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Early pregnancy exposure to antihistamines and risk of congenital heart defects: results of two case–control studies

  • PERINATAL EPIDEMIOLOGY
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Abstract

We aimed to study the association between use of antihistamines in early pregnancy and congenital heart defects (CHD) in the offspring. Design: Two case–control studies. Setting: HAVEN study, Erasmus MC, University Medical Centre, Rotterdam, and Eurocat Northern Netherlands (NNL), University Medical Center Groningen, Groningen, the Netherlands. We studied 361 children with CHD and 410 controls without congenital malformations from the HAVEN study and replicated the analyses in 445 children with CHD and 530 controls from the Eurocat NNL registry. Information about antihistamine use in early pregnancy and potential confounders was obtained from questionnaires postpartum. We calculated the association between antihistamines and CHD risk by multivariable logistic regression analysis. Main outcome measures: Odds ratios (OR) with 95 % confidence intervals (CI). In the HAVEN study, 25 of 771 mothers used antihistamines that were associated with an increased CHD risk (OR 3.0, 95 % CI 1.2–7.3), particularly atrioventricular septal defects (AVSD) (OR 5.1, 95 % CI 1.3–20.5) and perimembranous ventricular septal defects (pVSD) (OR 5.1, 95 % CI 1.8–14.4). Mothers with severe nausea who did not use antihistamines had a reduced risk (OR 0.7, 95 % CI 0.5–0.98), whereas nauseous mothers using antihistamines showed an almost fivefold increased risk of pVSD (OR 4.8, 95 % CI 1.1–21.8). The association between antihistamines and AVSD was confirmed in the Eurocat cohort (OR 3.5, 95 % CI 1.4–8.7), but we could not replicate the association with overall CHD risk. We found a positive association between antihistamine use in early pregnancy and CHD risk, particularly AVSD, which seemed to be independent of nausea/vomiting.

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Acknowledgments

We thank Professor W.A. Helbing, MD, PhD, Professor J. Ottenkamp, MD, PhD, and F.M.H. Siebel, MD, for their assistance in recruiting the case and control families. We are also grateful to Dr. M. Wildhagen, for data management and to Dr. A.C. Verkleij-Hagoort, Dr. L.M.J.W. van Driel and S. Borst for help in the data collection. We thank JL Senior for editing the final manuscript. The HAVEN study was financially supported by the Bo Hjelt Foundation (Grant 2005) and the Netherlands Heart Foundation (Grant 2002.B027). Eurocat NNL is funded by the Dutch Ministry of Health, Welfare and Sports.

Conflict of interest

There are no conflicts of interest to declare.

Ethical Standard

The study protocol was approved by the Central Committee of Research in Humans in The Hague, the Netherlands, and by the local Medical Ethics Committees of the four participating hospitals (CCMO07.1052/MA/P03.0200; MEC212.508/2002/91).

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Authors and Affiliations

  1. Department of Obstetrics and Gynaecology, Erasmus MC, University Medical Centre, Dr. Molewaterplein 40, Room Ee 2271a, 3015 GD, Rotterdam, The Netherlands

    Huberdina P. M. Smedts, Sarah J. G. Bandola & Régine P. M. Steegers-Theunissen

  2. Eurocat Registration Northern Netherlands, Department of Genetics, University of Groningen, University Medical Centre Groningen, Groningen, The Netherlands

    Linda de Jonge, Marlies E. Baardman & Marian K. Bakker

  3. Department of Epidemiology, Erasmus MC, University Medical Centre, Rotterdam, The Netherlands

    Bruno H. C. Stricker

  4. Drug Safety Unit, Inspectorate of Healthcare, The Hague, The Netherlands

    Bruno H. C. Stricker

  5. Department of Clinical Genetics, Erasmus MC, University Medical Centre, Rotterdam, The Netherlands

    Régine P. M. Steegers-Theunissen

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  1. Huberdina P. M. Smedts
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  2. Linda de Jonge
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  3. Sarah J. G. Bandola
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  4. Marlies E. Baardman
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  6. Bruno H. C. Stricker
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  7. Régine P. M. Steegers-Theunissen
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Correspondence to Régine P. M. Steegers-Theunissen.

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Smedts, H.P.M., de Jonge, L., Bandola, S.J.G. et al. Early pregnancy exposure to antihistamines and risk of congenital heart defects: results of two case–control studies. Eur J Epidemiol 29, 653–661 (2014). https://doi.org/10.1007/s10654-014-9925-0

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  • DOI: https://doi.org/10.1007/s10654-014-9925-0

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