Effects Of Gestational Hypothyroxinemia On Pregnancy Outcomes

Background: Thyroid hormone(TH)is a key hormone to promote body growth,nerve development and maintain normal metabolism of the body.The lack of TH can cause significant adverse effects at all stages of life and various diseases.Compared with non-pregnancy stage,thyroid function have significant changes during pregnancy stage,free thyroxine(FT4)level increases in first trimester,thyroid stimulating hormone(TSH)level feedback to drop,then FT4 level will gradually drop in second trimester,FT4 will drop to non-pregnant levels around 20 weeks of gestation.Hypothyroidism during pregnancy,including clinical hypothyroidism,subclinical hypothyroidism(SCH)and hypothroxinemia(HT).HT only presents as a mild FT4 deficiency,which refers to normal TSH level,FT4 level is below the lower limit of the reference range,and HT with negative thyroid peroxidase antibody(TPOAb)is also known as isolate maternal hypothyroxinemia(IMH).Depending on the iodine intake,the incidence of HT varies greatly,ranging from 1% to 2% in iodine-rich areas and more than 20% in iodine-deficient areas,indicating that the incidence of HT can not be underestimated.A large number of studies have confirmed that clinical hypothyroidism and SCH can significantly increase the risk of adverse pregnancy outcomes,such as abortion,premature delivery,premature rupture of membranes,etc.However,there is no unified conclusion on the impact of HT on pregnancy outcomes,and there are significant differences among the research conclusions.At the same time,some studies have pointed out that the influence of HT on pregnancy outcomes is still specific in pregnancy period,and the influence is inconsistent in different pregnancy period.There is also no unified conclusion as to whether HT needs treatment.European guidelines recommend HT supplementation with levothyroxine(LT4)in first trimester,while relevant guidelines in China and the United States neither recommend nor reject the use of LT4 for HT.So it is necessary to explore the influence of HT on pregnancy outcomes according to different pregnancy period.Previous studies were only limited to the effect of HT on adverse pregnancy outcomes in a single trimester,not considering pregnancy as a whole,which may have overlooked the effect of thyroid functional in other trimester on pregnancy outcomes.Therefore,it is valuable to analyze the influence of HT on adverse pregnancy outcomes under different circumstances by combining thyroid function in first and second trimester.Objective: To explore the effects of HT in first trimester alone,newly developed HT in the second trimester and persistent HT in both first and second trimester on adverse pregnancy outcomes.Methods: The cases of 1989 pregnant women in The Third Affiliated Hospital of Chongqing Medical University were retrospectively analyzed.According to the serum thyroid stimulating hormone(TSH),free thyroxine(FT4),they were divided into 4groups,including Group A: HT was diagnosed in first trimester and thyroid function was normal in second trimester;group B: thyroid function was normal in first trimester and HT was diagnosed in second trimester;group C: HT was diagnosed in first and second trimester;group D: thyroid function was normal in first and second trimester.Differences in baseline indices,pregnancy indices and pregnancy outcomes were compared between groups.Baseline indices included age,pre-pregnancy BMI,FT4,FT3,TSH,TPOAb,smoking history,drinking history,family history of diabetes,family history of hypertension,history of multiparity,and history of cesarean section.Pregnancy indices included: oral glucose tolerance test 0 hour blood glucose(OGTT0h),OGTT1 h,OGTT2h,neonatal weight,gestational weeks,and weight gain during pregnancy.Pregnancy outcomes included cesarean section,gestational hypertension,gestational diabetes mellitus(GDM),preeclampsia,preterm delivery,macrosomia,premature rupture of membranes,oligohydramnion,fetal distress,torsion of cord,cord entanglement,and precipitate labour.Results: Among the 1899 included pregnant women,190 cases(10.01%)in group A,125 cases(6.58%)in group B,45 cases(2.37%)in group C,and 1373 cases(72.3%)in group D.There were a total 243 cases of HT(12.8%)in first trimester,and a total178 cases of HT(9.37%)in second trimester.The incidence of cesarean section,gestational diabetes mellitus(GDM)and gestational hypertension in group A(54.7%,16.3%,6.3%)was higher than that in group D(45.2%,10%,2%),and the incidence of GDM in group B and C(22.4%,24.4%)was also higher than that in group D(10%),P<0.05.Multivariate Logistic regression showed that HT in first trimester alone(aOR1.7,95%CI 1.08-2.67,P=0.009),newly occurring HT in second trimester(aOR 2.51,95%CI 1.54-4.08,P<0.001)and persistent HT in both first and second trimester(aOR2.67,95%CI 1.26-5.64,P<0.001)were all risk factors for GDM and HT in first trimester alone(aOR 2.83,95%CI 1.36-5.91,P=0.005)was also a risk factor for gestational hypertension after correction for potential confounding factors.Conclusion: Either alone or persistent HT in both first and second trimester is a risk factor for GDM.Therefore,even for pregnant women with normal thyroid function in the first trimester,thyroid function detection in the second trimester is also very necessary.Meanwhile,HT under any circumstances should be vigilant against the occurrence of GDM and attach importance to blood glucose detection.