HIGHER MATERNAL TSH LEVELS IN EARLY PREGNANCY ARE ASSOCIATED WITH INCREASED RISK FOR MISCARRIAGE, FETAL OR NEONATAL DEATH

1Department of Endocrinology and Metabolism, Academic medical Centre Amsterdam, The Netherlands, 2Department of Clinical Epidemiology, Biostatistics and Bioinformatics, Academic Medical Centre Amsterdam, the Netherlands, 3Department of Social Science, Academic Medical Centre Amsterdam, The Netherlands

Abstract

Objective: To examine the relationship between maternal TSH and free T4 concentrations measured in early pregnancy and the subsequent risk of miscarriage, fetal death or neonatal death.
Method: Cohort study of 2497 native Dutch pregnant women living in the city of Amsterdam. Blood samples were drawn at first booking in which serum TSH, free T4 and TPO-Ab concentrations were determined. Child loss was operationalised as miscarriage, fetal or neonatal death. Women with overt thyroid dysfunction were excluded from analysis.
Results: A total of 32 cases of child loss were observed. The mean TSH and free T4 level in the women who lost their child was 1.45 mlU/L and 9.70 pmol/L compared to 1.1 mlU/L and 9.58 pmol/L in women without child loss. The incidence of child loss increased by 54% (OR=1.54; 95%CI: 1.03 to 2.28; p= 0.034) for every doubling in TSH concentration. The strength of this association did not change after adjustment for smoking, age, parity and the presence of TPO-Ab concentration (adjusted OR for TSH = 1.60; 95%CI: 1.03 to 2.50; p=0.037). The absolute increase in mortality is relatively small; the estimated risk for a woman with a TSH level of 0.49 mlU/l (P10 of total population) is 0.7 percent, increasing to 1.9 % in women with a TSH level of 2.36 mlU/l (P90). We found no association between free T4 concentrations and child loss (OR= 1.57; 95%CI; 0.28 to 8.70; P= 0.606).
Conclusion: In a cohort of native Dutch pregnant women without overt thyroid dysfunction, the risk of having a miscarriage, fetal death or neonatal death increased with higher levels of maternal TSH. Maternal free T4 concentations and child loss were not associated.