Reese Braam1, Joris Osinga1, Koen Verdonk2, Robin Peeters1, Tim Korevaar2
(1) Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands.
(2) Department of Internal Medicine and Obstetrics, Erasmus Medical Center, Rotterdam, The Netherlands.
Background
Pregnancy is a stress test for the thyroid gland. Although small studies suggest that gestational thyroid dysfunction or TPOAb positivity may be associated with a higher risk of later-life thyroid disease, large cohort data are needed to guide proper postpartum care.
Aim
Study association of gestational thyroid function and TPOAb positivity with hypothyroidism in later life in a prospective population-based cohort.
Methods
We included women from the Generation R cohort with thyroid function and/or TPOAb measurements before 18 weeks gestation and no history of thyroid disease or thyroid-affecting medication usage. Hypothyroidism was defined as postpartum levothyroxine use registered in the Dutch Foundation for Pharmaceutical Statistics or self-reported levothyroxine use or thyroid disease during follow-up. We estimated hazard ratios with proportional hazard models, adjusting for age, ethnicity, education, smoking, parity, sex and BMI.
Results
We included 5,724 women, 3.7% (N=166) developed hypothyroidism, median follow-up was 17.8 years (median time-to-diagnosis: 10.3 years). Higher TSH or lower FT4 was associated with a higher risk of later-life hypothyroidism (nonlinear; all P<0.001), even within the normal range. TPOAb positivity was associated with a 10.5-fold higher risk of later-life hypothyroidism (95% CI:7.27-15.02;P<0.001). Even TPOAb negative subclinical hypothyroidism was associated with a 3.6-fold higher risk of hypothyroidism in later life (95%CI:1.64-7.94;P=0.002).
Conclusions
Lower thyroid function, but especially TPOAb positivity is a key predictor for later-life hypothyroidism, likely mediated by postpartum thyroiditis. Active counseling for hypothyroidism symptomatology and lowering thresholds for postpartum TSH-screening should be considered for pregnant women with high TSH and/or TPOAb positivity.