Fish oil supplementation in pregnancy modifies neonatal allergen-specific immune responses and clinical outcomes in infants at high risk of atopy: A randomized, controlled trial

doi:10.1016/j.jaci.2003.09.009

Journal of Allergy and Clinical Immunology

Volume 112, Issue 6, December 2003, Pages 1178-1184

https://doi.org/10.1016/j.jaci.2003.09.009 Get rights and content

Abstract

Background

There is growing interest in the potential role of anti-inflammatory n-3 polyunsaturated fatty acids (n-3 PUFAs) in the prevention of allergic disease.

Objective

We sought to determine whether maternal dietary supplementation with n-3 PUFAs during pregnancy could modify immune responses in infants.

Methods

In a randomized, controlled trial 98 atopic, pregnant women received fish oil (3.7 g n-3 PUFAs per day) or placebo from 20 weeks' gestation until delivery. Neonatal PUFA levels and immunologic response to allergens were measured at birth.

Results

Eighty-three women completed the study. Fish oil supplementation (n = 40) achieved significantly higher proportions of n-3 PUFAs in neonatal erythrocyte membranes (mean ± SD, 17.75% ± 1.85% as a percentage of total fatty acids) compared with the control group (n = 43, 13.69% ± 1.22%, P < .001). All neonatal cytokine (IL-5, IL-13, IL-10, and IFN-γ) responses (to all allergens) tended to be lower in the fish oil group (statistically significant only for IL-10 in response to cat). Although this study was not designed to examine clinical effects, we noted that infants in the fish oil group were 3 times less likely to have a positive skin prick test to egg at 1 year of age (odds ratio, 0.34; 95% confidence interval, 0.11 to 1.02; P = .055). Although there was no difference in the frequency of atopic dermatitis at 1 year of age, infants in the fish oil group also had significantly less severe disease (odds ratio, 0.09; 95% confidence interval, 0.01 to 0.94; P = .045).

Conclusions

These data suggest a potential reduction in subsequent infant allergy after maternal PUFA supplementation. More detailed follow-up studies are required in larger cohorts to establish the robustness of these findings and to ascertain their significance in relation to longer-term modification of allergic disease in children.

Section snippets

Study design

Allergen-specific T-cell responses in cord blood were compared in fish-oil-supplemented and control groups in a double-blind, placebo-controlled study. The number of subjects in this study was based on previous studies by the host laboratory comparing cord blood immune responses of neonates with or without later allergy. Power calculations determined that our sample size was sufficient for the detection of a difference of 15% in cytokine levels between control and intervention groups at a

Characteristics of maternal and neonatal populations

As shown in the trial profile (Table I), 98 women entered the study. There was no significant difference in age, prepregnancy body mass index, allergic status (asthma or allergic rhinitis), or parity between the women in the fish oil and control groups. Eight women discontinued the study because of nausea that they associated with the capsules (7 of these were in the fish oil group). Four infants were subsequently excluded from the data analysis because they were born prematurely (1 in the

Discussion

It is now recognized that the increase in allergic disease might be the result of failure of normal immune regulation in early life, rather than simple “T_H2 skewing” of immune responses.¹⁵ This might explain the observations by a number of groups that allergic children have stronger T_H1 and T_H2 responses to allergens.16, 17 There is now an urgent need to identify environmental factors that might influence immune regulatory pathways in early life and the propensity for allergic disease. To our

Acknowledgments

We wish to acknowledge the staff and patients who assisted in this study. We are particularly grateful to the obstetricians and midwives at St John of God Hospital, Subiaco, Western Australia. Finally, we wish to acknowledge Prof Scott Weiss of Harvard University for his support in the original planning of this study.

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^☆: Supported by grants from the National Health and Medical Research Council and Raine Medical Research Foundation, Australia.

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Basic and clinical immunologyFish oil supplementation in pregnancy modifies neonatal allergen-specific immune responses and clinical outcomes in infants at high risk of atopy: A randomized, controlled trial☆

Abstract

Background

Objective

Methods

Results

Conclusions

Section snippets

Study design

Characteristics of maternal and neonatal populations

Discussion

Acknowledgments

Am J Clin Nutr

Diet as a risk factor for asthma

Risk factor: diet

Dietary fat and asthma: is there a connection?

Eur Respir J

Fatty acids and atopic disease

Pediatr Allergy Immunol.

Dietary marine fatty acids (fish oil) for asthma

Cochrane Database Syst Rev.

Transplacental priming of the human immune system to environmental allergens: universal skewing of initial T-cell responses towards Th-2 cytokine profile

J Immunol

Inhalant allergen-specific T-cell reactivity is detectable in close to 100% of atopic and normal individuals: covert responses are unmasked by serum-free medium

Clin Exp Allergy

Heterogeneity in diphtheria-tetanus-acellular pertussis vaccine-specific cellular immunity during infancy: relationship to variations in the kinetics of postnatal maturation of systemic Th1 function

J Infect Dis

A revised nomenclature for allergy: an EAACI position statement from the EAACI nomenclature task force

Allergy

Basic and clinical immunology
Fish oil supplementation in pregnancy modifies neonatal allergen-specific immune responses and clinical outcomes in infants at high risk of atopy: A randomized, controlled trial☆