Infertility Could Lead to ADHD in Children
A recent study published in the journal Human Reproduction shows a moderately increased risk of developing attention-deficit hyperactivity disorder (ADHD) in children born to infertile mothers or those receiving infertility treatment compared to children born by unaided conception.
About the study
The researchers investigated if the risk of ADHD development was higher in children born to mothers with infertility and/or receiving infertility treatment than mothers who conceived without any such assistance. The study was conducted from 2006 to 2014 in Ontario, Canada. Study samples comprised of single and multiple hospital live births at 24 weeks gestation by 18 to 55 year-old mothers with a valid Ontario health insurance program (OHIP) number.
Data on infertility treatment, hospital births, maternal health, pregnancy measures, and the child outcomes were obtained from the inpatient and outpatient care records of the institute for clinical evaluative sciences (ICES) datasets. Data on pregnancy characteristics such as conception type were obtained from the better outcomes registry & network (BORN) database and its associated Niday legacy datasets. The researchers excluded children through surrogacy due to the biological and gestational complexities involved. Pregnancies that resulted in induced abortions or child death before the age of four years or pregnancies with inadequate data records were also excluded from the analysis.
The main study exposure was the mode of conception as follows:
- unaided conception group (as the reference group),
- infertility without corresponding treatment, diagnosed within two years prior to conception (OHIP code ICD-9 628);
- ovulation induction (OI)/ intrauterine insemination (IUI),
- in vitro fertilization (IVF)/intracytoplasmic sperm injections (ICSI).
The prime outcome of the study was diagnosing ADHD in the child after four years of age, defined as two outpatient diagnoses (ICD-9 codes 312-14) by a pediatrician or a psychiatrist and/or one diagnosis during the period of hospital admission (ICD-10 F90,91). Outcomes were assessed till June 2020.
The team calculated hazard ratios (HRs) after data adjustments for the following
- maternal age,
- rural residency,
- the status of immigration,
- smoking habits,
- use of alcohol and/or drugs,
- mother’s medical history including mental illnesses (such as ADHD),
- chronic hypertension,
- pre-pregnancy diabetes,
- gender of the child.
Stratified analyses were also performed by mode of deliver (cesarean delivery or vaginal delivery), gender of the child, multiplicity (singleton or multiple), and the timing of birth (preterm birth or term birth).
A total of 925,488 infants of 663,144 women were included in the analysis, of which,
- 87% children were born after unassisted conception,
- 10% children were born to mothers with infertility who did not receive infertility treatment,
- 1% children were born after OI/IUI,
- 1.5% children were born after IVF/ICSI.
The children were followed up for four to eight years (median: six years). ADHD was diagnosed in
- 7% of children born by unassisted conception,
- 8% in children born to the mothers with infertility without infertility treatment,
- 7% in children born following OI/IUI,
- 6% in those born following IVF/ICSI.
The ADHD incidence rates (per 1000 individuals-years) were 12, 12.8, 12.9, and 12.2 among children of mothers of the unassisted conception group, infertility without infertility treatment group, OI/IUI group, and the IVF/ICSI group, respectively.
In relation to the unaided conception group, the adjusted HRs for ADHD diagnosis were 1.2, 1,1, and 1.1 among infertility with no infertility treatment, OI/IUI, and IVF/ICSI groups, respectively. The ADHD risk patterns were largely preserved in the stratified analysis, with an exception in the sex-stratified analyses, wherein the absolute rates of ADHD were lesser for females but the HRs were relatively higher than for males.
In the sensitivity analysis limited to the infertile group, in relation to infertility without infertility treatment group, the adjusted HR was 0.9 and 0.9 for children born after OI/IUI and after IVF/ICSI, respectively. On adding a birth year to the analysis or considering ADHD diagnosis at two years of age or limiting the analysis to children with maternal body mass index (BMI) availability(n=293,123), the results were similar to those obtained in the main analysis.
Based on the study findings, infertility, even without infertility treatment could be modestly associated with the risk of development of ADHD in the offspring, and the risk is not increased by infertility treatment for infertility.
Attention-deficit hyperactivity disorder in offspring born to mothers with infertility: a population-based cohort study. Alexa Fine, Natalie Dayan, Maya Djerboua, Jessica Pudwell, Deshayne B. Fell4, Simone N. Vigod, Joel G. Ray, and Maria P. Velez. Human Reproduction, pp. 1–9, 2022 https://doi.org/10.1093/humrep/deac129