Maternal Hypothyroidism and Adverse Outcomes of Pregnancy

Louise Knøsgaard; Stig Andersen; Annebirthe Bo Hansen; Peter Vestergaard; Stine Linding Andersen


Clin Endocrinol. 2023;98(5):719-729. 

In This Article

Abstract and Introduction


Objective: Hypothyroidism has been associated with pregnancy complications, but uncertainty prevail regarding the severity and the role of thyroid autoimmunity. This study aimed to evaluate adverse pregnancy outcomes by exposure to maternal hypothyroidism and thyroid autoimmunity.

Design: Retrospective cohort study.

Patients: 14,744 singleton pregnancies from the North Denmark Region Pregnancy Cohort (2011–2015).

Measurements: Maternal thyroid stimulating hormone (TSH), thyroid peroxidase antibodies (TPO-Ab), and thyroglobulin antibodies (Tg-Ab) were retrospectively measured in early pregnancy blood samples (ADVIA Centaur XPT, Siemens Healthineers). Adjusted odds ratio (aOR) with 95% confidence interval (CI) was used to estimate associations between maternal hypothyroidism (TSH cut-offs: 6.0 and 10 mIU/L), thyroid autoimmunity (TPO-Ab cut-off: 60 U/ml, Tg-Ab cut-off: 33 U/ml), and adverse pregnancy outcomes.

Results: Pregnancy outcomes were 93.2% live births, 6.5% spontaneous abortions, and 0.3% stillbirths. The frequency of spontaneous abortion was 6.5% when TSH was below 6.0 mIU/L, 6.5% when above 6.0 mIU/L (aOR 1.0 [95% CI: 0.5–2.0]), and 12.5% when above 10 mIU/L (aOR: 2.0 [95% CI: 0.8–5.2]). For outcome of preterm birth, the frequency was 5.4% when TSH was below 6.0 mIU/L, 7.8% when above 6.0 mIU/L (aOR 1.5 [95% CI: 0.7–2.9]), and 11.4% when above 10 mIU/L (aOR: 2.6 [95% CI: 0.9–7.3]). No association was found between thyroid autoantibodies and spontaneous abortion (TPO-Ab: aOR: 1.0 [0.8–1.3], Tg-Ab: 1.0 [0.8–1.2]) or preterm birth (TPO-Ab: aOR: 1.0 [0.8–1.2], Tg-Ab: 0.9 [0.7–1.2]).

Conclusion: A high frequency of adverse pregnancy outcomes was seen among pregnancies exposed to maternal TSH above 10 mIU/L, whereas no association with thyroid autoantibodies was seen.


Hypothyroidism is among the common chronic diseases in pregnant women.[1] During pregnancy, maternal thyroid hormones are vital for foetal growth and brain development[2] and a hypothesis of foetal programming by maternal hypothyroidism is biologically plausible.[3,4] Clinical guidelines unanimously state that overt hypothyroidism in pregnant women should be treated to prevent complications.[5] On the other hand, no universal screening for maternal overt hypothyroidism is implemented, and the current recommendation is limited to selective screening among pregnant women considered at risk for thyroid disease.[5]

The role of maternal thyroid hormones and the adverse effects of maternal hypothyroidism when left untreated is evident from experimental findings and from the historical descriptions of cretinism in children born to mothers with severe hypothyroidism caused by iodine deficiency.[6] Furthermore, the hallmark study by Haddow et al.[7] substantiated a risk of adverse child outcomes associated with untreated maternal hypothyroidism, which has been corroborated in other reports.[8] Large studies have substantiated that the frequency of undetected and untreated overt maternal hypothyroidism is around 0.3%,[9] which is about 10 times more frequent than congenital hypothyroidism revealed by universal newborn screening.[10] Thus, many criteria for screening[11] are met when considering overt hypothyroidism, but a critical determinant is on the definition of actual disease and indication for treatment.

Even if more evidence is needed regarding universal screening for overt hypothyroidism in pregnant women, the scientific focus has moved towards subclinical maternal thyroid function abnormalities, isolated changes in free thyroxine (fT4), and thyroid autoimmunity per se.[6] However, large randomized controlled trials (RCTs) have not shown any effect of treatment.[6] We recently showed within the North Denmark Region Pregnancy Cohort (NDRPC), that smaller aberrations in maternal thyroid function in early pregnancy thyroid stimulating hormone (TSH) just above the pregnancy-specific reference range) rarely persisted with repeated blood sampling, whereas markedly increased TSH (above 6.0 mIU/L) was likely to reflect persistent hypothyroidism in a pregnant woman.[12] In our view, a focus on persistent thyroid function abnormalities in pregnant women is needed to inform clinical practice.[6,12]

In the present study the aim was to identify pregnancies exposed to maternal hypothyroidism in an early pregnancy blood sample and to evaluate the association with adverse outcomes of pregnancy. Furthermore, we aimed to evaluate the role of thyroid autoimmunity per se as reflected by thyroid autoantibodies measured in the early pregnancy blood sample.