The main randomized controlled trial (RCT) that has reported both prenatal RBC DHA levels and ePT birth rates is Carlson et al. 2013 [17
]. This study tested whether 600 mg/day DHA would increase maternal DHA blood levels during pregnancy (and in cord blood), and affect gestation duration, birth weight and length as compared to a placebo group supplemented from <20 weeks gestation to birth. The average RBC DHA at the end of the study in the placebo group was 4.7 ± 1.3% and 7.3 ± 2.2% in the treatment group. Compared with the control group, the treated group experienced fewer ePT births (placebo: 4.8% vs. DHA: 0.6% of births; p
= 0.03), fewer very low birthweight infants (<1500 g; placebo: 3.4% vs. DHA: 0% of births; p
= 0.03), and fewer days spent in the hospital (placebo: 40.8 ± 44.0 days vs. DHA: 8.9 ± 10.1 days, p
= 0.03). However, there was no effect on rates of PT births (placebo: 8.8% vs. DHA: 7.8% of births, p
= not significant [NS]). In addition, the primary endpoints were also linked to RBC DHA levels during pregnancy, with higher levels in the mother and cord blood being associated with longer gestation duration and greater birth weights, lengths, and head circumferences (p
-values < 0.05). This study would argue for a target RBC DHA level of at least >5%.
While there is a dearth of data on prenatal blood DHA levels and risk for ePT birth, there have been several large RCTs giving fish oil or DHA supplements to pregnant women for a variety of outcomes, which have been compiled in meta-analyses. Makrides and colleagues recently updated a Cochrane review on this topic, including 70 RCTs with over 19,000 participants [18
]. The authors reported a significant 42% reduction in ePT birth risk (Relative Risk [RR] 0.58, 95% CI: 0.44, 0.77) based on findings in nine RCTs (n
= 5204) and a 11% reduction in PT birth risk (RR 0.89, 95% CI: 0.81, 0.97) from 26 RCTs (n
= 10,304). A probable increased risk for prolonged gestation (>42 weeks; RR 1.61, 95% CI: 1.11, 2.33) from six RCTs (n
= 5141) was noted in the fish oil or DHA supplemented groups. They did not find any significant effects of fish oil or DHA on post-term induction rates, maternal adverse events, postpartum depression, or child development and cognition. A 2016 meta-analysis including over 10,000 pregnancies found that the fish oil group had a significant 22% reduction in risk of ePT birth (RR 0.78, 95% CI: 0.64, 0.95) and marginally significant 10% reduction in risk of PT birth (RR 0.90, 95% CI: 0.81, 1.00), as well as ~6 days longer gestation [19
]. Another 2015 meta-analysis found risk for ePT birth was reduced by 58% (RR 0.42, 95% CI: 0.27, 0.66) and PT birth by 17% (RR 0.83, 95% CI: 0.70, 0.98) by the fish oil intervention, regardless of dose, timing of supplementation, or pregnancy risk status [20
]. A 2012 meta-analysis on this same topic found that women taking a fish oil or DHA supplement during pregnancy had a 26% reduced risk of ePT birth (RR 0.74, 95% CI: 0.58, 0.94) and a trend toward decreased PT birth risk (RR 0.91, 95% CI: 0.82, 1.01) [21
]. The authors also found that supplementation increased birthweight by 42.2 g (95% CI: 14.8, 69.7) and had a lower risk of low birthweight (RR 0.92, 95% CI: 0.83, 1.02). There appears to be a consistent effect of fish oil or DHA supplementation on duration of gestation, and on ePT birth specifically.
One of the seminal RCTs in this field is the DOMInO (DHA to Optimize Mother Infant Outcome) study conducted in Australia by Makrides and Gibson and colleagues [22
]. This study included 2399 pregnant women and tested the effects of 800 mg/day of DHA during pregnancy (<21 weeks gestation to birth) on maternal postpartum depression and child cognitive and language development. Unfortunately, only cord—not maternal—blood DHA levels were reported, and the latter (earlier in pregnancy) cannot be reliably inferred from the former. Compared to the control group, the DHA group had a lower rate of ePT birth (placebo: 2.25% vs. DHA: 1.09% of births, p
= 0.03), fewer admissions to the neonatal intensive care unit (placebo: 3.08% vs. DHA: 1.75% of births, p
= 0.04), fewer low birthweight infants (<2500 g; placebo: 3.41% vs. DHA: 5.27% of births, p
= 0.003), and higher birthweights (p
= 0.03). However, there were also more post-term inductions or pre-labor cesarean deliveries in the DHA group (placebo: 13.72% vs. DHA: 17.59%, p
= 0.01), indicating prolonged gestation. PT birth tended to be lower in the DHA group, but this difference was not significant (placebo: 7.34% vs. DHA: 5.60% of births, p
= 0.09). The primary endpoints of this study (postpartum depression and childhood language development) were not affected by increased DHA intake during pregnancy.