Maternal Omega-3 Supplementation Reduces Wheeze in Offspring

Nicola M. Parry, DVM

December 29, 2016

Supplementing a mother's diet with omega-3 (n-3) fatty acids during the third trimester of pregnancy may decrease the risk for persistent wheeze and asthma during her child's first 5 years, according to a new study published in the December 29 issue of the New England Journal of Medicine.

"Supplementation with n-3 LCPUFA [long-chain polyunsaturated fatty acid] in the third trimester of pregnancy reduced the absolute risk of persistent wheeze or asthma and infections of the lower respiratory tract in offspring by approximately 7 percentage points, or one third," write Hans Bisgaard, MD, DMSc, from Copenhagen Prospective Studies on Asthma in Childhood (COPSAC), Copenhagen University Hospital, Denmark, and colleagues.

Although increasing evidence has suggested that deficient maternal intake of n-3 LCPUFAs during pregnancy may be associated with increased risk for asthma and wheezing in the offspring, randomized controlled trials to evaluate the effect of maternal n-3 LCPUFA supplementation have shown conflicting results.

Dr Bisgaard and colleagues therefore conducted a double-blind, randomized, placebo-controlled trial to examine the effect of high-dose n-3 LCPUFA supplementation in pregnant women on the risk for persistent wheeze and asthma in the offspring.

They randomly assigned 736 pregnant women at 24 weeks of pregnancy to receive 2.4 g n-3 LCPUFA (n-3 polyunsaturated fatty acids eicosapentaenoic acid and docosahexaenoic acid; fish oil) or placebo (olive oil) per day. The women continued to take the supplements until 1 week after delivery.

After birth, the children then formed the Copenhagen Prospective Studies on Asthma in Childhood2010 (COPSAC2010) cohort and were followed for the first 3 years of life with comprehensive clinical phenotyping, after which there was a 2-year follow-up period.

The study's primary outcome was persistent wheeze or asthma. Secondary outcomes included lower respiratory tract infections, asthma exacerbations, eczema, and allergic sensitization.

The researchers found that high­n-3 LCPUFA supplementation during the third trimester of pregnancy significantly reduced the child's risk for persistent wheeze and asthma during the first 5 years of life (16.9% vs 23.7%; hazard ratio [HR], 0.69; 95% confidence interval [CI], 0.49 - 0.97; P = .035). This corresponded to a relative reduction of 30.7%, they add.

In addition, the effect of supplementation on the risk for persistent wheeze and asthma was greatest among children of mothers whose blood levels of n-3 LCPUFAs were in the lowest third of the trial population before supplementation began (17.5% vs 34.1%; HR, 0.46; 95% CI, 0.25 - 0.83; P = .011). This corresponded to a relative reduction of 54.1%.

Maternal n-3 LCPUFA supplementation also reduced the rate of lower respiratory infections (31.7% vs 39.1%; HR, 0.75; 95% CI, 0.58 - 0.98; P = .033) in the children. However, it did not significantly affect their risk for asthma exacerbations, eczema, or allergic sensitization.

The authors emphasize that these findings are enhanced by the study's use of centralized, longitudinal clinical follow-up, daily recording of children's symptoms, and frequent visits to the clinical research unit for care.

"COPSAC served as the de facto primary health care center for the birth cohort, thereby ensuring the use of a standardized approach to diagnosis and treatment," they write. "This approach greatly improves the reliability of the diagnoses."

In an accompanying editorial, Christopher E. Ramsden, MD, from the National Institute on Aging, Baltimore, and the National Institute on Alcohol Abuse and Alcoholism, Bethesda, Maryland, acknowledges the major strengths of this trial. These include its double-blind, randomized, placebo-controlled design, moderate to large sample size, low dropout rate, and extensive use of clinical phenotyping.

Dr Ramsden highlights the finding that the preventive effect of fish oil was driven almost exclusively by children of mothers with low baseline blood levels of eicosapentaenoic acid and docosahexaenoic acid. He adds that this preventive effect was also greatest in children of mothers with a variant of the gene encoding fatty acid desaturase, an enzyme associated with low ability to produce eicosapentaenoic acid (20:5n-3) and docosahexaenoic acid (22:6n-3) from their dietary alpha-linolenic acid.

"Together, these observations support the plausibility of the findings and point toward a precision-medicine approach in which factors such as blood levels of fatty acids, genotype, and parental history of asthma could potentially be used to tailor interventions to those most likely to benefit," he emphasizes.

However, Dr Ramsden also notes that the dose of eicosapentaenoic acid plus docosahexaenoic acid used in this trial (2.4 g/day) was about 15 to 20 times higher than the average American's dietary intake of these LCPUFAs. Before the results are applied to clinical practice, he therefore stresses the need to ensure that this high dose does not adversely affect long-term outcomes such as behavior or cognition.

"Future work is also needed to determine whether lower doses are effective and whether these results can be replicated in other populations," he concludes.

COPSAC has reported receiving core support from the Lundbeck Foundation, the Danish Ministry of Health, the Danish Council for Strategic Research, the Danish Council for Independent Research, and the Capital Region Research Foundation. One coauthor holds a Canada Research Chair in Nutritional Lipidomics and receives salary support from the Canada Research Chairs program. Another coauthor has reported receiving consulting fees from Chiesi Pharmaceuticals and Boehringer Ingelheim. Two coauthors are named on a pending patent related to the prevention of childhood asthma through FADS genotyping and the assessment of blood levels of eicosapentaenoic acid and docosahexaenoic acid in pregnant mothers. The editorialist has disclosed no relevant financial relationships.

N Engl J Med. 2016;26:2530-2539, 2596-2598. Article abstract, Editorial extract

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