School-age outcomes among IVF-conceived children: A population-wide cohort study.

Background: In vitro fertilisation (IVF) is a common mode of conception. Understanding the long-term implications for these children is important. The aim of this study was to determine the causal effect of IVF conception on primary school-age childhood developmental and educational outcomes, compared with outcomes following spontaneous conception. Methods and findings: Causal inference methods were used to analyse observational data in a way that emulates a target randomised clinical trial. The study cohort comprised statewide linked maternal and childhood administrative data. Participants included singleton infants conceived spontaneously or via IVF, born in Victoria, Australia between 2005 and 2014 and who had school-age developmental and educational outcomes assessed. The exposure examined was conception via IVF, with spontaneous conception the control condition. Two outcome measures were assessed. The first, childhood developmental vulnerability at school entry (age 4 to 6), was assessed using the Australian Early Developmental Census (AEDC) (n = 173,200) and defined as scoring <10th percentile in ≥2/5 developmental domains (physical health and wellbeing, social competence, emotional maturity, language and cognitive skills, communication skills, and general knowledge). The second, educational outcome at age 7 to 9, was assessed using National Assessment Program–Literacy and Numeracy (NAPLAN) data (n = 342,311) and defined by overall z-score across 5 domains (grammar and punctuation, reading, writing, spelling, and numeracy). Inverse probability weighting with regression adjustment was used to estimate population average causal effects. The study included 412,713 children across the 2 outcome cohorts. Linked records were available for 4,697 IVF-conceived cases and 168,503 controls for AEDC, and 8,976 cases and 333,335 controls for NAPLAN. There was no causal effect of IVF-conception on the risk of developmental vulnerability at school-entry compared with spontaneously conceived children (AEDC metrics), with an adjusted risk difference of −0.3% (95% CI −3.7% to 3.1%) and an adjusted risk ratio of 0.97 (95% CI 0.77 to 1.25). At age 7 to 9 years, there was no causal effect of IVF-conception on the NAPLAN overall z-score, with an adjusted mean difference of 0.030 (95% CI −0.018 to 0.077) between IVF- and spontaneously conceived children. The models were adjusted for sex at birth, age at assessment, language background other than English, socioeconomic status, maternal age, parity, and education. Study limitations included the use of observational data, the potential for unmeasured confounding, the presence of missing data, and the necessary restriction of the cohort to children attending school. Conclusions: In this analysis, under the given causal assumptions, the school-age developmental and educational outcomes for children conceived by IVF are equivalent to those of spontaneously conceived children. These findings provide important reassurance for current and prospective parents and for clinicians. In a population-wide cohort study, Dr Anthea C Lindquist and colleagues, examine school-age outcomes among IVF-conceived children in Australia. Author summary: Why was this study done?: More than 8 million children have been conceived globally with the assistance of in vitro fertilisation (IVF). Some studies suggest these children have an increased risk of congenital abnormalities, autism spectrum disorder, developmental delay, and intellectual disability. Educational and school-age developmental outcomes following IVF conception have not yet been adequately characterised. What did the researchers do and find?: Using statewide, linked population data from Victoria, Australia, we investigated the school-age developmental and educational outcomes for children born following IVF-assisted conception. The study examined 2 separate assessments of school-age development and educational outcomes among 585,659 children, including 11,059 children who were conceived via IVF. This study was designed and performed within a causal framework, in order to produce the best possible estimate of exposure effect using observational data. We found no difference in school-age childhood developmental and educational outcomes between IVF- and spontaneously conceived children. What do these findings mean?: These findings provide reassurance for current and prospective parents, as well as clinicians who are involved in IVF. This information may be useful in providing informed consent and education to those considering IVF and those with children conceived via IVF. [ABSTRACT FROM AUTHOR]