section name header

Evidence summaries

Subclinical Hypothyroidism and Pregnancy

Subclinical hypothyreoidism appears to be associated with preterm birth.Level of evidence: "B"

Comment: The quality of evidence is upgraded by large magnitude of effect.

Summary

A Cochrane review [Abstract] 1 included 4 studies with a total of 362 subjects. In one trial of 115 women, levothyroxine therapy to treat pregnant euthyroid (normal thyroid function) women with thyroid peroxidase antibodies was not shown to reduce pre-eclampsia significantly (risk ratio (RR) 0.61; 95% confidence interval (CI) 0.11 to 3.48) but did significantly reduce preterm birth by 72% (RR 0.28; 95% CI 0.10 to 0.80). Two trials of 30 and 48 hypothyroid women respectively compared levothyroxine doses, but both trials reported only biochemical outcomes. A trial of 169 women compared the trace element selenomethionine (selenium) with placebo and no significant differences were seen for either pre-eclampsia (RR 1.44; 95% CI 0.25 to 8.38) or preterm birth (RR 0.96; 95% CI 0.20 to 4.61). None of the four trials reported on childhood neurodevelopmental delay.

Several observational studies have assessed the association of subclinical hypothyreoidism and pregnancy outcomes.

In a prospective thyroid screening study 2 a total of 25 756 women underwent thyroid screening. There were 17 298 (67%) women enrolled for prenatal care at 20 weeks of gestation or less, and 404 (2.3%) of these were considered to have subclinical hypothyroidism. Preterm birth (< 34 weeks of gestation) was almost 2-fold higher in women with subclinical hypothyroidism (RR 1.8, 95% 1.1-2.9). In a prospective cohort study.

In a prospective study 3 maternal thyroid hormone concentrations were collected (8012 women; 371 with SCH, 7641 euthyroid). Compared with euthyroid status, SCH was associated with higher rates of gestational hypertension (1.8% vs. 3.5%, P = 0.020; OR 2.2, 95% CI 1.3 to 4.0), PROM (5.0% vs. 8.6%, P = 0.002; adjusted OR 6.0, 95% CI 4.0 to 9.1), intrauterine growth retardation (1.0% vs. 3.05%, <0.001; adjusted OR 3.3, 95% CI 1.7 to 6.3), and low birth weight (1.9% vs. 4.6%, P<0.001; adjusted OR 2.9, 95% CI 1.7 to 5.2).

A prospective population-based study 4 serum TSH, free T4 (FT4), T4, and TPO antibodies (TPOAbs) were determined during early pregnancy in 5971 pregnant women. Of all women, 5.0% had a premature delivery (<37 weeks), 4.4% had a spontaneous premature delivery, and 1.4% had a very premature delivery (<34 weeks). Maternal hypothyroxinemia was associated with a 2.5-fold increased risk of premature delivery, a 3.4-fold increased risk of spontaneous premature delivery, and a 3.6-fold increased risk of very premature delivery (all P < .01). TPOAb positivity was associated with a 1.7-fold increased risk of premature delivery (P = .01), a 2.1-fold increased risk of spontaneous premature delivery (P = .02), and a 2.5-fold increased risk of very premature delivery (P = .04). These effects remained similar after correction for TSH and FT4 levels.

In a prospective cohort study 5 3315 women at low risk for thyroid dysfunction at 4-8 weeks' gestation were screened and and divided into groups. Compared to euthyroid women, the risk of miscarriage was significantly higher among women with SCH (TSH 5.2-10) (7.1% vs. 2.2%, aOR 3.40, 95% CI 1.6 to 7.2; p = 0.002), isolated positive TPOAb or/and TgAb (5.7% vs. 2.2%, aOR 2.71, CI 1.4 to 5.1]; p = 0.003), SCH (TSH 2.5-5.21 plus positive TPOAb or/and TgAb (10.0% vs. 2.2%, aOR 4.96, CI 2.8 to 8.9; p = 0.000), and SCH (TSH 5.2-10) plus TAI (15.2% vs. 2.2%, aOR 9.56 CI 3.8 to 24.3; p = 0.000).

Clinical comments

Note

Date of latest search: 2019-12-30

    References

    • Reid SM, Middleton P, Cossich MC et al. Interventions for clinical and subclinical hypothyroidism pre-pregnancy and during pregnancy. Cochrane Database Syst Rev 2013;(5):CD007752. [PubMed]
    • Casey BM, Dashe JS, Wells CE et al. Subclinical hypothyroidism and pregnancy outcomes. Obstet Gynecol 2005;105(2):239-45. [PubMed]
    • Chen LM, Du WJ, Dai J et al. Effects of subclinical hypothyroidism on maternal and perinatal outcomes during pregnancy: a single-center cohort study of a Chinese population. PLoS One 2014;9(10):e109364. [PubMed]
    • Korevaar TI, Schalekamp-Timmermans S, de Rijke YB et al. Hypothyroxinemia and TPO-antibody positivity are risk factors for premature delivery: the generation R study. J Clin Endocrinol Metab 2013;98(11):4382-90. [PubMed]
    • Liu H, Shan Z, Li C et al. Maternal subclinical hypothyroidism, thyroid autoimmunity, and the risk of miscarriage: a prospective cohort study. Thyroid 2014;24(11):1642-9.[PubMed]

Primary/Secondary Keywords