How Are They Doing? Neurodevelopmental Outcomes at School Age of Children Born Following Assisted Reproductive Treatments

Abstract

Objective: The purpose of this study was to assess major neurodevelopmental aspects of children conceived by assisted reproductive treatments compared to spontaneously conceived children during the early school years. Material & Methods: In this follow-up study, mothers of 358 children born following assisted reproductive treatments and 401 spontaneously-conceived children were interviewed by telephone regarding their children’s health and development, when the children were 7-8 years old. The main outcomes were maternal responses to 4 questionnaires: Developmental Coordination Disorder Questionnaire, Short Sensory Profile, Autism Spectrum Screening Questionnaire, and the Attention-deficit hyperactive disorder (ADHD) Child Symptom Inventory-4 subscale. Mothers reported diagnoses of ADHD and autism spectrum disorder. Results: No significant differences were found between the groups in Developmental Coordination Disorder Questionnaire or Short Sensory Profile scores upon univariate or multivariable analyses. There was a slightly higher but nonsignificant rate of diagnosed ADHD among children in the assisted reproductive treatment group (9.6% vs 5.5%; P = .18); on multivariable analysis, a nonsignificant increase in ADHD was also found for assisted reproductive treatment children (hazard ratio 1.45, 95% confidence interval 0.81-2.61). Regarding the Child Symptom Inventory-4 criteria for ADHD among the children who had never been diagnosed, there was also a slightly higher but nonsignificant rate among the assisted reproductive treatments compared to spontaneously-conceived children on univariate (2.4% vs 1.8%; P = .50) and multivariable analysis (odds ratio 0.88, 95% confidence interval 0.27-2.86). Autism spectrum disorder diagnosis or Autism Spectrum Screening Questionnaire scores were not significantly different; however, 5 of the 6 children with autism spectrum disorder diagnoses were in the assisted reproductive treatment group. Conclusions: Neurodevelopmental measures were similar in both groups, although nonconclusive regarding ADHD and autism spectrum disorder risk. These findings contribute to the knowledge regarding long-term assisted reproductive treatment outcomes.

The Consequences of Assisted Reproduction Technologies on the Offspring Health Throughout Life: A Placental Contribution

“…There have been broad discussions about whether the use of ART is associated with the diagnosis of autism spectrum disorders (ASD) in the offspring. While most studies were unable to find any associations ( Sandin et al, 2013 ; Lung et al, 2018 ; Jenabi et al, 2020 ; Farhi et al, 2021b ), a few studies reported a significantly higher risk for ASD in ART offspring ( Fountain et al, 2015 ; reviewed in Liu et al, 2017 ). However, the effect was substantially reduced when adverse prenatal and perinatal outcomes and demographics were taken into account ( Fountain et al, 2015 ).…”

Neurodevelopmental Outcomes of Pregnancies Resulting from Assisted Reproduction: A Review of the Literature

“…Similarly, other smaller studies observed no statistically significant differences in the neurological outcomes after long-term follow up of offspring conceived via ART vs. children conceived naturally. Takeshige et al compared neurological outcomes of offspring conceived from vitrified oocytes after ICSI with the national average data from Japan at regular intervals between three months and six years of age [ 22 ]. No statistically significant differences were observed regarding the neurological outcomes [ 22 ].…”

“…Takeshige et al compared neurological outcomes of offspring conceived from vitrified oocytes after ICSI with the national average data from Japan at regular intervals between three months and six years of age [ 22 ]. No statistically significant differences were observed regarding the neurological outcomes [ 22 ]. Punamaki et al prospectively followed up 255 singleton children born after ART (164 IVF/76 ICSI) and compared their cognitive development and mental health at the age of 7–8 years old with 278 naturally conceived children without detecting any statistically significant differences [ 9 ].…”

“…Wagenar et al compared 139 adolescents born after IVF with 143 control adolescents regarding attention, information processing and visual-motor function, and did not detect any statistically significant differences [ 43 ]. A recent study from Farhi et al compared different neurodevelopmental measures of children conceived by ART ( n = 358) compared to spontaneously conceived offspring ( n = 401), concluding that there is no statistically significant difference between the two groups [ 22 ]. Finally, Bay et al conducted a prospective register-based cohort study in Denmark and included all the children born in Denmark between 1995 and 2003, with follow-up in 2012 when they were aged between 8 and 17 years old [ 19 ].…”

“…Several studies have looked into long-term neurodevelopmental outcomes of children born after ART. Long-term outcomes include comparisons of neurodevelopmental outcomes not only during early childhood but for the first two decades of their life [ 9 , 20 , 22 , 29 , 42 , 43 , 45 , 46 ]. None of the studies showed a greater risk of mental disorders for children born from ART, with the exception of a follow-up study from Denmark that showed a low but statistically significant risk of mental disorders after ovulation induction [ 19 ].…”