July 14, 2008 — Intake of n-3 polyunsaturated fatty acids (n-3 PUFAs) in late pregnancy may have prophylactic effects against asthma in children, according to the results of a randomized, prospective study reported in the July issue of the American Journal of Clinical Nutrition.

"Evidence suggests that asthma is rooted in the intrauterine environment and that intake of marine ...n-3 PUFAs in pregnancy may have immunomodulatory effects on the child," write Sjurdur F. Olsen, from Statens Serum Institut in Copenhagen, Denmark, and colleagues. "Our aim was to examine whether increasing maternal intake of n-3 PUFAs in pregnancy may affect offspring risk of asthma."

The study cohort was a population-based sample of 533 women with normal pregnancies in 1990 who were recruited and randomized at approximately gestational week 30 and who were asked to take study capsules until delivery. Participants were randomized 2:1:1 to receive four 1-g gelatin capsules per day containing fish oil providing 2.7 g n-3 PUFAs (n = 266); four 1-g, similar-appearing capsules per day containing olive oil (n = 136); or no oil capsules (n = 131).

Of 531 liveborn children, 528 were identified in registries, and 523 were still alive by August 2006. Using a mandatory registry that recorded diagnoses reported from hospital contacts, the investigators extracted diagnoses from the International Classification of Diseases, 10th Revision.

During a 16-year follow-up, an asthma-related diagnosis was reported in 19 children from the fish oil and olive oil groups, including 10 diagnosed with allergic asthma. For the fish oil vs the olive oil group, the hazard rate of asthma was reduced by 63% (95% confidence interval [CI], 8% - 85%; P = .03), and the hazard rate of allergic asthma was reduced by 87% (95% CI, 40% - 97%; P = .01).

"Under the assumption that intake of olive oil in the dose provided here was inert, our results support that increasing n-3 PUFAs in late pregnancy may carry an important prophylactic potential in relation to offspring asthma," the study authors write.

Limitations of this study include few data to evaluate the dose-response relationship between maternal intake of n-3 PUFAs and offspring asthma.

"Clearly, there is a need for both large RCTs [randomized clinical trials] with long follow-ups as well as mechanistic studies," the study authors conclude. "Trials should also be undertaken that test the potential immunomodulatory effects on the offspring of various doses of n-3 PUFAs supplemented during various time windows during gestation."

The European Union FP6 consortium, Early Nutrition Programming Project, The Danish Obesity Research Centre from the Danish Strategic Research Council, The Lundbeck Foundation, and The Danish Medical Research Council supported this study. The study authors have disclosed no relevant financial relationships.

Am J Clin Nutr. 2008;88:167-175.

Clinical Context

Study Highlights

• Included were 533 women from a midwife clinic in Denmark who were randomized in 2:1:1 ratio to receive 1 of 3 treatments during pregnancy.
• The primary goal of the study was to investigate the protective effect of marine fish oil on preventing preterm delivery.
• Excluded from the study were women with a history of placental abruption, any bleeding in the current pregnancy, multiple pregnancies, allergy to fish, and regular use of fish oil.
• Women were interviewed about lifestyle factors and after delivery about compliance to assigned treatment and adverse effects.
• The investigators estimated adherence by weighing boxes containing the medications at each clinic visit.
• The treatments were four 1-g gelatin capsules of Pikasol (Lube Ltd, Hadsund, Denmark) fish oil daily (32% EPA and 23% DHA with 2 mg of tocopherol/mL corresponding to 2.7-g marine n-3 PUFA daily), identical-appearing olive oil capsules, or no supplements.
• Olive oil was chosen as the placebo because it had no known effect on the risk for asthma or on the pregnancy.
• The supplements were taken from 30 weeks of gestation until delivery.
• A food frequency questionnaire was used to stratify women further by fish intake (low, medium, and high).
• The children were tracked with use of 10-digit identifiers linked to their mothers in the Danish National Patient Registry.
• For each child, diagnoses with International Classification of Diseases, 10th Revision, codes were extracted, and incidence of asthma and allergic conditions was documented.
• Most diagnoses of asthma were given by pediatricians or pediatric pulmonologists.
• Most children were tracked to age 15 to 16 years.
• The analysis compared only the fish oil with the olive oil group as placebo because the authors considered that the no-treatment group may have voluntarily ingested fish oil supplements, which would have confounded the findings.
• Of 533 assigned fetuses, 531 were born and 522 were still alive by 2006.
• There were 8 cases of asthma in the fish oil (n = 263) vs 11 cases in the olive oil group (n = 136).
• The corresponding hazard ratio (HR) for asthma for the fish oil group was 0.37 (95% CI, 0.15 - 0.92).
• The number of children with a diagnosis of allergic asthma was 2 in the fish oil and 8 in the olive oil group.
• The HR for allergic asthma in the fish oil vs the olive oil group was 0.13 (95% CI, 0.03 - 0.60).
• When the diagnoses were expanded to include other allergic conditions, there were 11 cases of asthma (all types), atopic dermatitis, or allergic rhinitis in the fish oil and 13 in the olive oil group.
• The corresponding HR for other allergic conditions in the fish oil vs the olive oil group was 0.43 (95% CI, 0.19 - 0.96).
• In the low, middle, and high fish intake groups, the HRs for all types of asthma were 0.13, 0.54, and 0.36, but none of these associations were statistically significant.
• The authors concluded that fish oil supplementation in pregnant mothers was associated with a decreased risk for asthma in their offspring, independent of fish intake.

Pearls for Practice

• Maternal use of fish oil during pregnancy is associated with a reduced incidence of asthma and allergic asthma in the offspring.
• Potential maternal causes of asthma in the offspring include smoking; infections; antibiotic use; dietary intake of antioxidants, vitamins A and D, and folate; and pollutants during pregnancy.

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