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

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.

尽管妊娠早期甲状腺功能异常可能对妊娠结局产生不良影响，但目前鲜有研究同时探讨妊娠早、晚两孕期母体游离甲状腺素（FT4）水平偏低与不良妊娠结局发生率之间的关联。本研究提出假说：妊娠早、晚任意一孕期的FT4水平偏低，可能对妊娠结局产生不同影响。本研究纳入6031名孕妇，所有研究对象均提供了妊娠早、晚两期的血清样本用于甲状腺功能检测分析。不良妊娠结局包括妊娠期糖尿病（GDM）、妊娠高血压疾病及子痫前期，分别通过口服葡萄糖耐量试验、血压检测及尿蛋白检测进行确诊。采用亲水作用液相色谱-串联质谱（HILIC-MS/MS）对腺苷及其类似物等血清代谢物进行鉴定。孕妇甲状腺功能减退症的发生率随年龄及孕前体重指数（BMI）的升高呈上升趋势。妊娠早期母体FT4水平与GDM发生率呈负相关，而妊娠晚期母体FT4水平与子痫前期发生率呈负相关；妊娠高血压疾病发生率与母体FT4水平无显著相关性。妊娠晚期确诊单纯性母体低甲状腺素血症（IMH）的孕妇，其发生子痫前期的风险显著升高。IMH孕妇血清中的腺苷及其类似物等部分代谢物水平发生显著变化。综上，孕期FT4水平偏低是GDM及子痫前期的危险因素。腺苷及其类似物可能是IMH与子痫前期之间的重要桥梁。