Prenatal docosahexaenoic acid effect on maternal-infant DHA-equilibrium and fetal neurodevelopment: a randomized clinical trial

Kathleen M Gustafson, Danielle N Christifano, Dirk Hoyer, Alexander Schmidt, Susan E Carlson, John Colombo, Nicole B Mathis, Scott A Sands, Lynn Chollet-Hinton, Alexandra R Brown, Dinesh Pal Mudaranthakam, Byron J Gajewski, Kathleen M Gustafson, Danielle N Christifano, Dirk Hoyer, Alexander Schmidt, Susan E Carlson, John Colombo, Nicole B Mathis, Scott A Sands, Lynn Chollet-Hinton, Alexandra R Brown, Dinesh Pal Mudaranthakam, Byron J Gajewski

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: Pregnant women who received a higher dose of docosahexaenoic acid (DHA) were more likely to achieve maternal-infant DHA equilibrium at delivery. Equilibrium status had no effect on fetal neurodevelopment in this sample. While DHA is crucial for early life neurodevelopment, the significance of achieving maternal-infant equilibrium above the lower threshold is uncertain. There is a lower threshold of maternal DHA status where maternal-infant DHA equilibrium never occurs. The lack of equilibrium associated with low maternal DHA status may indicate insufficient maternal status for optimal placental transfer.

Conflict of interest statement

S.E.C. and J.C. have received honorariums for presentations about DHA in infancy and pregnancy. The remaining authors declare no competing interests.

© 2021. The Author(s), under exclusive licence to the International Pediatric Research Foundation, Inc.

Figures

Fig. 1. CONSORT diagram.
Fig. 1. CONSORT diagram.
Flow chart illustrating determination of participant eligibility, allocation to treatment group, study visit assessments, and reasons for participant exclusion or loss (dashed boxes).
Fig. 2. Maternal and Infant RBC-DHA at…
Fig. 2. Maternal and Infant RBC-DHA at delivery.
Newborn cord blood RBC DHA is seen on the Y-axis, maternal postpartum RBC DHA on the X-axis. The diagonal line denotes a 1:1 relationship between maternal–infant DHA. Those dyads achieving equilibrium, i.e., maternal DHA ≥ infant DHA (coded yes) are below the diagonal line. Conversely, those dyads where infant DHA was > maternal DHA (coded no) are above the diagonal line.

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Source: PubMed

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