Racial disparity in efficacy of docosahexaenoic acid supplementation for prevention of preterm birth: secondary analysis from a randomized, double-blind trial

Objective There is a significant racial disparity in preterm birth, disproportionately affecting pregnancies among Black individuals. Docosahexaenoic acid (DHA) supplementation has been shown to decrease the risk of preterm birth1. It is unknown whether there are differences in DHA efficacy among pregnancies of differing races. The objective of this study was to investigate the efficacy of prenatal DHA supplementation to prevent preterm birth (PTB, <37 weeks) and early preterm birth (EPTB, <34 weeks) in Black pregnant individuals compared to those who were non-Black. Study Design Planned secondary analysis from a randomized-controlled adaptive-design multicenter trial that investigated the efficacy of DHA to reduce EPTB 2,3. Outcome data were available for 1032 of 1100 pregnant individuals who were randomized to receive a standard prenatal dose of DHA, 200 mg/day (low dose; n=492), or 1000 mg/day (high dose; n=540), from enrollment at <20 weeks until delivery. We compared DHA status (maternal red blood cell phospholipid fatty acid DHA, RBC-PL-DHA) at enrollment and delivery and pregnancy outcomes (PTB <37 weeks and EPTB <34 weeks) by maternal race. Maternal race and ethnicity were self-reported as American Indian or Alaskan Native, Asian, Non-Hispanic Black or African American, Hispanic, Native Hawaiian or Pacific Islander, White, Biracial and Multiracial. For this analysis, maternal race and ethnicity were categorized in two groups: Black (participants who categorized themselves as Non-Hispanic Black or African American, n=236) and non-Black (participants reporting any other race or ethnicity, n=796). Maternal RBC-PL-DHA as a weight percent of total fatty acids was measured at enrollment (baseline) and delivery to determine maternal DHA status. A cutoff of 6% RBC-PL-DHA was used to dichotomize high versus low DHA status 2,4. Bayesian two-sample binomial models were used to calculate a posterior probability (PP) that 1000 mg/day was better than 200 mg/day to reduce PTB and EPTB. Results Baseline DHA level at enrollment was lower among Black versus non-Black study participants (Table). Black participants were more likely to be unmarried, have low income, obesity and use tobacco in pregnancy. Risk factors of prior PTB <37 weeks and prior EPTB <34 weeks, were 2-fold and 4-fold more common among Black compared to non-Black study participants, respectively (Table). Maternal DHA status increased between enrollment and delivery in both race groups, and in both the 1000 mg dose resulted in a larger increase than the 200 mg dose, PP = 1.00. The absolute increase in maternal RBC-PL-DHA from enrollment to delivery was smaller for Black participants compared to non-Black (200 mg dose: 0.33% vs 1.33%; 1000 mg dose: 1.50% vs 3.97%), indicative of lower supplement adherence5. All participants in the trial had reductions in PTB <37 weeks with high dose DHA supplementation, however only Black participants also had reduction in EPTB with high dose DHA supplementation (Figure). The rate of PTB was more than 2-fold higher for Black participants than non-Black at both DHA doses while the rate of EPTB was 4.5-fold higher for the 200 mg dose and 2.9-fold higher for the 1000 mg dose. Participants who began the study with high baseline DHA status (≥6% RBC-PL-DHA) had a lower rate of EPTB than those who began with low status (<6% RBC-PL-DHA) in both race and DHA dose groups. Participants who had high baseline DHA levels at study entry and were assigned to high dose DHA had the lowest PTB rates, which were similar among race groups, 6.4% PTB in Black and 5.8% PTB in non-Black participants (shown in dark green bars, Figure). Conclusions There are racial differences in baseline DHA levels and DHA supplement adherence in pregnancy. High baseline DHA levels and supplementation with high dose DHA in pregnancy reduces the racial disparity in preterm birth rates, despite more risk factors for preterm birth among Black pregnant individuals. These data demonstrate the importance of optimizing DHA status of reproductive age women and supplementation with higher doses of DHA in pregnancy in effort to mitigate the racial disparity in PTB outcomes.