Maternal low thyroxin levels are associated with adverse pregnancy outcomes in a Chinese population

Abstract

Although thyroid dysfunction in early pregnancy may have adverse effects on pregnancy outcomes, few studies have examined the relationship between maternal low free thyroxin (FT4) levels in both first and third trimesters of pregnancy and the incidence of adverse pregnancy outcomes. We hypothesized that low FT4 levels in either first or third trimesters of pregnancy may have different effects on pregnancy outcomes. The study included 6,031 mothers who provided both first and third pregnancy serum samples for analyses of thyroid function. Adverse pregnancy outcomes, such as gestational diabetes mellitus (GDM), pregnancy-induced hypertension and preeclampsia, were diagnosed using the oral glucose tolerance test, blood pressure and urine protein test. Serum metabolites like adenosine and its analogues were identified using hydrophilic interaction liquid chromatography (HILIC)-tandem mass spectrometry (MS/MS). The incidence of hypothyroidism in pregnant women tended to increase with age and pre-pregnancy body mass index (BMI). The incidence of GDM was negatively correlated with maternal FT4 levels during early pregnancy while the incidence of preeclampsia was negatively correlated with maternal FT4 levels during late pregnancy. The incidence of pregnancy-induced hypertension was not significantly correlated with maternal FT4 levels. The women who had isolated maternal hypothyroxemia (IMH) in the third trimester of pregnancy had an increased risk of developing preeclampsia. Some metabolites like adenosine and its analogues in the serum were significantly changed in pregnant mothers with IMH. In conclusion, low FT4 levels during pregnancy are a risk factor for GDM and preeclampsia. Adenosine and its analogues may be important bridges between IMH and preeclampsia.

Fetal Sex-Dependent Associations Between Gestational Hormone Concentrations and Adverse Birth Outcomes: A Cohort Study

“…Previous work has suggested that fT4 concentrations early in pregnancy are inversely associated with odds of GDM [61,68]. In accordance with those ndings, the ratio of fT3 to fT4 has been observed to be positively associated with odds of GDM [69], suggesting that increased conversion of T4 to biologically active T3 may play a role in the onset of GDM.…”

“…Previous studies have found increased odds of preeclampsia with higher second trimester fT4 concentrations [20,60], and lower third trimester fT4 concentrations [61]. All associations we observed between fT4 and preeclampsia were inverse, although not statistically signi cant.…”

Thyroid Dysfunction and Diabetes Mellitus: Two Closely Associated Disorders

“…A prospective study of 6,031 Chinese pregnant women showed that low FT4 levels during pregnancy were a risk factor for GDM and preeclampsia (395). On the contrary, the incidence of GDM decreased in women with higher FT4 levels, showing a protective effect for the development of GDM (396).…”

The Need for Dynamic Clinical Guidelines: A Systematic Review of New Research Published After Release of the 2017 ATA Guidelines on Thyroid Disease During Pregnancy and the Postpartum

“…Both studies are thus vulnerable to a high risk of false positive findings; therefore, further studies are needed. Other studies showed association between maternal isolated hypothyroxinemia with breech presentation or Cesarean section (28), preeclampsia (29) and macrosomia (11,28), the results from these isolated observational studies require additional confirmation. Thus, current evidence continues to support the statements made in the 2017 ATA Guidelines regarding isolated hypothyroxinemia in pregnancy.…”

“…/228) of women with hypothyroxinemia in both the first and third trimesters, aOR 2.62, CI 1.23-5.62 and 2.87% (15/523) of women with hypothyroxinemia in only the third trimester, aOR 2.16, CI 1.22-3.82. Women in the second trimester of pregnancy were not included in this study(29). In the prospective study by Yang et al the authors reported an association between isolated hypothyroxinemia and rates of macrosomia compared to euthyroid controls, 19.6% (9/46) vs. 10.8% (95/882), aOR 2.22, CI 1.13-4.85…”