By Allison Gandey
January 15, 2009 — Investigators observed an 80% reduction in the proportion of baby girls with significant mental delays when they had a diet rich in docosahexaenoic acid (DHA). These are the findings of a randomized controlled trial published in the January 14, 2009 issue of the Journal of the American Medical Association.
Although the researchers did not see statistically significant benefits in boys or babies born weighing less than 1250 g, they say that there appeared to be a reduction in the proportion of babies with significant mental delay in these groups with high-DHA treatment.
"We recommend increased DHA for all preterm infants born at less than 33 weeks' gestation," lead author Maria Makrides, PhD, from the Women's and Children's Hospital in Adelaide, Australia told Medscape Neurology & Neurosurgery.
We think that the level of DHA used in the treatment arm of our study should become the new gold standard for preterm infants.
"We think that the level of DHA used in the treatment arm of our study should become the new gold standard for preterm infants, whether it is supplied through breast milk or infant formula," Dr. Makrides said.
"It is important to note that we did not find negative effects of increasing the dietary DHA content. The high-DHA babies grew as well as those fed standard DHA, and we have confidence that the level of DHA used in the study — around 1% of the total dietary fat — was safe," she added.
Mental Development Index Higher Among Girls Receiving Fatty Acids
The research team randomly assigned babies born at less than 33 weeks' gestation to either a high-DHA diet or a standard-DHA diet from about day 4 of life until the time they were due to be born. Infants were from 5 Australian tertiary hospitals.
"An important and unique aspect of the study was that the intervention was largely delivered to the baby through expressed breast milk," Dr. Makrides said. "We supplemented nursing women with about 1 g of DHA per day in tuna-oil supplements to increase the DHA content of their milk." If the mother could not express enough breast milk for her baby, an infant formula with a matching DHA content was provided.
Of the 657 infants enrolled, 93.5% completed the 18-month follow-up. Bayley Mental Development Index among girls fed the high-DHA diet was higher than for girls receiving standard DHA in unadjusted and adjusted analyses (unadjusted mean difference, 4.7; 95% CI 0.5 – 8.8; adjusted mean difference, 4.5; 95% CI, 0.5 – 8.5).
The Mental Development Index among boys did not differ between groups. For infants born weighing less than 1250 g, the index in the high-DHA group was higher than with standard DHA in the unadjusted comparison (mean difference, 4.7; 95% CI, 0.2 – 9.2). But this did not reach statistical significance following adjustment for gestational age, sex, maternal education, and birth order (mean difference, 3.8; 95% CI, -0.5 to 8.0).
No Improvements Found in Boys
"The lack of responsiveness of boys to the intervention is puzzling," the researchers write, "and the reasons are unclear."
"We can only speculate that there are differences in the metabolism of boys and girls that we do not yet understand," Dr. Makrides said during an interview. "The higher metabolic rate in boys may mean that they utilize much of the DHA they receive into energy. Also, boys may have a higher requirement for DHA. Clearly, this is an area of important research for the future."
Dr. Makrides pointed to a number of limitations to the study, including the fact that the majority of women in the high-DHA group correctly guessed their group allocation. "We tried to set up a double-blind study, but in the end about 70% of women correctly guessed they were in the DHA group. This was because they had fishy burps," she said. "This could have introduced bias."
The researchers plan to continue following this cohort. "Should these differences persist to school age, when we next plan to follow up these children," Dr. Makrides noted, "the potential significance to the children, the families, and the health and education system will be large."
This study was supported by a grant from the Australian National Health and Medical Research Council and by Channel 7 Children's Research Foundation of South Australia. Treatment and placebo capsules were donated by Clover Corp, and infant formula was donated by Mead Johnson Nutritionals and Nutricia Australasia. Dr. Maria Makrides serves on scientific advisory boards for Nestlé, Fonterra, and Nutricia. Coauthor Dr. Robert Gibson, also from the Women's and Children's Hospital in Adelaide, serves on scientific advisory boards for Wyeth, Fonterra, and Nestlé. Coauthor Dr. Karen Simmer, from King Edward Memorial Hospital and University of Western Australia, in Perth, serves on a scientific advisory board for Wyeth.
JAMA. 2009;301:175-182. Abstract
January 15, 2009 — Investigators observed an 80% reduction in the proportion of baby girls with significant mental delays when they had a diet rich in docosahexaenoic acid (DHA). These are the findings of a randomized controlled trial published in the January 14, 2009 issue of the Journal of the American Medical Association.
Although the researchers did not see statistically significant benefits in boys or babies born weighing less than 1250 g, they say that there appeared to be a reduction in the proportion of babies with significant mental delay in these groups with high-DHA treatment.
"We recommend increased DHA for all preterm infants born at less than 33 weeks' gestation," lead author Maria Makrides, PhD, from the Women's and Children's Hospital in Adelaide, Australia told Medscape Neurology & Neurosurgery.
We think that the level of DHA used in the treatment arm of our study should become the new gold standard for preterm infants.
"We think that the level of DHA used in the treatment arm of our study should become the new gold standard for preterm infants, whether it is supplied through breast milk or infant formula," Dr. Makrides said.
"It is important to note that we did not find negative effects of increasing the dietary DHA content. The high-DHA babies grew as well as those fed standard DHA, and we have confidence that the level of DHA used in the study — around 1% of the total dietary fat — was safe," she added.
Mental Development Index Higher Among Girls Receiving Fatty Acids
The research team randomly assigned babies born at less than 33 weeks' gestation to either a high-DHA diet or a standard-DHA diet from about day 4 of life until the time they were due to be born. Infants were from 5 Australian tertiary hospitals.
"An important and unique aspect of the study was that the intervention was largely delivered to the baby through expressed breast milk," Dr. Makrides said. "We supplemented nursing women with about 1 g of DHA per day in tuna-oil supplements to increase the DHA content of their milk." If the mother could not express enough breast milk for her baby, an infant formula with a matching DHA content was provided.
Of the 657 infants enrolled, 93.5% completed the 18-month follow-up. Bayley Mental Development Index among girls fed the high-DHA diet was higher than for girls receiving standard DHA in unadjusted and adjusted analyses (unadjusted mean difference, 4.7; 95% CI 0.5 – 8.8; adjusted mean difference, 4.5; 95% CI, 0.5 – 8.5).
The Mental Development Index among boys did not differ between groups. For infants born weighing less than 1250 g, the index in the high-DHA group was higher than with standard DHA in the unadjusted comparison (mean difference, 4.7; 95% CI, 0.2 – 9.2). But this did not reach statistical significance following adjustment for gestational age, sex, maternal education, and birth order (mean difference, 3.8; 95% CI, -0.5 to 8.0).
No Improvements Found in Boys
"The lack of responsiveness of boys to the intervention is puzzling," the researchers write, "and the reasons are unclear."
"We can only speculate that there are differences in the metabolism of boys and girls that we do not yet understand," Dr. Makrides said during an interview. "The higher metabolic rate in boys may mean that they utilize much of the DHA they receive into energy. Also, boys may have a higher requirement for DHA. Clearly, this is an area of important research for the future."
Dr. Makrides pointed to a number of limitations to the study, including the fact that the majority of women in the high-DHA group correctly guessed their group allocation. "We tried to set up a double-blind study, but in the end about 70% of women correctly guessed they were in the DHA group. This was because they had fishy burps," she said. "This could have introduced bias."
The researchers plan to continue following this cohort. "Should these differences persist to school age, when we next plan to follow up these children," Dr. Makrides noted, "the potential significance to the children, the families, and the health and education system will be large."
This study was supported by a grant from the Australian National Health and Medical Research Council and by Channel 7 Children's Research Foundation of South Australia. Treatment and placebo capsules were donated by Clover Corp, and infant formula was donated by Mead Johnson Nutritionals and Nutricia Australasia. Dr. Maria Makrides serves on scientific advisory boards for Nestlé, Fonterra, and Nutricia. Coauthor Dr. Robert Gibson, also from the Women's and Children's Hospital in Adelaide, serves on scientific advisory boards for Wyeth, Fonterra, and Nestlé. Coauthor Dr. Karen Simmer, from King Edward Memorial Hospital and University of Western Australia, in Perth, serves on a scientific advisory board for Wyeth.
JAMA. 2009;301:175-182. Abstract
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