Vitamin A and D Intake In Pregnancy Discussion Paper

Vitamin A and D Intake In Pregnancy Discussion Paper

Vitamin A and D intake in pregnancy, infant supplementation, and asthma development: the Norwegian Mother and Child Cohort

Christine L Parr,1,4 Maria C Magnus,1,5,6 Øystein Karlstad,1 Kristin Holvik,1 Nicolai A Lund-Blix,1,7 Margareta Haugen,2

Christian M Page,1 Per Nafstad,1,8 Per M Ueland,9,10 Stephanie J London,11 Siri E Håberg,1,3 and Wenche Nystad1

1Division of Mental and Physical Health; 2Department of Exposure and Risk Assessment; and 3Center for Fertility and Health, Norwegian Institute of Public Health, Oslo, Norway; 4Department of Nursing and Health Promotion, OsloMet–Oslo Metropolitan University, Oslo, Norway; 5Medical Research Council Integrative Epidemiology Unit, University of Bristol, Bristol, United Kingdom; 6Department of Population Health Sciences, Bristol Medical School, Bris- tol, United Kingdom; 7Division of Pediatric and Adolescent Medicine, Department of Pediatrics, Oslo University Hospital, Oslo, Norway; 8Department of Community Medicine, University of Oslo, Oslo, Norway; 9Department of Clinical Science, University of Bergen, Bergen, Norway; 10Laboratory of Clini- cal Biochemistry, Haukeland University Hospital, Bergen, Norway; and 11Epidemiology Branch, National Institute of Environmental Health Sciences, NIH, Department of Health and Human Services, Research Triangle Park, NC

ABSTRACT Background: Western diets may provide excess vitamin A, which is potentially toxic and could adversely affect respiratory health and counteract benefits from vitamin D. Objective: The aim of this study was to examine child asthma at age 7 y in relation to maternal intake of vitamins A and D during preg- nancy, infant supplementation with these vitamins, and their potential interaction. Design: We studied 61,676 school-age children (born during 2002– 2007) from the Norwegian Mother and Child Cohort with data on maternal total (food and supplement) nutrient intake in pregnancy (food-frequency questionnaire validated against biomarkers) and in- fant supplement use at age 6 mo (n = 54,142 children).

Linkage with the Norwegian Prescription Database enabled near-complete follow- up (end of second quarter in 2015) for dispensed medications to clas- sify asthma. We used log-binomial regression to calculate adjusted RRs (aRRs) for asthma with 95% CIs. Results: Asthma increased according to maternal intake of to- tal vitamin A [retinol activity equivalents (RAEs)] in the highest (≥2031 RAEs/d) compared with the lowest (≤779 RAEs/d) quin- tile (aRR: 1.21; 95% CI: 1.05, 1.40) and decreased for total vitamin D in the highest (≥13.6 µg/d) compared with the lowest (≤3.5 µg/d) quintile (aRR: 0.81; 95% CI: 0.67, 0.97) during pregnancy.

No as- sociation was observed for maternal intake in the highest quintiles of both nutrients (aRR: 0.99; 95% CI: 0.83, 1.18) and infant supple- mentation with vitamin D or cod liver oil. Conclusions: Excess vitamin A (≥2.5 times the recommended in- take) during pregnancy was associated with increased risk, whereas vitamin D intake close to recommendations was associated with a re- duced risk of asthma in school-age children. No association for high intakes of both nutrients suggests antagonistic effects of vitamins A and D. This trial was registered at http://www.clinicaltrials.gov as NCT03197233. Am J Clin Nutr 2018; 107:789–798.

Keywords: food-frequency questionnaire, dietary supplements, pregnant women, infants, vitamin A, vitamin D, pediatric asthma,

prescriptions, Norwegian Prescription Database, Norwegian Mother and Child Cohort

INTRODUCTION

Asthma is currently among the top 5 chronic conditions con- tributing to the global burden of disease in children aged 5–14 y (1). Unfavorable changes in diet have been hypothesized to in- crease the susceptibility to asthma (2) and dietary exposures in utero and infancy could play a role, in particular for childhood onset of the disease (3).

Fat-soluble vitamins have a broad range of effects related to antioxidant properties (4), immune function (5), and lung devel- opment (6). In particular, vitamin D has attracted much interest because of widespread deficiency in Western populations (7).

The Norwegian Mother and Child Cohort Study is supported by the Norwe- gian Ministry of Health and Care Services and the Ministry of Education and Research, NIH/National Institute of Environmental Health Sciences (contract no. N01-ES-75558), and NIH/National Institute of Neurological Disorders and Stroke (grant nos. 1 UO1 NS 047537-01 and 2 UO1 NS 047537-06A1). This work was also supported by the Norwegian Research Council (grant no. 221097; to WN) and by the Intramural Research Program of the NIH, Na- tional Institute of Environmental Health Sciences (ZO1 ES49019; to SJL). The funders of the study had no role in study design, data collection, data

analysis and interpretation, writing of the report, or the decision to submit the article for publication. Supplemental Figure 1 and Supplemental Tables 1–8 are available from the

“Supplementary data” link in the online posting of the article and from the same link in the online table of contents at https://academic.oup.com/ajcn/. Address correspondence to CLP (e-mail: christine-louise.parr@fhi.no). Abbreviations used: FFQ, food-frequency questionnaire; MoBa, Nor-

wegian Mother and Child Cohort Study; NorPD, Norwegian Prescription Database; RAE, retinol activity equivalent. Received June 13, 2017. Accepted for publication January 17, 2018. First published online April 20, 2018; doi: https://doi.org/10.1093/ajcn/

nqy016.

Am J Clin Nutr 2018;107:789–798. Printed in USA. © 2018 American Society for Nutrition. This work is written by (a) US Government employee(s) and is in the public domain in the US. 789

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