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J Clin Endocrinol Metab. 2019 Aug 13. pii: jc.2019-01343. doi: 10.1210/jc.2019-01343. [Epub ahead of print]

Maternal thyroid function, use of antithyroid drugs in early pregnancy and birth defects.

Author information

1
Department of Clinical Biochemistry, Aalborg University Hospital, Aalborg, Denmark.
2
Department of Clinical Medicine, Aalborg University, Aalborg, Denmark.
3
Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark.
4
Department of Endocrinology, Aalborg University Hospital, Aalborg, Denmark.
5
Steno Diabetes Center North Jutland, Aalborg, Denmark.
6
Department of Geriatrics, Aalborg University Hospital, Aalborg, Denmark.

Abstract

CONTEXT:

Antithyroid drug (ATD) therapy in early pregnancy is associated with birth defects, but more data are needed to substantiate the risk associated with different types of ATD. Furthermore, the role of abnormal maternal thyroid function per se remains unclarified.

OBJECTIVE:

To evaluate the risk of birth defects associated with the use of ATD in an extended nationwide cohort and the role of abnormal maternal thyroid function in birth cohorts including stored maternal blood samples from the early pregnancy.

PARTICIPANTS:

Danish pregnant women and their live-born children including 1,242,353 children from a Nationwide Register-Based Cohort (NRBC), 1997-2016; 8,803 children from the Danish National Birth Cohort (DNBC), 1997-2003; and 14,483 children from the North Denmark Region Pregnancy Cohort (NDRPC), 2011-2015.

MAIN OUTCOME MEASURES:

Birth defects diagnosed before two years of age.

RESULTS:

In the NRBC, altogether 2,718 (0.2%) children had been exposed to ATD in early pregnancy. The overall frequency of birth defects was 6.7% (95% confidence interval (CI): 6.7-6.8%) in non-exposed children, and higher after exposure to Methimazole/Carbimazole (9.6% (95% CI: 8.2-11.2%)) and Propylthiouracil (8.3% (6.7-10.3%). On the other hand, the frequency of maternal thyroid dysfunction in early pregnancy was similar in the random cohort and in cases of birth defect in the DNBC (12.4 vs. 12.6%, p=0.8) and the NDRPC (15.1 vs. 15.4%, p=0.8).

CONCLUSIONS:

Results corroborate an increased risk of birth defects associated with the use of ATD in early pregnancy, and suggest that abnormal maternal thyroid function is not a major risk factor for birth defects.

PMID:
31408173
DOI:
10.1210/jc.2019-01343

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