Chronic diseases in the children of women with maternal thyroid dysfunction: a nationwide cohort study

Line Riis Jølving,1,2 Jan Nielsen,1,2 Ulrik Schiøler Kesmodel,3,4 Rasmus Gaardskær Nielsen,2,5 Bente Mertz Nørgård,1,2 Signe Sparre Beck-Nielsen6,7 1Center for Clinical Epidemiology, Odense University Hospital, 2Institute of Clinical Research, University of Southern Denmark, Odense C, 3Department of Obstetrics and Gynaecology, Herlev University Hospital, Herlev, 4Institute for Clinical Medicine, University of Copenhagen, København, 5Hans Christian Andersen Children’s Hospital, Odense University Hospital, Odense C, 6Department of Pediatrics Kolding, Hospital Lillebaelt, Kolding, 7Department of Regional Health Research, University of Southern Denmark, Odense C, Denmark Objective: Maternal thyroid disease (TD) during pregnancy is associated with adverse birth outcomes, but little is known on its long-term outcomes. We aimed to examine if children born to mothers with TD have increased disease risk during childhood and adolescence. Patients and methods: A register-based cohort study was conducted on all live born children in Denmark from 1989 to 2013, including the association between maternal TD during pregnancy and somatic and psychiatric diseases in the children. Cox proportional hazards models were used to compute hazard ratios (HRs) according to the type of maternal TD, Graves’ disease, and Hashimoto’s thyroiditis. Results: A total of 2,618 children were born to women with Graves’ disease, 760 to women with Hashimoto’s thyroiditis (exposed), and 1,557,577 to women without any TD (unexposed). The median follow-up time for children born to mothers with Graves’ disease was 9.3 years (25/75 percentile 5.4/13.9 years) and with Hashimoto’s thyroiditis was 4.8 years (25/75 percentile 2.5/8.2 years). In children exposed to maternal Graves’ disease in utero, the adjusted HR of TD was 12.83 (95% CI, 9.74–16.90), Graves’ disease was 34.3 (95% CI, 20.23–58.35), and type 1 was diabetes 2.47 (95% CI, 1.46–4.18). In children exposed to maternal Hashimoto’s thyroiditis, the adjusted HR of Hashimoto’s thyroiditis was 24.04 (95% CI, 5.89–97.94). Conclusion: Our data suggest that children born to women with Graves’ disease and Hashimoto’s thyroiditis have excess long-term morbidities in childhood and adolescence. We particularly found an increased risk of any TD and type 1 diabetes to be diagnosed in children exposed in utero to Graves’ disease. These novel findings are relevant for pediatricians, stressing the importance of history of maternal disease when evaluating children with suspected endocrine disorders. Keywords: thyroid disease, Graves’ disease, Hashimoto’s thyroiditis, reproduction, child morbidity, clinical epidemiolog