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To estimate the association of free triiodothyronine (FT3) and total triiodothyronine (TT3) in early pregnancy and subsequent gestational diabetes mellitus (GDM) risk and define appropriate TT3 thresholds for GDM screening.This investigation is a hospital-based cohort study of pregnant women submitted to a universal thyroid function test before 24 weeks of gestation. GDM was diagnosed according to a 75-g oral glucose tolerance test. The association of maternal high FT3 and TT3 levels in early pregnancy with the risk of GDM was estimated using logistic regression. The potential nonlinear association was probed by the restricted cubic spline curve method.A total of 27 184 pregnant women and 3073 GDM cases were included in the analysis. FT3 and TT3 were associated with an increased subsequent risk of GDM in a nonlinear fashion. The adjusted odds ratios were 1.59 (95% confidence interval, 1.50-1.68) and 2.80 (95% confidence interval, 2.46-3.18) for FT3 and TT3 continuous levels, respectively. Associations were strong in euthyroid women, showed heterogeneity in women with mild thyroid dysfunction, and lacked in patients with overt hypothyroidism and hyperthyroidism. The TT3 thresholds of 1.5 and 2.0 ng/mL between 7 and 12 weeks of gestation and 1.6 and 2.1 ng/mL for 13 to 23 weeks of gestation effectively distinguished the subsequent risk of GDM.The increased FT3 and TT3 levels in early pregnancy were associated with a subsequent higher risk of GDM. These findings provide measures for early detection and potential prevention of GDM.

Aims: This systematic review and meta-analysis investigated maternal apelin levels in pregnant women with and without GDM. Secondary outcomes were glucose- and lipid-related results.Methods: Databases including PubMed, Embase, Cochrane Library, LILACS, CNKI, and Wang Fang were searched. The methodological quality of included studies was evaluated with the Newcastle-Ottawa Scale. Mean differences (MDs) or standardized MDs (SMDs) with their 95% confidence intervals (CIs) were evaluated. Random effect model analyses were carried out and heterogeneity with the I2 and Tau2 statistics.Results: Fourteen observational studies (sample size: 1033 women with GDM and 1053 for control women) with a low or moderate risk of bias were included in the analysis. During the second half of pregnancy, maternal apelin estimate was significantly higher in women with GDM (SMD = 0.64; 95% CI: 0.03 to 1.25), as well as insulin (SMD = 1.41% CI: 0.84 to 1.99), glucose (SMD = 1.56; 95% CI 1.20 to 1.91), glycated hemoglobin (SMD = 1.11, 95% CI: 0.69 to 1.54), HOMA-IR (MD = 2.25; 95%CI: 1.51 to 2.98), BMI (MD = 0.80 kg/m2, 95%CI: 0.52 to 1.08), total cholesterol (SMD = 0.42, 0.12 to 0.73), LDL-cholesterol (SMD = 0.63, 95%CI: 0.23 to 1.02), and triglycerides (SMD = 0.40, 95%CI: 0.19 to 0.61) as compared to control women. There was heterogeneity between studies as evidence by high I2 values. Meta-regression analysis indicated statistically significant regression coefficients for age of women, glucose and total cholesterol.Conclusions: GDM was associated with increased circulating apelin, insulin, glucose, glycated hemoglobin, total cholesterol, LDL-cholesterol levels, and HOMA-IR index.

A successful pregnancy requires sufficient decidualization of endometrial stromal cells (ESCs). CD82, a metastasis suppressor, is a critical regulator for trophoblast invasion but the effect in decidualization was largely unknown. Here we reported that there was a high level of CD82 in DSC by the immunohistochemistry staining and flow cytometer analysis. Stimulation with prostaglandin E2 (PGE2) elevated the expression of CD82 in ESCs. In contrast, celecoxib, a selective COX-2 inhibitor, significantly downregulated the expression of CD82 in decidual stromal cells (DSCs). Bioinformatics analysis and further research showed that recombinant human interleukin (IL)-1β protein (rhIL-1β) upregulated CD82 in ESCs. Of note, blocking IL-1β signaling with anti-human IL-1β neutralizing antibody could reverse the stimulatory effect of PGE2 on CD82 in ESCs. Silencing CD82 resulted in the decease of the decidualization markers PRL and IGFBP1 mRNA levels in DSCs. More importantly, we observed rhIL-1β also upregulated the expression of COX-2, and the upregulation of PRL and IGFBP1 induced by rhIL-1β could be abolished by celecoxib in ESCs or CD82 deficiency in DSCs. This study suggests that CD82 should be a novel promotor for decidualization under a positive regulation of the COX-2/PGE2/IL-1β positive feedback loop.

Acute lung injury (ALI) is a common acute respiratory disease with high morbidity and mortality rate in pregnant women. Receptor activator of NF-κB ligand (TNFSF11, also known as RANKL) exerts either pro-inflammatory or anti-inflammatory effects on the immune response. LPS administration reduced the survival time (n = 10, p 0.01), increased wet/dry ratio (n = 10, p 0.001) and lung injury score (n = 10, p 0.001), the elevated proportions of plasmacytoid dendritic cells (pDCs) (n = 10, p 0.0001), tissue-resident DCs (resDCs) (n = 10, p 0.0001), macrophages (n = 10, p 0.0001), and neutrophils (n = 10, p 0.0001), and the expressions of costimulatory molecules and inflammation cytokines (n = 10, p 0.05) in lungs of pregnant mice, compared with non-pregnant mice. In vitro, progesterone up-regulated the expression of RANKL (n 6, p 0.05) on pulmonary fibroblasts. The results of cytokine arrays showed that the cytokines associated with inflammatory response and leukocyte differentiation were decreased in pulmonary fibroblasts after treatment with anti-RANKL neutralizing antibody, compared with control pulmonary fibroblasts. More notably, we found that Tnfsf11

Rationale: Estrogen-dependent cancers (e.g., breast, endometrial, and ovarian cancers) are among the leading causes of morbidity and mortality in women worldwide. Recently, exosomes released by tumor-infiltrating CD8+ T cells have been under the spotlight in the field of cancer immunotherapy. Our study aims at elucidating the underlying mechanisms of the crosstalk between estrogen signaling and CD8+ T cells, and possible intervention values in uterine corpus endometrial cancer (UCEC). Methods: Micro RNA-seq was conducted to screen differentially expressed micro RNA in UCEC. Bioinformatic analysis was processed to predict the target of miR-765. RNA silencing or overexpressing and pharmacologic inhibitors were used to assess the functions of ERβ/miR-765/PLP2/Notch axis in UCEC cell proliferation and invasion in vivo and in vitro. In vivo imaging was performed to evaluate the metastasis of tumor in mice. Combined fluorescent in situ hybridization for miR-765 and immunofluorescent labeling for CD8 was carried out to prove the co-localization between miR-765 and CD8+ T cells. Exosomes derived from CD45RO-CD8+ T cells were isolated to detect the regulatory effects on UCEC. Results: miR-765 is characterized as the most downregulated miRNA in UCEC, and there is a negative correlation between miR-765 and Proteolipid protein 2 (PLP2) in UCEC lesion. Estrogen significantly down-regulates miR-765 level, and facilitates the development of UCEC by estrogen receptor (ER) β. Mechanistically, this process is mediated through the miRNAs (e.g., miR-3584-5p, miR-7-5p, miR-150-5p, and miR-124-3p) cluster-controlled regulation of the PLP2, which further regulates Ki-67 and multiple epithelial-mesenchymal transition (EMT)-related molecules (e.g, E-cadherin and Vimentin) in a Notch signaling pathway-dependent manner. Interestingly, the selective ER degrader Fulvestrant alleviates estrogen-mediated miR-765/PLP2 expression regulation and UCEC development in ERβ-dependent and -independent manners. Additionally, CD45RO-CD8+ T cell-derived exosomes release more miR-765 than that from CD45RO+CD8+ T cells. In therapeutic studies, these exosomes limit estrogen-driven disease development via regulation of the miR-765/PLP2 axis. Conclusions: This observation reveals novel molecular mechanisms underlying estrogen signaling and CD8+ T cell-released exosomes in UCEC development, and provides a potential therapeutic strategy for UCEC patients with aberrant ERβ/miR-765/PLP2/Notch signaling axis.

Intrauterine adhesion (IUA) is a fibrotic disease, with complex and multifactorial process, causing menstrual disorders, pregnancy loss or infertility. LIGHT (also named TNFSF14), mainly expressed by immune cells, has been reported to be associated with tissue fibrosis. However, the features of immunocyte subsets, the expression and roles of LIGHT and its receptor HVEM (herpes virus entry mediator) and LTβR (lymphotoxin beta receptor) in IUA remain largely unknown. Compared with the control group, we observed increased ratios of CD45

Background A lack of information on specific and interventional factors for stillbirth has made designing preventive strategies difficult, and the stillbirth rate has declined more slowly than the neonatal death rate. We compared the prevalence of stillbirth among the offspring of women with or without abnormal placental perfusion (APP). Methods We conducted a hospital-based retrospective cohort study involving women with a singleton pregnancy between 2012 and 2016 (N = 41,632). Multivariate analysis was performed to compare the prevalence of stillbirth in infants exposed to APP (defined as any abnormality in right or left uterine artery pulsatility index or resistance index [UtA-PI, −RI] [e.g., > 95th percentile] or presence of early diastolic notching) with that in those not exposed to APP. Results Stillbirths were more common among women with APP than among those with normal placental perfusion (stillbirth rate, 4.3 ‰ vs 0.9 ‰; odds ratio (OR), 4.2; 95% confidence interval (CI), 2.2 to 8.0). The association strengths were consistent across groups of infants exposed to APP that separately defined by abnormality in right or left UtA-PI or -RI (OR ranged from 3.2 to 5.3; all P ≤ 0.008). The associations were slightly stronger for the unexplained stillbirths. Most of the unexplained stillbirth risk was attributed to APP (59.0%), while a foetal sex disparity existed (94.5% for males and 58.0% for females). Women with normal placental perfusion and a male foetus had higher credibility (e.g., higher specificities) in excluding stillbirths than those with APP and a female foetus at any given false negative rate from 1 to 10% (93.4% ~ 94.1% vs. 12.3% ~ 14.0%). Conclusions APP is associated with and accounts for most of the unexplained stillbirth risk. Different mechanisms exist between the sexes. The performance of screening for stillbirth may be improved by stratification according to sex and placental perfusion.

Appropriate decidualization is of great importance for embryo implantation, placental development and successful pregnancy. Although it has been well-acknowledged that decidualization relies on activation of progesterone-mediated signaling pathway, the exact mechanisms have not been elucidated. Here, we demonstrated that both IL-27 and IL27RA were highly expressed in decidua than those in endometrium during secretory phase. Estrogen plus progesterone significantly upregulated the expression of IL-27 and IL-27RA in endometrium stromal cells (ESCs). In addition, inhibiting IL-27 signaling with IL-27 neutralization antibody (anti-IL-27) suppressed the expression of decidualization-related molecules, receptors of estrogen (gene coded by ESR) and progesterone (PGR) induced by cAMP or estrogen plus progesterone. Similar results were obtained from Il27ra

The survival and development of a semi-allogeneic fetus during pregnancy require the involvement of decidual stromal cells (DSCs), a series of cytokines and immune cells. Insulin-like growth factor 1 (IGF1) is a low molecular weight peptide hormone with similar metabolic activity and structural characteristics of proinsulin, which exerts its biological effects by binding with its receptor. Emerging evidence has shown that IGF1 is expressed at the maternal–fetal interface, but its special role in establishment and maintenance of pregnancy is largely unknown. Here, we found that the expression of IGF1 in the decidua was significantly higher than that in the endometrium. Additionally, decidua from women with normal pregnancy had high levels of IGF1 compared with that from women with unexplained recurrent spontaneous miscarriage. Estrogen and progesterone led to the increase of IGF1 in DSCs through upregulating the expression of WISP2. Recombinant IGF1 or DSCs-derived IGF1 increased the survival, reduced the apoptosis of DSCs, and downregulated the cytotoxicity of decidual NK cells (dNK) through interaction with IGF1R. These data suggest that estrogen and progesterone stimulate the growth of DSCs and impair the cytotoxicity of dNK possibly by the WISP2/IGF1 signaling pathway.

To estimate the association of maternal thyroid dysfunction with the risk of gestational hypertension and diabetes. Whether the association was affected by gestational age at diagnosis and thyroid autoimmunity was further explored.A cohort study of 41 647 participants was conducted. Thyroid function (ie, thyroid-stimulating hormone [TSH] and free thyroxine [FT4]) was measured by electrochemiluminescence immunoassay. Thyroid antibody positivity (eg, thyroperoxidase, thyroglobulin, and TSH receptor antibody) was indicated if the values of these antibodies exceeded the upper targets of the reference range. The relationship between maternal thyroid dysfunction and the risk of pre-eclampsia (PE) and gestational diabetes mellitus (GDM) was assessed by multivariate logistic regression.Isolated hypothyroxinemia (defined as 5th ≤ TSH ≤ 95th percentile, FT45th percentile) was associated with the risk of PE (odds ratio [OR], 1.32; 95% CI, 1.10-1.58). Overt hypothyroidism (TSH95th percentile; FT45th percentile) was related to the risk of severe PE (OR, 2.59; 95% CI, 1.05-6.37). Being positive for TSH receptor antibody was associated with a decreased risk of GDM (OR, 0.49; 95% CI, 0.35-0.70). A marginally significant association between overt hypothyroidism detected at the first trimester and the risk of GDM was found (OR, 1.60; 95% CI, 1.00-2.83). The association of thyroid dysfunction with the risk of PE and GDM was stronger among pregnant women who were negative for autoantibodies.Some types of thyroid dysfunction during pregnancy were associated with the risk of PE and GDM. The associations varied by gestational age at diagnosis and by thyroid autoantibody status.

Background: Early identification of patients who are at high risk of poor clinical outcomes is of great important in saving lives for patients with the novel corona virus disease 2019 (COVID-19) in context of limited medical resources. Objective: To evaluate value of the neutrophil to lymphocyte ratio (NLR), calculated at hospital admission and in isolation, for prediction of the subsequent presence of disease aggravation and serious clinical outcomes (e.g., shock, death).Methods: We designed a prospective cohort study of 352 hospitalized patients with COVID-19 between January 9 and February 26, 2020 in Yichang city, Hubei province. Patients with a NLR equal to and higher than the cutoff value derived from the receiver operating characteristic curve method were classified as the exposure group. The primary outcome was disease deterioration, defined as promotion of clinical classifications of the disease during hospitalization (e.g., moderate to severe/critical; severe to critical,). The secondary outcomes were shock and death occurred during the treatment.Results: During the follow up, 51 (14.5%) patients’ condition deteriorated, 15 patients (4.3%) complicated septic shock, and 15 patients (4.3%) died. NLR was higher in patients with deterioration than those without (median: 5.33 vs. 2.14, P 0.80). The sensitivity of ≥ 2.6937 for the NLR in predicting subsequent disease deterioration, shock and death were 82.0% (95% confidence interval, 69.0 to 91.0), 93.3% (68.0 to 100), and 92.9% (66.0 to 100); and the corresponding negative predictive values were 95.7% (93.0 to 99.2), 99.5% (98.6 to 100) and 99.5% (98.6 to 100), respectively. Conclusions: The NLR measured at admission and in isolation can be used to effectively predict subsequent presence of disease deterioration and serious clinical outcomes for patients with COVID-19.

Problem Endometrial hyperplasia (EH) is characterized by an endometrial gland-to-stroma ratio >1 and is one of the most common gynecological diseases in the world. The role of immunocyte subsets in the development of EH remains unknown. Methods Patients who underwent dilatation and curettage due to abnormal uterine bleeding were recruited in the present study. Alterations in the numbers of different types of immune cell subsets in the endometrium of patients were analyzed by flow cytometry. Results The present study included 48 patients who were divided into three groups, based on the pathological results: (a) proliferative period (PP, n = 12); (b) simple EH (SEH, n = 30); and (c) complex EH (CEH, n = 6). The results showed that immune cell subpopulations were significantly different between these three groups. Compared with the PP group, the proportion of CD45+ cells and neutrophils and the subtypes of T cells and macrophages were significantly increased in the SEH patients. Compared with the PP and SEH groups, subsets of immunocytes in the CEH group were significantly decreased, including the population of CD45+ cells and the subtypes of T cells and natural killer cells; in contrast, the proportion of macrophages was significantly increased. There were no significant differences between the other cell subsets in each group. Conclusion The changes in immune cell subsets may be closely associated with the progression of EH. Although the specific role of different immune cell subsets in the development of the diseases requires further study, the changes in the proportions of immune cell subsets should not be ignored.

Background The effect and extent of abnormal placental perfusion (APP) on the risk of male hypospadias are poorly understood. We compared the prevalence of male hypospadias in the offspring of women with APP and quantify the extent of the APP effect on the anomaly. Methods A hospital-based retrospective analysis of births from 2012 to 2016 was conducted in 2018. Women of singleton pregnancy and male infants born to them were included (N = 21,447). A multivariate analysis was performed to compare the prevalence of male hypospadias in infants exposed to APP with those that were not exposed to APP. Results Compared with the infants of women without APP, infants of women with APP showed an increased risk of male hypospadias (odds ratio, 2.40; 95% confidence interval, 1.09–5.29). The male hypospadias cumulative risk increased with the severity of APP. Infants exposed to severe APP had a significantly higher risk of male hypospadias than those without APP exposure (9.2 versus 1.7 per 1000 infants, P Conclusions Male hypospadias risk was associated with APP and increased with APP severity, as measured in the second trimester. APP had an important role in the development of the anomaly.

Background. Gestational diabetes mellitus (GDM) contributes to adverse pregnancy and birth outcomes. In recent decades, extensive research has been devoted to the early prediction of GDM by various methods. Machine learning methods are flexible prediction algorithms with potential advantages over conventional regression. Objective. The purpose of this study was to use machine learning methods to predict GDM and compare their performance with that of logistic regressions. Methods. We performed a retrospective, observational study including women who attended their routine first hospital visits during early pregnancy and had Down’s syndrome screening at 16-20 gestational weeks in a tertiary maternity hospital in China from 2013.1.1 to 2017.12.31. A total of 22,242 singleton pregnancies were included, and 3182 (14.31%) women developed GDM. Candidate predictors included maternal demographic characteristics and medical history (maternal factors) and laboratory values at early pregnancy. The models were derived from the first 70% of the data and then validated with the next 30%. Variables were trained in different machine learning models and traditional logistic regression models. Eight common machine learning methods (GDBT, AdaBoost, LGB, Logistic, Vote, XGB, Decision Tree, and Random Forest) and two common regressions (stepwise logistic regression and logistic regression with RCS) were implemented to predict the occurrence of GDM. Models were compared on discrimination and calibration metrics. Results. In the validation dataset, the machine learning and logistic regression models performed moderately (AUC 0.59-0.74). Overall, the GBDT model performed best (AUC 0.74, 95% CI 0.71-0.76) among the machine learning methods, with negligible differences between them. Fasting blood glucose, HbA1c, triglycerides, and BMI strongly contributed to GDM. A cutoff point for the predictive value at 0.3 in the GBDT model had a negative predictive value of 74.1% (95% CI 69.5%-78.2%) and a sensitivity of 90% (95% CI 88.0%-91.7%), and the cutoff point at 0.7 had a positive predictive value of 93.2% (95% CI 88.2%-96.1%) and a specificity of 99% (95% CI 98.2%-99.4%). Conclusion. In this study, we found that several machine learning methods did not outperform logistic regression in predicting GDM. We developed a model with cutoff points for risk stratification of GDM.

Background/objectives Gestational weight gain (GWG) recommendations for pregnant women with gestational diabetes mellitus (GDM) in China are lacking. The present study aims to examine whether specific GWG targets for women with GDM can improve pregnancy outcomes in comparison with GWG according to the Institute of Medicine (IOM) targets. Subjects/methods Pregnant women diagnosed with GDM were selected from a retrospective cohort study of 8299 singleton pregnant women aged 18–45 years in 2012 (n = 1820). GWG ranges were calculated using a receiver operating characteristic (ROC) curve analysis (ROC targets) and the interquartile range (IR) method (the range from the 25th to 75th percentiles of the GWG among GDM women without adverse pregnancy outcomes, IR targets). Results The incidences of small for gestational age (SGA) births and pregnancy hypertension among women with GDM who gained weight within the ROC targets were lower than the incidences in women who gained weight within the IOM targets (SGA, 7.5% vs. 8.6%; pregnancy hypertension, 12.6% vs. 14.1%; both P

Background Although recent studies have indicated the potential adverse effects of maternal bisphenol A (BPA) exposure on pregnancy such as increasing the risk of pre-eclampsia, epidemiological evidence is limited. We aimed to evaluate the relationship between maternal BPA exposure and the risk of pre-eclampsia. Methods We conducted a nested case–control study among 173 women (74 cases of pre-eclampsia and 99 controls). BPA concentrations were measured using liquid chromatography-mass spectrometry in the maternal serum samples collected during 16–20 gestational weeks. Multivariate logistic models were used to examine the relationship between maternal serum BPA concentrations and the risk of pre-eclampsia. Results BPA was detectable (>0.1 µg/l) in 78.6% of the maternal serum samples at three levels: low (4.44 µg/l). BPA concentrations were significantly higher in the serum samples collected from the pre-eclampsia cases than those from controls (median: 3.40 vs. 1.50 µg/l, P < 0.01). With adjustment for maternal age, primiparous and BMI, the odds of developing pre-eclampsia were significantly elevated in subjects with high serum BPA levels compared with those with low levels (adjusted OR = 16.46, 95%CI = 5.42–49.85) regardless of subcategories of pre-eclampsia including severity and onset time. Among the pre-eclampsia subjects, the maternal serum concentration of BPA was not different between the early- and late-onset subjects (median: 3.09 vs. 3.50 µg/l, P = 0.57), but surprisingly higher in mild pre-eclampsia subjects compared with severe pre-eclampsia subjects (median: 5.20 vs. 1.80 µg/l, P < 0.01). Conclusions These results demonstrated that maternal exposure to high level of BPA could be associated with an increased risk of pre-eclampsia.

The precise pathophysiological mechanisms of preeclampsia (PE) and preventative strategies remain unknown. Laboratory markers which can help in identifying PE patients from pregnant women and assessing the severity of PE during pregnancy are worthy to be explored. In this study, a retrospective case-control study was designed to assess whether the serum levels of albumin (ALB), total protein (TP), prealbumin (PA), alkaline phosphatase (ALP), lactic dehydrogenase (LDH), D-dimer, fibrinogen (Fbg), platelet (PLT) count, mean platelet volume (MPV), and platelet distribution width (PDW) can help in assessing PE and evaluate its severity. 256 pregnant women were enrolled and classified into 3 groups: mild preeclampsia (mPE,n=85), severe preeclampsia (sPE,n=78), and healthy normotensive controls (control,n=93). Our result showed that the serum levels of ALP, LDH, and D-dimer were significantly higher in mild or severe PE patients compared with the healthy controls (66 (52.5-76.5) vs. 168 (141.5-201.25) vs. 182.5 (120-191.5), 152 (139.75-166.25) vs. 183.5 (163.25-307) vs. 282 (215.25-306), 1.05 (0.65-1.57) vs. 3.05 (2.25-4.08) vs. 5.65 (2.29-7.71)), while ALB, TP, and PA are lower (38 (37-42) vs. 31.5 (25.5-34.5) vs. 28.5 (24-33), 65 (63-68.25) vs. 56.5 (52-61) vs. 51.5 (49-58),219.14±68.25vs.167.88±52.21vs.143.22±50.46). On the other hand, compared with the mPE group, the sPE group showed significantly lower PLT count but higher level of LDH, D-dimer, and Fbg. No significant differences in MPV or PDW were found between any of the two groups. In conclusion, the above markers except for the MPV and PDW may be correlated with PE severity in this patient cohort, indicating possible values of these potential biomarkers in auxiliary diagnosis and severity assessment of PE.

An Illumina-based next-generation sequencing was employed to characterise the sediment microbiome adjacent to coastal industrial and tourist cities, Taizhou and Xiamen, in China, and their associations with chemical pollution were explored. The results indicated that chemical pollution of sediments from Taizhou was higher than that from Xiamen. The number of sediment bacterial genera was negatively (Taizhou) or positively (Xiamen) correlated with offshore distance, owing to shifts in the primary and secondary status of organic matter and chemical pollutants for the promotion or inhibition of the sediment microbiome. The total number of the operational taxonomic units (OTUs) in sediments from Taizhou was larger than from Xiamen, while the number of core OTUs was smaller indicating that Taizhou had more impact on core microbes in sediments than Xiamen. This study suggests that chemical pollutants and organic matter result in different co-regulation of the off-shore sediment microbiome of coastal industrial and tourist cities.

Background: Little is known about the association between the initiation of hepatitis B vaccine (HB vaccine) at birth and completion of the HB vaccine and the national immunization program vaccine (NIPV) series in Fujian, China. Methods: A provincial survey, including children in the community and newborns in hospital, was conducted to evaluate coverage with a timely first dose of HB vaccine and the completion of three doses of HB vaccine and the NIPV series in 2013. A proportion of the samples was rechecked to investigate the relationship between the administration of a timely first dose of HB vaccine and completion of the HB vaccine series and the NIPV series (three doses of HB vaccine, one dose of Bacillus Calmette–Guérin vaccine, three doses of oral poliomyelitis vaccine, three doses of diphtheria–tetanus–pertussis vaccine, one dose of measles-containing vaccine, one dose of Japanese encephalitis attenuated live vaccine, and two doses of group A meningococcal polysaccharide vaccine). Results: A total of 6589 subjects (including 3785 community children and 2804 hospital newborns) were included in this study; 97.34% of them received a timely first dose of HB vaccine (≤24 h after birth) and 99.10% and 88.27% completed the HB vaccine series and the NIPV series, respectively. Among the 1680 children from eight counties who were rechecked, those with a timely first dose of HB vaccine had higher completion rates of the HB vaccine series and the NIPV series than those with a delayed first dose of HB vaccine (99.69% and 88.90% vs. 83.05% and 79.66%, respectively; both p

Little is known about the clinical value of the Hadlock and INTERGROWTH-21st EFW standards for predicting adverse perinatal outcomes (APOs) in the third trimester. The purpose of this study was to study the association between low estimated fetal weight percentile (EFWc) in the third trimester and the risk of APOs and compare predictions of APOs between Hadlock and INTERGROWTH-21st EFW standards. A prospective cohort of 690 singleton pregnancies with ultrasonography performed in the third trimester between March 2015 and March 2016 in China was conducted. EFW and the corresponding EFWc were measured using the Hadlock and INTERGROWTH-21st standards, respectively. Cox proportional hazard models were used to assess the relationship between low EFWc (i.e., 1st standard.

Little is known about the clinical value of the Hadlock and INTERGROWTH-21st EFW standards for predicting adverse perinatal outcomes (APOs) in the third trimester. The purpose of this study was to study the association between low estimated fetal weight percentile (EFWc) in the third trimester and the risk of APOs and compare predictions of APOs between Hadlock and INTERGROWTH-21st EFW standards. A prospective cohort of 690 singleton pregnancies with ultrasonography performed in the third trimester between March 2015 and March 2016 in China was conducted. EFW and the corresponding EFWc were measured using the Hadlock and INTERGROWTH-21st standards, respectively. Cox proportional hazard models were used to assess the relationship between low EFWc (i.e.

Assisted reproductive technology (ART) has been widely used among women with infertility. However, the association of ART with birth defects and stillbirth remains controversial and has rarely been reported in China. A retrospective cohort study of 112,043 pregnant women and 114,522 newborns from 2006 to 2016 was performed. Compared to spontaneously conceived infants, ART-conceived infants had a higher likelihood of any birth defect, with an adjusted odds ratio (OR) of 2.10 (95% confidence interval, 1.63–2.69). ART-conceived infants also had a significantly increased risk for subcategories of cardiovascular, musculoskeletal, urogenital, gastrointestinal, and respiratory defects. Most (62.25%) of the effect of ART on birth defects was a direct effect, whereas 37.75% of the effect of ART on birth defects was due to multiple pregnancies (i.e., an indirect effect). Compared with naturally conceived singletons, the combined effect of ART and twins on the risk of birth defects was lower than that of the sum of the individual effects of ART and twins on the risk of birth defects, with an adjusted OR of 0.54 (0.32–0.92). These findings clearly show that ART is associated with an increased risk of birth defects in China and may provide guidance to couples and obstetricians in selecting numbers of pregnancies and in identifying organs at a high risk of birth defects.

Background The dynamic methylation of human papillomavirus (HPV) 16 DNA is thought to be associated with the progression of cervical lesions. Previous studies that did not consider the physical status of HPV 16 may have incorrectly mapped HPV 16 methylomes. In order to identify reliable biomarkers for squamous cervical cancer (SCC), we comprehensively evaluated the methylation of HPV 16 depending on the integration incidence of each sample. Methods Based on the integration status of 115 HPV 16-infected patients (50 SCC, 30 high-grade squamous intraepithelial lesion [HSIL], and 35 low-grade squamous intraepithelial lesion [LSIL]) and HPV 16-infected Caski cell lines by PCR detection of integrated papillomavirus sequences, we designed a series of primers that would not be influenced by breakpoints for a high-resolution melting (HRM) PCR method to detect the genome methylation. Results A few regions with recurrent interruptions were identified in E1, E2/E4, L1, and L2 despite scattering of breakpoints throughout all eight genes of HPV 16. Frequent integration sites often occurred concomitantly with methylated CpG sites. The HRM PCR method showed 100% agreement with pyrosequencing when 3% was set as the cutoff value. A panel of CpG sites such as nt5606, nt5609, nt5615, and nt5378 can be combined in reweighing calculations to distinguish SCC from HSIL and LSIL patients which have high sensitivity and specificity (88% and 92.31%, respectively). Conclusions Our research shows that combination of CpG sites nt5606, nt5609, nt5615, and nt5378 can be used as potential diagnosis biomarkers for SCC, and the HRM PCR method is suitable for clinical methylation analysis. Electronic supplementary material The online version of this article (10.1186/s13148-018-0445-8) contains supplementary material, which is available to authorized users.

To study the impact of pre-pregnancy body mass index (BMI) and gestational weight gain (GWG) on neonatal birth weight in women with gestational diabetes mellitus (GDM).This was a prospective cohort study of 622 singleton pregnant women diagnosed with GDM recruited from 1 April 2014 and 30 December 2014 in a university teaching hospital in China. Binary logistic regression was used to analyze the factors influencing macrosomia.Pre-pregnancy BMI categories were: underweight (10.6%), normal (65.6%), overweight (18.0%) and obese (5.8%). Mean GWG was 14.4 ± 4.8 kg and birth weight 3353.1 ± 467.3 g. The incidence of macrosomia was 7.8% and low birth weight 2.3%. Logistic regression analysis showed that pre-pregnancy BMI was not associated with macrosomia. However, excessive GWG was a risk factor for macrosomia (odds ratio (OR) 2.884, 95% confidence interval (CI) 1.385-6.004, p 0.01). In addition, high maternal fasting plasma glucose (FPG) (OR 1.933, 95% CI 1.126-3.316) and serum triglyceride (TG) (OR 1.235, 95% CI 1.053-1.449) in the third trimester of pregnancy were risk factors for macrosomia.Patients with GDM can be advised that excessive GWG and uncontrolled hyperglycaemia influence their chances for macrosomia.

The extent to which the free-vaccine policy impacts the initiation and completion of a hepatitis B vaccine series is poorly understood. The aim of this study was to evaluate the impact of the free-vaccine policy on hepatitis B vaccination. A provincial survey was conducted in 2006 in Fujian Province, south-east of China, where the free-vaccine policy for hepatitis B was announced in 2002 and implemented in 2003. A total of 1628 children were investigated, and 1443 (88.6%) were included in this analysis. Among the children studied, 55.2% were vaccinated within 24 h of birth, and 76.1% completed the hepatitis B vaccine series on time. The rate of hepatitis B surface antibody positivity increased from 29.9% among children born in 1992 to 90.5% among children born in 2005, while the corresponding HBV infection rate decreased from 30.4% to 1.72%. Logistic regression indicated that, compared to children born between 1996 and 2001, the odds ratios (ORs) for timely initiation were 2.57 (95% confidence interval [CI], 1.71-3.84), 5.24 (95% CI, 3.26-8.43) and 9.06 (95% CI, 4.48-18.34) among children born in 2003, 2004 and 2005, respectively; the corresponding ORs for completing the vaccine series were 4.23 (95% CI, 1.97-9.10), 3.76 (95% CI, 1.81-7.82) and 4.94 (95% CI, 1.74-14.00) among children born in 2003, 2004 and 2005, respectively. Children with delayed vaccine initiation (>24 h after birth) were less likely to complete the vaccine series than those who received a timely first dose (OR = 0.02, 95% CI, 0.005-0.09). The impact of the free-vaccine policy on vaccine initiation and vaccine series completion did not differ by children's residence area (rural vs urban). As hypothesized, the odds of completing the vaccine series increased after the free-vaccine policy was announced in 2002 among children with delayed initiation (>24 h after birth) but not among those with timely initiation (≤ 24 h after birth). In conclusion, the free-vaccine policy significantly improved the timely initiation and completion of the vaccine series. The impact of this policy on completion of the vaccine series was larger among children with delayed vaccine initiation.