Maternal Thyroid Hypofunction and Pregnancy Outcome

Abstract

OBJECTIVE-To estimate whether maternal thyroid hypofunction is associated with complications.METHODS-A total of 10,990 patients had first-and second-trimester serum assayed for thyroid-stimulating hormone (TSH), free thyroxine (freeT4), and antithyroglobulin and antithyroid peroxidase antibodies. Thyroid hypofunction was defined as 1) subclinical hypothyroidism: TSH levels above the 97.5th percentile and free T4 between the 2.5th and 97.5th percentiles or 2) hypothyroxinemia: TSH between the 2.5th and 97.5th percentiles and free T4 below the 2.5th percentile. Adverse outcomes were evaluated. Patients with thyroid hypofunction were compared with euthyroid patients (TSH and free T4 between the 2.5th and 97.5th percentiles). Patients with and without antibodies were compared. Multivariable logistic regression analysis adjusted for confounders was used.RESULTS-Subclinical hypothyroidism was documented in 2.2% (240 of 10,990) in the first and 2.2% (243 of 10,990) in the second trimester. Hypothyroxinemia was documented in 2.1% (232 of 10,990) in the first and 2.3% (247 of 10,990) in the second trimester. Subclinical hypothyroidism was not associated with adverse outcomes. In the first trimester, hypothyroxinemia was associated with preterm labor (adjusted odds ratio [aOR] 1.62; 95% confidence interval [CI] 1.00-2.62) and macrosomia (aOR 1.97; 95% CI 1.37-2.83). In the second trimester, it was associated with gestational diabetes (aOR 1.7; 95% CI 1.02-2.84). Fifteen percent (1,585 of 10,990) in the first and 14% (1,491 of 10,990) in the second trimester had antithyroid antibodies. When both antibodies were positive in either trimester, there was an increased risk for preterm premature rupture of membranes (P = .002 and P<.001, respectively). Although it is established that overt hypothyroidism in pregnancy is detrimental to the developing fetal brain, the effect of asymptomatic thyroid hypofunction on pediatric neurodevelopment is controversial. 1-4 Since 1999, several provocative studies have proposed that mild thyroid hypofunction during pregnancy affects brain development in utero and seems to be associated with abnormal pediatric neurologic outcome. 5-9 Antithyroid antibodies may also have an influence on the fetal brain and subsequent pediatric neurodevelopment. [10][11][12] Obstetric factors may be responsible for some of the differences in neurologic outcomes seen in the offspring of women with maternal thyroid hypofunction compared with their euthyroid counterparts. 4,13 The purpose of this study was to estimate if maternal thyroid hypofunction, diagnosed during the first or second trimesters, affects obstetric outcomes in a subset of patients from the First And Second Trimester Evaluation of Risk (FASTER) Trial. The relationship between antithyroid antibodies in the first and second trimesters and obstetric outcomes was also explored. HHS Public Access MATERIALS AND METHODSThe FASTER Trial, a National Institute of Child Health and Human Developmentsponsored study, was a prospective multicenter invest...

Diagnosis and management of subclinical hypothyroidism in pregnancy

“…Figure 1 presents the 16 studies, all of which have been published in the past 20 years. 27 30 34 36 39 50-60 In these mostly prospective observational studies, the cut off used to define subclinical hypothyroidism and the point in gestation at which thyrotropin was assessed varied. Some evaluated fewer than 100 women with subclinical hypothyroidism and are therefore underpowered to detect the pregnancy and neonatal complications studied, which occur in a small proportion of pregnant women.…”

Controversies in the Management of Hypothyroidism During Pregnancy

“…While a number of investigators have reported an increased risk, 54,63-66 larger observational studies comparing preterm delivery rates (<37 weeks) in antibody-positive versus antibody-negative women including Männistö et al (5.9 vs 4.3%), 4,42 Haddow et al 67 (7.5 vs 6.4%) and Abbassi-Ghanavati et al 68 (6.6 vs 5.7%) failed to support these findings. While a number of investigators have reported an increased risk, 54,63-66 larger observational studies comparing preterm delivery rates (<37 weeks) in antibody-positive versus antibody-negative women including Männistö et al (5.9 vs 4.3%), 4,42 Haddow et al 67 (7.5 vs 6.4%) and Abbassi-Ghanavati et al 68 (6.6 vs 5.7%) failed to support these findings.…”

“…The major risk of maternal isolated hypothyroxinemia is the potential for impaired neurodevelopment in offspring. 3,4 The ES supports partial replacement therapy of isolated hypothyroxinemia at the discretion of the caregiver. In 1 study, only 14% of women who initially had low FT4 during early pregnancy remained hypothyroxinemic during pregnancy.…”

“…1 Similar findings were reported in the Colorado Thyroid Disease prevalence study, which found that 4% to 6% of reproductive-age women have an elevated TSH level. 3,4 During pregnancy, the incidence of hypothyroidism ranges from 0.4% to 11% worldwide, with a mean of 2.4%. Isolated hypothyroxinemia (normal TSH but low FT4) occurs in a much smaller percentage of women (1%-2%).…”

Subclinical hypothyroidism after pre-eclampsia

“…Moreover, previous studies suggest that subclinical hypothyroidism itself is unlikely to predispose to pre-eclampsia. 4 Many investigators have reported that the plasma concentration of sFlt-1, which binds the angiogenic factors vascular endothelial growth factor and placental growth factor, is raised in pre-eclampsia, and that it rises about five weeks before the clinical diagnosis. 5 In women who developed pre-eclampsia and in controls, the change in thyroid stimulating hormone concentrations from early pregnancy to pre-delivery positively correlated with serum sFlt-1 measured in late pregnancy, with higher concentrations of sFlt-1 being associated with the greatest rise in thyroid stimulating hormone.…”