Discussion
subfertility
REGRESSION
Using a causal inference approach, we found no effect of IVF conception on developmental vulnerability at school entry in Victorian children born between 2005 and 2014. Additionally, IVF-conceived children performed as well as their spontaneously conceived peers in school-based psychometric testing at age 7 to 9 years.For the first time, our study has estimated the causal effect of IVF conception on global childhood development at school entry and educational outcomes at primary school, under the assumptions of causal inference. Using an updated epidemiological approach [Two large Scandinavian studies have reported on childhood outcomes following IVF conception. Norrman and colleagues found that IVF-conceived children perform worse on school-based assessment in year 9 [These past studies are limited by examining historical birth cohorts dating back prior to the year 2001. Our study examines a more contemporary birth cohort (2005 to 2014), which is important given the advances in artificial reproductive techniques that have occurred since the turn of the century. IVF technologies that have evolved since this time include the introduction of blastocyst culture, vitrification, and single-embryo transfer [Given the use of observational data, there were missing data and inherent differences in the covariate profile of the exposure cohorts. An a priori SAP was developed to overcome these limitations. First, inverse probability weighting with regression adjustment was used to mimic exchangeable treatment and control comparison groups, similar to those that would be generated by randomisation in a controlled trial. The success of this procedure is demonstrated by achieving adequate covariate balance and thus sufficient overlap of covariate distributions between exposure groups after inverse probability weighting (Figs A–D in It is possible that unmeasured common cause confounders may have led to bias in estimating the ATEs. Many important factors (socioeconomic status, maternal age, and education) were identified a priori, measured, and included in the estimation procedure. Potential known but unmeasured sources of bias include subfertility and maternal BMI. Current evidence suggests that subfertility is likely to be associated with poorer childhood outcomes [Unmeasured variables may have had an impact on the outcome. Factors such as childcare attendance or grandparent involvement will be preceded on causal pathways by covariates that were measured and included in the model, such as maternal age and socioeconomic status [Generalisation of our findings to all IVF births is a potential study limitation. As described in our Methods, observations with non-overlapping PSs were excluded from analysis in order to meet the assumption of positivity, required for causal inference under the potential outcomes framework. Generalisation of our findings to all IVF births therefore requires the consideration that the baseline characteristics of the population of interest are comparable to the IVF cases analysed in our final cohort.Due to the use of school-based outcome assessments, our cohort was limited to children attending school. AEDC, as a triennial assessment, limited our sample to children captured during assessment years, and the later years of our birth cohort had not yet reached the assessment age for NAPLAN outcomes to be captured. However, our study included 70% of the relevant birth cohort for the study timeframe and in the years where both AEDC and NAPLAN data were available, over 95% of the Victorian birth cohort was sampled (Table A in Furthermore, through the examination of school-based outcomes, our study was inherently designed to examine outcomes for liveborn children. “Live birth bias” as it is known, is a recognised limitation of observational studies that investigate periconception and antenatal exposures [Under the specified assumptions, this analysis has demonstrated that there is no causal effect within the population studied of IVF conception on early childhood developmental vulnerability and school-age educational outcomes. Compared with spontaneously conceived children, children conceived by IVF were no more likely to be developmentally vulnerable at school entry and had equivalent numeracy and literacy performance by age 7 to 9 years. These findings provide important reassurance for current and prospective parents and their treating clinicians.