Maternal Hypothyroidism during Pregnancy and the Risk of Pediatric Endocrine Morbidity in the Offspring

Abstract

Objective Previous studies suggested maternal hypothyroidism during pregnancy to be associated with cognitive impairment of the offspring. Scarce data exist regarding long-term endocrine health of the offspring. This study was aimed to assess whether children born to mothers with hypothyroidism during pregnancy are at an increased risk for long-term endocrine morbidity.

Study Design A retrospective population-based cohort study compared long-term endocrine morbidity of children born between the years 1991 and 2014 to mothers with and without hypothyroidism. Multiple gestations, fetuses with congenital malformations, and women lacking prenatal care were excluded. Hospitalizations of the offspring up to the age of 18 years involving endocrine morbidity were evaluated according to a predefined set of ICD-9 codes. Kaplan–Meier's survival curves were used to compare the cumulative risk and a Cox multivariable model was used to adjust for confounders.

Results During the study period, 217,910 deliveries met the inclusion criteria; 1.1% of which were with maternal hypothyroidism (n = 2,403). During the follow-up period, the cumulative incidence of endocrine morbidity among children born to mothers with hypothyroidism was 27 per 1,000 person-years and 0.47 per 1,000 person-years in the comparison group (relative risk: 2.14; 95% confidence interval [CI]: 1.21–3.79). The Kaplan–Meier's survival curve demonstrated a significantly higher cumulative endocrine morbidity in children born to mothers with hypothyroidism (log-rank test, p = 0.007). In the Cox regression model controlled for maternal age, birth weight, preterm birth, maternal diabetes, hypertensive disorders of pregnancy, induction of labor, and mode of delivery, maternal hypothyroidism was found to be independently associated with pediatric endocrine morbidity in the offspring (adjusted hazard ratio = 1.92, 95% CI: 1.08–3.4, p = 0.025).

Conclusion Maternal hypothyroidism appears to be independently associated with long-term pediatric endocrine morbidity of the offspring.

Keywords

offspring - hypothyroidism - endocrine - pregnancy

Note

This study was presented in part at the 38th SMFM Annual Meeting, January 29–February 3, 2018, Dallas, TX.

Authors' Contributions

The authors are responsible for study design; collection, analysis, and interpretation of data; writing of the report; and the decision to submit the report for publication.

• References

• 1 Nazarpour S, Ramezani Tehrani F, Simbar M, Azizi F. Thyroid dysfunction and pregnancy outcomes. Iran J Reprod Med 2015; 13 (07) 387-396
• 2 Alexander EK, Pearce EN, Brent GA. , et al. 2017 guidelines of the American Thyroid Association for the diagnosis and management of thyroid disease during pregnancy and the postpartum. Thyroid 2017; 27 (03) 315-389
• 3 Yamamoto T, Amino N, Tanizawa O. , et al. Longitudinal study or serum thyroid hormones, chorionic gonadotrophin and thyrotrophin during and after normal pregnancy. Clin Endocrinol (Oxf) 1979; 10 (05) 459-468
• 4 Hirsch D, Levy S, Nadler V, Kopel V, Shainberg B, Toledano Y. Pregnancy outcomes in women with severe hypothyroidism. Eur J Endocrinol 2013; 169 (03) 313-320
• 5 Spencer L, Bubner T, Bain E, Middleton P. Screening and subsequent management for thyroid dysfunction pre-pregnancy and during pregnancy for improving maternal and infant health. Cochrane Database Syst Rev 2015; (09) CD011263
• 6 Cohen N, Levy A, Wiznitzer A, Sheiner E. Perinatal outcomes in post-thyroidectomy pregnancies. Gynecol Endocrinol 2011; 27 (05) 314-318
• 7 Matalon S, Sheiner E, Levy A, Mazor M, Wiznitzer A. Relationship of treated maternal hypothyroidism and perinatal outcome. J Reprod Med 2006; 51 (01) 59-63
• 8 Casey BM, Thom EA. Subclinical hypothyroidism or hypothyroxinemia in pregnancy. N Engl J Med 2017; 377 (07) 701
• 9 Stagnaro-Green A, Pearce E. Thyroid disorders in pregnancy. Nat Rev Endocrinol 2012; 8 (11) 650-658
• 10 Statistics TCBo. Israel in Figures 2013. Available at: http://www.cbs.gov.il/www/publications/isr_in_n13e.pdf . Accessed May 25, 2015
• 11 Korevaar TI, Chaker L, Jaddoe VW, Visser TJ, Medici M, Peeters RP. Maternal and birth characteristics are determinants of offspring thyroid function. J Clin Endocrinol Metab 2016; 101 (01) 206-213
• 12 Feingold SB, Brown RS. Neonatal thyroid function. Neoreviews 2010; 11 (11) e640-e646
• 13 Ozdemir H, Akman I, Coskun S. , et al. Maternal thyroid dysfunction and neonatal thyroid problems. Int J Endocrinol 2013; 2013: 987843
• 14 Dussault JH, Fisher DA. Thyroid function in mothers of hypothyroid newborns. Obstet Gynecol 1999; 93 (01) 15-20
• 15 Paz Levy D, Sheiner E, Wainstock T, Sergienko R, Landau D, Walfisch A. Evidence that children born at early term (37-38 6/7 weeks) are at increased risk for diabetes and obesity-related disorders. Am J Obstet Gynecol 2017; 217 (05) 588.e1-588.e11