BMJ, doi: 10.1136/bmj.38919.495718.AE, (Published 7 August 2006)

RESEARCH

Infertility, infertility treatment, and congenital malformations: Danish national birth cohort

Jin Liang Zhu ^1*, Olga Basso ², Carsten Obel ³, Camilla Bille ⁴, Jørn Olsen ⁵

¹ Danish Epidemiology Science Centre, Department of Epidemiology, Institute of Public Health, University of Aarhus, DK 8000 Aarhus C, Denmark
² Epidemiology Branch, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, MD A3-05, USA
³ Perinatal Epidemiological Research Unit, Department of Gynaecology and Obstetrics, Aarhus University Hospital, DK 8200 Aarhus N, Denmark
⁴ Center for the Prevention of Congenital Malformations, Institute of Public Health, University of Southern Denmark, DK 5000 Odense C, Denmark
⁵ Department of Epidemiology, School of Public Health, UCLA, Los Angeles, CA 90095-1772, USA

^* Correspondence to: zjl{at}soci.au.dk..

Objectives To examine whether infertile couples (with a time to pregnancy of >12 months), who conceive naturally or after treatment, give birth to children with an increased prevalence of congenital malformations.

Design Longitudinal study.

Setting Danish national birth cohort.

Participants Three groups of liveborn children and their mothers: 50 897 singletons and 1366 twins born of fertile couples (time to pregnancy 12 months), 5764 singletons and 100 twins born of infertile couples who conceived naturally (time to pregnancy >12 months), and 4588 singletons and 1690 twins born after infertility treatment.

Main outcome measures Prevalence of congenital malformations determined from hospital discharge diagnoses.

Results Compared with singletons born of fertile couples, singletons born of infertile couples who conceived naturally or after treatment had a higher prevalence of congenital malformations--hazard ratios 1.20 (95% confidence interval 1.07 to 1.35) and 1.39 (1.23 to 1.57). The overall prevalence of congenital malformations increased with increasing time to pregnancy. When the analysis was restricted to singletons born of infertile couples, babies born after treatment had an increased prevalence of genital organ malformations (hazard ratio 2.32, 1.24 to 4.35) compared with babies conceived naturally. No significant differences existed in the overall prevalence of congenital malformations among twins.

Conclusions Hormonal treatment for infertility may be related to the occurrence of malformations of genital organs, but our results suggest that the reported increased prevalence of congenital malformations seen in singletons born after assisted reproductive technology is partly due to the underlying infertility or its determinants. The association between untreated infertility and congenital malformations warrants further examination.

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(Accepted 14 July 2006)
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STROBE recommends reporting absolute differences

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