Running title : Prenatal fatty acid levels , childhood lung function and atopic diseases

Background Maternal fatty acid status during pregnancy might influence fetal immunological development and subsequently the risk of childhood atopic diseases. Objective To examine the associations of maternal fatty acid levels during pregnancy with airway resistance and inflammation, asthma and eczema, in school-age children. Methods This study among 4,976 subjects was embedded in a population-based prospective cohort study. We measured maternal plasma glycerophospholipid fatty acid levels by gas chromatography during the second trimester of pregnancy (mean gestational age: 20.7 (± 1.1) weeks). At the age of 6 years, airway resistance and inflammation were measured by interrupter technique (Rint) and Fractional exhaled Nitric Oxide (FeNO), and current physician-diagnosed asthma and eczema were assessed by ISAAC-based questionnaires. Multiple linear and logistic regression models were adjusted for sociodemographic, lifestyle and anthropometric factors. Results We did not observe consistent associations of maternal total polyunsaturated fatty acid (PUFA), total n-6 PUFA, total n-3 PUFA levels and n-6/n-3 PUFA ratio during pregnancy with child’s Rint and FeNO. Higher maternal total PUFA and total n-6 PUFA levels were associated with a decreased risk of childhood asthma (Odds Ratios (95% Confidence Interval): 0.76 (0.60, 0.97) and 0.71 (0.52, 0.96) per Standard Deviation Score (SDS) increase of total PUFA and total n-6 PUFA levels, respectively) and with an increased risk of childhood eczema (1.16 (1.05, 1.28) and 1.21 (1.07, 1.37)). The observed associations were partly explained by Linoleic acid (LA, C18:2n-6) levels. Maternal total n-3 PUFA levels and n-6/n-3 PUFA ratio were not associated with current asthma and eczema. The observed associations were not explained by child’s PUFA intake. A cc ep te d A rt ic le This article is protected by copyright. All rights reserved. Conclusions & Clinical Relevance Higher maternal total PUFA and total n-6 PUFA levels during pregnancy seem to influence the risk of atopic diseases in childhood. The underlying mechanisms need to be further explored.

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