according to a study published in Pediatrics.
The findings, based on an analysis of data from more than 1.5 million children in Sweden, provide “additional reassurance concerning offspring neurodevelopment after use of ART,” study author Chen Wang, MPH, and colleagues said. The results show the importance of accounting for underlying infertility when studying ART safety, they added. Mr. Wang is a researcher in the department of medical epidemiology and biostatistics at Karolinska Institutet in Stockholm.
Prior research has not shown major differences during early childhood between children conceived with ART and those conceived spontaneously. To examine long-term neurodevelopmental outcomes, including ADHD and school performance, the investigators analyzed data in Swedish population registers from children born between 1986 and 2012.
Infertility and the use of ART became increasingly common during the study period, the researchers noted. Between 1986 and 2001, 7% of births were to couples with known infertility, and 13% of these births were achieved with ART. Between 1996 and 2012, 11% of births were to couples with infertility, and 26% of these births were achieved with ART.
“Couples with infertility were more likely older and married or cohabiting, compared with couples with no known infertility,” Mr. Wang and colleagues reported. “Among infertile couples, those that conceived with ART had, on average, higher age and education, and the women were less likely to smoke.”
The investigators estimated that the cumulative incidence of ADHD by age 15 years was 6.2% in children conceived with ART, 7.3% among children of couples with infertility who did not use ART, and 7.1% in children born to couples with no known infertility.
Overall, children conceived with ART were at lower risk of ADHD (hazard ratio, 0.83). But after adjusting for parental characteristics and health factors, the researchers found a “slightly elevated risk of ADHD with ART,” with adjusted HRs of 1.05-1.07.
When the researchers focused on children born to couples with infertility, ART was associated with a lower risk of ADHD (adjusted HR, 0.80), compared with spontaneous conception. Accounting for parental characteristics and health history, however, “attenuated the association toward the null,” the researchers reported.
The researchers also compared ART methods, including intracytoplasmic sperm injection versus standard in vitro fertilization (IVF), and fresh embryo transfer versus frozen embryo transfer. The various procedures were not associated with substantially different risks.
Patterns for school performance were generally similar to those for ADHD.
“In this large follow-up of nationwide birth cohorts, we observed lower risk of ADHD and slightly better overall school performance in children conceived with ART, compared with all other children. Differences in parental characteristics appeared to completely explain and even slightly reverse the associations,” the study authors said. “When the comparison was restricted to children of couples with known infertility, no differences were seen.”
The study was well designed and “spans more than 25 years of ART during which treatments have changed dramatically,” commented Barbara Luke, ScD, MPH, professor of obstetrics, gynecology, and reproductive biology at Michigan State University, East Lansing.
Dr. Luke and colleagues have studied academic achievement in children conceived with IVF in Texas. The results of the Swedish study “are in line with U.S. studies, and are generally reassuring,” Dr. Luke said.
The U.S. studies also showed that parental factors may play a role in understanding academic performance.
“In our studies of third-grade and sixth-grade academic outcomes, we found differences by racial/Hispanic origin groups, gender, and maternal age,” she said.
The study by Mr. Wang and coauthors was funded by grants from a Swedish government agency and the National Institutes of Health. The researchers and Dr. Luke had no relevant financial disclosures.