The impact of isolated maternal hypothyroxinemia during the first and second trimester of gestation on pregnancy outcomes: an intervention and prospective cohort study in China

Abstract

Objectives To explore the effect of isolated maternal hypothyroxinemia (IMH) during the first and second trimester of gestation on pregnancy outcomes. To explore whether levothyroxine (L-T4) treatment of women who had IMH identified in the first trimester improves pregnancy outcomes. Methods Women in the early pregnancy in the iodine-sufficient area ( n = 3398) were recruited to this prospective cohort study (ChiCTR-TRC-12002326). Serum thyroid-stimulating hormone (TSH), free thyroxine (FT4), and thyroid peroxidase antibody (TPOAb) were detected. Women with IMH before 12 weeks chose to receive L-T4 or remain untreated. The L-T4 dose was adjusted to attain a normal FT4 and TSH level. Pregnancy outcomes were evaluated during follow-up. Results IMH in the first trimester was not associated with increased risk of adverse pregnancy outcome compared with controls. The incidence of macrosomia ( p = 0.022) and gestational hypertension ( p = 0.018) was significantly higher in IMH identified in the second trimester of gestation compared with controls. IMH identified in the second trimester of gestation was a risk factor for macrosomia [adjusted odds ratio (aOR) 1.942, 95% CI 1.076–3.503, p = 0.027] and gestational hypertension (aOR 4.203, 95% CI 1.611–10.968, p < 0.01), when body mass index in the early pregnancy was < 25 kg/m 2 . Conclusions IMH in the first trimester did not increase the risk of adverse outcomes irrespective of whether women received L-T4 treatment. However, IMH identified in the second trimester was associated with increased risk of adverse pregnancy outcome. The results suggest that thyroid function follow-up during the second trimester is necessary, even if thyroid function is normal during the first trimester. Electronic supplementary material The online version of this article (10.1007/s40618-018-0960-7) contains supplementary material, which is available to authorized users.

Isolated Maternal Hypothyroxinemia and Adverse Pregnancy Outcomes: A Systematic Review

“…The articles were published in various geographical region: North America (15) and USA (14,20)], South America [Brazil (16)], Europe [Netherland (21,24,29), Spain (22), Finland (23) and Ireland (28)] and Asia / Australia [China (6,11,26,27) and Australia (25)]. All studies were prospective or retrospective cohorts and 47% (7/15) had a population-based design (21-23, 26, 27, 29, 30).…”

“…Nine studies investigated the association of maternal IMH and gestational HTN, preeclampsia and eclampsia (6,11,14,16,20,(23)(24)(25)28). Neither preeclampsia nor eclampsia were associated with IMH diagnosed in rst or second trimesters of pregnancy; in addition, all the above studies except for two (6,11) found no signi cant association between maternal IMH and gestational HTN. Gong et al (2019) however reported that IMH identi ed in the second trimester was associated with increased risk of only gestational HTN, particularly among women with BMI < 25 kg/m 2 , (adjusted OR: 4.2, 95% CI: 1.61-10.96) (6).…”

“…The prevalence of preterm birth among women with IMH ranged between 2.3%-10.3%, although 90.9% of the studies included found no signi cant association between preterm birth and IMH, a prospective population-based cohort study with large sample size from Netherlands reported that maternal hypothyroxinemia in the rst trimester of pregnancy was associated with a 2.5-fold increased risk of preterm birth (adjusted OR: 2.54, 95% CI: 1.42-4.54), a 3.4-fold increased risk of spontaneous preterm birth (adjusted OR: 3.44, 95% CI: 1.76-6.70) and a 3.6-fold increased risk of early preterm birth before 34 week of gestations (adjusted OR: 3.56, 95% CI: 1.50-8.43) (all P ≤ .01) (21). However, one study reported that IMH in the rst trimester was associated with preterm labor (OR: 1.62, 95% CI: 1.00-2.62) without increasing the risk of preterm birth (20) and one (21) of four studies (6,20,21,28) evaluating the risk of preterm PROM, showed a positive association between IMH and preterm PROM (adjusted OR: 2.35, 95% CI: 1.18-4.69)…”

“…Moreover, Su et al (2019), showed that IMH was associated with a 2.2-fold increased risk of gestational HTN (adjusted OR: 2.2, 95% CI: 1.28-3.82) (11). Of 8 studies (6,11,14,16,20,23,25,28) that assessed the association between maternal IMH and placenta abruption, all except one (28), showed no association between IMH and placenta abruption. Two studies assessed the risk of breech presentation in mothers with IMH (6,29) and one (29) reported increased risk of breech presentation in women diagnosed with IMH in the rst trimester of pregnancy (adjusted OR: 4.7, 95% CI: 1.1-19).…”

Retrospective analysis of the effects induced by maternal thyroid dysfunction on obstetrical complications and outcomes

“…It is worth noting that the effects isolated hypothyroxinemia on gravidas and fetus. At present, there were few studies on the relationship between the isolated hypothyroxinemia and adverse pregnant outcomes, and the results of studies were controversies [29][30][31]. Some studies have reported increased risk of premature delivery, fetal distress, and premature rupture of membranes and higher mean birth weight in isolated hypothyroxinemia [32].…”