Summary: A study involving 1.3 million children found that children born to parents with fertility issues have a slightly higher risk of autism spectrum disorder (ASD). The research suggests that the risk of ASD is increased in children of parents previously diagnosed with infertility, regardless of whether fertility treatments were involved.
The study also highlights the role of obstetrical factors like multiple pregnancies and preterm births in mediating this association. Further research is needed to explore the mechanisms behind this link.
- Children born to parents with infertility issues have a slightly elevated risk of developing autism spectrum disorder (ASD).
- This increased risk is independent of whether fertility treatments were used.
- Obstetrical factors, such as having twins or preterm birth, mediate a significant portion of the association between parental infertility and ASD.
Source: Queen’s University
One in 50 Canadian children have autism spectrum disorder (ASD), a neurodevelopmental condition that can impact sensory processing, communication, and emotional, and behavioural regulation. Yet, the causes of this lifelong disorder remain unclear and likely include a combination of genetic and environmental factors.
A new study published today in JAMA Network Open reports on a cohort study of over 1.3 million children born in Ontario between 2006 and 2018. Findings suggest that children born to individuals who have been diagnosed as having fertility issues are at a slightly higher risk of ASD.
As infertility diagnosis is increasing – it is estimated that one in six couples go through this challenge – publicly funded fertility programs have also increased access to fertility treatment in Canada. Alongside this growth is the need to answer questions about health outcomes for mothers and children that receive fertility treatment.
The newly published study, led by Maria Velez (Obstetrics and Gynecology), evaluated pregnancy and infant characteristics in relation to infertility, its treatments, and ASD using existing linked administrative health data.
Children were classified by mode of conception, namely, unassisted conception (86.5 percent), infertility without fertility treatment or subfertility (10.3 percent), ovulation induction or intrauterine insemination (1.5 percent), and in vitro fertilization or intracytoplasmic sperm injection (1.7 percent).
Starting at 18 months, children were followed by a period of 5 to 11 years, and 22,409 children were diagnosed with ASD, or 1.6 percent of the total. Because kids were not all followed for the same time, the ASD incidence rate was calculated in person-years – a type of measurement that considers both the number of people in the study and the amount of time each person spends in the study.
For example, a study that follows 1,000 people for one year each would contain 1,000 person-years of data.
In this study, the ASD incidence rate was 1.9 per 1,000 person-years among children in the first group, and higher among children in the subfertility (2.5) and after fertility treatment (2.7) groups.
The results suggest that there is a slightly increased risk of ASD in children born to patients previously diagnosed with infertility, independent of whether they received fertility treatment or not.
“Additionally, our results also show that some obstetrical factors, like having twins or triplets, or giving birth preterm, mediate a large proportion of the association between parental infertility and ASD,” says Dr. Velez.
According to the authors, the findings support the continuation of ongoing efforts to minimize the chances of multiple pregnancy and preterm birth following fertility treatments, as well as the importance of providing early care plans for pregnant patients that received such treatments, aiming to reduce adverse pregnancy outcomes in this population.
Further studies are needed to understand some of the mechanisms by which a parental diagnosis of infertility, independent of fertility treatment, may be associated with the slightly higher risk of ASD in the child.
“For example, we need more granular details about the baseline infertility diagnosis, paternal factors, and whether the oocyte (egg) or sperm are from the parent or a donor, among other factors,” explains Dr. Velez.
About this Autism research news
Original Research: Open access.
“Infertility and Risk of Autism Spectrum Disorder in Children” by Maria Velez et al. JAMA Network Open
Infertility and Risk of Autism Spectrum Disorder in Children
Previous studies on the risk of childhood autism spectrum disorder (ASD) following fertility treatment did not account for the infertility itself or the mediating effect of obstetrical and neonatal factors.
To assess the association between infertility and its treatments on the risk of ASD and the mediating effect of selected adverse pregnancy outcomes on that association.
Design, Setting, and Participants
This was a population-based cohort study in Ontario, Canada. Participants were all singleton and multifetal live births at 24 or more weeks’ gestation from 2006 to 2018. Data were analyzed from October 2022 to October 2023.
The exposure was mode of conception, namely, (1) unassisted conception, (2) infertility without fertility treatment (ie, subfertility), (3) ovulation induction (OI) or intrauterine insemination (IUI), or (4) in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI).
Main Outcome and Measures
The study outcome was a diagnosis of ASD at age 18 months or older. Cox regression models generated hazard ratios (HR) adjusted for maternal and infant characteristics. Mediation analysis further accounted for the separate effect of (1) preeclampsia, (2) cesarean birth, (3) multifetal pregnancy, (4) preterm birth at less than 37 weeks, and (5) severe neonatal morbidity.
A total of 1 370 152 children (703 407 male [51.3%]) were included: 1 185 024 (86.5%) with unassisted conception, 141 180 (10.3%) with parental subfertility, 20 429 (1.5%) following OI or IUI, and 23 519 (1.7%) following IVF or ICSI. Individuals with subfertility or fertility treatment were older and resided in higher-income areas; the mean (SD) age of each group was as follows: 30.1 (5.2) years in the unassisted conception group, 33.3 (4.7) years in the subfertility group, 33.1 (4.4) years in the OI or IUI group, and 35.8 (4.9) years in the IVF or ICSI group.
The incidence rate of ASD was 1.93 per 1000 person-years among children in the unassisted conception group. Relative to the latter, the adjusted HR for ASD was 1.20 (95% CI, 1.15-1.25) in the subfertility group, 1.21 (95% CI, 1.09-1.34) following OI or IUI, and 1.16 (95% CI, 1.04-1.28) after IVF or ICSI. Obstetrical and neonatal factors appeared to mediate a sizeable proportion of the aforementioned association between mode of conception and ASD risk. For example, following IVF or ICSI, the proportion mediated by cesarean birth was 29%, multifetal pregnancy was 78%, preterm birth was 50%, and severe neonatal morbidity was 25%.
Conclusions and Relevance
In this cohort study, a slightly higher risk of ASD was observed in children born to individuals with infertility, which appears partly mediated by certain obstetrical and neonatal factors. To optimize child neurodevelopment, strategies should further explore these other factors in individuals with infertility, even among those not receiving fertility treatment.