Maternal factors and the risk of birth defects after IVF and ICSI: a whole of population cohort study

Objective To assess the contribution of maternal factors to major birth defects after in vitro fertilisation (IVF), intracytoplasmic sperm injection (ICSI), and natural conception. Design Retrospective cohort study in South Australia for the period January 1986 to December 2002. Setting A whole of population study. Population A census of all IVF and ICSI linked to registries for births, pregnancy terminations, and birth defects (diagnosed before a child's fifth birthday). Methods Odds ratios (ORs) for birth defects were calculated among IVF, ICSI, and natural conceptions for maternal age, parity, pre-pregnancy BMI, smoking, pre-existing diseases, and conditions in pregnancy, with adjustment for confounding factors. Main outcome measures Birth defects classified by International Classification of Diseases (ninth revision) and British Paediatric Association (ICD9-BPA) codes. Results There were 2211 IVF, 1399 ICSI, and 301 060 naturally conceived births. The unadjusted prevalence of any birth defect was 7.1, 9.9, and 5.7% in the IVF, ICSI, and natural conception groups, respectively. As expected, the risk of birth defects increased with maternal age among the natural conceptions. In contrast, for IVF and ICSI combined, relative to natural conceptions, births to women aged <= 29 years had a higher risk (adjusted odds ratio, aOR 1.42; 95% confidence interval, 95% CI 1.04-1.94), births to women aged 35-39 years had no difference in risk (aOR 1.01; 95% CI 0.74-1.37), and births to women aged >= 40 years had a lower risk of defects (aOR 0.45; 95% CI 0.22-0.92). Defects were also elevated for nulliparity, anaemia, and urinary tract infection in births after ICSI, but not after IVF. Conclusions The usual age-birth defect relationship is reversed in births after IVF and ICSI, and the associations for other maternal factors and defects vary between IVF and ICSI.