Giving DHA to Preemies Doesn’t Improve Behavioral Outcomes Later On

Administration of supplemental docosahexaenoic acid (DHA) to infants born at less than 29 weeks’ gestation did not improve behavioral functioning at 5 years of age, a follow-up to a randomized trial showed.

In more than 700 kids with a mean corrected age of 5.4 years at follow-up, average Total Difficulties score on the Strengths and Difficulties Questionnaire (SDQ) was 11.8 in both the group who received supplemental DHA as a newborn and the group who did not (mean difference adjusted for sex, gestational age stratum, and hospital 0.01, 95% CI -0.87 to 0.89, P=0.98), reported Jacqueline Gould, PhD, of the South Australian Health and Medical Research Institute in North Adelaide, and colleagues.

Itemized SDQ scores, including emotional symptoms, hyperactivity/inattention, and peer relationship problems, also did not differ between groups, they noted in JAMA Pediatrics.

“Infants born extremely preterm miss the in-utero supply of DHA during a crucial period of brain development, and over half have some form of neurobehavioral disability, such as a behavioral problem or learning disorder,” Gould told MedPage Today in an email.

“It has long been hypothesised that supplementing these infants with DHA during the neonatal period will improve neurobehavioral outcomes,” she said. “However, the handful of previous trials have included a more mature preterm population and an intervention that relies on infants receiving full enteral feeds to get the prescribed dose of DHA.”

“Our trial administered a unique emulsion given immediately prior to a milk feed to ensure infants received the full dose regardless of reaching full enteral feeds,” she noted. “We found no effect on any outcome — no benefit, but also no indication of an adverse outcome.”

In the primary analysis of the multicenter, double-blind, parallel-placebo N-3 Fatty Acids for Improvement in Respiratory Outcomes (N3RO) trial, Gould and colleagues assessed bronchopulmonary dysplasia (BPD) at 36 weeks’ postmenstrual age. They found that enteral DHA supplementation of 60 mg/kg daily did not result in a lower risk of BPD compared with a control emulsion, and may in fact have resulted in a greater risk.

However, in another follow-up analysis of N3RO, they found that children in the DHA supplementation arm had full-scale intelligence quotient scores that were 3.5 points higher at 5 years versus those who did not receive DHA.

Follow-up for the current analysis was completed from August 2018 to May 2021. Parents of surviving children recruited from 10 Australian health centers were invited to complete questionnaires when their child turned 5 years old.

As infants, participants were randomized to receive enteral emulsions providing 60 mg/kg daily of DHA or a soy-oil emulsion (with no DHA) from the first 3 days of enteral feeding until 36 weeks’ postmenstrual age or discharge home, whichever occurred first. At follow-up, there were 361 children in the intervention group and 370 in the control group; 47% were girls.

Similar to SDQ scores, executive functioning scores measured by the Behavior Rating Inventory of Executive Functioning (BRIEF) questionnaire did not significantly differ between groups.

Gould and team also examined health outcomes, including several basic respiratory outcomes, “given children born extremely preterm frequently have poorer health than term children, and the DHA intervention [previously] increased BPD, which is commonly associated with poor long-term respiratory functioning,” Gould noted.

There were no differences between groups in health-related quality of life as assessed by the Pediatric Quality of Life Inventory. Approximately 30% of children in both groups had asthma. There were no differences between groups in the proportion of kids with wheezing.

A substantial proportion of children in both groups had either been hospitalized for respiratory-related conditions (46.3% in the intervention group vs 49.6% in the control group), or had undergone a surgical procedure since initial discharge (36.6% vs 39.8%, respectively).

There were three deaths (two in the intervention group and one in the control group) during the follow-up period. However, none of the deaths were deemed to be related to DHA or study participation by the independent mortality review committee.

Limitations to the study included that the behavior and health of children lost to follow-up may have differed from that of kids who participated, Gould and colleagues noted. In addition, outcomes were parent-reported and not verified by medical or psychological examination.

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