Maternal DHA supplementation: Does it deliver brain benefits in very preterm infants?

High-dose supplementation of docosahexaenoic acid (DHA) in breastfeeding mums did not improve behavioural functioning and neurodevelopmental outcomes at 5 years in children born very preterm. However, it may be of benefit to some subgroups of children, according to the results of the 5-year follow-up of a subgroup from the MOBYDIck* trial.

“For the primary outcome of Total Difficulties Score from the Strength and Difficulties Questionnaire (SDQ), there was a mean difference (MD) of -0.9 between groups; however, it was not statistically significant (10.4 vs 11.4; p=0.3),” said presenting author Sara-Pier Paquet, MSc, from the CHU de Quebec – Université Laval, Québec, Canada, at PAS 2024.

The SDQ measures children’s behavioural difficulties, with a higher score being more problematic, she noted. Among the individual SDQ scales, only the peer problem score was significantly better with DHA than with placebo (1.1 vs 1.6; MD, -0.5; p=0.04). [Paquet, et al, PAS 2024]

Subgroup analyses for sex, gestational age

“We identified some subgroups that might benefit more from DHA supplementation, more specifically for girls and for children born at <27 weeks of gestation,” said Paquet.

The interaction for sex was significant for some outcomes (communication [p=0.03] and personal social [p=0.04]). “What’s interesting here is that there was a consistent signal suggesting that girls benefit more from DHA supplementation,” Paquet said. In females, the respective MDs for peer problems, communication, personal social, and working memory were -0.8, -6.2, 4.3, and -5.4. The corresponding MDs in males were -0.05, -3.1, -3.5, and 1.9.

On subgroup analyses for gestational age, there was a significant interaction for the BRIEF-P** scales of flexibility index (p=0.01), metacognition index (p=0.03), and global executive composite (p=0.01).

Among neonates born <27 weeks’ gestation, those with DHA exposure had better results in their global executive composite score vs those on placebo (MD, -6.7). “This suggests that children with DHA supplementation have better executive functioning scores if they are born <27 weeks,” Paquet explained.

Neonates born <27 weeks with DHA exposure also had better flexibility index (MD, -5.1) and metacognition index scores (MD, -6.8) than those who received placebo.

DHA deficiency in very preterm infants

Given the relative deficit of DHA in very preterm children, there has been a long-standing question on whether DHA supplementation can improve their brain development, Paquet noted.

The team evaluated 132 breastfed infants born <29 weeks’ gestation and randomized in one of the five Quebec sites of MOBYDIck (n=64 [DHA] and 68 [placebo]). Fifty-three lactating mums (mean age 31 years) received 1.2 g of DHA daily within 72 hours of delivery until 36 weeks postmenstrual age; 61 (mean age 31.8 years) were given placebo.

While the findings may not be generalized owing to the limited sample size, “our study stands out for its longitudinal follow-up from the neonatal period, which is well-characterized until 5 years of age, with a 75-percent retention rate of eligible children. Moreover, [we used] reliable and validated neurodevelopmental questionnaires,” Paquet said.

“Our study also contributes to the advancement of knowledge on the role of high-dose DHA supplementation for children born very preterm,” she continued. But given that the findings were exploratory, these still merit validation, she added.

Future studies should look into the neurodevelopmental profile at preschool age, as this is a critical period for adult functions.