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

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.

Maternal Docosahexaenoic Acid Exposure Needed to Achieve Maternal–Newborn EQ

“…DHA is preferentially transferred across the placenta [5] and transfer appears to be at the expense of the mother's DHA status until EQ is reached [6]. As evidenced in Figure 2, maternal and fetal RBC-DHA levels increase throughout gestation.…”

“…Using a combination of dietary DHA intake and supplement intake during pregnancy, we estimate the optimal DHA intake for most women to achieve EQ is close to 650 mg/day. Prior to this, we knew only that the women randomized to receive 800 mg of DHA/day were more likely to achieve EQ when compared to women who received 200 mg of DHA/day [6].…”

“…In our recent clinical trial [6], women randomized to consume 800 mg of DHA/day during pregnancy were more likely to achieve EQ at delivery when compared to those randomized to 200 mg DHA/day. EQ never occurred among women with low DHA status at delivery (defined as red blood cell phospholipid DHA, or RBC-PL-DHA, below 6.96% of total fatty acids) [6]. However, this trial did not identify the amount of DHA a pregnant woman should consume through diet and supplements to increase the potential for EQ.…”

“…The data for this analysis come from two recently completed randomized control trials: PANDA and ADORE. Both trials were registered in ClinicalTrials.gov and primary outcomes have been published [6,7]. Women who participated in the PANDA and ADORE trials were age 18 or older with singleton pregnancies and were English or Spanish speaking (ADORE only).…”

“…Participants were included in this analysis (n = 1145) if they provided dietary intake data at baseline and had maternal and cord blood RBC-PL-DHA levels at delivery. CONSORT diagrams and demographics for each parent trial are available in the primary publications [6,7].…”