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Background/Objective Previous studies have consistently demonstrated that maternal weight status both before and during pregnancy is associated with infant birthweight. However, a fundamental limitation across this literature remains that previous studies have not evaluated the concomitant impact of paternal weight at conception, owing to the paucity of studies in which fathers were assessed prior to pregnancy. Thus, we established a cohort of preconception couples to prospectively evaluate the associations of maternal and paternal weight prior to pregnancy with infant birthweight at delivery. Methods In this prospective observational cohort study, 1292 newly-married women and their partners in Liuyang, China, were assessed at median of 23.3 weeks before a singleton pregnancy, thereby enabling concomitant assessment of preconception maternal and paternal body mass index (BMI) in relation to infant birthweight. Results Mean birthweight was 3294 ± 450 g with 147 neonates (11.4%) born large-for-gestational-age (LGA) and 94 (7.3%) small-for-gestational-age (SGA). After adjustment for maternal and paternal factors prior to conception (age, education, smoking, BMI, household income), length of gestation, total gestational weight gain, gestational diabetes, preeclampsia, and infant sex, it was noted that infant birthweight increased by 42.2 g (95% CI 29.5–54.8; p p = 0.04) per unit increase in paternal pregravid BMI. Maternal pregravid BMI explained 6.2% of the variance in birthweight whereas paternal BMI explained only 0.7%. Independent predictors of LGA delivery were maternal pregravid BMI (aOR = 1.91, 95% CI 1.50–2.44), maternal age (aOR = 1.48, 95% CI 1.09–2.00), and gestational weight gain (aOR = 1.80, 95% CI 1.40–2.30). Paternal pregravid BMI was not independently associated with LGA or SGA. Conclusion Paternal BMI prior to conception is associated with infant birthweight but only modestly so, in contrast to the dominant impact of maternal weight.

Background: Women with a history of certain adverse outcomes in pregnancy (preterm birth, delivery of a small-for-gestational age [SGA] infant, preeclampsia, and gestational diabetes mellitus [GDM]) have an elevated lifetime prevalence of metabolic syndrome (MetS) and cardiovascular disease, compared with their peers. However, it is not known if MetS precedes the index pregnancy in young, nulliparous women who experience these antepartum outcomes. Thus, we sought to evaluate the relationship between pregravid cardiovascular risk factor profile and these pregnancy outcomes in low-risk women. Methods: In this prospective preconception cohort study, 1183 newly married women underwent systematic assessment of cardiovascular risk factors (anthropometry, blood pressure, lipids, glucose) at median 24.7 weeks before pregnancy, whereupon they were followed for the outcomes of preterm birth, SGA delivery, preeclampsia, and GDM. Results: Women who had pregravid MetS (harmonized definition) (n = 49) were more likely to have a Caesarean delivery than their peers (61.4% vs. 38.6%, p = 0.003). However, they did not have a higher incidence of preterm delivery, SGA, preeclampsia, or GDM. Similarly, women who had at least one of these adverse pregnancy outcomes (n = 141) did not have a higher prevalence of MetS or any of its component disorders before pregnancy. Indeed, before pregnancy, there were no significant differences between these women and their peers in waist circumference, body mass index, blood pressure, fasting glucose, triglycerides, low-density-lipoprotein, or high-density-lipoprotein cholesterol. Conclusions: The adverse cardiovascular risk factor profile that is seen in women with a history of preterm birth, SGA, preeclampsia, or GDM does not necessarily manifest before their pregnancy.

BACKGROUND mTOR gene is a key component of the PI3K/Akt/mTOR signaling pathway, and its dysregulation is associated with various diseases. Several studies have demonstrated that tea drinking is a protective factor against tuberculosis (TB). This study was designed to explore five single nucleotide polymorphisms (SNPs) of mTOR in the Han population of China to determine how their interactions with tea drinking affect susceptibility to TB. AIM To investigate if the polymorphisms of mTOR gene and the gene-tea interaction are associated with susceptibility to TB. METHODS In this case-control study, 503 patients with TB and 494 healthy controls were enrolled by a stratified sampling method. The cases were newly registered TB patients from the county-level centers for disease control and prevention, and the healthy controls were permanent residents from Xin’ansi Community, Changsha city. Demographic data and environmental exposure information including tea drinking were obtained from the study participants. We genotyped five potentially functional SNP sites (rs2295080, rs2024627, rs1057079, rs12137958, and rs7525957) of mTOR gene and assessed their associations with the risk of TB using logistic regression analysis, and marginal structural linear odds models were used to estimate the gene-environment interactions. RESULTS The frequencies of four SNPs (rs2295080, rs2024627, rs1057079, and rs7525957) were found to be associated with susceptibility to TB (P < 0.05). Genotypes GT (OR 1.334), GG (OR 2.224), and GT + GG (OR 1.403) at rs2295080; genotypes CT (OR 1.562) and CT + TT (OR 1.578) at rs2024627, genotypes CT (OR 1.597), CC (OR 2.858), and CT + CC (OR 1.682) at rs1057079; and genotypes CT (OR 1.559) and CT + CC (OR 1.568) at rs7525957 of mTOR gene were significantly more prevalent in TB patients than in healthy controls. The relative excess risk of interaction between the four SNPs (rs2295080, rs2024627, rs1057079, and rs7525957) of mTOR genes and tea drinking were found to be -1.5187 (95%CI: -1.9826, -1.0547, P < 0.05), -1.8270 (95%CI: -2.3587, -1.2952, P < 0.05), -2.3246 (95%CI: -2.9417, -1.7076, P < 0.05) and -0.4235 (95%CI: -0.7756, -0.0714, P < 0.05), respectively, which suggest negative interactions. CONCLUSION The polymorphisms of mTOR (rs2295080, rs2024627, rs1057079, and rs7525957) are associated with susceptibility to TB, and there is a negative interaction between each of the four SNPs and tea drinking.

ELABELA (ELA) is considered to be implicated in the pathophysiology of preeclampsia (PE), since ELA-deficient mice exhibited PE-like symptoms and infusion of exogenous ELA normalized the gestational hypertension (GH) and proteinuria. However, no evidence show that circulating ELA is deficient in early placental development among women who destined to develop GH/PE. This nested case-control study was conducted to investigate the association between serum ELA concentration in early pregnancy and the risk of later GH/PE. Participants were recruited and sampled in 10-14+6 weeks of gestation. Definite GH/PE cases were matched 1 : 3 to controls with respect to age and gestational age. Serum concentration of ELA was measured using enzyme immunoassay. Women with later GH ( N = 28 ) had a slightly lower median concentration of ELA (46.72 ng/mL versus 53.54 ng/mL), while those with later PE ( N = 16 ) had a slightly higher median concentration of ELA (74.8 ng/mL versus 66.30 ng/mL) compared to the controls. Yet, both the increments did not reach statistically significant difference (GH: P = 0.380 , PE: P = 0.799 ). ELA serum concentrations were unchanged in first trimester in women with GH/PE. Further studies are still needed to identify the dynamic changes in serum ELA concentrations during the whole pregnancy, especially in those with pregnancy-induced hypertensive disorders.

Genome-wide DNA methylation profiling have been used to find maternal CpG sites related to the occurrence of gestational diabetes mellitus (GDM). However, none of these differential sites found has been verified in a larger sample. Here, our aim was to evaluate whether first trimester changes in target CpG sites in the peripheral blood of pregnancy women predict subsequent development of GDM. This nested case–control study was based upon an early pregnancy follow-up cohort (ChiCTR1900020652). Target CpG sites were extracted from related published literature and bioinformatics analysis. The DNA methylation levels at 337 CpG sites of 80 GDM cases and 80 matched healthy controls during the early pregnancy (10–15 weeks) were assessed using MethylTarget sequencing. The best cut-off level for methylation of CpG site was determined using the generated ROC curve. The independent effect of CpG site methylation status on GDM was analyzed using conditional logistic regression. Methylation levels at 6 CpG sites were significantly higher in the GDM group than in controls, whereas those at another 6 CpG sites were significantly lower (FDR

Background As a country with one-fifth of the global population, China has experienced explosive growth in ischaemic stroke (IS) burden with significant ethnic and geographic disparities. The aim of this study was to examine the differences in potentially modifiable risk factors for ischaemic stroke among the Han population and two ethnic minorities (Tujia and Miao). Methods A case-control study was conducted with 324 cases of first-ever ischaemic stroke from the hospitals of the Xiangxi Tujia and Miao Autonomous Prefecture and 394 controls from communities covering the same area between May 1, 2018, and April 30, 2019. Structured questionnaires were administered, and physical examinations were performed in the same manner for cases and controls. Univariate and multivariate logistic regression analyses with adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were used to examine the association between risk factors and ischaemic stroke. An additive model was used to study the interaction between the modifiable risk factors and ethnicity with R software. Results Higher high-sensitivity C-reactive protein levels (OR 50.54, 95%CI 29.76–85.85), higher monthly family income (4.18, 2.40–7.28), increased frequency of hot pot consumption (2.90, 1.21–6.93), diabetes mellitus (2.62, 1.48–4.62), a higher apolipoprotein (Apo)B/ApoA1 ratio (2.60, 1.39–4.85), hypertension (2.52, 1.45–4.40) and moderate-intensity physical activity (0.50, 0.28–0.89) were associated with ischaemic stroke. There was an additive interaction between the ApoB/ApoA1 ratio and ethnicity in the Tujia and Miao populations with first-ever ischaemic stroke (the relative excess risk due to the interaction was 5.75, 95% CI 0.58 ~ 10.92; the attributable proportion due to the interaction was 0.65, 95% CI 0.38 ~ 0.91; the synergy index was 3.66, 95% CI 1.35 ~ 9.93). Conclusions This is the first case-control study examining modifiable risk factors for ischaemic stroke among the Han population and two ethnic minorities (Tujia and Miao) in China. Some differences were observed in the impact of risk factors among these ethnic groups. Our results may help interpret health-related data, including surveillance and research, when developing strategies for stroke prevention.

Background Adiponectin (ADIPOQ) is an important factor involved in the regulation of both carbohydrate and lipid metabolism. Polymorphisms in the ADIPOQ gene are known to influence an individual's predisposition to metabolic syndrome and type 2 diabetes. Moreover, women with gestational diabetes mellitus (GDM) are at an increased risk of developing type 2 diabetes. Several studies have been conducted previously to assess the association between ADIPOQ polymorphisms and GDM; however, the results of the association are inconclusive. Aim To quantitatively evaluate the association between ADIPOQ +45T/G, +276G/T, and -11377C/G polymorphisms and the risk of GDM. Methods A systematic search of EMBASE, PubMed, CNKI, Web of Science, and WANFANG DATA was conducted up to October 20, 2018. We calculated merged odds ratios (ORs) with 95% confidence intervals (CIs) using a fixed-effects or random-effects model depending on the between-study heterogeneity to evaluate the association between AIDPOQ +45T/G, +276G/T, and -11377C/G polymorphisms and the risk of GDM. Subgroup analysis was performed by ethnicity. Publication and sensitivity bias analyses were performed to test the robustness of the association. All statistical analyses were conducted using Stata12.0. Results Nine studies of +45T/G included 1024 GDM cases and 1059 controls, five studies of +276G/T included 590 GDM cases and 595 controls, and five studies of -11377C/G included 722 GDM cases and 791 controls. Pooled ORs indicated that +45T/G increased GDM risk in Asians (allelic model: OR = 1.47, 95%CI: 1.27-1.70, P = 0.000; dominant model: OR = 1.54, 95%CI: 1.27-1.85, P = 0.000; recessive model: OR=2.00, 95%CI: 1.43-2.85, P = 0.000), not in South Americans (allelic model: OR = 1.21, 95%CI: 0.68-2.41, P = 0.510; dominant model: OR = 1.13, 95%CI: 0.59-2.15, P = 0.710; recessive model: OR = 2.18, 95%CI: 0.43-11.07, P = 0.350). There were no significant associations between +276G/T (allelic model: OR = 0.88, 95%CI: 0.74-1.05, P = 0.158; dominant model: OR = 0.91, 95%CI: 0.65-1.26, P = 0.561; recessive model: OR = 0.82, 95%CI: 0.64-1.05, P = 0.118) or -11377C/G (allelic model: OR = 0.96, 95%CI: 0.72-1.26, P = 0.750; dominant model: OR = 1.00, 95%CI: 0.73-1.37, P = 0.980; recessive model: OR = 0.90, 95%CI: 0.61-1.32, P = 0.570) and the risk of GDM. Conclusion Our meta-analysis shows the critical role of the ADIPOQ +45T/G polymorphism in GDM, especially in Asians. Studies focused on delineating ethnicity-specific factors with larger sample sizes are needed.

Background. Solute carrier family 2 member 4- (SLC2A4-) retinol binding protein-4- (RBP4-) phosphoenolpyruvate carboxykinase 1 (PCK1)/phosphoinositide 3-kinase (PI3K) is an adipocyte derived “signalling pathway” that may contribute to the pathogenesis of type 2 diabetes mellitus (T2DM). We explored whether single nucleotide polymorphisms (SNPs) of these “signalling pathway” genes are associated with gestational diabetes mellitus (GDM). Methods. Case-control studies were conducted to compare GDM and control groups. A total of 334 cases and 367 controls were recruited. Seventeen candidate SNPs of the pathway were selected. Chi-square tests, logistic regression, and linear regression were used to estimate the relationships of SNPs with GDM risk and oral glucose tolerance test (OGTT), fasting insulin, and homeostasis model assessment of insulin resistance (HOMA-IR) levels. Model-based multifactor dimensionality reduction was used to estimate the adjusted interactions between genes. Regression and interaction analyses were adjusted by maternal age, prepregnancy BMI, and weekly BMI growth. The Bonferroni correction was applied for multiple comparisons. Results. RBP4 rs7091052 was significantly associated with GDM risk. SLC2A4 rs5435, RBP4 rs7091052, PCK1 rs1042531 and rs2236745, and PIK3R1 (coding gene of the PI3K P85 subunit) rs34309 were associated with OGTT, fasting insulin, and HOMA-IR levels in the linear regression analysis. The gene-gene interaction analysis showed that, compared with pregnant women with other genotype combinations, women with SLC2A4 rs5435 (CC/CT), RBP4 rs7091052 (CC), PCK1 rs1042531 (TT/TG) and rs2236745 (TT), and PIK3R1 rs34309 (AA) had lower GDM risk. Conclusion. SLC2A4, RBP4, PCK1, and PIK3R1 genes may be involved in the pathogenesis of GDM.

As a metabolic disorder during pregnancy, gestational diabetes mellitus (GDM) has an important effects on fetal development, neonatal health and maternal long-term health, and is one of the pregnancy complications with high incidence. It is of great significance that we have an accurate understanding of the etiology and risk factors of GDM for its prevention and control. GDM is a complex disease with multiple etiologies. Current studies have shown that the occurrence of GDM may be the result of combined effect of heredity and environment, but the exact etiology is still unclear. In this paper, we summarized the possible etiologies and risk factors of GDM, so as to understand the occurrence and development of GDM better and to provide possible references for prevention and further etiological studies of GDM.

AIM To compare the accuracy of the scoring systems Child-Turcotte-Pugh (CTP), Model for End-stage Liver Disease score (MELD), MELD-Na, and MELD to Serum Sodium ratio (MESO) to predict the mortality in decompensated liver cirrhosis. METHODS The PubMed, Web of Science, Cochrane Library, EMBASE, and Ovid databases were systematically searched from inception to September 2018 for relevant articles, and we evaluated the quality of the included studies. The accuracy of scoring systems was analyzed with Stata 12 and MetaDiSc 1.4. RESULTS Sixteen studies involving 2337 patients were included. The pooled areas under the summary receiver operating characteristic curves (AUROCs) of CTP, MELD, MELD-Na, and MESO to predict mortality were 0.81, 0.78, 0.85, and 0.86, respectively. Within 3 mo, the AUROCs of CTP, MELD, and MELD-Na in predicting mortality were 0.78, 0.76, and 0.89, respectively. The AUROCs of CTP, MELD, and MELD-Na at 3 mo were 0.86, 0.78, and 0.86, respectively. The AUROCs of CTP, MELD, and MELD-Na at 6 mo were 0.91, 0.83, and 0.90, respectively. The AUROCs of CTP, MELD, and MELD-Na at 12 mo were 0.72, 0.75 and 0.84, respectively. In cirrhotic patients with bleeding, the AUROCs of CTP and MELD were 0.76 and 0.88, respectively. CONCLUSION MESO has the highest AUROC in all assessed scoring systems. Considering the different time points, MELD-Na has good accuracy in predicting the mortality of decompensated liver cirrhosis. Compared to CTP, MELD is better in predicting variceal bleeding.

This study aimed to examine effect modification of maternal risk factor exposures and congenital heart disease (CHD) by maternal folic acid supplementation (FAS)/non-FAS. We included 8379 CHD cases and 6918 CHD-free controls from 40 clinical centers in Guangdong Province, Southern China, 2004–2016. Controls were randomly chosen from malformation-free fetuses and infants and frequency matched to the echocardiogram-confirmed cases by enrollment hospital and year of birth. We used multiple regression models to evaluate interactions between FAS/non-FAS and risk factors on CHDs and major CHD categories, adjusted for confounding variables. We detected statistically significant additive and multiplicative interactions between maternal FAS/non-FAS and first-trimester fever, viral infection, and threatened abortion on CHDs. An additive interaction on CHDs was also identified between non-FAS and living in a newly renovated home. We observed a statistically significant dose-response relationship between non-FAS and a greater number of maternal risk factors on CHDs. Non-FAS and maternal risk factors interacted additively on multiple critical CHDs, conotruncal defects, and right ventricular outflow tract obstruction. Maternal risk factor exposures may have differential associations with CHD risk in offspring, according to FAS. These findings may inform the design of targeted interventions to prevent CHDs in highly susceptible population groups.

Introduction: Genome-wide DNA methylation profiling has been used to identify CpG sites relevant to gestational diabetes mellitus (GDM). However, these sites have not been verified in larger samples. Here, our aim was to evaluate the changes in target CpG sites in the peripheral blood of pregnant women with GDM in their first trimester. Research Design and Methods: This nested case-control study examined a large cohort of women with GDM in early pregnancy (10–15 weeks; n = 80). Target CpG sites were extracted from related published literature and bioinformatics analysis. The DNA methylation levels at 337 CpG sites located in 27 target genes were determined using MethylTarget™ sequencing. The best cut-off levels for methylation of CpG sites were determined using the generated ROC curve. The independent effect of CpG site methylation status on GDM was analyzed using conditional logistic regression. Results Methylation levels at 6 CpG sites were significantly higher in the GDM group than in controls, whereas those at 7 CpG sites were significantly lower (P

Mannan-binding lectin-associated serine protease-2 (MASP-2) has been reported to play an important role as a key enzyme in the lectin pathway of the complement system. The objectives of our study were to determine whether the single-nucleotide polymorphism (SNPs) of MASP2 and the gene-tea drinking interaction were associated with the susceptibility to TB. In total, 503 patients and 494 healthy controls were contained. Three SNPs (rs12142107, rs12711521, and rs7548659) were genotyped. The association between the SNPs and susceptibility to TB were investigated by conducting multivariate unconditional logistic regression analysis. The gene-tea drinking interactions were analyzed by the additive model of marginal structural linear odds models. Both genotype AC + AA at rs12711521 of MASP2 genes and genotype GT + GG at rs7548659 of MASP2 genes were more prevalent in the TB patient group than the healthy control group (OR: 1.423 and 1.439, respectively, P MASP2 genes was found to suggest negative interactions, which reached − 0.2311 (95% confidence interval (CI): − 0.4736, − 0.0113), − 0.7080 (95% CI − 1.3998, − 0.0163), and − 0.5140 (95% CI − 0.8988, − 0.1291), respectively (P MASP2 were associated with the susceptibility to TB. Furthermore, there were negative interactions between tea drinking and rs12142107, rs12711521, and rs75548659 of MASP2 gene, respectively. Our research provides a basis for studying the pathogenesis and prevention of tuberculosis.

The aim of this study was to explore the impact of polymorphism of PD-1 gene and its interaction with tea drinking on susceptibility to tuberculosis (TB). A total of 503 patients with TB and 494 controls were enrolled in this case–control study. Three single-nucleotide polymorphisms of PD-1 (rs7568402, rs2227982 and rs36084323) were genotyped and unconditional logistic regression analysis was used to identify the association between PD-1 polymorphism and TB, while marginal structural linear odds models were used to estimate the interactions. Genotypes GA (OR 1.434), AA (OR 1.891) and GA + AA (OR 1.493) at rs7568402 were more prevalent in the TB patients than in the controls (P < 0.05). The relative excess risk of interaction (RERI) between rs7568402 of PD-1 genes and tea drinking was −0.3856 (95% confidence interval −0.7920 to −0.0209, P < 0.05), which showed a negative interaction. However, the RERIs between tea drinking and both rs2227982 and rs36084323 of PD-1 genes were not statistically significant. Our data demonstrate that rs7568402 of PD-1 genes was associated with susceptibility to TB, and there was a significant negative interaction between rs7568402 and tea drinking. Therefore, preventive measures through promoting the consumption of tea should be emphasised in the high-risk populations.

Objective. Gestational diabetes mellitus (GDM) is a common metabolic disorder with onset during pregnancy. However, the etiology and pathogenesis of GDM have not been fully elucidated. In this study, we used a metabolomics approach to investigate the relationship between maternal serum metabolites and GDM in early pregnancy. Methods. A nested case-control study was performed. To establish an early pregnancy cohort, pregnant women in early pregnancy ( 10 ‐ 13 + 6 weeks) were recruited. In total, 51 patients with GDM and 51 healthy controls were included. Serum samples were analyzed using an untargeted high-performance liquid chromatography mass spectrometry metabolomics approach. The relationships between metabolites and GDM were analyzed by an orthogonal partial least-squares discriminant analysis. Differential metabolites were evaluated using a KEGG pathway analysis. Results. A total of 44 differential metabolites were identified between GDM cases and healthy controls during early pregnancy. Of these, 26 significant metabolites were obtained in early pregnancy after false discovery rate ( FDR < 0.1 ) correction. In the GDM group, the levels of L-pyroglutamic acid, L-glutamic acid, phenylacetic acid, pantothenic acid, and xanthine were significantly higher and the levels of 1,5-anhydro-D-glucitol, calcitriol, and 4-oxoproline were significantly lower than those in the control group. These metabolites were involved in multiple metabolic pathways, including those for amino acid, carbohydrate, lipid, energy, nucleotide, cofactor, and vitamin metabolism. Conclusions. We identified significant differentially expressed metabolites associated with the risk of GDM, providing insight into the mechanisms underlying GDM in early pregnancy and candidate predictive markers.

Background: DNA methylation has been widely assessed as a potential biomarker for the early detection of cervical cancer (CC). Herein, we assessed the associations of SOX1 promoter hypermethylation with squamous intraepithelial lesion and CC.Methods: Published studies and genome-wide methylation datasets were searched from electronic databases (up to April 2019). The associations of SOX1 hypermethylation with high-grade squamous intraepithelial lesion (HSIL) and CC risks were evaluated by odds ratios (ORs) and 95% confidence intervals (CIs). The summary receiver operator characteristic test was used to assess the diagnostic value of the SOX1 promoter hypermethylation of CC and intraepithelial neoplasia type III or worse (CIN3+). Trial sequential analysis (TSA) was performed to evaluate the stability of results and estimate the required information size (RIS).Results: In this meta-analysis of 17 published studies, the SOX1 methylation rates increased among low-grade SIL (LSIL, 27.27%), HSIL (40.75%), and CC (84.56%) specimens. Compared with control specimens, SOX1 promoter hypermethylation progressively increased the risk of HSIL by 4.20-fold (p < 0.001) and CC by 41.26-fold (p < 0.001). The pooled sensitivity of SOX1 methylation was estimated to be 0.85 (95% CI: 0.81–0.88) in differentiating patients with CC, corresponding to a specificity of 0.72 (95% CI: 0.69–0.75) and an area under the curve (AUC) of 0.93. Furthermore, the pooled sensitivity of SOX1 methylation was estimated to be 0.75 (95% CI: 0.72–0.78) in differentiating patients with CIN3+, corresponding to a specificity of 0.71 (95% CI: 0.69–0.73) and an AUC of 0.84. The pooled results of TCGA and GEO datasets showed that all CpG sites in SOX1 were associated with CC and 16 of 19 CpG sites were associated with HSIL. The results of TSA illustrated that the size was sufficient and significant associations were observed.Conclusion: This meta-analysis indicated that SOX1 promoter hypermethylation might have a potential value in the clinical diagnosis of CC and CIN3+.

Background Maternal folic acid supplementation (FAS) reduces the risk of neural tube defects in offspring. However, its effect on congenital heart disease (CHDs), especially on the severe ones remains uncertain. This study aimed to assess the individual and joint effect of first‐trimester maternal FAS and multivitamin use on CHDs in offspring. Methods and Results This is a case‐control study including 8379 confirmed CHD cases and 6918 controls from 40 healthcare centers of 21 cities in Guangdong Province, China. Adjusted odds ratios (aORs) of FAS and multivitamin use between CHD cases (overall and specific CHD phenotypes) and controls were calculated by controlling for parental confounders. The multiplicative interaction effect of FAS and multivitamin use on CHDs was estimated. A significantly protective association was detected between first‐trimester maternal FAS and CHDs among offspring (aOR, 0.69; 95% CI, 0.62–0.76), but not for multivitamin use alone (aOR, 1.42; 95% CI, 0.73–2.78). There was no interaction between FAS and multivitamin use on CHDs ( P =0.292). Most CHD phenotypes benefited from FAS (aORs ranged from 0.03–0.85), especially the most severe categories (ie, multiple critical CHDs [aOR, 0.16; 95% CI, 0.12–0.22]) and phenotypes (ie, single ventricle [aOR, 0.03; 95% CI, 0.004–0.21]). Conclusions First‐trimester maternal FAS, but not multivitamin use, was substantially associated with lower risk of CHDs, and the association was strongest for the most severe CHD phenotypes. We recommend that women of childbearing age should supplement with folic acid as early as possible, ensuring coverage of the critical window for fetal heart development to prevent CHDs.

In the production of fireworks, various pollutants including particles of metals and organic compounds are released into the environment. Although the adverse effects of these air pollutants are known, the impact on pregnant women residing in this area remains to be determined. The aim of this study was to examine the association between maternal exposure to fireworks production chemicals and frequency of preterm birth in Liuyang, China. Maternal exposure to fireworks production was estimated at the residential district level and assessed using factory density, which was defined as the number of fireworks factories per 1000 residents in each district. The association of maternal exposure to particulates released from fireworks production plants with frequency of preterm birth was determined using data obtained from a cohort study conducted in Liuyang, China. Data were analyzed utilizing linear regression and logistic regression. There was no significant association between factory density and spontaneous preterm or medically induced preterm birth. Unexpectedly, pregnant women residing in areas with higher density of fireworks factories were at a reduced risk of preterm premature rupture of membranes (PPROM). Data demonstrated that residential density of fireworks factories appeared to be negatively correlated with preterm birth rate as evidenced by PPROM. At present, it is difficult to reconcile the inverse relationship between firework chemical exposure and frequency of preterm births as ambient particulate inhalation is known to adversely affect preterm birth occurrence.

BACKGROUND:In this research, an meta-analysis was performed for assessment of the associations between O6-methyguanine-DNA methyltransferase (MGMT) promoter hypermethylation possessing low-grade intraepithelial lesion (LSIL), high-grade intraepithelial lesion (HSIL), cervical cancer (CC), and clinicopathological characters of CC. METHODS:Literature selection were conducted through searching PubMed, Web of science, EMBASE, China National Knowledge Infrastructure and Wanfang databases (up to November 2018). An assessment of associations between MGMT methylation and LSIL, HSIL, CC risk and clinicopathological characteristics was performed through pooled odds ratios (ORs) with relevant 95% confidence intervals (CIs). Subgroup analyses, meta-regressions and Galbraith plots were conducted to conduct an exploration on the possible sources of heterogeneity. The genome-wide DNA methylation array studies were extracted from Gene Expression Omnibus (GEO) databases for validation of these outcomes. RESULTS:In this meta-analysis of 25 published articles, MGMT hypermethylation gradually elevated the rates among control group (12.16%), LSIL (20.92%), HSIL (36.33%) and CC (41.50%) specimens. MGMT promoter methylation was significant associated with the increased risk of LSIL by 1.74-fold (P

Women with a history of adverse outcomes in pregnancy (including pre-term birth, delivery of a small-for-gestational-age (SGA) infant, preeclampsia, and gestational diabetes (GDM)) have a higher prevalence of metabolic syndrome (MetS) and cardiovascular disease, as compared to their peers. However, it is not known if MetS precedes the index pregnancy in women who develop these outcomes. Thus, we sought to evaluate the impact of pre-gravid MetS on the risk of adverse outcomes in pregnancy. In this prospective pre-conception cohort study, 1183 newly-married women underwent systematic assessment of cardiovascular risk factors (anthropometry, blood pressure, lipids, glucose) and then were followed across a subsequent pregnancy for the outcomes of interest. The women were stratified into two groups based on the presence (n=49) or absence (n=1134) of pre-gravid MetS (harmonized definition). The groups did not differ in length of gestation (p=0.31) or infant birthweight (p=0.21). Of note, women with pre-gravid MetS were more likely to have a Caesarean delivery (61.4% vs. 38.6%, p=0.003). However, there were no differences between the groups in the incidence of pre-term delivery, SGA, LGA, preeclampsia or GDM (Table). In conclusion, the increased lifetime risk of MetS observed in women with a history of these adverse pregnancy outcomes does not necessarily manifest prior to their pregnancy. Disclosure R. Retnakaran: Consultant; Self; Eli Lilly and Company, Novo Nordisk Inc., Sanofi. Research Support; Self; Boehringer Ingelheim International GmbH, Novo Nordisk Inc. S. Wen: None. H. Tan: None. C. Ye: None. M. Shen: None. G.N. Smith: None. M.C. Walker: None. Funding Canadian Institutes of Health Research

The aim of this study was to investigate the relationships between uterine size and volume and clinical pregnancy rate. This longitudinal study was conducted among patients undergoing assisted reproduction technology (ART) treatment at the Reproductive Medicine Center from January 2010 to May 2017, all of whom provided informed consent to participate in the study. The uterine size, for all patients, was measured by transvaginal ultrasonography before ovarian stimulation. Clinical pregnancy was diagnosed by ultrasound confirmation of at least an intrauterine gestational sac and fetal cardiac activity 4 weeks after embryo transfer. A total of 11,924 patients were enrolled in this study. Compared to patients with uterine lengths of 50 to 59 mm (referent), patients with uterine lengths ≥60 mm had a lower clinical pregnancy rate. Compared to patients with uterine widths of 30 to 39 mm (referent), patients with uterine widths of 40 to 49 mm and those with uterine widths of ≥50 mm had a lower clinical pregnancy rate. Compared with those with a uterine anteroposterior diameter of

Background. Previous studies showed that probiotics could improve glycemic control and attenuate some of the adverse effects of type 2 diabetes. However, whether the effects are generalizable to gestational diabetes mellitus (GDM) remains uncertain. Objective. We conducted a systematic review and meta-analysis to evaluate the effects of probiotic supplement in GDM. Method. PubMed, EMBASE, the Cochrane Library, and EBSCO were systematically searched for relevant literature published through January 2019. Randomized controlled trials (RCTs) assessing the effects of probiotic supplement on one or more of the following in GDM were included: pregnancy outcome (the primary outcome), glycemic control, blood lipid profile, and inflammation and oxidative stress. Two reviewers independently extracted data and assessed the risk of bias in studies. Meta-analysis was conducted by using the fixed effects model unless substantial heterogeneity was found among studies. Results. Eleven randomized trials involving 719 participants were included for analysis. Eight of the trials were from Iran. Probiotics were given alone in eight trials and synbiotics in three trials. Though the components of probiotics varied, Lactobacillus was included in all trials and Bifidobacterium in all except one. The duration of intervention ranged from 4 to 8 weeks. Almost all trials (10/11) had a low risk of bias. Probiotic supplementation reduced the risk of a newborn’s hyperbilirubinemia by 74% and improved four biomarkers for glycemic control (fasting blood glucose, fasting serum insulin, homeostasis model assessment insulin resistance, and quantitative insulin sensitivity check index), two biomarkers for lipid profile (triglycerides and HDL-cholesterol), and four biomarkers for inflammation and oxidative stress (total glutathione, malondialdehyde, nitric oxide, and total antioxidant capacity). But significant heterogeneity was observed in the meta-analyses on the four biomarkers related to glycemic control and on triglycerides, which could not be explained by prespecified subgroup analyses according to the mean age of participants and intervention type (i.e., probiotics or synbiotics). The effects on the risk of preterm delivery, macrosomia and a newborns’ hypoglycemia, gestational age, total cholesterol, and LDL-cholesterol were not statistically significant. Conclusion. Probiotic supplementation seemed to be able to reduce the risk of a newborn’s hyperbilirubinemia and improve glycemic control, blood lipid profiles and inflammation and oxidative stress in pregnant women with GDM. However, due to the heterogeneity among existing studies, the surrogate nature of outcomes, and/or the fact that most studies were from Iran, the clinical significance and generalizability of the above findings remain uncertain. Further studies are warranted to address the limitations of existing evidence and better inform the management of GDM.

BACKGROUND Resistin is most likely involved in the pathogenesis of gestational diabetes mellitus (GDM), but the existing findings are inconsistent. AIM To review the literature investigating the associations of the risk of GDM with serum level of resistin. METHODS A systematic literature search was performed using MEDLINE, EMBASE, and Web of Science (all databases). This meta-analysis included eligible studies that: (1) investigated the relationship between the risk of GDM and serum resistin; (2) included GDM cases and controls without GDM; (3) diagnosed GDM according to the oral glucose-tolerance test; (4) were performed in humans; (5) were published as full text articles in English; and (6) provided data with median and quartile range, median and minimum and maximum values, or mean and standard deviation. The pooled standardized mean difference (SMD) and 95% confidence interval (CI) were calculated to estimate the association between the risk of GDM and serum resistin. To analyze the potential influences of need for insulin in GDM patients and gestational age at blood sampling, we performed a subgroup analysis. Meta-regression with restricted maximum likelihood estimation was performed to assess the potentially important covariate exerting substantial impact on between-study heterogeneity. RESULTS The meta-analysis for the association between serum resistin level and GDM risk included 18 studies (22 comparisons) with 1041 cases and 1292 controls. The total results showed that the risk of GDM was associated with higher serum resistin level (SMD = 0.250, 95%CI: 0.116, 0.384). The “after 28 wk” subgroup, “no need for insulin” subgroup, and “need for insulin” subgroup indicated that higher serum resistin level was related to GDM risk (“after 28 wk” subgroup: SMD = 0.394, 95%CI: 0.108, 0.680; “no need for insulin” subgroup: SMD = 0.177, 95%CI: 0.018, 0.336; “need for insulin” subgroup: SMD = 0.403, 95%CI: 0.119, 0.687). The “before 14 wk” subgroup, “14-28 wk” subgroup, and “no information of need for insulin” subgroup showed a nonsignificant association between serum resistin level and GDM risk (“before 14 wk” subgroup: SMD = 0.087, 95%CI: -0.055, 0.230; “14-28 wk” subgroup: SMD = 0.217, 95%CI: -0.003, 0.436; “no information of need for insulin” subgroup: SMD = 0.356, 95%CI: -0.143, 0.855). The postpartum subgroup included only one study and showed that higher serum resistin level was related to GDM risk (SMD = 0.571, 95%CI: 0.054, 1.087) The meta-regression revealed that no need for insulin in GDM patients, age distribution similar between cases and controls, and ELISA all had a significant impact on between-study heterogeneity. CONCLUSION This meta-analysis supports that the maternal serum resistin level is associated with GDM risk.

A nationwide survey of hepatitis B virus (HBV)-associated economic burden has not previously been performed in China. The purpose of this study was to examine the direct, indirect, and intangible costs of HBV-related diseases within the span of one year. A random sample was taken from specialty and general hospitals across 12 cities in six provinces of China. Intangible costs were estimated based on willingness to pay or open-ended answers provided by patients. The results showed that 27 hospitals were enrolled, with a sample population of 4726 patients (77.7% response rate). The average annual costs were $4454.0 (direct), $924.3 (indirect), and $6611.10 (intangible), corresponding to 37.3%, 7.7%, and 55.1% of the total costs, respectively. The direct medical fees were substantially greater than the non-medical fees. Annual indirect costs were divided into outpatient ($112.9) and inpatient ($811.40) loss of income. The intangible costs of chronic HBV were notably higher than either the direct or indirect costs, consistent with the social stigma in China. The comparison amongst individual cities for the average ratio of direct to indirect costs revealed that the sizes of ratios were negatively correlated with the socioeconomic status of the regions. This study suggested that as a whole in China, the HBV-related diseases caused a heavy financial burden which was positively associated with disease severity. Although the intangible costs coincided with a high prevalence of discrimination against CHB patients in Chinese society, our study may serve as future reference for detailed exploration.

Objective To evaluate the impact of microRNA (miRNA) machinery gene polymorphisms on the risk of gestational hypertension (GH) and preeclampsia (PE). Study design A case-control study among Han Chinese with a total of 143 patients diagnosed with PE, 79 with GH, and 330 healthy controls was conducted. Nine candidate SNPs in 4 selected miRNA biogenesis genes were genotyped, including three DICER1 SNPs (rs3742330, rs1057035 and rs13078), two DROSHA SNPs (rs17409893 and rs642321), two RAN SNPs (rs3803012 and rs14035), and two XPO5 SNPs (rs1106841 and rs2257082). Logistic regression was used to estimate the odds ratios (OR) and 95% confidence intervals (CIs) for the associations. Results The DICER1 rs13078 TA genotype was still strongly associated with an increased risk of GH (OR = 3.17 (95% CI: 1.55, 6.48)), and the RAN rs3803012 AG genotype was associated with an increased risk of PE (OR = 2.15 (1.26, 3.66)). The RAN rs14035/rs3803012 haplotype C-G was associated with PE susceptibility (OR = 2.08 (95% CI: 1.19, 3.62)); however, the haplotype C-A was a protective factor for PE (OR = 0.68 (95% CI: 0.50, 0.93)). The DICER1 rs1057035/ rs13078/ rs3742330 haplotype T-A-A and DORSHA rs17409893/rs642321 haplotype A-T were both associated with increased risk of GH (OR = 2.75 (95% CI:1.40, 5.38) and OR = 1.60 (95% CI:1.12, 2.29), respectively). These significant associations were retained after false-positive discovery rate correction (p Conclusions Genetic variants in miRNA machinery genes might participate in the development of pregnancy-induced hypertension. The DICER1 rs1078 polymorphism is associated with GH and the RAN rs3803012 polymorphism is associated with PE.

SUMMARYChitotriosidase, secreted by activated macrophages, is a biomarker of activated macrophages. In this study, we explored whether chitotriosidase could be adopted as a biomarker to evaluate the curative effect on tuberculosis (TB). Five counties were randomly selected out of 122 counties/cities/districts in Hunan Province, China. Our cases were all TB patients who were newly diagnosed or had been receiving treatment at the Centers for Disease Control (CDCs) of these five counties between April and August in 2009. Healthy controls were selected from a community health facility in the Kaifu district of Changsha City after frequency-matching of gender and age with the cases. Chitotriosidase activity was evaluated by a fluorometric assay. Categorical variables were analysed with the χ2 test. Measurement data in multiple groups were tested with analysis of variance and least significant difference (LSD). Correlation between chitotriosidase activity and the degree of radiological extent (DRE) was examined by Spearman's rank correlation test. The average chitotriosidase activity levels of new TB cases, TB cases with different periods of treatment (6 months) and the control group were 54·47, 34·77, 21·54, 12·73 and 10·53 nmol/h.ml, respectively. Chitotriosidase activity in TB patients declined along with the continuity of treatment. The chitotriosidase activity of both smear-positive and the smear-negative pulmonary TB patients decreased after 6 months' treatment to normal levels (P < 0·05). Moreover, chitotriosidase activity was positively correlated with DRE (r = 0·607, P < 0·001). Our results indicate that chitotriosidase might be a marker of TB treatment effects. However, further follow-up study of TB patients is needed in the future.

Background Hand, foot and mouth disease (HFMD) is one of the highest reported infectious diseases with several outbreaks across the world. This study aimed at describing epidemiological characteristics, investigating spatio-temporal clustering changes, and identifying determinant factors in different clustering areas of HFMD. Methods Descriptive statistics was used to evaluate the epidemic characteristics of HFMD from 2009 to 2015. Spatial autocorrelation and spatio-temporal cluster analysis were used to explore the spatial temporal patterns. An autologistic regression model was employed to explore determinants of HFMD clustering. Results The incidence rates of HFMD ranged from 54.31/10 million to 318.06/10 million between 2009 and 2015 in Hunan. Cases were mainly prevalent in children aged 5 years and even younger, with an average male-to-female sex ratio of 1.66, and two epidemic periods in each year. Clustering areas gathered in the northern regions in 2009 and in the central regions from 2010 to 2012. They moved to central-southern regions in 2013 and 2014 and central-western regions in 2015. The significant risk factors of HFMD clusters were rainfall (OR = 2.187), temperature (OR = 4.329) and humidity (OR = 2.070). The protect factor was wind speed (OR = 0.258). Conclusions The HFMD incidence from 2009 to 2015 in Hunan showed a new spatiotemporal clustering tendency, with the shifting trend of clustering areas toward south and west. Meteorological factors showed a strong association with HFMD clustering, which may assist in predicting future spatial-temporal clusters. Electronic supplementary material The online version of this article (10.1186/s12879-017-2742-9) contains supplementary material, which is available to authorized users.

Supplemental Digital Content is available in the text, Background: The safety and efficacy of different drugs in treatment of gestational diabetes mellitus (GDM) patients who could not maintain normal glucose level only through diet and exercise remains to be debated. We performed this network meta-analysis (NAM) to compare and rank different antidiabetic drugs in glucose level control and pregnancy outcomes in GDM patients. Methods: We searched PubMed, Cochrane Library, Web of Science, and Embase up to December 31, 2016. Randomized controlled trials (RCTs) related to different drugs in the treatment of GDM patients were enrolled. We extracted the relevant information and assessed the risk of bias with the Cochrane risk of bias tool. We did pair-wise meta-analyses using the fixed-effects model or random-effects model and then adopted random-effects NAM combining both direct and indirect evidence within a Bayesian framework, to calculate the odds ratio (OR) or standardized mean difference (SMD) and to draw a surface under the cumulative ranking curve of the neonatal and maternal outcomes of different treatments in GDM patients. Results: Thirty-two randomized controlled trials (RCTs) were included in this NAM, including 6 kinds of treatments (metformin, metformin plus insulin, insulin, glyburide, acarbose, and placebo). The results of the NAM showed that regarding the incidence of macrosomia and LGA, metformin had lower incidence than glyburide (OR, 0.5411 and 0.4177). In terms of the incidence of admission to the NICU, insulin had higher incidence compared with glyburide (OR, 1.844). As for the incidence of neonatal hypoglycemia, metformin had lower incidence than insulin and glyburide (OR, 0.6331 and 0.3898), and insulin was lower than glyburide (OR, 0.6236). For mean birth weight, metformin plus insulin was lower than insulin (SMD, -0.5806), glyburide (SMD, -0.7388), and placebo (SMD, -0.6649). Besides, metformin was observed to have lower birth weight than glyburide (SMD, 0.2591). As for weight gain, metformin and metformin plus insulin were lower than insulin (SMD, -0.9166, -1.53). Ranking results showed that glyburide might be the optimum treatment regarding average glucose control, and metformin is the fastest in glucose control for GDM patients; glyburide have the highest incidence of macrosomia, preeclampsia, hyperbilirubinemia, neonatal hypoglycemia, shortest gestational age at delivery, and lowest mean birth weight; metformin (plus insulin when required) have the lowest incidence of macrosomia, PIH, LGA, RDS, low gestational age at delivery, and low birth weight. Besides, insulin had the highest incidence of NICU admission, acarbose had the lowest risk of neonatal hypoglycemia. Conclusion: Our study concluded that metformin is fastest in glucose control, with a more favorable pregnancy outcomes—would be a better option, but its rate of glucose control is the lowest.However, glyburide is the optimumtreatment regarding the rate of glucose control, but withmore adverse outcomes. This NAMbased on 32 RCTs will strongly help to guide further development of management for GDM patients, clinicians should carefully balance the risk–benefit profile of different treatments according to various situations.

Objectives To investigate the association between transforming growth factor beta 1 related gene polymorphisms and the occurrence of pregnancy induced hypertension, including gestational hypertension and preeclampsia. Study design This is a case control candidate gene association study. A total of 130 patients with preeclampsia, 67 with gestational hypertension, and 316 controls were recruited. Eleven candidate SNPs of were examined, including four TGFβ1 SNPs (rs1800469, rs4803455, rs4803457, and rs8179181), one TGFβR1 SNP (rs10739778), four TGFβR2 SNPs (rs1346907, rs3087465, rs6550005, and rs877572), and two ENG SNPs (rs10121110 and rs11792480). Main outcome measures Logistic regression was used to estimate the OR and the 95% CI under different genetic models. Chi-square test was used to determine whether haplotype frequency distributions differed between the case and control groups and logistic regression was used to estimate ORs. To explore the associations between SNPs and blood pressure, SBP/DBP in different genotype groups in healthy women were compared by Wilcoxon rank sum test. Results We did not find significant association between investigated SNPs and pregnancy induced hypertension. The C-T-A-G haplotype of four TGFβR2 SNPs (rs877572, rs1346907, rs3087465, and rs6550005) was significantly associated with preeclampsia (OR = 4.71, 95%CI: 1.944, 11.409) and gestational hypertension (OR = 3.157, 95%CI: 1.003, 9.938). The AA genotype of TGFβR1 rs10739778 was found to be associated with higher blood pressure in healthy women (p ≤ .008). Conclusions Polymorphisms in TGFβR2 might participate in the pathologic process of pregnancy induced hypertension, and TGFβR1 rs10739778 was associated with blood pressure in our healthy participants.

OBJECTIVE To assess the effect of weight gain during pregnancy on intertwin delivery weight discordance. METHODS In the present retrospective cohort study using twin delivery records, data were extracted from the 2011-2015 USA birth registration dataset created by the Centers for Disease Control and Prevention. The outcome variable was delivery weight discordance. The nonlinear association of weight gain during pregnancy with delivery weight discordance was examined using a generalized additive model, adjusting for potential confounders. RESULTS A total of 255 627 twin pairs were included in this analysis. Weight gain during pregnancy showed an inverse, yet nonlinear, association with intertwin delivery weight discordance. Women with weight gain of approximately 25 kg exhibited the lowest level of discordance. When stratified by pre-pregnancy body mass index, the association of weight gain with discordance became insignificant among obese women. When categorizing weight gain according to recommendations from the Institute of Medicine, inadequate weight gain was associated with increased risk of discordance among women of any pre-pregnancy body mass index. CONCLUSION Twin pregnancies with maternal weight gain of approximately 25 kg demonstrated the lowest risk of developing intertwin delivery weight discordance, while inadequate weight gain was a risk factor for delivery weight discordance in all pre-pregnancy body mass index categories.

Background Twins with discordant growth have increased risks of perinatal mortality and morbidity. Previous studies have identified a number of risk factors for inter-twin birth weight discordance, yet no study has examined the effect of maternal hepatitis C infection. Methods We used the twin birth records extracted from the 2011 to 2015 United States birth records created by the Centers for Disease Control and Prevention. The outcome variable of this study was inter-twin birth weight discordance, defined as [(birth weight of larger twin–birth weight of smaller twin) / birth weight of larger twin]. The independent association of hepatitis C infection with birth weight discordance was examined using the gamma regression or log binomial regression, adjusted by potential confounders. Results Of the 270,256 twin pairs included in the final analysis, 850 (0.31%) had positive hepatitis C. Compared to mothers without hepatitis C, mothers with hepatitis C positive tended to have higher risk of birth weight discordance, but with no statistical significance. After adjustment for potential confounding factors, hepatitis C positive became a significant risk factor for birth weight discordance >25% (relative risk 1.14, 95% confidence interval 1.02−1.29). Sensitivity analyses (by treating birth weight discordance as a continuous outcome or dichotomizing into by different cutoffs) yielded similar results, with relative risks ranging from 1.07 to 1.12 (all P

Background and aims Both low birthweight and high birthweight have been associated with the development of cardiometabolic disease in adulthood, possibly reflecting the effect of intrauterine fetal programming. As developmental programming can begin before conception, pre-gravid factors that predict birthweight may be relevant in this context. However, little is known about such factors. Thus, we established a pre-conception cohort to identify maternal pre-gravid cardiometabolic determinants of infant birthweight. Methods and results In this prospective observational cohort study, 1484 newly-married women in Liuyang, China, underwent baseline (pre-gravid) evaluation and then were followed across a subsequent pregnancy. Pre-gravid cardiometabolic characterization consisted of clinical (anthropometry, blood pressure) and biochemical evaluation (total/LDL/HDL cholesterol, triglycerides, glucose) at median 20 weeks before a singleton pregnancy. Mean birthweight was 3294 ± 444 g, with 173 neonates large-for-gestational-age (LGA) and 110 small-for-gestational-age (SGA). On multiple linear regression analysis, positive determinants of birthweight were maternal age, pre-gravid body mass index (BMI), weight gain in pregnancy, length of gestation, and male infant (all p ≤ 0.0003). On logistic regression analysis, independent predictors of an LGA delivery were maternal age (OR = 1.10 per year, 95%CI 1.03–1.18), pre-gravid BMI (OR = 1.21 per kg/m 2 , 1.07–1.37), and gestational weight gain (OR = 1.10 per kg, 1.06–1.14). The only independent predictor of SGA was gestational weight gain (OR = 0.93 per kg, 0.89–0.97). Conclusion Maternal weight before and during pregnancy is the predominant cardiometabolic determinant of infant birthweight, rather than pre-gravid blood pressure, glucose or lipid profile.

The purpose of this investigation was to assess the effectiveness of an intervention program on mother-to-child transmission (MTCT) of syphilis and investigate determinants of congenital syphilis (CS) and adverse pregnancy outcomes (APOs). The Shenzhen local government initiated an intervention program of MTCT of syphilis in 2001. Based on this program, maternal and paternal factors associated with CS and APOs among syphilitic women were investigated from 2007 to 2012 by a prospective cohort study. From 2002 to 2012, 2,441,237 pregnant women were screened and screening coverage reached 97.2 % in 2012. In the background of continuing growth of CS in China, CS in Shenzhen significantly decreased from 109.3 cases in 2002 to 9.9 cases in 2012 per 100,000 live births. Maternal education (adjusted odds ratio [aOR]CS = 0.65; aORAPOs = 0.79) and history of syphilis (aORCS = 0.28; aORAPOs = 0.61), as well as paternal age (aORCS = 0.62; aORAPOs = 0.86) and education (aORCS = 0.66; aORAPOs = 0.86) were negatively associated with CS and APOs, but maternal unmarried status (aORCS = 1.95; aORAPOs = 2.61), inadequate antenatal care (ANC) (aORCS = 3.61; aORAPOs = 1.79), more sexual partners (aORCS = 1.51; aORAPOs = 1.39), every week of delay in treatment (aORCS = 2.82; aORAPOs = 1.27), higher baseline titers of nontreponemal antibodies (aORCS = 5.65; aORAPOs = 1.47), early syphilis (aORCS = 23.24; aORAPOs = 26.95), and non-penicillin treatment (aORCS = 3.00; aORAPOs = 2.16), as well as paternal history of cocaine use (aORCS = 2.70; aORAPOs = 2.44) and positive (aORCS = 4.14; aORAPOs = 1.50) or unknown (aORCS = 2.37; aORAPOs = 2.06) status of syphilis increased the risk of CS and APOs. Condom use (aOR = 0.70) decreased MTCT of syphilis. A ten-year program consisting of screening and treatment, early ANC, health education, partners tracking, detection, and treatment, follow-up visits, and information management is an effective means to block MTCT of syphilis. Maternal and paternal factors constituted two separate profiles associated with MTCT of syphilis.

Pregnancy-induced hypertension (PIH, including preeclampsia [PE] and gestational hypertension [GH]) and cardiovascular diseases (CVDs) have some metabolic changes and risk factors in common. Many studies have reported associations between single nucleotide polymorphisms (SNPs) of renin–angiotensin–aldosterone system (RAAS) genes and CVDs (particularly hypertension), and their findings have provided candidate SNPs for research on genetic correlates of PIH. We explored the association between hypertension-related RAAS SNPs and PIH in a Chinese population. A total of 130 cases with PE, 67 cases with GH, and 316 controls were recruited. Six candidate SNPs of the RAAS system were selected. Multiple logistic regression analysis adjusting for maternal age, fetal sex, and gestational diabetes mellitus showed significant associations between angiotensinogen (AGT) rs3789678 T/C and GH (p = 0.0088) and between angiotensin II receptor type 1 (AGTR1) rs275645 G/A and PE (p = 0.0082). The study population was further stratified by maternal age (

To investigate how uterine size and volume are associated with live birth rate in patients undergoing assisted reproduction technology.This prospective cohort study was conducted at the Reproductive Medicine Centre from January 2010 to May 2017. Multivariate binary logistic regression was used to evaluate the relations between uterine size, total volume, and live birth outcomes, after they were adjusted for the main influencing factors.A total of 7320 women of clinical pregnancy were enrolled. Compared with uterine lengths of 50 to 59 mm (referent), women with uterine lengths ≥60 mm had a lower live birth rate (RR = 1.541). Compared with uterine widths of ≥50 mm (referent), women with uterine widths

Cell and animal experiments have found that in addition to being a retinol transporter, Stimulated by Retinoic Acid 6 (STRA6) also functions as a surface signaling receptor by which retinol regulates insulin responses. Several studies revealed that the STRA6 gene may contribute to the pathogenesis of type 2 diabetes mellitus (T2DM). Gestational diabetes mellitus (GDM) and T2DM have some risk factors in common. The present study was directed to investigate whether the 3 single nucleotide polymorphism (SNPs) (rs11633768, rs351219, and rs736118) of STRA6 correlate with the development of GDM in Chinese pregnant women. We also aimed to estimate the relationship between SNPs with fasting blood glucose level, 1-hour and 2-hour blood glucose levels after 75 g oral glucose intake, fasting insulin and insulin resistance levels to better study the relationship between STRA6 and glucose metabolism. Case–control studies were conducted to compare the GDM and control groups. A total of 334 cases and 367 controls were recruited. Three tagSNPs of STRA6, rs11633768, rs351219, and rs736118, were selected. A chi-square test, logistic regression, and linear regression were used to estimate the relationship between SNPs with GDM risk and oral glucose tolerance test (OGTT), fasting insulin and homeostasis model assessment of insulin resistance (HOMA-IR) levels. Regression analyses were all adjusted by maternal age, pre-pregnancy BMI, and weekly BMI growth. The Bonferroni correction was applied for multiple comparisons. After adjusting the maternal age, pre-pregnancy BMI and weekly BMI growth, STRA6 rs736118 was associated with fasting insulin level (Beta = −1.468, P = .036), and the association between rs736118 and HOMA-IR was of borderline significance (Beta = −0.290, P = .093) under the dominance model. This study found that there is a significant association between STRA6 polymorphism and GDM.

The study aims to examine the blood pressure (BP) trajectory during pregnancy and its association with pre-gravid BP level. In a pre-conception cohort study, newly-married women in Liuyang, China underwent pre-gravid measurements and were followed throughout the pregnancy. BP was measured at pre-conception and again throughout pregnancy. The functional principal component analysis was used to examine the trajectory of BP changes during pregnancy. A total of 1282 women with a singleton pregnancy who had both pre-conception and gestational BP measurements performed were included in the final analysis. The results showed that BP decreased significantly in early pregnancy and increased thereafter, without BP drop around 20 weeks of gestation. Pre-gravid BP level was inversely associated with the BP drop in early pregnancy, such that women with higher pre-gravid BP had greater BP drop at the beginning, while women with the lowest pre-gravid BP level demonstrated no obvious BP drop throughout the entire pregnancy.

// Shu-Juan Ma 1 , Yi-Xiang Zheng 2 , Peng-Cheng Zhou 2 , Yan-Ni Xiao 1 and Hong-Zhuan Tan 1 1 Department of Epidemiology and Health Statistics, Xiangya School of Public Health, Central South University, Changsha, China 2 Department of Infectious Disease, Viral Hepatitis Key Laboratory of Hunan Province, Xiangya Hospital, Central South University, Changsha, China Correspondence to: Hong-Zhuan Tan, email: // Keywords : metformin, liver cancer, survival, diabetes mellitus, meta-analysis Received : May 22, 2016 Accepted : July 19, 2016 Published : August 02, 2016 Abstract Metformin has garnered considerable interest as a chemo-preventive and chemo-therapeutic agent given the increased risk of liver cancer among diabetic patients. This work was performed to illustrate the association between metformin use and survival of diabetic liver cancer patients. We conducted a comprehensive literature search of PubMed, Web of Science, Embase, BIOSIS Previews, Cochrane Library from inception to 12 May 2016. Meta-analyses were performed using Stata (version 12.0), with hazard ratios (HRs) and corresponding 95% confidence intervals (CIs) as effect measures. Eleven cohort studies involving 3452 liver cancer patients fulfilled the inclusion criteria. Meta-analyses showed that metformin use was associated with better survival (HR = 0.59; 95% CI, 0.42-0.83; p = 0.002) of liver cancer patients, and the beneficial effect persisted (HR = 0.64; 95% CI, 0.42-0.97; p = 0.035) when the population was restricted to diabetic liver cancer patients. After adjusting for age, etiology, index of tumor severity and treatment of liver cancer, the association between metformin use and better survival of liver cancer patients was stable, pooled HR ranged from 0.47 to 0.57. The results indicated that metformin use improved survival of diabetic liver cancer patients. However, the results should be interpreted with caution given the possibility of residual confounding. Further prospective studies are still needed to confirm the prognostic benefit of metformin use.

Background Retinol-binding protein-4 (RBP4) has been reported to be potentially involved in the pathogenesis of gestational diabetes mellitus (GDM); however, the findings are inconsistent. Our aims were to review the studies that investigated the association of serum levels and polymorphisms of RBP4 with GDM risk, and to provide recommendations for future research. Methods The databases PubMed, EBSCO, ScienceDirect, and Web of Knowledge were searched up to October 2015 to find out studies evaluating the relationship between serum RBP4 level/ RBP4 polymorphisms and GDM risk. In the meta-analysis of serum RBP4 levels the key inclusion was that studies were designed as BMI-matched studies or had observed non-significant differences in BMI between cases and controls. Results Fourteen case–control studies (647 cases and 620 controls) reporting the association between serum RBP4 level and GDM risk, and three studies (1012 cases and 1605 controls) investigating the association between RBP4 polymorphisms and GDM risk were involved. Our results showed that high serum RBP4 levels represent a risk factor for GDM (pooled standardized mean difference =0.758, 95 % confidence interval [0.387, 1.128]). The results of subgroup analyses based on “gestational age at blood sampling” or “diagnostic criteria” are consistent with the overall results. However, the postpartum subgroup and “before 24 weeks” subgroup both only include one article and indicate no association between serum RBP4 level and GDM risk. The meta-analysis on the association between rs3758539 polymorphism and GDM risk shows that RBP4 rs3758539 polymorphism is not associated with the development of GDM. Conclusions The results of this meta-analysis support the hypothesis that RBP4 is a modest independent risk factor for GDM (i.e., nonobese patients with GDM might express RBP4 at abnormal levels). The serum RBP4 level is associated with the risk of GDM. However, the association in the first-trimester and postpartum period should be validated by further research. The association between RBP4 rs3758539 polymorphism and GDM risk was not confirmed. Electronic supplementary material The online version of this article (doi:10.1186/s12884-016-0838-7) contains supplementary material, which is available to authorized users.

We used the 2005 and 2006 national surveillance data to elucidate some of the risk factors for treatment default and death among tuberculosis (TB) patients in Hunan, China. Risk of default was higher in males (odds ratio (OR) 1.25; 95% confidence interval (CI) 1.08, 1.44); lowest in patients aged 15-24 y (OR 0.60; 95% CI 0.49, 0.75), and generally increased with increasing age; lower in patients living in cities with per capita gross domestic product (GDP) of less than 1000 US$ (OR 0.60, 95% CI 0.49, 0.72), and increased with increasing per capita GDP of city of residence; and higher in patients with previously treated smear-positive pulmonary TB (diagnostic category II according to the World Health Organization definition; OR 1.99; 95% CI 1.22, 3.23). Risk of death was lowest in patients aged 15-24 y (OR 0.07; 95% CI 0.05, 0.10), and increased with increasing age; lower in new cases (OR 0.50; 95% CI 0.33, 0.76); and highest in patients who treated themselves (OR 3.47; 95% CI 1.27, 9.46). We conclude that male TB patients, elderly TB patients, patients resident in cities with higher per capita GDP, and patients receiving category II treatment need special attention to reduce TB treatment default in the province. Furthermore, elderly TB patients and patients with a long history of TB need special attention to reduce mortality. Self-treatment also needs to be discouraged to reduce mortality.

The objective of the study was to construct a short screening scale for posttraumatic stress disorder (PTSD). We used data from our previous study on PTSD among flood victims in 1998 and 1999 in Hunan, China, which was a representative population sample of 27,267 subjects from 16 to 94 years old. Multistage sampling was used to select the subjects from the flood areas and PTSD was ascertained with the Diagnostic and Statistical Manual of Mental Disorders: 4th Edition (DSM-IV). We randomly assigned 80% (n=21,762) of study subjects to construct the screening scale (construct model) and the remaining 20% (n=5505) to test the model. Logistic regression analysis and receiver operating characteristic analysis were used to select a subset of items (symptoms) from the full scale that would effectively predict PTSD. A seven-symptom screening scale for PTSD was selected. A score of 3 or more on this scale was used to define positive cases of PTSD, with a sensitivity of 87.9%, specificity of 97.9%, positive predictive value of 81.3%, and negative predictive value of 98.7%. The short screening scale developed in this study is highly valid, reliable, and predictable. It is an efficient tool to screen PTSD in epidemiological and clinical studies.

The objective of this paper is to develop a brief screening instrument of posttraumatic stress disorder (PTSD) for young victims of natural disasters. Data were derived from flood victims in 1998 and 1999 in Hunan, China. A representative population sample of 6,852 subjects 7-15 years of age was selected. Among them, 6,073 (88.6%) were interviewed. Multistage sampling was used to select the subjects and PTSD was ascertained with Diagnostic and Statistical Manual of Mental Disorders: 4th Edition (DSM-IV). We randomly assigned 80% (4,851) of the study subjects to construct the screening instrument (construct model) and the remaining 20% (1,222) subjects to examine the model (validation model). Logistic regression analysis and receiver operating characteristics curves were utilized to select a subset of symptoms and cutoff point from the pre-structured questionnaires. A seven-symptom instrument for PTSD screening was selected. Scores of 3 or more on this instrument were employed to define positive cases of PTSD with a sensitivity of 96.9%, specificity 99.0%, positive predictive value (PPV) 82.6%, and negative predictive value (NPV) 99.8%. The brief screening instrument developed in this study is highly valid, reliable, and predictable.

Objectives To compare the risk factors for gestational hypertension (GH) and preeclampsia (PE) in the same population, which may provide clues to better understanding of their etiologic mechanisms. Methods We conducted a cohort study in Liuyang, China, during 2010–2011. Twelve potential risk factors were investigated, including maternal age, body mass index at first antenatal visit, gender of newborn, parity, abortion history, smoking history, family history of hypertension, gestational diabetes mellitus, pregnancy complications of diabetes mellitus/renal disease/cardiac disease, reproductive tract infection, season of delivery, and district level average per capita income. Logistic regression were used to estimate odds ratios for potential risk factors. Results Of 6223 pregnancies, 1.8% was complicated by PE, and 5.4% by GH. Maternal age older than 35, body mass index above 24, and pregnancy complicated with gestational diabetes mellitus increased the risk of both PE and GH, while with different effect sizes. Primiparity and deliver in winter and spring (compared with summer delivery) were risk factors for GH only. Pregnancy complicated with diabetes mellitus/renal disease/cardiac disease was risk factor for PE only. Significantly lower risk of GH was observed for women younger than 25 or with low body mass index in the first trimester. Mothers carrying a male fetus were more likely to develop PE. Conclusions Risk factors for GH and PE were not exactly the same. Underling those differences might be their different etiology and mechanism. To confirm the similarities and differences been found in single study, it is important to conduct investigation in other population.

Background Mannose-binding lectin (MBL) and MBL-associated serine proteases 2 (MASP-2) are important proteins in the lectin pathway of the immune system. Polymorphism of MBL and MASP-2 genes may affect the serum concentration of MBL and MASP-2. This study explores the association between MBL and MASP-2 gene polymorphism and their interactions and the susceptibility to tuberculosis (TB). Method A total of 503 patients with TB and 419 healthy controls were recruited to participate in this case-control study. PCR-SSP technology was applied to genotype rs7096206 of MBL genes and rs2273346 and rs6695096 of MASP-2 genes. Demographic data and some exposure information were also obtained from study participants. Unconditional logistic regression analysis was used to identify association between the various factors and TB whilst Marginal Structural Linear Odds Models were used to estimate the interactions. Results Both genotype GC at rs7096206 of MBL genes and genotype TC at rs2273346 and rs6695096 of MASP-2 genes were more prevalent in the TB patient group than the healthy control group (P

A rapid, simple, and effective method using questionnaires is described for screening of high-risk individuals of schistosomiasis japonica after the occurrence of major flooding. A case-control study design was adopted in two randomly selected villages from Dongting Lake area in the People's Republic of China that are endemic for Schistosoma japonicum. Information about contagious water exposure history and several other risk factors were collected retrospectively from 246 individuals, aged 9-60 years. A probability model was developed by logistic regression analysis, which included six variables, namely (i) knowledge of Schistosoma transmission, (ii) education attainment, (iii) annual income before flood year per person, (iv) duration of contagious water exposure due to swimming and paddling, (v) intensity of contagious water exposure due to occupational activities, and (vi) duration of contagious water exposure due to recreational activities. The receiver-operating characteristic (ROC) curve was plotted and the sensitivity and specificity were calculated. The internal consistency of the probability model was good. The area below the ROC curve was 0.90. If the probability cutoff value of diagnosing an infection with S. japonicum was defined as 0.35, both sensitivity and specificity were above 82%, whereas positive and negative predictive values were 70 and 91%, respectively. We conclude that questionnaires are a viable tool for screening of high-risk individuals of S. japonicum infections in lake communities of China after flooding occurred, opening new avenues for schistosomiasis control.

To assess the association between the fetal sex and preterm birth.We performed a retrospective population-based cohort study using the 1995-1997 registration twin data in the United States (148,234 live-birth twin pairs). The twin pairs were divided into 3 groups: male-male (male-male), female-female, and opposite sex. We used 3 different cutoff values of preterm birth: less than 28, 32, and 36 gestational weeks. The preterm birth rates among the 3 study groups were compared, and the adjusted risk ratios (relative risk) were estimated by multiple logistic regression.The male-male twin pairs had the highest pre-term birth rate (less than 28 weeks: 4.9%; less than 32 weeks: 12.4%; less than 36 weeks: 40.2%), the female-female twin pairs were intermediate (less than 28 weeks: 4.1%; less than 32 weeks: 10.6%; less than 36 weeks: 37.8%), and the opposite-sex twin pairs had the lowest rate (less than 28 weeks: 4.1%; less than 32 weeks: 10.1%; less than 36 weeks: 36.8%). Adjustment for important confounding factors or excluding twin pairs born to mothers who had an induction of labor or a cesarean delivery with medical complications did not change the results. The adjusted relative risks (95% confidence intervals) were 1.19 (1.11, 1.27), 1.21 (1.16, 1.26), and 1.09 (1.07, 1.11), respectively, for male-male twins compared with the opposite-sex twins under the 3 different cutoff values of preterm births.Male sex is associated with increased risk of preterm births in twin pregnancy.II-2

Post-traumatic stress disorder (PTSD) and anxiety are both prevalent in trauma-related populations. However, comorbidity of these 2 psychiatric disorders has not been investigated in flood survivors. This study aimed to estimate the extent to which PTSD and anxiety co-occur in flood survivors, and identify shared risk factors for PTSD only and comorbidity of PTSD and anxiety. Individuals who experienced Dongting Lake flood in 1998 were enrolled in this study using stratified and systematic random sampling method. Information on social support, personality traits, PTSD, and anxiety was collected using self-report questionnaires. The intensity of exposure to the flood was measured by some questions. Logistic regression analyses were used to identify factors associated with PTSD only and comorbidity of PTSD and anxiety. In all, 325 participants were enrolled in this study. The prevalence of PTSD, anxiety, and comorbidity of PTSD and anxiety among survivors of the 1998 Dongting Lake flood at 17-year follow-up was 9.54%, 9.23%, and 6.15%, respectively. Furthermore, 64.52% of those with PTSD had anxiety and 66.67% of those with anxiety had PTSD. Loss of relative, injury of body, damage of house, and emotional instability were shared risk factors for PTSD only and comorbidity of PTSD and anxiety, in comparison with neither PTSD nor anxiety. Post-traumatic stress disorder only and comorbidity of PTSD and anxiety are prevalent in flood survivors, and are both related to the intensity of exposure to the flood and personality traits, indicating that integrated intervention strategies of PTSD and anxiety for flood survivors are needed.