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Docosahexaenoic Acid Linked to Better Neurocognitive Outcomes for Preterm Baby Girls

A study of hundreds of premature infants fed standard and high doses of the omega 3-fatty acid docosahexaenoic acid (DHA) found that girls performed better on cognitive tests more than a year after the intervention ended. DHA is a fatty acid — found in the algae eaten by fish that people consume — that has been associated with protecting against cognitive decline and heart disease.

The randomized, controlled trial is the largest to date and suggests that preterm infants, especially girls, would have better outcomes with a higher-than-usual dose of DHA, according to a paper in the Jan. 14 Journal of the American Medical Association.


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Maria Makrides, PhD, and her colleagues at the Child Nutrition Research Center at Women and Children's Hospital in Australia, randomly assigned 657 babies born less than 33 weeks gestation to either a high DHA diet — about 50 mg/kg daily — or a standard DHA amount — about 16 mg/kg daily — from about day four of life until the time they were due to be born.

“The intervention was largely delivered to the baby through expressed breast milk. We supplemented nursing women with about 1g of DHA per day in order to increase the DHA content of their milk,” said Dr. Makrides. “If the mother could not express enough breast milk for her baby, an infant formula with a matching DHA content was provided.” Then, at 18 months old the children were assessed using the Mental Development Index (MDI) of the Bayley Scales of Infant Development, which measures memory, habituation, problem solving, early number concepts, and language. The premature children received supplementation for an average of 9.4 weeks.

There was a five-point difference in mental development scores between the two groups — those receiving a high dose or standard dose of DHA. “There was a 55 percent reduction in the proportion of girls with mild mental delay and an 80 percent reduction in the proportion of girls with significant mental delays if fed high-DHA,” explained Dr. Makrides. “Should these differences persist to school age when we next plan to follow-up these children, the potential significance to the children, the families, and the health and education system will be large.”


DR. MARIA MAKRIDES: “There was a 55 percent reduction in the proportion of girls with mild mental delay and an 80 percent reduction in the proportion of girls with significant mental delays if fed high-DHA.”

DHA experts are unsure why there would be a gender difference, but fish oil expert Barry Sears, PhD, said that it is possible that the amount wasn't large enough to show a difference in the boys. “The article demonstrates the benefit of DHA in premature, low birth-weight children,” said Dr. Sears. “However, the amount normally used is too low to see a more significant effect. I usually recommend about 2.4 grams of EPA and DHA for pregnant women.”

According to Dr. Makrides, DHA is the main structural omega-3 fat in the brain. The retina and brain are rich in DHA. Past trials had demonstrated that if preterm infants were given low doses of DHA, improvement in visual development could be seen but there was uncertainty about effects on mental development.

Based on these findings, the Australian scientists recommend increasing DHA for all preterm infants born earlier than 33 weeks gestation. “We did not find negative effects of increasing the dietary DHA content,” Dr. Makrides said. “The babies fed high-DHA grew as well as those fed standard-DHA and we have confidence that the level of DHA used in the study (around 1 percent of the total dietary fat) was safe.”


J. Thomas Brenna, PhD, a professor of human nutrition at Cornell University in Ithaca, NY, studies the effects of DHA and said its role in the brain explains why it's important to know how much is necessary to make a difference in preterm babies who don't have the benefit of that large burst of DHA in the third trimester.

“DHA has a long and established history. It optimizes function, specifically retinal response to light and neural functioning. The brain preferentially uses DHA in certain membranes, including retinal rod outer segments in the eye, and synaptic membranes in the neurons. The functions involving these membranes do not function well without DHA.” He said that the results seen in this study may be due to both of these processes, as well as others.

Dr. Brenna added that the findings support the obvious link between nutrition and fetal development. “Mothers should be well nourished. DHA is low in many women's diets. If these results are confirmed, as seems to be the case for other, as yet unpublished, studies in humans and consistent with animal studies that we have published, it will further point to DHA being a key nutrient in pregnant and lactating women's diets.” Norman Salem, Jr., PhD, a scientist who spent decades researching DHA at the NIH, agrees. He recently retired from his federal post to become chief scientific officer at Martek Biosciences Corp., a company that makes DHA supplements used in infant formula. “Scientists are just beginning to explore the optimal doses of DHA,” he said.




APRIL 25–MAY 2, 2009


APRIL 10–APRIL 17, 2010


• Makrides M, Gibson RA, Ryan P, et al. Neurodevelopmental outcomes of preterm infants fed high-dose docosahexaenoic acid: A Randomized controlled trial. JAMA 2009;301(2):175–182.