New research published in JAMA Network Open suggests that the underlying difficulty of conceiving, rather than in‑vitro fertilization (IVF) itself, may be linked to higher rates of behavioral issues and autism spectrum disorder (ASD) in children.
Study design and key findings
The team used data from the National Institutes of Health Environmental Influences on Child Health Outcomes (ECHO) Cohort, covering mother‑child pairs whose infants were born between 1998 and 2022. The analysis included 15,382 dyads, representing 14,191 mothers with an average age of 30.9 years at delivery. Subfecundity was defined by any prior infertility consultation, at least two miscarriages, or a year of unprotected intercourse without conception.
Neurodevelopmental outcomes were measured for children aged 2 to 10 using caregiver‑completed questionnaires, including the Strengths and Difficulties Questionnaire, the Child Behavior Checklist, and the Social Responsiveness Scale. Physicians’ reports of ASD and attention‑deficit/hyperactivity disorder (ADHD) were also recorded, yielding diagnoses in 7.6% and 7.1% of the sample, respectively.
Statistical models showed that subfecundity correlated with higher externalizing problem scores (b = 0.47, 95% CI 0.14‑0.81) and raised autism‑like symptom scores (b = 1.08, 95% CI 0.01‑2.14). When the analysis was limited to natural conceptions, the associations persisted, with externalizing scores (b = 0.45, 95% CI 0.07‑0.83) and autism‑like scores (b = 1.12, 95% CI ‑0.09‑2.34). The odds of an ASD diagnosis were 27% higher for children of subfecund parents (OR = 1.27, 95% CI 1.03‑1.57) and 31% higher when only natural conceptions were considered (OR = 1.31, 95% CI 1.04‑1.64).
IVF versus non‑IVF treatment outcomes
Children conceived through non‑IVF infertility treatment faced a greater likelihood of ADHD compared with those conceived naturally, both with (OR = 1.77, 95% CI 1.16‑2.68) and without subfecundity (OR = 1.54, 95% CI 1.05‑2.25). By contrast, IVF itself showed no statistically significant connection to any of the neurodevelopmental measures examined.
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The authors note that IVF has long been scrutinized for possible effects on fetal brain development, partly because fertility protocols involve exogenous hormones. IVF is also associated with higher rates of preterm birth and low birth weight, factors that can independently affect neurodevelopment. However, the current study’s findings align with more than three dozen earlier investigations that generally reported no link between assisted reproduction and cognitive, behavioral, or language outcomes.
Despite the clear association between subfecundity and certain neurodevelopmental challenges, the mechanisms remain uncertain. They call for further investigation into the specific causes of reduced fertility and how they might intersect with prenatal development.
Understanding whether hormonal, genetic, or lifestyle elements underlie both subfecundity and child outcomes could help refine clinical guidance for families considering fertility treatment.
In summary, the ECHO Cohort analysis indicates that subfecundity is tied to higher rates of externalizing behavior problems and ASD, regardless of whether IVF was used.
Non‑IVF infertility treatment appears linked to increased ADHD risk, while IVF itself does not show a measurable impact on the outcomes studied. Future research will need to untangle the biological pathways that connect difficulty conceiving with child neurodevelopment.
