Maternal thyroid peroxidase antibody positivity and its association with incidence of low birth weight in infants.

Background: Autoimmune thyroid disease is a prevalent condition affecting women of reproductive age, leading to thyroid dysfunction and impacting pregnancy outcomes. While the critical role of thyroid hormone in pregnancy outcomes is well-established, the potential association between positive anti-thyroid peroxidase antibodies (TPOAb) and adverse pregnancy outcomes in pregnant women with normal thyroid function remains unclear. Objective: This study aims to investigate the relationship between maternal TPOAb positivity and adverse pregnancy outcomes with normal thyroid function. Methods: We collected baseline information from pregnant women who visited our hospital between February 2009 and June 2012. Blood samples were taken to measure thyroid stimulating hormone (TSH), free thyroxine (FT4), TPOAb, and anti-thyroglobulin antibodies (TGAb). The incidence of adverse pregnancy outcomes was compared between TPOAb-positive and TPOAb-negative groups among participants with normal thyroid function. Results: A total of 7,046 pregnant women with normal thyroid function were included, comprising 6,700 with negative TPOAb and 346 with positive TPOAb. The TPOAb-positive group exhibited a higher age (26.0 vs. 27.0 years, p = 0.02) and greater serum TSH levels (1.72 vs. 1.94 mIU/L, p = 0.029), while the gestational week of blood collection was lower (31.9 vs. 26.5 weeks, p = 0.001). Univariate analysis revealed a higher incidence of low birth weight (LBW) in offspring of TPOAb-positive women compared to the TPOAb-negative group (3.5% vs. 1.9%, p = 0.035). After adjusting for confounding factors such as age, gestational week of blood collection, menstrual history, education level, gestational diabetes, gestational hypertension, TGAb, TSH, and FT4, TPOAb positivity emerged as an independent risk factor for LBW infants (OR: 2.317, 95% CI: 1.057-5.076, p = 0.036), while other adverse pregnancy outcomes did not show a significant correlation with TPOAb positivity. Conclusion: Our findings suggest that TPOAb-positive pregnant women with normal thyroid function are more likely to deliver LBW infants. Regular monitoring of TPOAb-positive pregnancies and timely interventions throughout all stages of pregnancy are crucial.

Association between third trimester maternal isolated hypothyroxinemia and adverse pregnancy outcomes.

To study the effects of third trimester maternal isolated hypothyroxinemia (serum low free thyroxine and normal thyroid stimulating hormone level) on pregnancy outcomes, we performed a retrospective cohort study in women with singleton pregnancy between February 2009 and June 2012. Pregnant women were assigned to two groups, a hypothyroxinemia group (with maternal isolated hypothyroxinemia in the third trimester and normal thyroid function in the first and second trimesters) and a control group (with normal serum thyroid functions). The pregnancy outcomes, including preterm birth, fetal distress, birth weight, premature rupture of membranes, and Apgar score at one minute after the birth, were recorded and compared between the two groups. A total of 3,945 pregnant women (median age 26 year old) were included in the study, with 195 women in the hypothyroxinemia group and 3,750 women in the control group. Compared with the women in the control group, women in the hypothyroxinemia group had higher incidences of premature rupture of membranes and low Apgar score at one minute after the birth. The multivariate logistic regression analysis showed that the low third trimester serum thyroxine level was the independent risk factor for the premature rupture of membranes and low Apgar score. There were no statistically significant differences in preterm birth, macrosomia, and intrauterine fetal distress between two groups. Third trimester maternal isolated hypothyroxinemia was associated with adverse pregnancy outcomes. The maternal serum thyroxine level should be monitored during late pregnancy and necessary management should be applied to improve the pregnancy outcomes.

Insignificant Effect of Isolated Hypothyroxinemia on Pregnancy Outcomes During the First and Second Trimester of Pregnancy.

Objective: Adverse maternal outcomes and perinatal complications are associated with overt and subclinical maternal hypothyroidism. It is not clear whether these complications also occur in women with isolated hypothyroxinemia during pregnancy. The aim of this study was to evaluate the effects of isolated hypothyroxinemia on maternal and perinatal outcomes during pregnancy. Methods: This study included data from 2,864 pregnant women in the first trimester (67 women with isolated hypothyroxinemia, 784 euthyroid women) and the second trimester (70 women with isolated hypothyroxinemia, 1,943 euthyroid women) of pregnancy. Maternal serum samples were collected in the first and second trimesters to examine thyroid hormone concentration. Hypothyroxinemia was defined as a normal maternal thyroid-stimulating hormone concentration with a low maternal free thyroxine concentration and negative thyroid autoantibodies. The following maternal outcomes were recorded: gestational hypertension, gestational diabetes mellitus, placenta previa, placental abruption, prelabor rupture of membranes, and premature delivery. Perinatal outcomes, including fetal growth restriction, fetal distress, low birth weight, intrauterine fetal death, and malformation. The incidence of adverse pregnancy outcomes and perinatal complications was compared between women in the first trimester and second trimester with isolated hypothyroxinemia. Results: There were no significant differences in the incidence rates of adverse maternal outcomes and perinatal complications between patients in the first and second trimesters with isolated hypothyroxinemia. Conclusion: The results of this study indicate that isolated hypothyroidism does not increase the incidence of adverse maternal outcomes and perinatal complications.

Clinical and radiographic characteristics, management and short-term outcomes of patients with COVID-19 in Wenzhou, China.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is an emerging viral disease. Here, we report the clinical features, management, and short-term outcomes of COVID-19 patients in Wenzhou, China, an area outside Wuhan. METHODS: Patients admitted to the Infectious Diseases Department of Ruian People's Hospital in Wenzhou, from January 21 to February 7, 2020, were recruited. Medical data on epidemiological history, demographics, clinical characteristics, laboratory tests, chest computerized tomography (CT) examination, treatment, and short-term outcomes were retrospectively reviewed. Blood biochemistry and routine tests were examined using standard methods and automatic machines. CT examination was performed several times during hospitalization as necessary. RESULTS: A total of 67 confirmed COVID-19 cases were diagnosed; 64 (95.4%) were common cases and three (4.5%) were severe cases. The most common symptoms at admission were fever (86.6%), cough (77.6%), productive cough (52.2%), chest distress (17.9%), and sore throat (11.9%), followed by diarrhea (7.4%), headache (7.4%), shortness of breath (6.0%), dizziness (4.5%), muscular soreness (4.5%), and running nose (4.5%). Thirty patients (47.8%) had increased C-reactive protein levels. The CT radiographs at admission showed abnormal findings in 54 (80.6%) patients. The patients were treated mainly by oxygen therapy and antiviral drugs. By March 3, 2020, all 67 patients completely recovered and had negative nucleic acid tests. The patients were discharged from the hospital and transferred to a medical observation isolation center for further observation. CONCLUSION: Cases of COVID-19 in Wenzhou are milder and have a better prognosis, compared to those in Wuhan. Timely and appropriate screening, diagnosis, and treatment are the key to achieve good outcomes.

Epidemiological and clinical characteristics of three family clusters of COVID-19 transmitted by latent patients in China.

From 21 January 2020 to 9 February 2020, three family clusters involving 31 patients with coronavirus disease 2019 were identified in Wenzhou, China. The epidemiological and clinical characteristics of the family cluster patients were analysed and compared with those of 43 contemporaneous sporadic cases. The three index cases transmitted the infection to 28 family members 2-10 days before illness onset. Overall, 28 of the 41 sporadic cases and three of 31 patients in the family clusters came back from Wuhan (65.12 vs. 9.68%, P< 0.001). In terms of epidemiological characters and clinical symptoms, no significant differences were observed between the family cluster and sporadic cases. However, the lymphocyte counts of sporadic cases were significantly lower than those of family cluster cases ((1.32 ± 0.55) × 109/l vs. (1.63 ± 0.70) × 109/l, P = 0.037), and the proportion of hypoalbuminaemia was higher in sporadic cases (18/43, 41.86%) than in the family clusters (6/31, 19.35%) (P < 0.05). Within the family cluster, the second- and third-generation cases had milder clinical manifestations, without severe conditions, compared with the index and first-generation cases, indicating that the virulence gradually decreased following passage through generations within the family clusters. Close surveillance, timely recognition and isolation of the suspected or latent patient is crucial in preventing family cluster infection.

A novel compound heterozygous mutation in the CYP17A1 gene in a patient with 17α-hydroxylase/17,20-lyase deficiency.

PURPOSE: 17α-hydroxylase/17,20-lyase deficiency is a rare disease caused by mutation of the CYP17A1 gene, resulting in hypertension, hypokalemia, alkalosis, female hypogonadism, and male pseudohermaphroditism. Here we report a case of a 15-year-old girl with 17α-hydroxylase/17,20-lyase deficiency, and analyze her clinical and molecular genetic characteristics. PATIENT AND METHODS: A 15-year-old Chinese girl had fever, fatigue, high blood pressure, and blood potassium level being significantly lower than normal. Physical examination showed that the patient's breasts were in Tanner stage 1, and she had no armpit hair or pubic hair, but had a normal external genital formation. The hormone concentrations of the patient were measured. Genomic DNA from the patient and her immediate family members was amplified and sequenced. Mutational analysis of the CYP17A1 gene was performed and 17alpha-hydroxylase/17,20-lyase enzymatic activities were assessed in vitro. RESULTS: The patient had clinical features of 17α-hydroxylase/17,20-lyase deficiency, including hypokalemia, hypertension, female sexual infantilism, low blood cortisol, estradiol, and plasma renin activity, and increased adrenocorticotropic hormone. DNA sequence analysis revealed compound heterozygous mutations (Ser106Pro/His373Tyr) in CYP17A1. The heterozygous Ser106Pro mutation was detected in the patient's father, whereas the novel heterozygous His373Tyr mutation (c.1117C>T) was detected in her mother. In vitro expression and functional analysis in HEK293 cells showed that this novel mutation His373Tyr resulted in complete loss of 17alpha-hydroxylase and 17,20-lyase activities. CONCLUSION: We identified a novel compound heterozygous CYP17A1 mutation His373Tyr (c.1117C>T) in a patient with 17α-hydroxylase/17,20-lyase deficiency.

Associations between thyroid autoantibody status and abnormal pregnancy outcomes in euthyroid women.

We investigated whether thyroid autoantibody status influences pregnancy outcomes in euthyroid women, by comparing abnormal pregnancy outcome rates between those who tested positive for thyroid autoantibodies (Ab+) and those who tested autoantibody-negative (Ab-). Euthyroid pregnant women (n=7,641) underwent tests for serum thyroid peroxidase antibody (TPOAb) and thyroglobulin antibody (TgAb). The subjects were divided into 4 groups according to thyroid antibody status: TPOAb-/TgAb- (92.9%); TPOAb+/TgAb- (3.2%); TPOAb-/TgAb+ (2.0%); and TPOAb+/TgAb+ (1.9%). The incidence rates of the following abnormal pregnancy outcomes were compared among the 4 groups and analyzed by Fisher's exact test: gestational diabetes, gestational hypertension, placenta previa, placental abruption, premature rupture of fetal membrane (PROM), intrauterine growth restriction, fetal distress, fetal anomalies, stillbirth, preterm birth, and low birth weight. Among the 4 groups, there were no significant differences in age, gestational age, or in the incidence rates of abnormal pregnancy outcomes, except for PROM and low birth weight. The highest incidence rates for PROM and low birth weight were in the TPOAb-/TgAb+ and TPOAb+/TgAb+ subjects, respectively. TgAb positivity and TPOAb positivity were associated with PROM and low birth weight, respectively. Underlying factors that govern the association between thyroid autoantibodies and PROM and low birth weight require further investigation.

Adiponectin gene polymorphism rs2241766 T/G is associated with response to pioglitazone treatment in type 2 diabetic patients from southern China.

INTRODUCTION: Insulin sensitizing drugs such as pioglitazone are not uniformly treatment effective among individual type 2 diabetic patients. Here, the relationship of pioglitazone efficacy to single nucleotide polymorphisms (SNP) of the adiponectin gene, a critical gene directly regulated by the drug, was examined in a cohort of Chinese Han type 2 diabetic patients. METHODS: Eighty type 2 diabetic patients were treated with pioglitazone (15 mg/day) for 12 weeks without interruption of their current therapeutic regimen. Fasting plasma glucose, fasting insulin, homeostasis model assessment for insulin resistance (HOMA-IR), and glycated hemoglobin (HbA1c%) were collected both prior to and following pioglitazone treatment. Response to pioglitazone was defined as a decrease of at least 15% in HbA1c% levels. Three regions of the adiponectin gene containing SNPs (promoter, intron 2 and exon 2, and exon 3) were amplified and sequenced to determine genotype. RESULTS: Serum adiponectin levels were significantly increased (p<0.001) whereas fasting plasma glucose, fasting insulin, HOMA-IR, and HbA1c% values were significantly decreased relative to baseline measurements (p<0.001). Response of patients with TG and TT genotypes at rs2241766 (exon2; 52.9% vs. 12.7%, respectively p = 0.001) was statistically significant relative to all other patients. Amongst rs2241766 TG and TT patients, the mean decrease in HbA1c% levels was greater where the genotype was TG (1.15±0.80 vs. 0.52±0.64, p = 0.001). CONCLUSIONS: The adiponectin gene polymorphism rs2241766 T/G is associated with pioglitazone efficacy in type 2 diabetic patients, and status of the polymorphism may be an important clinical factor to consider prior to pioglitazone treatment.

Effects of subclinical hypothyroidism on maternal and perinatal outcomes during pregnancy: a single-center cohort study of a Chinese population.

OBJECTIVE: Adverse maternal outcomes and perinatal complications are closely associated with overt maternal hypothyroidism, but whether these complications occur in women with subclinical hypothyroidism (SCH) during pregnancy remains controversial. The aim of this study was to evaluate the effects of SCH on maternal and perinatal outcomes during pregnancy. METHODS: A prospective study of data from 8012 pregnant women (371 women with SCH, 7641 euthyroid women) was performed. Maternal serum samples were collected in different trimesters to examine thyroid hormone concentrations. SCH was defined as a thyroid stimulating hormone concentration exceeding the trimester-specific reference value with a normal free thyroxine concentration. The occurrence of maternal outcomes, including gestational hypertension (GH), gestational diabetes mellitus, placenta previa, placental abruption, prelabor rupture of membranes (PROM), and premature delivery; and perinatal outcomes, including intrauterine growth restriction (IUGR), fetal distress, low birth weight (LBW; live birth weight ≤ 2500 g), stillbirth, and malformation, was recorded. Logistic regression with adjustment for confounding demographic and medical factors was used to determine the risks of adverse outcomes in patients with SCH. RESULTS: Compared with euthyroid status, SCH was associated with higher rates of GH (1.819% vs. 3.504%, P = 0.020; χ2 = 7.345; odds ratio (OR), 2.243; 95% confidence interval (CI), 1.251-4.024), PROM (4.973% vs. 8.625%, P = 0.002; χ2 = 72.102; adjusted OR, 6.014; 95% CI, 3.975-9.099), IUGR (1.008% vs. 2.965%, <0.001; χ2 = 13.272; adjusted OR, 3.336; 95% CI, 1.745-6.377), and LBW (1.885% vs. 4.582%, P<0.001; χ2 = 13.558; adjusted OR, 2.919; 95% CI, 1.650-5.163). CONCLUSIONS: The results of this study indicate that pregnant women with SCH had increased risks of GH and PROM, and their fetuses and infants had increased risks of IUGR and LBW. Thus, routine maternal thyroid function testing is necessary to improve maternal and perinatal outcomes.

Adiponectin and peroxisome proliferator-activated receptor-γ gene polymorphisms and gene-gene interactions with type 2 diabetes.

AIMS: To investigate whether gene polymorphisms of both adiponectin and peroxisome proliferator-activated receptor gamma (PPARγ) influence type 2 diabetes mellitus (T2DM) respectively in the Han people of the Wenzhou region of China and whether the interaction of gene polymorphism between adiponectin and PPARγ influences T2DM in the same subjects. MAIN METHODS: This study included 198 patients with T2DM and 255 healthy individuals. Polymerase chain reaction-restriction fragment length polymorphism analyses were used to detect single nucleotide polymorphisms (SNPs). Logistic regression and multifactor dimensionality reduction (MDR) methods were used to analyze gene-gene interactions. KEY FINDINGS: The frequency distribution of adiponectin SNP11377 was not different (p=0.792), but the frequency of CC, CG and GG genotypes showed the difference between two groups (T2DM: 57.1%, 33.3%, and 9.6%; control: 53.7%, 41.6%, and 4.7%, respectively; p=0.047). Adiponectin SNP45, SNP276 and PPAR γ SNPp12a were equally distributed between the two groups (p=0.586, 0.119, 0.437, respectively), and there were no significant differences in genotype frequencies between the two groups (p=0.751, 0.144, 0.479, respectively). Linkage disequilibrium existed between SNP11377 and SNP45 (p<0.001) and SNP45 and SNP276 (p<0.001). Haplotype analyses showed no significant differences between the T2DM and control groups. According to the logistic regression and MDR gene-gene interaction analyses, SNP11377GG and SNP276GT interactions increased the risk of T2DM (odds ratio=6.984, p=0.012). SIGNIFICANCE: Adiponectin SNP11377 and SNP276 gene-gene interactions are associated with the increased risk of T2DM in this population.