M F Svahn1, M Hargreave1, T S S Nielsen1, K J Plessen2, S M Jensen3, S K Kjaer4, A Jensen5. 1. Virus, Lifestyle and Genes, Danish Cancer Society Research Center, Strandboulevarden 49, DK-2100 Copenhagen Ø, Denmark. 2. Child and Adolescent Mental Health Center, Mental Health Services, Capital Region, DK-2100 Copenhagen Ø, Denmark Department of Clinical Medicine, Faculty of Medicine and Health Sciences, University of Copenhagen, DK-2100 Copenhagen Ø, Denmark. 3. Statistics, Bioinformatics and Registry, Danish Cancer Society Research Center, Strandboulevarden 49, DK-2100 Copenhagen Ø, Denmark. 4. Virus, Lifestyle and Genes, Danish Cancer Society Research Center, Strandboulevarden 49, DK-2100 Copenhagen Ø, Denmark Department of Gynaecology, Rigshospitalet, University of Copenhagen, Blegdamsvej 9, DK-2100 Copenhagen Ø, Denmark. 5. Virus, Lifestyle and Genes, Danish Cancer Society Research Center, Strandboulevarden 49, DK-2100 Copenhagen Ø, Denmark allan@cancer.dk.
Abstract
STUDY QUESTION: Is the risk of hospital admission or outpatient contact for mental disorders increased in children born to women with fertility problems compared with children born to women without fertility problems? SUMMARY ANSWER: We found an increased risk of hospital admission or outpatient contact for mental disorders in children born to women with fertility problems. WHAT IS KNOWN ALREADY: Few studies have investigated the risk of mental disorders in children born after fertility treatment and although some studies have pointed to an increased risk, others found no association. The inconsistent results may be due to methodological constraints in many previous studies, including small sample size and short follow-up, resulting in imprecise risk estimates and lack of information on risk patterns of mental disorders in adulthood. STUDY DESIGN, SIZE, DURATION: This nationwide retrospective register-based cohort study included all 2 412 721 children born in Denmark between 1969 and 2006. All children were followed from date of birth until date of hospital contact for a mental disorder, date of emigration, date of death or 31 December 2009, whichever occurred first. PARTICIPANTS/MATERIALS, SETTING, METHODS: Information concerning maternal fertility status for all children in the cohort was obtained by linkage to the Danish Infertility Cohort, which contains data on nearly all women with fertility problems in Denmark since 1963. A total of 124 269 (5%) children were born to women with fertility problems and 2 288 452 (95%) to women without fertility problems. To identify children hospitalized for a mental disorder, the cohort was linked to the Danish Psychiatric Central Research Registry. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between maternal fertility status and the risk of hospital admission or outpatient contact for various groups of mental disorders, including any mental disorder and all 11 main discharge diagnostic groups, classified according to the International Classification of Diseases, version 10. MAIN RESULTS AND THE ROLE OF CHANCE: During a mean follow-up period of 21 years (range, 0-40 years), 168 686 (7%) children were admitted to hospital or had an outpatient contact for a mental disorder. Children born to women with fertility problems had a significantly higher risk of any mental disorder (HR 1.23; 95% CI 1.20-1.26) and for most of the 11 main discharge groups, including schizophrenia (HR 1.16; 95% CI 1.07-1.27), mood (affective) disorders (HR 1.21; 95% CI 1.15-1.28) and disorders of psychological development (HR 1.15; 95% CI 1.09-1.21) as well as the subgroup of attention-deficit/hyperactivity disorders (HR 1.36; 95% CI 1.29-1.45) compared with children born to women without fertility problems. The risk estimates did not change markedly when analyses were performed separately for mental disorders diagnosed during childhood (0-19 years) and in young adulthood (20-40 years). LIMITATIONS, REASON FOR CAUTION: The true risk of mental disorders may be somewhat underestimated, as only severe disorders requiring hospital admission or outpatient contact were considered as events. Furthermore, we could not determine whether the increased risks observed were due to factors related to the underlying infertility or to fertility treatment procedures. WIDER IMPLICATIONS OF THE FINDINGS: This is the first report on mental disorders in adulthood among children born to women with fertility problems. Furthermore, we have assessed the risk of several severe mental disorders not previously studied (e.g. neurotic, stress-related and somatoform disorders and disorders of adult personality and behaviour). These important findings should be investigated further in large epidemiological studies designed to differentiate between factors related to fertility treatment and to the underlying infertility. STUDY FUNDING/COMPETING INTERESTS: The study was supported by internal funding from the Unit of Virus, Lifestyle and Genes at the Danish Cancer Society Research Center. All authors report no conflicts of interest.
STUDY QUESTION: Is the risk of hospital admission or outpatient contact for mental disorders increased in children born to women with fertility problems compared with children born to women without fertility problems? SUMMARY ANSWER: We found an increased risk of hospital admission or outpatient contact for mental disorders in children born to women with fertility problems. WHAT IS KNOWN ALREADY: Few studies have investigated the risk of mental disorders in children born after fertility treatment and although some studies have pointed to an increased risk, others found no association. The inconsistent results may be due to methodological constraints in many previous studies, including small sample size and short follow-up, resulting in imprecise risk estimates and lack of information on risk patterns of mental disorders in adulthood. STUDY DESIGN, SIZE, DURATION: This nationwide retrospective register-based cohort study included all 2 412 721 children born in Denmark between 1969 and 2006. All children were followed from date of birth until date of hospital contact for a mental disorder, date of emigration, date of death or 31 December 2009, whichever occurred first. PARTICIPANTS/MATERIALS, SETTING, METHODS: Information concerning maternal fertility status for all children in the cohort was obtained by linkage to the Danish Infertility Cohort, which contains data on nearly all women with fertility problems in Denmark since 1963. A total of 124 269 (5%) children were born to women with fertility problems and 2 288 452 (95%) to women without fertility problems. To identify children hospitalized for a mental disorder, the cohort was linked to the Danish Psychiatric Central Research Registry. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between maternal fertility status and the risk of hospital admission or outpatient contact for various groups of mental disorders, including any mental disorder and all 11 main discharge diagnostic groups, classified according to the International Classification of Diseases, version 10. MAIN RESULTS AND THE ROLE OF CHANCE: During a mean follow-up period of 21 years (range, 0-40 years), 168 686 (7%) children were admitted to hospital or had an outpatient contact for a mental disorder. Children born to women with fertility problems had a significantly higher risk of any mental disorder (HR 1.23; 95% CI 1.20-1.26) and for most of the 11 main discharge groups, including schizophrenia (HR 1.16; 95% CI 1.07-1.27), mood (affective) disorders (HR 1.21; 95% CI 1.15-1.28) and disorders of psychological development (HR 1.15; 95% CI 1.09-1.21) as well as the subgroup of attention-deficit/hyperactivity disorders (HR 1.36; 95% CI 1.29-1.45) compared with children born to women without fertility problems. The risk estimates did not change markedly when analyses were performed separately for mental disorders diagnosed during childhood (0-19 years) and in young adulthood (20-40 years). LIMITATIONS, REASON FOR CAUTION: The true risk of mental disorders may be somewhat underestimated, as only severe disorders requiring hospital admission or outpatient contact were considered as events. Furthermore, we could not determine whether the increased risks observed were due to factors related to the underlying infertility or to fertility treatment procedures. WIDER IMPLICATIONS OF THE FINDINGS: This is the first report on mental disorders in adulthood among children born to women with fertility problems. Furthermore, we have assessed the risk of several severe mental disorders not previously studied (e.g. neurotic, stress-related and somatoform disorders and disorders of adult personality and behaviour). These important findings should be investigated further in large epidemiological studies designed to differentiate between factors related to fertility treatment and to the underlying infertility. STUDY FUNDING/COMPETING INTERESTS: The study was supported by internal funding from the Unit of Virus, Lifestyle and Genes at the Danish Cancer Society Research Center. All authors report no conflicts of interest.
Authors: Hua He; Yongfu Yu; Zeyan Liew; Mika Gissler; Krisztina D László; Unnur Anna Valdimarsdóttir; Jun Zhang; Fei Li; Jiong Li Journal: JAMA Netw Open Date: 2022-04-01
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