Fish oil supplementation during pregnancy may reduce the risk of persistent asthma or wheezing in children at 5 years of age

Resident Focus - Volume 12, Issue 9

Reference: N Engl J Med 2016 Dec 29; 375(26): 2530
Level 2 [mid-level] evidence

An African American G1P1001 with history of mild intermittent asthma presents to discuss pre-conception counseling. During your visit, she asks if there are any vitamins or medications that can help reduce the risk of asthma in her children. Asthma affects over 7 million children in the United States, with higher prevalence and complication rates among minority populations. While earlier epidemiological studies reported an association between high intake of long-chain n-3 polyunsaturated fatty acids (LCPUFA) during pregnancy and lower rates of asthma in children (Curr Allergy Asthma Rep. 2012 Dec;12(6):564-73) a 2015 Cochrane review of eight randomized trials reported no evidence of benefit with prenatal LCPUFA supplementation (Cochrane Database Syst Rev. 2015 Jul 22;(7):CD010085). However, this Cochrane review had limited evidence, with the eight trials precluding meta-analysis due to heterogeneity in regimens, trimester of initiation, duration of follow-up, and baseline risk of allergy. Given the limited evidence, one wonders if fish oil should be recommended to pregnant women to reduce the risk of asthma in their offspring.

To answer this question, investigators enrolled pregnant women between 22-26 weeks gestation into a single-center, double-blinded, randomized controlled trial. Women taking supplemental vitamin D in doses > 600 units or with any heart, endocrine, or kidney disorder were excluded. At week 24 of pregnancy, 736 women were randomized to receive either a 2.4-gram fish oil (LCPUFA) capsule or olive oil placebo capsule once daily until one week after delivery. The use of olive oil, which may have its own unique set of health benefits, as a placebo comparator may limit the ability of this trial to find a benefit. Overall, an average of about 26% of enrolled mothers had previously diagnosed asthma. Six percent of women dropped out or were lost to follow-up. To assess adherence and perform pre-specified subgroup analyses, women had whole blood levels of LCPUFA analyzed at randomization and 1-week post-partum. Infants were evaluated for asthma or persistent wheeze at 1 week, and then at months 1, 3, 6, 12, 18, 24, 30, and 36, and yearly thereafter until age 5 years.

Overall, the rate of persistent wheeze or asthma in offspring at age 5 years was lower in the fish oil group compared to controls (17.4% vs. 24.6%, hazard ratio [HR] 0.68, 95% CI 0.49-0.95). The rate of lower respiratory tract infections at age 5 years was also lower in the fish oil group compared to controls (38.8% vs. 45.4%, HR 0.77, 95% CI 0.61-0.99). While the hazard ratios are significant, these results have confidence intervals which may include clinically nonsignificant results, attenuating the validity of the apparent benefit. A number of prespecified subgroup analyses were performed to determine if women thought to be at higher risk of having children with asthma or wheeze benefited from fish oil supplementation. Results were similar in a sensitivity analysis adjusted for maternal asthma (HR for asthma or wheezing with fish oil supplementation 0.70, 95% CI 0.50-0.98). A second prespecified subgroup analysis demonstrated that the benefit of fish oil was only statistically significant among women with baseline LCPUFA accounting for less than 4.3% of total blood fatty acids (p = 0.011, estimated NNT 6). This suggests that the apparent reduced risk of asthma or wheeze reported with supplementation might only affect children of women with baseline lower levels of LCPUFA intake. There were no significant differences in other outcomes in children at age 5 years including asthma exacerbations, eczema and allergen sensitization by skin prick.

This trial suggests that supplementation with fish oil in the third trimester of pregnancy may reduce the incidence of asthma or wheezing in children. The population of Danish women from one center was largely Caucasian with a higher intake of omega-3 fatty acids than most women worldwide and may not apply to other more diverse populations. It has been found that African Americans have a lower intake of omega-3 fatty acids than Caucasians, and African American children are 1.6 times more likely to develop asthma, particularly severe asthma requiring hospitalization (Pediatric Allergy, Immunology, and Pulmonology, 25(2), 64-75). Future studies targeting high-risk women with low omega-3 fatty acid intake would be helpful to determine any additional benefit for their children.

For more information, see the Asthma in Children and Nutrition in Pregnancy topics in Dynamed Plus. DynaMed users, see the Asthma in children and Nutrition in pregnancy topics in Dynamed Classic.

CARINA BROWN, MD
attended Penn State College of Medicine and is currently Chief Resident in Family Medicine at the University of Virginia. She is interested in undergraduate medical education and the role of evidence based medicine in medical education. She plans to pursue a career in academic family medicine in the future.

Faculty contributions by Katharine C. DeGeorge, MD, MS.


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