Maternal use of oral contraceptives and risk of birth defects in Denmark: prospective, nationwide cohort studyBMJ 2016; 352 doi: https://doi.org/10.1136/bmj.h6712 (Published 06 January 2016) Cite this as: BMJ 2016;352:h6712
- Brittany M Charlton, instructor123,
- Ditte Mølgaard-Nielsen, researcher4,
- Henrik Svanström, statistician4,
- Jan Wohlfahrt, chief statistician4,
- Björn Pasternak, research fellow4,
- Mads Melbye, professor456
- 1Department of Epidemiology, Harvard T H Chan School of Public Health, Boston, MA 02115, USA
- 2Division of Adolescent and Young Adult Medicine, Boston Children’s Hospital, Boston, MA, USA
- 3Department of Pediatrics, Harvard Medical School, Boston, MA, USA
- 4Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark
- 5Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark
- 6Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA
- Correspondence to: B M Charlton
- Accepted 18 November 2015
Study question Is oral contraceptive use around the time of pregnancy onset associated with an increased risk of major birth defects?
Methods In a prospective observational cohort study, data on oral contraceptive use and major birth defects were collected among 880 694 live births from Danish registries between 1997 and 2011. We conservatively assumed that oral contraceptive exposure lasted up to the most recently filled prescription. The main outcome measure was the number of major birth defects throughout one year follow-up (defined according to the European Surveillance of Congenital Anomalies classification). Logistic regression estimated prevalence odds ratios of any major birth defect as well as categories of birth defect subgroups.
Study answer and limitations Prevalence of major birth defects (per 1000 births) was consistent across each oral contraceptive exposure group (25.1, never users; 25.0, use >3 months before pregnancy onset (reference group); 24.9, use 0-3 months before pregnancy onset (that is, recent use); 24.8, use after pregnancy onset). No increase in prevalence of major birth defects was seen with oral contraceptive exposure among women with recent use before pregnancy (prevalence odds ratio 0.98 (95% confidence interval 0.93 to 1.03)) or use after pregnancy onset (0.95 (0.84 to 1.08)), compared with the reference group. There was also no increase in prevalence of any birth defect subgroup (for example, limb defects). It is unknown whether women took oral contraceptives up to the date of their most recently filled prescription. Also, the rarity of birth defects made disaggregation of the results difficult. Residual confounding was possible, and the analysis lacked information on folate, one of the proposed mechanisms.
What this study adds Oral contraceptive exposure just before or during pregnancy does not appear to be associated with an increased risk of major birth defects.
Funding, competing interests, data sharing BMC was funded by the Harvard T H Chan School of Public Health’s Maternal Health Task Force and Department of Epidemiology Rose Traveling Fellowship; training grant T32HD060454 in reproductive, perinatal, and paediatric epidemiology and award F32HD084000 from the Eunice Kennedy Shriver National Institute of Child Health and Human Development; and grant T32CA09001 from the National Cancer Institute. The authors have no competing interests or additional data to share.
An abstract of this work was presented as an oral presentation at the annual meeting of the Society for Reproductive Investigation in March 2014. The complete manuscript has not been published in any other form.
Contributors: BMC and MM were responsible for study concept and design. BMC and HS analysed the data. BMC wrote the manuscript while all authors critically reviewed the manuscript and approved the final version. All authors also had full access to all of the data (including statistical reports and tables) in the study and can take responsibility for the integrity of the data and the accuracy of the data analysis. BMC acts as guarantor of the study.
Funding: BMC was supported by funds from the Harvard T H Chan School of Public Health’s Maternal Health Task Force and Department of Epidemiology Rose Travelling Fellowship; training grant T32HD060454 in reproductive, perinatal, and paediatric epidemiology and award number F32HD084000 from the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, and the training program in cancer epidemiology under grant T32CA09001 from the National Cancer Institute, National Institutes of Health. The funding agencies had no role in the design and conduct of the study; the collection, management, analysis, and interpretation of the data; the preparation, review, or approval of the manuscript; or the decision to submit the manuscript for publication.
Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf (available on request from the corresponding author) and declare: support from the Harvard T H Chan School of Public Health, Eunice Kennedy Shriver National Institute of Child Health and Human Development, and National Cancer Institute for the submitted work; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work.
Ethical approval: The study was approved by the Danish Data Protection Agency; ethics approval was not required for Danish registry based research.
Data sharing: No additional data available.
BMC affirms that the manuscript is an honest, accurate, and transparent account of the study being reported; that no important aspects of the study have been omitted; and that any discrepancies from the study as planned (and, if relevant, registered) have been explained.
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