Dietary vitamin A intake below the recommended daily intake during pregnancy and the risk of congenital diaphragmatic hernia in the offspring §

Authors

  • Leonardus W. J. E. Beurskens,

    1. Department of Pediatric Surgery, Sophia Children's Hospital
    Current affiliation:
    1. Department of General Practice, Maastricht University Medical Center, Maastricht, The Netherlands
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  • Lieske H. Schrijver,

    1. Department of Obstetrics and Gynecology, Erasmus MC - University Medical Center Rotterdam, The Netherlands
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  • Dick Tibboel,

    1. Department of Pediatric Surgery, Sophia Children's Hospital
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  • Mark F. Wildhagen,

    1. Department of Obstetrics and Gynecology, Erasmus MC - University Medical Center Rotterdam, The Netherlands
    2. Department of Urology, Erasmus MC - University Medical Center Rotterdam, The Netherlands
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  • Maarten F. C. M. Knapen,

    1. Department of Obstetrics and Gynecology, Erasmus MC - University Medical Center Rotterdam, The Netherlands
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  • Jan Lindemans,

    1. Department of Clinical Chemistry, Erasmus MC - University Medical Center Rotterdam, The Netherlands
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  • Jeanne de Vries,

    1. Department of Nutrition, Wageningen University, The Netherlands
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  • Régine P. M. Steegers-Theunissen

    Corresponding author
    1. Department of Obstetrics and Gynecology, Erasmus MC - University Medical Center Rotterdam, The Netherlands
    2. Department of Clinical Genetics, Erasmus MC - University Medical Center Rotterdam, The Netherlands
    • Erasmus Medical Centre – University Medical Center Rotterdam, Department of Obstetrics and Gynecology, Building Ee Room 22-71a, PO Box 2040, 3000 CA Rotterdam, The Netherlands
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  • Disclosure of interest: The authors declare that they have no conflicts of interest.

  • Contribution to authorship: L.W.J.E. Beurskens: inclusion of patients, data input and analysis, drafting manuscript; L.H. Schrijver: data input and analysis, drafting manuscript; D. Tibboel: primary researcher, inclusion of patients, manuscript revision; M.F. Wildhagen: database management and data extraction; M.F.C. Knapen: inclusion of patients, manuscript revision; J. Lindemans: sample analysis, manuscript revision; J. de Vries: design questionnaires and data analysis, manuscript revision; R.P.M. Steegers-Theunissen, primary researcher, data analysis, manuscript revisions.

  • §

    Details of ethics approval: Permission to conduct the study was granted by the Central Committee of Research in Human in The Hague, The Netherlands, and by the Medical Ethical Committee of Erasmus University Rotterdam (MEC-2006-158; July 20, 2006).

  • Supported by a grant from the Mother and Child Center of the Erasmus Medical Centre – Sophia's Children's Hospital.

Abstract

BACKGROUND

Vitamin A has been related to the etiology of congenital diaphragmatic hernia (CDH). We performed a case-control study to investigate whether maternal dietary vitamin A intake is related to CDH in the offspring.

METHODS

Thirty-one pregnancies diagnosed with CDH and 46 control pregnancies were included during the study. After CDH diagnosis and inclusion of controls by risk set sampling, maternal vitamin A intake was investigated with a food frequency questionnaire. Serum retinol and retinol-binding protein were determined. Univariable and multivariable logistic regression models were used to calculate risk estimates with adjustment for potential confounders.

RESULTS

We found no significant differences in the overall nutrient and vitamin A intake between case and control mothers. After stratification in body mass index (BMI) categories, case mothers with normal weight showed a lower energy adjusted vitamin A intake (685 vs. 843 μg retinol activity equivalents [RAEs] / day; p = 0.04) and a slightly lower serum retinol (1.58 vs. 1.67 μmol/L; p = 0.08) than control mothers. Vitamin A intake <800 μg retinol activity equivalents (recommended daily intake) in normal weight mothers was associated with a significantly increased CDH risk (odds ratio [OR], 7.2; 95% confidence interval [CI], 1.5–34.4; p = 0.01). Associations were not significantly different in underweight and overweight mothers.

CONCLUSIONS

In normal-weight mothers, dietary vitamin A intake during pregnancy below the recommended daily intake is significantly associated with an increased risk of a child with CDH. This finding supports the retinoid hypothesis in human CDH, but warrants further investigation in larger study populations. Birth Defects Research (Part A), 2013. © 2013 Wiley Periodicals, Inc.

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