment. The purpose of this study was to test the effect of maternal DHA supplementation on equilibrium status and fetal neurodevelopment.
Methods
Women enrolled between 12 and 20 weeks gestation and were randomized to 200 or 800 mg DHA/day until delivery. Maternal red blood cell (RBC) phospholipids were measured at enrollment, 32 weeks, delivery, and in cord blood at delivery. Fetal neurodevelopment was measured at 32 and 36 weeks gestation. Intent-to-treat analyses were conducted to test differences in equilibrium status by group. Fetal outcomes were assessed by equilibrium status and group.
Results
Three hundred women enrolled and 262 maternal–infant dyads provided blood samples at delivery. No maternal–infant dyads with maternal RBC-DHA ≤ 6.96% at delivery achieved equilibrium. The incidence of equilibrium was significantly higher in the 800 mg group. There was no effect of maternal group or equilibrium status on fetal neurodevelopment.
Conclusion
The significance of maternal–infant DHA equilibrium remains unknown. Ongoing research will test the effect of treatment group, equilibrium, and nutrient status on infant behavior and brain function.
Impact
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Pregnant women who received a higher dose of docosahexaenoic acid (DHA) were more likely to achieve maternal–infant DHA equilibrium at delivery.
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Equilibrium status had no effect on fetal neurodevelopment in this sample.
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While DHA is crucial for early life neurodevelopment, the significance of achieving maternal–infant equilibrium above the lower threshold is uncertain.
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There is a lower threshold of maternal DHA status where maternal–infant DHA equilibrium never occurs.
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The lack of equilibrium associated with low maternal DHA status may indicate insufficient maternal status for optimal placental transfer.
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Data availability
We are willing to share deidentified data from the study with a signed data access agreement that includes the study principal investigators, contingent on approval of the planned use of the data. As the data are entered into an electronic system, a specific request to K.M.G. (kgustafson@kumc.edu) or D.N.C (dchristifano@kumc.edu) would be needed to generate a data output for other investigators. We plan to publish secondary results and longitudinal outcomes of the trial and cannot share some data until the study is final.
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Acknowledgements
We are grateful for the support of study personnel who were responsible for initiation of the study, recruiting participants, communicating with them monthly, and collecting the data critical for the study, especially Sheri Copeland, Sara Macone, Jocelyn Thodosoff, Beth Kerling, Sarah Crawford, and Sarah Touchette. The success of this trial is due to their diligence and care. We recognize the nurses who cared for the women in the trial and collected the blood samples. We are grateful to DSM Nutritional Products for providing the study capsules. We appreciate the time and effort of our DSMB; Michael Georgieff, MD of the University of Minnesota Masonic Children’s Hospital, Minneapolis, MN; Vishal Pandey, MD, Courtney Marsh, MD, and Jianghua He, PhD, of the University of Kansas Medical Center, Kansas City, KS. Finally, we are most grateful to the 300 women who enrolled in the study.
Funding information
This study was supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD).
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K.M.G. was the principal investigator and designed the study with input from S.E.C., J.C., D.H., and B.J.G.; D.N.C. and N.B.M. maintained regulatory documents, oversaw conduct of study operation, and verified the data entered from medical records; K.M.G., D.N.C., and N.B.M. obtained all maternal–fetal measures at the study visits and processed the MCG data; D.H. and A.S. performed the fABAS analysis; S.A.S. performed the RBC fatty acid analysis; A.R.B. and D.P.M. were responsible for verifying the data within Velos; D.P.M. developed the electronic records for data entry in conjunction with A.R.B.; L.C.-H. and B.J.G. were responsible for the statistical analysis; K.M.G., D.N.C., S.E.C., L.C.-H., J.C., and B.J.G. wrote the manuscript, but all authors contributed their insights to the final version.
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S.E.C. and J.C. have received honorariums for presentations about DHA in infancy and pregnancy. The remaining authors declare no competing interests.
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Gustafson, K.M., Christifano, D.N., Hoyer, D. et al. Prenatal docosahexaenoic acid effect on maternal-infant DHA-equilibrium and fetal neurodevelopment: a randomized clinical trial. Pediatr Res 92, 255–264 (2022). https://doi.org/10.1038/s41390-021-01742-w
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DOI: https://doi.org/10.1038/s41390-021-01742-w
