For gravidas, in a 20-year follow-up study of 5805 women who were screened in early pregnancy, only 3 percent developed thyroid disease. Of the 224 women identified with subclinical hypothyroidism during pregnancy, 17 percent developed thy roid disease in the next 20 years, and most of these had either
TPO or thyroglobulin antibodies during pregnancy (Mannisto, 2010). hus, the likelihood of progression to overt hypothy roidism during pregnancy in otherwise healthy women with subclinical hypothyroidism seems remote.
Earlier studies were suggestive that subclinical hypothyroidism might be associated with adverse pregnancy outcomes. In 1999, interest was heightened by two studies indicating that undiagnosed maternal thyroid hypofunction may impair fetal neuropsychological development. In one study, Pop and associates (1999) described 22 women with free T 4 levels < 10th percentile whose ofspring were at higher risk for impaired psychomotor development. In the other study, Haddow and coworkers (1999) retrospectively evaluated children born to 48 untreated women whose serum TSH values were >98th percentile. Some had diminished school performance, reading recognition, and intelligent quotient (IQ) scores. Although described as "subclinically hypothyroid," these women had an abnormally low mean serum free thyroxine level, and thus, many had overt hypothyroidism.
To further evaluate any adverse efects, Casey and colleagues (2005) identiied subclinical hypothyroidism in 2.3 percent of 17,298 women screened at Parkland Hospital before midpregnancy. hese women had small but signiicantly higher incidences of preterm birth, placental abruption, and neonates admitted to the intensive care nursery compared with euthyroid women. In another study of 10,990 similar women, however, ClearyGoldman and associates (2008) did not ind such associations.
Other studies subsequently conirmed a link between subclinical thyroid function and adverse outcomes (Chen, 2017; Maraka, 2016). One included 24,883 women screened throughout pregnancy and showed an almost twofold greater risk of severe preeclampsia (Wilson, 2012). In an analysis of the same cohort, a consistent relationship was shown between rising TSH levels and the risk for gestational diabetes (Tudela, 2012). Finally, Nelson and colleagues (2014) found an elevated risk for diabetes and stillbirth.
Lazarus and colleagues (2012) reported the indings of the international multicenter Controlled Antenatal Thyroid Screening (CATS) study. his study evaluated prenatal thyroid screening and randomized treatment of both subclinical hypothyroidism and isolated maternal hypothyroxinemia. They rior in the treated pregnancies.
Despite these indings, the unanswered question concerned whether treatment of subclinical hypothyroidism would miti gate any or all of these reported adverse outcomes. To address this, the Maternal-Fetal Medicine Units Network screened more than 97,000 pregnant women for thyroid disorders and reported that 3.3 percent had subclinical hypothyroid ism. hese 677 women were randomly assigned to thyroxine replacement therapy or placebo. As reported by Casey and col leagues (2017), and shown in Table 58-5, maternal adverse pregnancy outcomes or cognitive development in the ofspring at 5 years did not difer between groups. Annual developmental disorder results also did not difer.