Thyroid function reference ranges during pregnancy in a large Chinese population and comparison with current guidelines

Background: A correct thyroid function reference range is important for the accurate diagnosis of thyroid disease during pregnancy. However, there is no consensus on whether thyroid function reference ranges in Chinese population should follow the America Thyroid Association (ATA) guidelines. This study aimed to establish a thyroid function reference range more suited to the Chinese population by evaluating the current thyroid function reference range in pregnant Chinese women and comparing it to the ATA guidelines. Methods: A total of 52,027 pregnant women were enrolled from January 2013 to December 2016. Thyroid stimulating hormone (TSH), free thyroxine (FT4), and thyroid peroxidase antibody (TPOAb) levels were tested during the first and third trimesters of pregnancy. Reference ranges of TSH and FT4 were established from the 2.5th and 97.5th percentiles of the TPOAb-negative population of women. The Mann-Whitney U test was used to compare thyroid hormones between the TPOAb-positive and TPOAbnegative groups. Results: We obtained that the TSH reference ranges were 0.03 to 3.52 mU/L and 0.39 to 3.67 mU/L, and the FT4 reference ranges were 11.7 to 19.7 pmol/L and 9.1 to 14.4pmol/L, in the firstand third trimester, respectively. If we used the 2011 ATA criteria about 7.0% and 4.0% pregnant women would be over diagnosed in first and third trimester, respectively, compared with local population thyroid hormone reference. When we compared our local criteria with the new 2017 ATA criteria, about 1.2% and 0.8% pregnant women would have a missed diagnosis in first and third trimester, respectively. Conclusions: Based on our data, which is in line with the current ATA guidelines, a population-based thyroid function reference range would be the first choice for diagnosis of thyroid disease during pregnancy in China. In case such population-based thyroid function reference ranges are unavailable in the east of China, our reference ranges can be adopted, if the same assay is used.

Comparison of the Reference Intervals Used for the Evaluation of Maternal Thyroid Function During Pregnancy Using Sequential and Nonsequential Methods

Background： Maternal thyroid dysfunction is common during pregnancy, and physiological changes during pregnancy can lead to the overdiagnosis of hyperthyroidism and misdiagnosis of hypothyroidism with nongestation-specific reference intervals. Our aim was to compare sequential with nonsequential methods for the evaluation of thyroid function in pregnant women. Methods： We tested pregnant women who underwent their trimester prenatal screening at our hospital from February 2011 to September 2012 for serum thyroid stimulating hormone （TSH） and free thyroxine （FT4） using the Abbott and Roche kits. There were 447 and 200 patients enrolled in the nonsequential and sequential groups, respectively. The central 95% range between the 2.5th and the 97.5th percentiles was used as the reference interval for the thyroid function parameter. Results： The nonsequential group exhibited a significantly larger degree of dispersion in the TSH reference interval during the 2nd and 3rd trimesters as measured using both the Abbott and Roche kits （all P 〈 0.05）. The TSH reference intervals were significantly larger in the nonsequential group than in the sequential group during the 3rd trimester as measured with both the Abbott （4.95 vs. 3.77 mU/L, P 〈 0.001） and Roche kits （6.62 vs. 5.01 mU/L, P〈 0.004）. The nonsequential group had a significantly larger FT4 reference interval as measured with the Abbott kit during all trimesters （ 12.64 vs. 5.82 pmol/L; 7,96 vs. 4.77 pmol/L; 8.10 vs. 4.77 pmol/L, respectively, all P 〈 0.05）, whereas a significantly larger FT4 reference interval was only observed during the 2nd trimester with the Roche kit （7.76 vs. 5.52 pmol/L, P = 0.002）. Conclusions： It was more reasonable to establish reference intervals for the evaluation of maternal thyroid function using the sequential method during each trimester of pregnancy. Moreover, the exclusion of pregnancy-related complications should be considered in the inclusion criteria for thyroid function tests.

Intravaginal Misoprostol for Cervical Ripening and Labor Induction in Nulliparous Women： A Double-blinded, Prospective Randomized Controlled Study

Background： In China, no multicenter double-blinded prospective randomized controlled study on labor induction has been conducted till now. This study is to evaluate the efficacy and safety ofintravaginal accurate 25-μg misoprostol tablets for cervical ripening and labor induction in term pregnancy in nulliparous women. Methods： This was a double-blinded, prospective randomized controlled study including nulliparous women from 6 university hospitals across China. Subjects were randomized into misoprostol or placebo group with the sample size ratio set to 7：2. lntravaginal 25-μg misoprostol or placebo was applied at an interval of 4 h （repeated tip to 3 times） for labor induction. Primary outcome measures were the incidence of cumulative Bishop score increases ≥3 within 1211 or vaginal delivery within 24 h. Safety assessments included the incidences of maternal morbidity and adverse fetal/neonatal outcomes. Results： A total of 173 women for misoprostol group and 49 women for placebo were analyzed. The incidence of cumulative Bishop score increases ≥3 within 12 h or vaginal delivery within 24 h was higher in the misoprostol group than in the placebo （64.2% vs. 22.5%, relative risk [RR]： 2.9, 95% confidence interval [C/]： 1.4-6.0）. The incidence of onset of labor within 24 h was significantly higher in the misoprostol group than in the placebo group （48.0% vs. 18.4%, RR： 2.6, 95% CI： 1.2-5.7）; and the induction-onset of labor interval was significantly shorter in the misoprostol group （P = 0.0003）. However, there were no significant differences in the median process time of vaginal labor （6.4 vs. 6.8 h; P = 0.695）, incidence （39.3% vs. 49.0%, RR： 0.8, 95% CI： 0.4-1.5） and indications （P = 0.683） of cesarean section deliveries, and frequencies of maternal, fetal/neonatal adverse events between the groups. Conclusion： Intravaginal misoprostol 25 μg every 4 h is efficacious and safe in labor induction and cervical ripening.

Altered Matrix Metalloproteinases Expression in Placenta from Patients with Gestational Diabetes Mellitus

To the Editor：Gestational diabetes mellitus （GDM） is defined as glucose intolerance with the onset of pregnancy and is related to increased maternal and fetal risks.Incidence of GDM varies in different countries and the prevalence ranges between 4% and 17%. GDM is one of the most common medical complications of pregnancy,negatively affecting fetal development and metabolic balance.If untreated,GDM can cause fetal malformation,macrosomia,fetal growth retardation,and even intrauterine fetal death.Recent studies have shown correlations between GDM and postpartum insulin resistance,pregnancy-induced hypertension,and dyslipidemia.GDM has also been shown to be associated with placental abnormalities including altered placental function,oxidative stress,and vascular dysfunction.