Thyroid function reference ranges during pregnancy in a large Chinese population and comparison with current guidelines / 中华医学杂志(英文版)

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 TPOAb-negative 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 14.4 pmol/L, in the first and 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.@*TRIAL REGISTRATION@#www.chictr.org.cn (No. ChiCTR1800014394).

Comparison of the Reference Intervals Used for the Evaluation of Maternal Thyroid Function During Pregnancy Using Sequential and Nonsequential Methods / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>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.</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>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).</p><p><b>CONCLUSIONS</b>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.</p>

Intravaginal Misoprostol for Cervical Ripening and Labor Induction in Nulliparous Women: A Double-blinded, Prospective Randomized Controlled Study / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>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 of intravaginal accurate 25-μg misoprostol tablets for cervical ripening and labor induction in term pregnancy in nulliparous women.</p><p><b>METHODS</b>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. Intravaginal 25-μg misoprostol or placebo was applied at an interval of 4 h (repeated up to 3 times) for labor induction. Primary outcome measures were the incidence of cumulative Bishop score increases ≥3 within 12 h or vaginal delivery within 24 h. Safety assessments included the incidences of maternal morbidity and adverse fetal/neonatal outcomes.</p><p><b>RESULTS</b>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 [CI]: 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.</p><p><b>CONCLUSION</b>Intravaginal misoprostol 25 μg every 4 h is efficacious and safe in labor induction and cervical ripening.</p>

Reference intervals for common thyroid function tests, during different stages of pregnancy in Chinese women / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>The importance of diagnosis of thyroid dysfunction during pregnancy has been widely recognized. Our study was designed to compare two different detection reagents between Abbott and Roche and to establish the gestational related reference intervals for thyroid function tests (TFT) in Chinese women and to assay the reference ranges with the American Thyroid Association recommended standard.</p><p><b>METHODS</b>Serum samples were collected from 693 normal pregnant Chinese women and divided into five groups according to their gestational age: 9-13, 16-20, 24-28, 32-34 and 37-40 weeks. Thyroid stimulating hormone (TSH) and free thyroxine (FT4) levels were determined by two different detection reagents: Abbott Architect I 2000 and Roche Cobas Elecsys 600. The reference ranges of the TFT indexes were calculated according to the National Academy of Clinical Biochemistry (NACB). The 2.5th and 97.5th percentiles of each stage were calculated, and the results were analyzed by one-way analysis of variances, t-test, and Spearman correlation analysis.</p><p><b>RESULTS</b>Thyroid hormone levels varied greatly among different gestational stages. TSH levels, as assessed via two different TSH ELISA kits showed consistent changing pattern during pregnancy and displayed linear correlation (P < 0.001). In 9-13 gestational weeks, TSH levels were significantly lower than that of other groups; and in 37-40 gestational weeks, it was higher than that of other groups (all P < 0.001). TSH reference ranges determined by Roche detection reagent in each group were higher than those by Abbott detection reagent (P < 0.01 respectively). FT4 levels were higher in 9-13 gestational weeks than that of other groups (P < 0.001). FT4 levels determined by Roche reagent were higher than Abbott reagent in 9-13 weeks, (P < 0.001), and lower in 24-28 and 37-40 weeks (P < 0.001 and P = 0.016, respectively). The TSH level was correlated with FT4 levels in 9-13 gestational weeks by detection reagents (for Abbott reagent, r=-0.319 for FT4 P < 0.001; for Roche reagent, r=-0.352 for FT4, P <0.001).</p><p><b>CONCLUSION</b>Accurate evaluation of TFT in pregnant women should be based on the gestational-related reference intervals in Chinese population, and different detection reagents should also establish their own reference intervals.</p>