Does fish oil during pregnancy help prevent asthma in kids? The evidence on fish oil has been mixed, but this study affirms its benefits--in certain women. PRACTICE CHANGER: Fish oil supplementation taken by women in the third trimester of pregnancy can reduce the risk of persistent wheeze, asthma, and infections of the lower respiratory tract in their children.Authors: Dana Neutze, MD, PhD; Kelly Lacy Evans, MD; Marianne Koenig, PharmD, BCPS; Gregory Castelli, PharmD, BCPS, BC-ADM; Anne Mounsey, MD Department of Family Medicine, University of North Carolina at Chapel Hill (Drs. Neutze, Evans, and Mounsey); UPMC St. Margaret Family Medicine Residency Program, Pittsburgh, Pa (Drs. Koenig and Castelli)

Castelli, Gregory

Evans, Kelly Lacy

Koenig, Marianne

Mounsey, Anne

Neutze, Dana

University of Missouri: MOspace

100 THE JOURNAL OF FAMILY PRACTICE  |   FEBRUARY 2018  |   VOL 67, NO 2Priority Updates from the Research Literature from the Family Physicians Inquiries NetworkPURLs®Dana Neutze, MD, PhD; Kelly Lacy Evans, MD; Marianne Koenig, PharmD, BCPS; Gregory Castelli, PharmD, BCPS, BC-ADM; Anne Mounsey, MDDepartment of Family Medicine, University of North Carolina at Chapel Hill (Drs. Neutze, Evans, and Mounsey); UPMC St. Margaret Family Medicine Residency Program,  Pittsburgh, Pa (Drs. Koenig and Castelli)D E P U T Y  E D I T O RJames J. Stevermer, MD, MSPHDepartment of Family and Community Medicine, University of Missouri-ColumbiaDoes fish oil during pregnancy help prevent asthma in kids?The evidence on fish oil has been mixed, but this study affirms its benefits—in certain women.PRACTICE CHANGERFish oil supplementation taken by women in the third trimester of pregnancy can reduce the risk of persistent wheeze, asthma, and in-fections of the lower respiratory tract in their children.1 STRENGTH OF RECOMMENDATIONB: Based on 2 double-blinded randomized controlled trials (RCTs).Bisgaard H, Stokholm J, Chawes BL, et al. Fish oil-derived fatty ac-ids in pregnancy and wheeze and asthma in offspring. N Engl J Med. 2016;375:2530-2539.1ILLUSTRATIVE CASEA 24-year-old G2P1 at 24 weeks’ gestation presents to your clinic for a routine prenatal visit. Her older daughter has asthma and she is inquiring as to whether there is anything she can do to lower the risk of her second child developing asthma in the future. What do you recommend?Asthma is the most common chronic disease in children in resource-rich countries such as the United States.2 The Centers for Disease Control and Preven-tion (CDC) reported that 8.4% of children were diagnosed with asthma in 2015.3 Omega-3 fatty acids, found naturally in fish oil, are thought to confer anti- inflammatory properties that offer protection against asthma. Clinical trials have shown that fish oil supplementation in pregnancy results in higher levels of omega-3 fatty acids, along with anti-inflammatory changes, in off-spring.4 Previous epidemiologic studies have also found that consumption of omega-3 fatty acids decreased the risk of atopy and asthma in offspring.5,6 ❚ A Cochrane review published in 2015, however, concluded that omega-3 supple-mentation during pregnancy had no ben-efit on wheeze or asthma in offspring.7 Five RCTs were included in the analysis. The largest trial by Palmer et al, which included 706 women, showed no benefit for omega-3 supplementation.8 The second largest by Ol-sen et al, which included 533 women, did show a benefit (hazard ratio [HR]=0.37; 95% confidence interval [CI], 0.15-0.92; number needed to treat [NNT]=19.6).9 These results, however, were limited by heterogeneity in the amount of fish oil supplemented and duration of follow-up. For example, the children in the Palmer study were followed only until 3 years of age, which is around the time that asthma can be formally diagnosed, potentially leading to under-reporting.8 In addition, the diagno-sis of asthma was based on parent report of 3 episodes of wheezing, use of daily asthma medication, or use of a national registry—all of which can underestimate the incidence of asthma. The reported rate of childhood asthma with IgE-sensitization (they did not report the rate without sensitization) was 1.8% in both arms, which is much lower than the CDC’s rate of 8.4%, suggesting under-diagnosis.3,8 Due to these biases and other potential confounders, no firm conclusions can be drawn from the Cochrane review. 101JFPONLINE.COM VOL 67, NO 2  |  FEBRUARY 2018  |  THE JOURNAL OF FAMILY PRACTICESTUDY SUMMARYMaternal fish oil supplementation  reduces incidence of asthma in childrenThis single-center, double-blinded RCT of 736 pregnant women evaluated the effect of 2.4 g/d of n-3 long-chain polyunsaturated fatty acids (eicosapentaenoic acid [EPA] and docosahexaenoic acid [DHA]) or placebo (ol-ive oil), starting at an estimated gestational age of 24 to 26 weeks, on wheeze or asthma incidence in their offspring.1 Eligible women were between 22 and 26 weeks’ pregnant at the time of recruitment. Exclusion criteria included supplementa-tion of 600 IU/d or more of vitamin D, or hav-ing any endocrine, cardiac, or renal disorders. The investigators randomized the women in a 1:1 ratio to either fish oil or placebo. Maternal EPA and DHA blood levels were tested at the time of randomization and one week after birth.❚ The primary outcome was persistent wheeze or asthma (after 3 years of age, the diagnosis of persistent wheeze was termed asthma) based on daily diary recordings of 5 episodes of troublesome lung symptoms within the last 6 months (each lasting for at least 3 consecutive days), rescue use of in-haled beta2-agonists, and/or relapse after a 3-month course of inhaled glucocorticoids. Secondary outcomes included lower respira-tory tract infections, asthma exacerbations, eczema, and allergic sensitization. In total, 695 offspring were included in the study with 95.5% follow-up at 3 years and 93.1% follow-up at 5 years. The children had scheduled pediatric visits at 1 week; 1, 3, 6, 12, 18, 24, 30, and 36 months; and at 4 and 5 years, and acute visits for any pulmonary, al-lergic, or dermatologic symptoms that arose. ❚ Results. The investigators found that the children of the mothers who received the fish oil had a lower risk of persistent wheeze or asthma at ages 3 to 5 years com-pared to those who received placebo (16.9% vs 23.7%; HR=0.69; 95% CI, 0.49-0.97; P=.035; NNT=14.7). But the effect of the fish oil supplementation was significant only in the children of the mothers with baseline EPA and DHA levels in the lowest third (17.5% vs 34.1%; HR=0.46; 95% CI, 0.25-0.83; P=.011; NNT=5.6). Similarly, in mothers who con-sumed the least EPA and DHA before the start of the study, fish oil supplementation had a greater benefit in terms of decreased wheeze and asthma (18.5% vs 32.4%; HR=0.55; 95% CI, 0.30-0.98; P=.043; NNT=7.2). As for the secondary outcomes, only a re-duction in lower respiratory tract infections was associated with the fish oil supplementation vs the control (38.8% vs 45.5%; HR=0.77; 95% CI, 0.61-0.99; P=.041; NNT=14.9). There was no reduction in asthma exacerbations, eczema, or risk of sensitization in the fish oil group.WHAT’S NEW?Study adds fuel to the fireThis study strengthens the case for fish oil sup-plementation during pregnancy to reduce the risk of asthma in offspring, despite the recent Cochrane review that showed no benefit.1,7 The Palmer study used a much lower amount of omega-3s (900 mg/d fish oil vs 2400 mg/d in the current trial).1,8 Olsen et al supplemented with a greater amount of omega-3s (2700 mg/d) and did find a benefit.9 The NNT from the Olsen study (19.6) is consistent with that of the current investigation, suggesting that a higher dosage may be necessary to prevent the onset of asthma. Additionally, this study followed children for a longer period than did the Palmer study, which may have led to more accurate diagno-ses of asthma.1,8 Lastly, the diagnosis of asthma in the Palmer study was based on parent survey data and use of daily asthma medicine rather than on daily diary cards, which are often more accurate. ❚ Consider fish consumption. Both this study and the Olsen trial were performed in Denmark.1,9 While Denmark and the United States have had a relatively similar level of fish consumption since the 1990s, women in Denmark may eat a higher proportion of oily fish than women in the United States, given the more common inclusion of mackerel and herring in their diet.10 Thus, the effect of supplementation may be more pronounced in women in the United States.CAVEATSQuestions remain: Ideal dose  and which women to treat?The US Food and Drug Administration cur-This study strengthens the case for fish oil supplementation during  pregnancy to reduce the risk of asthma  in children.102 THE JOURNAL OF FAMILY PRACTICE  |   FEBRUARY 2018  |   VOL 67, NO 2PURLs®Only women whose blood levels of EPA and DHA are low to begin with will likely benefit from this intervention.rently recommends 8 to 12 ounces of fish per week for pregnant women, but there are no guidelines on the ideal amount of fish oil to be consumed.11 The Palmer study,8 using 900 mg/d fish oil, did not show a benefit, whereas there did appear to be benefit in this study (2400 mg/d)1 and the Olsen study (2700 mg/d).9 Further research is needed to determine the optimal dosage. The decreased risk of persistent wheeze or asthma was seen only in the children of the women whose EPA and DHA blood levels were in the lowest third of the study popula-tion. Thus, only women whose blood levels are low to begin with will likely benefit from this intervention. Currently, EPA and DHA levels are not routinely checked, but there may be some benefit to doing so. One proxy for blood levels is maternal intake of fish at baseline. The investigators found that there was an association between dietary intake of fish and blood levels of EPA and DHA (r=0.32; P<.001).1 Therefore, ad-ditional screening questions to determine fish consumption would be useful for iden-tifying women most likely to benefit from supplementation. CHALLENGES TO IMPLEMENTATIONMultiple pills and additional costSince omega-3 fatty acids are relatively safe and the NNT in the general population is low, it may be worth supplementing all preg-nant women, even without a commercially- available blood test for EPA or DHA. Never-theless, some women may find it challeng-ing to take up to an additional 4 pills/d for 13 or more weeks. Also, there is an associ-ated cost with these supplements, although it is low.                                JFPACKNOWLEDGEMENTThe PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the National Center For Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsi-bility of the authors and does not necessarily represent the official views of the National Center For Research Resources or the National Institutes of Health.Copyright © 2018. The Family Physicians Inquiries Network. All rights reserved. References  1.   Bisgaard H, Stokholm J, Chawes BL, et al. Fish oil-derived fatty acids in pregnancy and wheeze and asthma in offspring. N Engl J Med. 2016;375:2530-2539. 2.  Masoli M, Fabian D, Holt S, et al. The global burden of asthma: ex-ecutive summary of the GINA Dessemination Committee Report. Allergy. 2004;59:469-478. 3.   Centers for Disease Control and Prevention. Asthma. Available at: https://www.cdc.gov/asthma/most_recent_data.htm. Ac-cessed October 9, 2017. 4.   Miyata J, Arita M. Role of omega-3 fatty acids and their metabo-lites in asthma and allergic diseases. Allergol Int. 2015;64:27-34.  5.   Salam MT, Li YF, Langholz B, et al. Maternal fish consumption during pregnancy and risk of early childhood asthma. J Asthma. 2005;42:513-518. 6.   Calvani M, Alessandri C, Sopo SM, et al. Consumption of fish, butter and margarine during pregnancy and development of al-lergic sensitizations in the offspring: role of maternal atopy. Pedi-atr Allergy Immunol. 2006;17:94-102. 7.   Gunaratne AW, Makrides M, Collins CT. Maternal prenatal and/or postnatal n-3 long chain polyunsaturated fatty acids (LCPUFA) supplementation for preventing allergies in early childhood. Co-chrane Database Syst Rev. 2015;22:CD010085. 8.   Palmer D, Sullivan T, Gold M, et al. Randomized controlled trial of fish oil supplementation in pregnancy on childhood allergies. Allergy. 2013;68:1370-1376. 9.   Olsen SF, Østerdal ML, Salvig JD, et al. Fish oil intake compared with olive oil intake in late pregnancy and asthma in the off-spring: 16 y of registry-based follow-up from a randomized con-trolled trial. Am J Clin Nutr. 2008;88:167-175. 10.   Helgi Library. Fish consumption per capita by country. Available at: http://www.helgilibrary.com/indicators/fish-consumption-per-capita/. Accessed September 27, 2017. 11.   FDA Advice About Eating Fish, From the Environmental Protec-tion Agency and Food and Drug Administration; Revised Fish Advice; Availability. Federal Register.2017;82:6571-6574.

Does fish oil during pregnancy help prevent asthma in kids?

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Does fish oil during pregnancy help prevent asthma in kids?

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