Lea L H Lunddorf1, Andreas Ernst2, Nis Brix3, Linn H Arendt4, Stine L Andersen5, Jørn Olsen6, Cecilia H Ramlau-Hansen7. 1. Department of Public Health, Research Unit for Epidemiology, Aarhus University, Aarhus, Denmark. Electronic address: llbl@ph.au.dk. 2. Department of Public Health, Research Unit for Epidemiology, Aarhus University, Aarhus, Denmark; Department of Urology, Aarhus University Hospital, Aarhus, Denmark. 3. Department of Public Health, Research Unit for Epidemiology, Aarhus University, Aarhus, Denmark; Department of Clinical Genetics, and Aarhus University Hospital, Aarhus, Denmark. 4. Department of Public Health, Research Unit for Epidemiology, Aarhus University, Aarhus, Denmark; Department of Obstetrics and Gynecology, Aarhus University Hospital, Aarhus, Denmark. 5. Department of Clinical Medicine, Aalborg University, Aalborg, Denmark; Department of Clinical Biochemistry, Aalborg University Hospital, Aalborg, Denmark. 6. Department of Public Health, Research Unit for Epidemiology, Aarhus University, Aarhus, Denmark; Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark. 7. Department of Public Health, Research Unit for Epidemiology, Aarhus University, Aarhus, Denmark.
Abstract
OBJECTIVE: To study whether maternal thyroid disease in pregnancy is associated with pubertal timing in sons and daughters. DESIGN: Cohort study. SETTING: National birth cohort and health registers. PATIENT(S): A total of 15,763 mothers and children from the Danish National Birth Cohort and its Puberty Cohort. INTERVENTION(S): Register-based and self-reported information on maternal thyroid diseases during pregnancy (hyperthyroidism, hypothyroidism, benign goiter, or no thyroid disease [reference group]). MAIN OUTCOME MEASURE(S): The adjusted mean age difference (months) at attaining several self-reported pubertal milestones collected every 6 months using an interval-censored regression and the average difference in age at attaining all pubertal milestones using the Huber-White robust variance estimation (primary outcome). RESULT(S): Sons of mothers with hyperthyroidism had earlier pubertal development (average difference, -2.9 [95% confidence interval (CI), -5.0 to -0.7] months) than unexposed sons. Maternal hypothyroidism was not associated with pubertal development in sons (average difference, -1.2 [95% CI, -5.1 to 2.7] months). We observed nonstatistically significant indications of earlier pubertal development in sons of mothers with benign goiter (average difference, -1.9 [95% CI, -4.6 to 0.9] months). Maternal thyroid disease was not associated with pubertal development in daughters (average difference (months), hyperthyroidism, -0.8 [95% CI, -2.8 to 1.2]; hypothyroidism, 0.3 [95% CI, -3.1 to 3.8]; and benign goiter, 0.7 [95% CI, -2.0 to 3.4]). CONCLUSION(S): We found indications of earlier pubertal development in sons of mothers with hyperthyroidism. More research is needed to further investigate the observed sex-specific association.
OBJECTIVE: To study whether maternal thyroid disease in pregnancy is associated with pubertal timing in sons and daughters. DESIGN: Cohort study. SETTING: National birth cohort and health registers. PATIENT(S): A total of 15,763 mothers and children from the Danish National Birth Cohort and its Puberty Cohort. INTERVENTION(S): Register-based and self-reported information on maternal thyroid diseases during pregnancy (hyperthyroidism, hypothyroidism, benign goiter, or no thyroid disease [reference group]). MAIN OUTCOME MEASURE(S): The adjusted mean age difference (months) at attaining several self-reported pubertal milestones collected every 6 months using an interval-censored regression and the average difference in age at attaining all pubertal milestones using the Huber-White robust variance estimation (primary outcome). RESULT(S): Sons of mothers with hyperthyroidism had earlier pubertal development (average difference, -2.9 [95% confidence interval (CI), -5.0 to -0.7] months) than unexposed sons. Maternal hypothyroidism was not associated with pubertal development in sons (average difference, -1.2 [95% CI, -5.1 to 2.7] months). We observed nonstatistically significant indications of earlier pubertal development in sons of mothers with benign goiter (average difference, -1.9 [95% CI, -4.6 to 0.9] months). Maternal thyroid disease was not associated with pubertal development in daughters (average difference (months), hyperthyroidism, -0.8 [95% CI, -2.8 to 1.2]; hypothyroidism, 0.3 [95% CI, -3.1 to 3.8]; and benign goiter, 0.7 [95% CI, -2.0 to 3.4]). CONCLUSION(S): We found indications of earlier pubertal development in sons of mothers with hyperthyroidism. More research is needed to further investigate the observed sex-specific association.