Impact of TSH During the First Trimester of Pregnancy on Obstetric and Foetal Complications

Usefulness of 2.5 mIU/L Cut-Off Value

Marta Hernández; Carolina López; Berta Soldevila; Laura Cecenarro; María Martínez-Barahona; Elisabet Palomera; Ferran Rius; Albert Lecube; Maria José Pelegay; Jordi García; Dídac Mauricio; Manel Puig Domingo


Clin Endocrinol. 2018;88(5):728-734. 

In This Article

Abstract and Introduction


Objective An association of pregnancy outcomes with subclinical hypothyroidism has been reported; however, there still exists a strong controversy regarding whether subclinical hypothyroidism ought to be dealt with or not. The objective of the study was to evaluate the association of foetal–maternal complications with first trimester maternal Thyrotropin (TSH) values.

Design A retrospective study in a single tertiary care hospital was performed.

Patients A total of 1981 pregnant women were studied during 2012.

Measurements Thyrotropin (TSH) universal screening was performed between 9 and 12 weeks of gestation. Outcomes included foetal–maternal complications and newborn health parameters.

Results Median TSH was 1.72 (0.99–2.61) mIU/L. The incidence of perinatal loss, miscarriage and stillbirth was 7.2%, 5.9% and 1.1%, respectively. Median TSH of women with and without miscarriage was 1.97 (1.29–3.28) vs 1.71 (0.96–2.58) mIU/L (P = .009). Incidence of pre–eclampsia was 3.2%; TSH in these women was 2.10 (1.40–2.74) vs 1.71 (0.98–2.59) mIU/L in those without (P = .027). TSH in women with dystocia in labour was 1.76 (1.00–2.53) vs 1.68 (0.94–2.59) mIU/L in those who gave birth with normal progression (P = .044). Women with TSH 2.5–5.1 mIU/L had a higher risk of perinatal loss [OR 1.589 (1.085–2.329)], miscarriage [OR 1.702 (1.126–2.572)] and premature birth [OR 1.39 (1.013–1.876)], adjusted by mother's age. There was no association with the other outcomes analysed.

Conclusions There is a positive association between maternal TSH in the first trimester of pregnancy and the incidence of perinatal loss and miscarriage. The TSH cut–off value of 2.5 mIU/L identified women with higher adverse pregnancy outcomes.


There is currently no doubt that the treatment of clinical hypothyroidism in pregnancy for avoiding foetal–maternal complications requires an early diagnosis; however, there still exists a strong controversy regarding whether subclinical hypothyroidism ought to be dealt with or not. Several clinical guidelines from scientific societies and some research groups have suggested that the thyrotropin (TSH) value of 2.5 mIU/L at first trimester may be useful as the upper boundary of normality in early pregnancy in the absence of local normative data,[1–3] although the latest guideline of the American Thyroid Association (ATA) gives support to a higher TSH upper reference range of 4 mIU/L than the one proposed few years ago of 2.5 mIU/L for the first trimester of pregnancy.[4] In spite of this, the controversy regarding the upper limit of TSH during pregnancy for the treatment of subclinical gestational hypothyroidism seems to be far for being clarified. Data indicating associations of pregnancy outcomes with subclinical hypothyroidism have been consistently reported in the literature; however, local factors related to specific populations may modulate this association. As a consequence, most of the guidelines strongly recommend generating local normative trimester–specific data for thyroid function in pregnant women to be applied to specific populations.

The TSH cut–off value of 2.5 mIU/L for the first trimester of pregnancy proposed by international recommendations has generated an important debate. A high number of apparently normal pregnant women of most countries in the European Union and worldwide may be categorized as having an abnormal TSH value with this cut–off. These recommendations have also generated an intense debate in Spain as to whether treatment is required when TSH is higher than 2.5 mIU/L at first trimester and whether this was eventually affordable in the setting of the current organization of pregnant care in most countries. However, at present, no consistent relationship has yet been demonstrated, with regard to what the proposed cut–off value of TSH is linked to unfavourable pregnancy outcomes in Spanish population and specifically in women living in Catalonia and, moreover, if the previously proposed TSH concentration of 2.5 mIU/L during the first trimester is of value in identifying a significant risk for the mother and the foetus.

Therefore, the aim of this study was to evaluate the incidence of foetal and obstetric pathological outcomes and its possible association with maternal first trimester TSH values during the year 2012 in the homogeneously well–iodized and geographically restricted population of pregnant women of the province of Lleida (Catalonia), in North–eastern Spain.