Published 03 February 2023
A large cohort study from Australia using ‘causal’ analysis has found that children conceived by IVF, when compared with naturally conceived children, were no more likely to be developmentally vulnerable at school entry and had equivalent numeracy and literacy performance by age 7 to 9 years.
Following an analysis of school-age development and educational outcomes of more than 400,000 children, Australian researchers have concluded that those conceived by ART have met an equivalent level to those conceived naturally.(1) They found that children conceived by ART were no more likely to be developmentally vulnerable at school entry and had equivalent numeracy and literacy performance by age 7-9 years. ‘These findings provide important reassurance for current and prospective parents and their treating clinicians,’ they said.
The study was performed using childhood and maternal registry data from the state of Victoria, Australia, and included singleton infants conceived spontaneously (controls) or by ART born between 2005 and 2014 and who later had educational levels assessed. The study examined two separate assessments of school-age development and educational level among 585,659 originally identified children, including 11,059 who were conceived via IVF.
Crucial to the study’s methodology was analysis by ‘causal inference methods’, by which ‘a causal question reflecting the effect of an intervention at a specific clinical decision point on a prespecified outcome’ is addressed. The method makes assumptions which, if met, allow causal interpretation. The observational cohort thus takes on the model of a ‘simulated clinical trial’, and in this study allowed the researchers to produce ‘exchangeable’ comparison groups to estimate the causal effect of the two conception methods on educational achievement. The two ‘specific clinical decision points’ were school entry (at ages 4-6 years) and grade 3 (at 7-9 years), both of which were measured by two standardised national assessments.
After an extremely complex analysis, the total cohort comprised 11,059 ART-conceived children and 401,654 spontaneously conceived controls. ‘Our findings,’ reported the authors, ‘suggest no causal effect of IVF conception on developmental vulnerability,’ with 13.6% of IVF-conceived children predicted and 13.9% of spontaneously conceived children to be developmentally vulnerable - a difference which they described as ‘indistinguishable from zero’. Results showed similar comparability in the two groups when analysed according to psychometric testing at age 7-9 years. The evidence, they add, is ‘robust’ about the longer-term implications of ART and offer clinics and couples ‘timely reassurance’.
The long-term effects and safety of ART since the early stages of its history have long been a subject of study. Long-term follow-up studies were a condition of ethical approval for the initial studies of ICSI in Brussels in the early 1990s. Studies based on birth cohorts in the Nordic countries have examined the risks of preterm birth and low birthweight among IVF infants and later neurodevelopment and risks of specific diseases. Similarly, educational development has been the subject of cohort studies. In 2018, for example, a Swedish study compared 8323 ART singletons with 1,499,667 spontaneously conceived children born between 1985 and 2001. A crude analysis of school performance suggested that the ART children had done slightly better, though after adjustment for confounders results appeared similar in both groups.(2) By contrast, a similarly designed cohort study from Denmark found after adjustments a statistically significant lower level of 9th-grade attainment in those children conceived by ART.(3) This result, however, was somewhat modified by analyses in fertile and subfertile women cross-linked with those who had and not had fertility treatment. The conclusion, as found in several follow-up studies of different risks, was that ‘fertility problems’ (rather than conception) were more likely to explain the slightly lower academic performance.
These earlier studies, say the present authors, relied on historical birth cohorts, while this study’s cohort (birth between 2005 and 2014) is more likely to reflect the advances in ART since the beginning of the century. Thus, the authors write, ‘our study findings are more generalisable to contemporary fertility practice . . . and our use of updated epidemiological and statistical methods ensures that we have estimated effects that have a causal interpretation’. The authors seem thus confident in their conclusion that ‘there is no causal effect’ of IVF conception on early childhood development.
1. Kennedy AL, Vollenhoven BJ, Hiscock RJ, et al. School-age outcomes among IVF-conceived children: A population-wide cohort study. PLoS Med 2023; 20: e1004148. https://doi.org/10.1371/ journal.pmed.1004148
2. Norrman E, Petzold M, Bergh C, Wennerholm UB. School performance in singletons born after assisted reproductive technology. Hum Reprod 2018; 33: 1948–1959. doi.org/10.1093/humrep/dey273
3. Wienecke LS, Kjaer SK, Frederiksen K, et al. Ninth-grade school achievement in Danish children conceived following fertility treatment: a population-based cohort study. Fertil Steril 2020; 113: 1014–1023.
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