Long-term Follow-up of Psychiatric Disorders in Children and Adolescents Conceived by Assisted Reproductive Techniques in Sweden

JAMA Psychiatry. 2021 Dec 15;e213647. doi: 10.1001/jamapsychiatry.2021.3647. Online ahead of print.

Abstract

Importance: Individuals conceived with assisted reproductive techniques (ARTs) could be at elevated risk of psychiatric disorders owing to potential adverse effects of the procedures themselves, or because such traits or their risk factors may be more common in couples with infertility.

Objective: To investigate the risk of psychiatric disorders in adolescents and young adults conceived with ARTs and to evaluate the role of treatment-related parental characteristics.

Design, setting, and participants: This prospective follow-up of a nationwide birth cohort used linkage of Swedish population registers with coverage through 2018. All children born in Sweden from January 1, 1994, to December 31, 2006, were included in the analysis. Follow-up was completed on December 31, 2018, when participants were 12 to 25 years of age, and data was analyzed from March 17, 2020, to September 10, 2021.

Exposures: In vitro fertilization with or without intracytoplasmic sperm injection and transfer of fresh or frozen-thawed embryos.

Main outcomes and measures: Clinical diagnoses of mood disorder, including major depression, anxiety, obsessive-compulsive disorder (OCD), or suicidal behavior, were identified from hospital records and outpatient specialist care. Suicide was additionally identified from death certificates. Antidepressant use was identified from dispensations of prescribed medications.

Results: A total of 1 221 812 children (48.6% female, 51.4% male) born between 1994 and 2006 were followed up to a median age of 18 (IQR, 15-21) years. Among these participants, 31 565 (2.6%) were conceived with ART. Compared with all others, adolescents conceived with ART had an elevated risk of OCD (hazard ratio [HR], 1.35 [95% CI, 1.20-1.51]), but the association was attenuated and no longer statistically significant after adjustment for parental characteristics (adjusted HR [aHR], 1.10 [95% CI, 0.98-1.24]) and was no longer present when restricted to individuals born to couples with known infertility (aHR, 1.02 [95% CI, 0.89-1.17]). Adolescents conceived with ARTs were not at elevated risk of depression or suicidal behavior compared with other adolescents (irrespective of parental infertility). Type of fertilization (standard in vitro fertilization or intracytoplasmic sperm injection) had no association with outcomes. Compared with non-ART-conceived children of couples with infertility, fresh, but not frozen, embryo transfer was associated with a lower risk of mood disorders (aHR, 0.90 [95% CI, 0.83-0.97]), making frozen embryo transfer appear less advantageous when directly contrasted with fresh embryo transfer.

Conclusions and relevance: These findings suggest that adolescents conceived with ARTs around the millennium are not at risk of poor psychiatric health compared with the general population, except for an elevated risk of OCD that may be explained by differences in parental characteristics.