No Benefit of DHA Fish Oil for Postpartum Depression, Child Neurodevelopment

Deborah Brauser

October 20, 2010

October 20, 2010 — Fish oil capsules enhanced with docosahexaenoic acid (DHA) and given to women during pregnancy do not decrease postpartum depression or improve neurodevelopment in the women's offspring compared with vegetable oil capsules, suggests new research from Australia.

In fact, results from the DHA to Optimize Mother Infant Outcome (or DOMInO) study — a double-blind, multicenter, randomized controlled trial — found no statistically significant differences between the 2 groups in the mothers' depression symptoms 6 months postpartum or in their children's mean cognitive or language scores at 18 months of age.

The most important thing to take away from this study is that "apparently healthy women with normal pregnancies do not require DHA supplements," lead author Maria Makrides, PhD, deputy director at the Women's and Children's Health Research Institute and professor of human nutrition at the University of Adelaide, Australia, told Medscape Medical News.

"We obviously undertook the trial expecting to find a positive effect. The fact that we essentially found no effect was a surprise," added Dr. Makrides.

The investigators note that their results "are at odds" with the findings from other large-scale trials. "It may be that even well-conducted epidemiological studies overestimate effect size and do not adequately deal with residual confounding, or that other nutrients in fish and seafood, beyond DHA, contribute to [our] observations."

Dr. Makrides said they are not suggesting that all people should stop taking this supplement. "If they are taking fish oil to improve circulation or lower blood pressure, then there is evidence that this works. If they are taking fish oil to reduce the inflammation in their stiff joints, then this also works. All we are saying is that we have not been able to determine a clinical role for fish oil supplements in women with normal pregnancies."

The study appears in the October 20 issue of the Journal of the American Medical Association.

Questioning DHA Recommendations

"Despite the paucity of evidence, recommendations exist to increase intake of DHA in pregnancy, and the nutritional supplement industry successfully markets prenatal supplements with DHA to optimize brain function of mother and infant," write the study authors.

"Before DHA supplementation in pregnancy becomes widespread, it is important to know not only if there are benefits, but also of any risks for either the mother or child," they add.

For this study, 2399 pregnant women at less than 21 weeks' gestation were enrolled between October 2005 and January 2008 at 1 of 5 Australian maternity hospitals. The women were then randomly assigned to receive either 800 mg daily of DHA-rich fish oil capsules (n = 1197) or matching vegetable oil capsules without DHA (placebo/control group, n = 1202) at baseline, continuing until they gave birth.

The mean age for both groups was 29.9 years, and the median gestational age at trial entry for both groups was 19.0 weeks.

Assessments for adverse gastrointestinal or bleeding events were conducted by telephone at 22, 28, and 36 weeks' gestation.

At 6 weeks and at 6 months postpartum, the mothers were assessed for depressive symptoms using the self-administered Edinburgh Postnatal Depression Scale. The study's primary maternal outcome was a high level of depressive symptoms, which was defined as "a score of more than 12."

Follow-ups were conducted with 694 of the children at the age of 18 months (DHA group, n = 333; placebo group, n = 361). The investigators used the Bayley Scales of Infant and Toddler Development, Third Edition, to evaluate both cognitive and language development.

Neurodevelopment was the study's primary childhood outcome. Secondary outcome measures included an evaluation scale of gross and fine motor functioning and parental report scales of social–emotional behavior and adaptive behavior.

Little to No Effect

Results showed that 96.7% of the enrolled women completed the study.

During the first 6 months postpartum, high levels of depressive symptoms in those taking the DHA capsules (9.67%) and those taking the placebo (11.19%) did not differ significantly (adjusted relative risk [RR], 0.85; 95% confidence interval [CI], 0.70 - 1.02; P = .09).

"Interestingly, our data did suggest a 3% to 4% reduction in depressive symptoms in the subgroup of women who had a previous history of depression," said Dr. Makrides. "It may be that these women [would] benefit from supplementation, but other studies are needed to confirm this."

However, "the percentage of women with a new medical diagnosis for depression during the trial or a diagnosis requiring treatment did not differ between groups," write the study authors.

There were also no significant differences in mean cognitive composite scores for the children of mothers in the DHA group vs those in the control group (adjusted mean difference, 0.01; 95% CI, −1.36 to 1.37; P = .99).

However, fewer infants in the DHA group had scores indicating delayed cognitive development than did those in the control group (2.71% vs 6.64%; P = .007).

Although there were no overall between-group differences in mean language composite scores (adjusted mean difference, −1.42; 95% CI, −3.07 to 0.22; P = .09), or between boys in both treatment groups, the girls in the DHA group had a lower mean language score (P < .001) and an increased risk for delayed language development (P = .03) than did the girls in the control group.

No overall between-group differences were found for motor development, social–emotional behavior, and adaptive behavior. However, the girls in the DHA group had poorer mean adaptive behavior scores than did those in the control group (P = .003).

The DHA-treated group had fewer preterm births of less than 34 weeks' gestation (1.09%) compared with those treated with placebo (2.25%; adjusted RR, 0.49; P = .03), but the DHA group had "more postterm births requiring obstetric intervention," including inductions or cesarean deliveries (17.59% vs 13.72%; adjusted RR, 1.28; P = .01).

"Clearly these trade-offs are important to consider, and it may be that DHA supplementation may be most useful to women at risk of having a preterm baby," noted Dr. Makrides.

Finally, at least 1 serious adverse event was reported for 36 of the DHA-group infants vs 54% of those in the control group (RR, 0.67; P = .06). Eructations were reported by more women in the DHA group than in the control group at both 28 weeks' (43.6% vs 25.6%) and 36 weeks' (41.5% vs 29.2%) gestation (P < .001 for both time points).

"This is the largest and most well-conducted study of its type, [and] we have a conclusive result about the fact that there is little or no effect of DHA supplementation during normal pregnancy on postpartum depression or early childhood neurodevelopment in the first 18 months of life," summarized Dr. Makrides.

However, "further studies are required to determine whether there are specific benefits of DHA supplementation for women with a previous history of depression and for women at risk of preterm birth," note the study authors.

Dr. Makrides reported that the investigators plan a 4-year neurodevelopmental follow-up for all of the children who were assessed at 18 months. She noted that it is especially important to reexamine language development in the girls from the DHA group.

"As language skills are emerging, it will be important to have a longer-term assessment to determine whether this effect is simply a reflection of the milestones reached at 18 months or whether there is any longer-term effect."

DHA Still Recommended

"Fish oil supplements are safe, well-tolerated, and reduce risks for early preterm birth, which is associated with poor neurocognitive outcomes and maternal depression," write Emily Oken, MD, MPH, from the Department of Population Medicine at the Harvard Pilgrim Health Care Institute and Harvard Medical School in Boston, and Mandy B. Belfort, MD, MPH, from the Division of Newborn Medicine at Children's Hospital Boston, in Massachusetts, in an accompanying editorial.

The editorial authors, who were not involved in this study, note that the DOMInO results, showing no overall effect of DHA on neurodevelopment, are similar to most trials of infant formulas supplemented with polyunsaturated fatty acids (PUFAs) but differ from observational studies that focused on fish consumption.

"These discrepancies might be explained by residual confounding in observational studies or because eating fish is better than taking a supplement," they write. "It may be that the [omega-3] PUFAs in fish are more bioactive or that other beneficial nutrients within fish, such as selenium, vitamin D, and iodine, are also important."

They also point out that the Bayley scales used in this study "are not sufficiently sensitive."

However, "a noteworthy result of the DOMInO trial" was the lower risk of very preterm birth for the women in the DHA group, leading to lower rates of low birth rate, fewer admissions to the neonatal intensive care unit, and a 30% reduction in infant death, they add.

"Although the absolute numbers of these outcomes were small, the relative benefits were large," write the editorial authors.

For now, they write that all pregnant women should take the consensus guidelines' recommended daily 200-mg dose of DHA, "either by including low-mercury, high-DHA fish in their diets or by taking a daily [omega-3] PUFA supplement. The benefit of higher intakes remains unclear."

The study was funded by a grant from the Australian National Health and Medical Research Council. Treatment and placebo capsules were donated by Efamol, England. Dr. Makrides reported serving on scientific advisory boards for Nestle, Fonterra, and Nutricia. One other study author reported serving on scientific advisory boards for Nestle and Fonterra. The editorial writers have disclosed no relevant financial relationships.

JAMA. 2010;304:1675-1683, 1717-1718.

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