Fertility treatment and risk of cerebral palsy: has the association changed in Australia?

STUDY QUESTION: What is the association between treated (ART, ovulation induction (OI)) and untreated subfertility and risk of cerebral palsy (CP)? SUMMARY ANSWER: There is no increased risk of CP in births to subfertile untreated women; the risk of CP has declined in ART conceptions (IVF, ICSI) and is greatest in births conceived using OI medications as a sole therapy. WHAT IS KNOWN ALREADY: Nordic data suggest a decline in risk of CP for ART births over time with the shift to single embryo transfer (SET), but there are no recent data from other countries and no Australian data for births after 2002. Few studies have examined the risk of CP in births conceived after OI or untreated subfertility; these comparison groups may assist in separating ART treatment effects from potential effects of subfertility itself. STUDY DESIGN, SIZE, DURATION: Retrospective cohort study using linked population-based data for women with a live birth (LB) in Western Australia from 2003 to 2014, corresponding to 10 126 ART births (3.1%), 4102 births after OI (1.2%), 11 554 births to subfertile untreated women (3.5%), and 305 508 (92.2%) births to fertile women conceiving naturally. PARTICIPANTS/MATERIALS, SETTING, METHODS: Statutory ART, birth, hospital, CP, and pharmacy data were linked to identify four 'conception groups' (ART, OI, subfertile untreated, and fertile natural conceptions), outcome data, and potential confounders. CP descriptions were verified at 5 years of age. Birth prevalence of CP was calculated for each conception group per 1000 LB. Poisson regression with robust standard errors was used to estimate adjusted risk ratios (aRR) for CP with adjustment for maternal demographic characteristics, pre-existing conditions, and adverse obstetric history (with 95% CI). Births to fertile women were the reference group. Analyses included all children and singletons and twins separately. Weinberg's differential rule was used to estimate the rate of monozygotic twinning across our four conception groups and, for ART births, by length of embryo culture. MAIN RESULTS AND THE ROLE OF CHANCE: CP was diagnosed in 29 ART children (2.9/1000 LB; 95% CI 1.92-4.11), 16 children born after OI (3.9/1000 LB; 95% CI 2.23-6.33), 23 children in the subfertile untreated group (2.0/1000 LB; 95% CI 1.26-2.99), and 610 in the fertile group (2.0/1000 LB; 95% CI 1.84-2.16). When stratified by plurality and prematurity, risk was increased only for ART twins (aRR 2.8, 95% CI 1.42-5.39) born preterm (