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Giving omega-3 fatty acid supplements in the first few months of life to preterm infants born before 29 weeks gestation appeared to modestly boost IQ scores at 5 years of age, researchers reported.

The study involved a subset of children originally enrolled as preterm infants in the randomized N-3 Fatty Acids for Improvement in Respiratory Outcomes (N3RO) trial, which assessed the impact of docosahexaenoic acid (DHA) supplementation on the common preterm birth complication bronchopulmonary dysplasia.

At 5 years of age, children in the DHA supplementation arm of the original trial had full-scale intelligence quotient (FSIQ) scores that were 3.5 points higher than those who did not receive the supplements, Jacqueline Gould, PhD, of the South Australian Health and Medical Research Institute in North Adelaide, and colleagues, reported in the .

In an email exchange with 麻豆传媒, Gould characterized the 3.5-point difference as a modest but meaningful difference that could have an impact on educational and vocational outcomes.

"It is difficult to pinpoint the impact [of a 3.5-point IQ difference] for an individual child as there is so much variability from child to child, and IQ is a summary of multiple cognitive abilities that may be differently affected in different children," Gould said, adding that in some children the benefit may be restricted to memory or attention, and in others it may be more global.

In the infants born before 29 weeks gestation were randomized to receive daily doses of 60 mg of DHA per kg of body weight or a control emulsion from the first 3 days of life through week 36 of postmenstrual age or discharge from the neonatal intensive care unit, whichever came first.

Gould explained that infants born this early do not get the DHA from the placenta that full-term babies get. Placental DHA accumulates in the brain during the final trimester of pregnancy, making up approximately 30% of the brain's lipid content.

"Infants born this early miss over 10 weeks of the placental supply of DHA during a key period of development, and are the most at-risk subgroups of preterm infants likely to have a DHA insufficiency as well as cognitive impairment and a lower IQ," Gould said.

The follow-up study included 480 of the 702 children who underwent randomization for the original trial at five Australian centers and who also had FSIQ scores available at 5 years of age (241 in the DHA group and 239 in the control group).

Mean corrected age at IQ assessment was similar in the two treatment groups (roughly 5.3 years in both groups), and other characteristics were also similar.

Mean FSIQ scores at approximately 5 years of age were 95.4±17.3 in the DHA group and 91.9±19.1 in the control group, for a difference of 3.45 points (95% CI 0.38-6.53, P=0.03).

Children who did not get DHA supplementation in the first few months of life were no more likely than those who did to have a diagnosis of autism spectrum disorder, attention deficit-hyperactivity disorder, or other behavioral disorders at age 5 years (below 7.0% in both groups).

The researchers noted that there have been three earlier randomized, controlled trials that have examined the impact of supplemental DHA from birth in preterm infants that "showed mostly null effects on cognition."

And in the original N3NO study and the newly reported follow-up study, the premature birth complication bronchopulmonary dysplasia was slightly more common in the infants given DHA supplements.

Bronchopulmonary dysplasia in preterm infants increases the risk for lower IQ, and Gould and colleagues wrote that the higher IQ scores in the children who received the DHA supplements in the follow-up study suggest "that the possible mechanisms underlying the cognitive effects may be independent of those underlying the effects on the risk of bronchopulmonary dysplasia."

The follow-up study's higher than expected attrition due to the COVID-19 pandemic was cited by the researchers as a study limitation, but they noted that the trial "met the sample size that was calculated to provide 80% power to detect a 4-point difference between groups."

"The effect that we detected (3.5 points) was smaller than the 4-point effect size that has previously been a catalyst for changes to public health policy, yet an effect of 3.5 points may confer a benefit to individual infants," the researchers wrote.

Gould noted that there are currently no set guidelines for DHA supplementation in preterm infants.

"One of our next steps in this research is to work with clinicians to determine recommendations and guidelines," she said. "This DHA intervention is one of the first that clinicians may be able to use while infants born before 29 weeks gestation are still in the hospital to improve their IQ. We suggest clinicians consider and discuss these findings with caregivers of preterm infants."

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