Subfecundity, not IVF, linked to elevated neurodevelopmental risk in offspring

Underlying subfecundity, rather than in vitro fertilization (IVF) itself, was associated with elevated rates of behavioral problems and autism spectrum disorder diagnosis in children, according to a cohort study published in JAMA Network Open. The findings add to a longstanding question about whether assisted reproduction or the conditions prompting it are responsible for observed differences in offspring neurodevelopment.

The study authors noted that questions about a potential link between assisted reproduction and child neurodevelopment have persisted since the advent of IVF, with concerns centering on how exogenous hormones used in fertility protocols may influence fetal brain development. IVF is also associated with higher rates of preterm birth and low birth weight, both of which carry their own neurodevelopmental consequences.

More than 3 dozen studies have examined this question, and most have found no associations between assisted reproduction and cognitive, behavioral, motor, or language outcomes, autism spectrum disorder (ASD), or mental health problems, noted the study authors.

“In this study, we sought to disentangle the association of infertility treatment with adverse child neurodevelopmental outcomes from that of underlying subfecundity using data from a large US cohort,” the authors wrote. “We extended prior research by comparing caregiver-reported behavioral problems, autism-like symptoms, and neurodevelopmental diagnoses among children born to those with subfecundity vs no subfecundity, and also contrasted outcomes among those who conceived using IVF or non-IVF treatment with those who conceived naturally, with and without subfecundity.”

Study design and population

Researchers drew on data from the National Institutes of Health Environmental Influences on Child Health Outcomes Cohort, including mother-child dyads with infants conceived between 1998 and 2022. Among 15,382 mother-infant dyads, there were 14,191 unique maternal participants with a mean age at delivery of 30.9 years (SD 5.33 years), of whom 8780 (57.1%) were parous. Data were analyzed from May 14, 2025, to March 31, 2026.

Subfecundity was defined as:

• Prior consultation for, treatment of, or diagnosis of infertility for either partner
• At least 2 prior miscarriages
• Ever having had unprotected heterosexual intercourse for 12 months without conceiving

Infertility treatment was categorized as IVF or non-IVF treatment. Neurodevelopmental outcomes were assessed in children ages 2 to 10 years using harmonized caregiver responses to the Strengths and Difficulties Questionnaire and the Child Behavior Checklist for externalizing and internalizing problem scores, and the Social Responsiveness Scale (SRS) for autism-like symptoms. Caregiver-reported physician diagnoses of ASD and attention-deficit/hyperactivity disorder (ADHD) were also collected. ASD and ADHD were diagnosed in 876 offspring (7.6%) and 819 offspring (7.1%), respectively.

Was IVF associated with child neurodevelopment?

In generalized linear models, subfecundity was associated with higher externalizing problem scores and SRS scores across all pregnancies (externalizing problems: b = 0.47 [95% CI, 0.14-0.81]; SRS score: b = 1.08 [95% CI, 0.01-2.14]) and when the analysis was restricted to natural conceptions (externalizing problems: b = 0.45 [95% CI, 0.07-0.83]; SRS score: b = 1.12 [95% CI, -0.09 to 2.34]). Offspring of parents with subfecundity also had higher odds of ASD overall (OR, 1.27 [95% CI, 1.03-1.57]) and when restricted to natural conceptions (OR, 1.31 [95% CI, 1.04-1.64]).

Children conceived via non-IVF treatment had higher odds of ADHD compared with those conceived naturally with subfecundity (OR, 1.77 [95% CI, 1.16-2.68]) and those conceived naturally without subfecundity (OR, 1.54 [95% CI, 1.05-2.25]). No significant associations were identified for IVF treatment across any neurodevelopmental outcome.

“In this ECHO Cohort study, subfecundity was associated with offspring behavior problems and ASD regardless of infertility treatment, and non-IVF infertility treatment was associated with child ADHD,” wrote the study authors. “Future studies are needed to identify specific causes of subfecundity and indications for infertility treatment that may explain these results and help to elucidate biological mechanisms.”

Reference:

Dachew BA, et al. Subfecundity, infertility treatment, and child neurodevelopment. JAMA Netw Open. 2026;9(6):e2513713. doi:10.1001/jamanetworkopen.2025.13713