Investigating continuation of folic acid supplementation during peri-conceptional period: a community-based cross-sectional study.

BACKGROUND: Maternal folate may not reach an optimal level to prevent neural tube defects if supplementation commenced post-conception or took place pre-conception only. Our study aimed to investigate the continuation of folic acid (FA) supplementation from pre-conception to post-conception during peri-conceptional period and to examine its differences in FA supplementation between the subgroups taking the initiation timing into consideration. METHODS: This study was conducted in two community health service centers in Jing-an District of Shanghai. Women accompanying their children to pediatric health clinics of the centers were recruited and asked to recall information concerning their socioeconomic and previous obstetric characteristics, utilization of healthcare and FA supplementation before and/or during pregnancy. The continuation of FA supplementation during peri-conceptional period were categorized into three subgroups: Supplementing with FA pre- and post-conception; supplementing with FA preconception only or post-conception only; no FA supplements pre-conception and post-conception. The relationship between FA continuation and couples' characteristics were examined as setting the first subgroup as the base reference. RESULTS: Three hundred and ninety-six women were recruited. Over 40% of the women started FA supplementation after conception and 30.3% of them supplemented with FA from pre-conception to the first trimester of their pregnancy. Compared to this one-third of participants, women who didn't supplemented with any FA during peri-conceptional period were more likely to have no utilization of pre-conception healthcare ([Formula: see text]= 2.47, 95% [Formula: see text]: 1.33-4.61) or antenatal care ([Formula: see text]= 4.05, 95% [Formula: see text]: 1.76-9.34), or who had a lower family socioeconomic status ([Formula: see text]= 4.36, 95% [Formula: see text]: 1.79-10.64). Women who supplemented with FA pre-conception only or post-conception only were more likely to have no utilization of pre-conception healthcare ([Formula: see text]= 2.94, 95% [Formula: see text]: 1.79-4.82), or to have no previous pregnancy complication ([Formula: see text]=1.80, 95% [Formula: see text]: 0.99-3.28). CONCLUSION: Over two-fifth of the women started FA supplementation and only one-third of them had an optimal supplementation from pre-conception to the first trimester. Maternal utilization of healthcare before or during pregnancy together with maternal and paternal socioeconomic status may play a role in the continuation to FA supplementation pre- and post-conception.

Preconception thyroid-stimulating hormone levels and adverse pregnancy outcomes.

OBJECTIVE: Evidence for the association between subclinical thyroid dysfunction before conception and its pregnancy outcomes is inconsistent. Thus, we evaluated the relationship between preconception thyroid-stimulating hormone (TSH) levels and adverse pregnancy outcomes. DESIGN: Retrospective cohort study. METHODS: A total of 50,217 women without prior thyroid disease who became pregnant within 1 year after undertaking a routine TSH test in the Chongqing Municipality of China (2010-2016) were studied. Restricted cubic spline regression and logistic regression were used to estimate the association between preconception TSH levels and pregnancy outcomes. The main outcomes were individual and composite adverse pregnancy outcomes (CAPOs) comprising pregnancy loss, small for gestational age, large for gestational age, and preterm birth. RESULTS: Incidence of CAPO was 24.19%. Increased preconception TSH level was positively associated with CAPO (odds ratio [OR]/SD: 1.04, 95% confidence interval [CI]: 1.01-1.07) when TSH was ≥2.1 mIU/L, positively associated with pregnancy loss (OR/SD: 1.06, 95% CI: 1.01-1.12) when TSH was <2.1 mIU/L, negatively and positively associated with preterm delivery when TSH levels were <1.3 mIU/L (OR/SD: 0.90, 95% CI: 0.83-0.97) and >3.0 mIU/L (OR/SD: 1.08, 95% CI: 1.00-1.17), respectively. Women with subclinical hypothyroidism before conception were at a higher risk for CAPO (adjusted odds ratio [aOR]: 1.12, 95% CI: 1.04-1.22), while those with subclinical hyperthyroidism had a higher risk of preterm delivery (aOR: 1.31, 95% CI: 1.01-1.70). CONCLUSIONS: Nonlinear associations were indicated between preconception TSH levels and pregnancy outcomes. Subclinical thyroid dysfunction before conception was associated with an increased risk of adverse pregnancy outcomes.

Preconception reproductive tract infections status and adverse pregnancy outcomes: a population-based retrospective cohort study.

BACKGROUND: Reproductive tract infections can cause serious adverse outcomes for pregnant women such as spontaneous abortion and preterm birth. However, it is unclear whether maternal reproductive tract infection before pregnancy would also be related to any adverse pregnancy outcomes. This study aims to investigate the association of maternal preconception reproductive tract infections with subsequent adverse pregnancy outcomes. METHODS: A retrospective cohort study was conducted in the Chongqing Municipality of China between April 2010 and December 2016. A total of 57,586 women (57,708 pregnancies) from all 39 counties of Chongqing who participated in the National Free Preconception Health Examination Project were included. They all took preconception examinations for gonorrhea, chlamydia, trichomoniasis, syphilis, bacterial vaginosis and candidiasis before pregnancy within one year. Primary outcomes included spontaneous abortion (< 28 weeks gestation), preterm birth (< 37 weeks gestation), macrosomia and low birthweight. RESULTS: Of the 57,708 pregnancies, 2438 (4.22%) had at least one type of reproductive tract infections. Compared with women who were not infected with any reproductive tract infection before pregnancy, women with reproductive tract infections had a higher rate of spontaneous abortion (7.88% vs. 5.62%, p < 0.001). After analyzing by each infection, there were few significant associations between pre-pregnancy infections and adverse outcomes. Preconception syphilis infection was significantly associated with increased odds of spontaneous abortion (aOR = 2.07, 95%CI 1.50-2.85), induced abortion/labour due to medical reasons (aOR = 1.60, 95%CI 1.01-2.54) and preterm birth (aOR = 1.60, 95%CI 1.12-2.30) after adjusting for potential confounders. Preconception trichomoniasis was intended to relate to a higher risk of spontaneous abortion (aOR = 1.65, 95%CI 1.01-2.71), but its impact seemed to be attributed to its co-infection with other RTIs. Women who were chlamydia or bacterial vaginosis positive before pregnancy showed higher odds of macrosomia (aOR = 2.00, 95% CI 1.07-3.74 for chlamydia; aOR = 1.58, 95% CI 1.06-2.34 for bacterial vaginosis). Preconception bacterial vaginosis might also be associated with higher risks of very preterm birth (aOR = 2.16, 95%CI 1.23-3.78) and large for gestational age (aOR = 1.36, 95%CI 1.02-1.81). CONCLUSIONS: Women with infections of the genital tract before pregnancy might also have increased risks of subsequent adverse outcomes including spontaneous abortion, preterm birth and macrosomia.

Prevalence of reproductive tract infections among women preparing to conceive in Chongqing, China: trends and risk factors.

BACKGROUND: Reproductive tract infection has become a major public health issue all over the world for its high and growing prevalence. It can cause adverse pregnancy outcomes in pregnant women and their foetuses. This study aimed to investigate the trends and risk factors of the prevalence of reproductive tract infections among women who prepared to conceive in the Chongqing Municipality (China) from 2012 to 2016. METHODS: A multi-center cross-sectional study was conducted between January 2012 and December 2016. Women aged 20-49 years who intended to get pregnant were recruited for this study. All participants underwent preconception examination, which included testing for Neisseria gonorrhoeae, Chlamydia trachomatis, Trichomonas vaginalis, syphilis, bacterial vaginosis and candidiasis according to the national diagnostic standard. A total of 439,372 women with testing results for all six types of reproductive tract infections were included in our final analyses. Logistic regression and factor analysis were used to determine the possible sociodemographic factors associated with prevalence trends. RESULTS: In our study, the overall positive rate of RTIs among the 439,372 women of reproductive age was 5.03%. Candidiasis was the most common infection in our population (2.47%), followed by bacterial vaginosis (1.28%), syphilis (0.73%), T. vaginalis (0.49%), C. trachomatis (0.20%) and N. gonorrhoeae (0.06%). The prevalence of reproductive tract infections was highest among women aged 35 years and above, with a primary or lower education level, history of pregnancy, delivery, induced abortion, or spontaneous abortion. From 2012 to 2016, the trend of the overall prevalence of reproductive tract infections was V-shaped, decreasing steadily from 2012 to 2015, with a slight rise in 2016. Our results suggest that the distribution change of age, education level, gravidity, parity, and history of induced abortion influenced this trend. CONCLUSION: Since the number of high-risk women who intend to become pregnant is growing in the Chongqing Municipality, pre-conception positive preventions including health education, regular screening, and timely treatment of reproductive tract infections are needed to prevent the impact of reproductive tract infections on maternal health and infant safety.

Reproductive tract infections (RTIs) can cause serious health problems, such as spontaneous abortion and congenital diseases in pregnant women and their foetuses. However, there is a lack of studies focusing on the prevalence of RTIs and their trends among women who intend to conceive. This cross-sectional study examined data collected from 439,372 women during their preconception care to investigate the trend and related risk factors of the prevalence of RTIs, thereby providing essential data for their prevention. Participants were women from all 39 counties in the Chongqing Municipality of China, and data were collected between 2012 and 2016. We found that the overall prevalence of the six types of RTIs among these women was 5.03%, which was relatively lower than that in other populations in previous studies. Age, education level, history of pregnancy or delivery, and history of abortion were all associated with the prevalence of RTIs. The prevalence trend from 2012 to 2016 was V-shaped decreased steadily from 2012 until 2015 and rose slightly in 2016. Our data suggested that this trend might be influenced by changes in the proportion of 'high-risk' women, that is, women with higher age, lower education level, and a history of pregnancy or induced abortion. This study suggests that health education and regular screening are necessary to face new challenges experienced by older women or women with previous pregnancies who intended to get pregnant in recent years in China.

Assessment of the health status of middle-aged and elderly men with head scale, SF-36, IIEF5, AMS, and IPSS.

BACKGROUND: Identifying practical and distinguished indicators and influencing factors of male aging may be useful in predicting subsequent aging trends, designing personalized prevention, and improving lifestyle and health. METHODS: A cross-sectional, population-based study was performed in Jiashan County, China in 2016. A total of 690 local male residents, aged 40 to 80 years, were eligible for recruitment. Demographic and lifestyle information was collected through structured interviews. A self-designed head scale, the Medical Outcomes Study 36-item Short Form (SF-36), International Index of Erectile Function (IIEF5), Aging Males' Symptoms (AMS), and International Prostate Symptom Score (IPSS) were used. Analysis of variance, local polynomial regression smoothing curves, multiple linear regression, and partial correlation analyses were performed. RESULTS: All the scales deteriorated with increasing age (P < 0.01), especially from the age of 60. The most significant changes between adjacent age groups were found in IIEF5 scores (16.7, 43.5 and 39.4%). Income, nutrition, personality and neighborhood relationship had an effect on SF-36 and AMS after adjusting for age (P < 0.01). Furthermore, neighborhood relationship modified the age effect on the head scale score and IIEF5 (P = 0.03); nutrition modified the relationship between age and SF-36 (P < 0.01). CONCLUSIONS: Recession of reproductive health may be a distinct predictor of male aging. The associations of social inequalities or personality and health offer potential interventions for men's health in aging. Self-reported scales may limit the precision and more physical fitness tests could be combined for a more precise assessment.

Co-occurrence subgroups of child sexual abuse, health risk behaviors and their associations among secondary school students in China.

BACKGROUND: Little is known on the co-occurrence and heterogeneity of child sexual abuse (CSA) or health risk behavior (HRB) prevalence nor the associations among the victims. OBJECTIVES: To detect the prevalence and subgroups of adolescents reporting CSAs or HRBs, and to examine the association between the subgroups. METHODS: Participants were secondary school students in a national survey in China (N = 8746). Self-reported CSA and HRB experiences were collected through a computer assisted questionnaire. Prevalence and confidence intervals were calculated. Multigroup latent class analysis (LCA) was used to examine latent subgroups of CSA and HRB. Dual latent class regression analysis was used to examine the association between CSA and HRB classes. RESULTS: A total of 8746 students participated in our study. The prevalence of having ever experienced any of the reported seven CSA items was 12.9%. The preferred LCA model consisted of a three-class CSA latent variable, i.e. "Low CSAs"(95.7% of the total respondents), "Verbal or exhibitionism CSAs"(3.3%), and "high multiple CSAs" (1.1%); and a three-class HRB latent variable, i.e. "Low HRBs"(70.5%), "externalizing HRBs" (20.7%), and "internalizing HRBs" (8.7%). Students in the "Verbal or exhibitionism CSAs" or "high multiple CSAs" classes had higher probabilities of being in "externalizing HRBs" or "internalizing HRBs" classes. The probabilities were higher in "high multiple CSAs" class(male externalizing OR 4.05, 95%CI 1.71-9.57; internalizing OR 11.77, 95%CI 4.76-29.13; female externalizing OR 4.97, 95%CI 1.99-12.44; internalizing OR 9.87, 95%CI 3.71-26.25) than those in "Verbal or exhibitionism CSA"(male externalizing OR 2.51, 95%CI 1.50-4.20; internalizing OR 3.08, 95%CI 1.48-6.40; female externalizing OR 2.53, 95%CI 1.63-3.95; internalizing OR 6.05, 95%CI 3.73-9.80). CONCLUSIONS: Prevalence of CSA items varies. Non-contact CSAs are the most common forms of child sexual abuse among Chinese school students. There are different latent class co-occurrence patterns of CSA items or HRB items among the respondents. CSA experiences are in association with HRB experiences and the associations between latent classes are dose-responded. Multi-victimization has more significantly negative effects. The results could help identify high-risk subgroups and promote more nuanced interventions addressing adverse experiences and risk behaviors among at-risk adolescents.

Epigenetic alternations of microRNAs and DNA methylation contribute to gestational diabetes mellitus.

This study aimed to identify epigenetic alternations of microRNAs and DNA methylation for gestational diabetes mellitus (GDM) diagnosis and treatment using in silico approach. Data of mRNA and miRNA expression microarray (GSE103552 and GSE104297) and DNA methylation data set (GSE106099) were obtained from the GEO database. Differentially expressed genes (DEGs), differentially expressed miRNAs (DEMs) and differentially methylated genes (DMGs) were obtained by limma package. Functional and enrichment analyses were performed with the DAVID database. The protein-protein interaction (PPI) network was constructed by STRING and visualized in Cytoscape. Simultaneously, a connectivity map (CMap) analysis was performed to screen potential therapeutic agents for GDM. In GDM, 184 low miRNA-targeting up-regulated genes and 234 high miRNA-targeting down-regulated genes as well as 364 hypomethylation-high-expressed genes and 541 hypermethylation-low-expressed genes were obtained. They were mainly enriched in terms of axon guidance, purine metabolism, focal adhesion and proteasome, respectively. In addition, 115 genes (67 up-regulated and 48 down-regulated) were regulated by both aberrant alternations of miRNAs and DNA methylation. Ten chemicals were identified as putative therapeutic agents for GDM and four hub genes (IGF1R, ATG7, DICER1 and RANBP2) were found in PPI and may be associated with GDM. Overall, this study identified a series of differentially expressed genes that are associated with epigenetic alternations of miRNA and DNA methylation in GDM. Ten chemicals and four hub genes may be further explored as potential drugs and targets for GDM diagnosis and treatment, respectively.

Examining the Effect of Fish Oil Supplementation in Chinese Pregnant Women on Gestation Duration and Risk of Preterm Delivery.

BACKGROUND: Intervention studies have shown that long-chain (LC) n-3 PUFA intake can prolong gestation but the dose-time-effect relations remain unresolved. OBJECTIVES: We examined the effect on gestation duration of 2 doses of supplemental LC n-3 PUFAs. METHODS: We undertook a 3-group parallel randomized controlled trial in areas of China with low (median: 2.1 g/d) and higher (14.3 g/d) fish intake. Unselected women (median: age, 26.2 y; BMI, 20. kg/m2) were randomly assigned at midgestation to take four 0.72-g identical gelatin capsules per day until the last day of the preterm period (<259 days of gestation), when they were asked to stop. Capsules contained fish oil [high fish oil (HFO) group (60% w/w LC n-3 PUFAs)], a 1:3 mixture of fish oil to olive oil [low fish oil (LFO) group (20%)], or olive oil [control (CON) group (0%)], providing 2.0, 0.5, and 0 g/d of LC n-3 PUFAs, respectively. Habitual fish intake was recorded at baseline. Hazard rate ratios (HRRs) for spontaneous delivery <259 days of gestation and <273 days of gestation across groups were estimated by Cox regression. RESULTS: Among 5531 women randomly assigned, 92.5% were included in analyses (1706/1825, 1695/1851, and 1717/1855, respectively). The groups were similar with respect to hazard rates <259 days of gestation [HRR: 1.04 (95% CI: 0.70, 1.53) for LFO compared with CON and 0.90 (95% CI: 0.60, 1.35) for HFO compared with CON], hazard rates <273 days of gestation [HRR: 1.00 (95% CI: 0.86, 1.18) and 0.91 (95% CI: 0.77, 1.07), respectively], and mean gestation durations [differences: 0.2 d (95% CI: -0.5, 0.8) and 0.6 d (95% CI: -0.06, 1.2), respectively]. Inspection of pregnancy survival curves suggested that LC n-3 PUFAs delayed delivery in low fish consumers by 5-10 d and that this effect ceased rapidly after stopping taking the capsules. CONCLUSION: This trial could not substantiate that fish oil prevents preterm birth in Chinese women, possibly because statistical power was too low. This trial was registered at clinicaltrials.gov as NCT02770456.

Longitudinal Trends of AMS and IIEF-5 Scores in Randomly-Selected Community Men 40 to 80 Years Old: Preliminary Results.

INTRODUCTION: Most of conclusions on the relationship between age and reproductive health in aging men relied on cross-sectional data. AIM: To better characterize the natural degradation trajectory of reproductive health of aging men based on longitudinal data. METHODS: A community cohort study was performed in randomly selected men 40 to 80 years old, initiated in 2012 and followed up in 2014 and 2016. Participants were investigated by face-to-face structured interview, including demographic information and International Index of Erectile Function (IIEF-5) and Aging Males' Symptoms (AMS) scales. MAIN OUTCOME MEASURES: The differences among the 3 assessments of IIEF-5 and AMS were analyzed, and progression trajectories were traced. RESULTS: The high degree of variability on AMS and IIEF-5 was evident across individual subjects, as was the variability within individuals. The average IIEF-5 score of 248 subjects decreased from 16.9 to 14.1 during the 4 years, and the total AMS score increased from 22.6-27.0 (P < .001). Longitudinal data, both of individuals and of groups, showed the more rapid increase or decrease on AMS or IIEF-5 scores over 4 years in the 61-70 age group than in other age groups. CLINICAL IMPLICATION: The evidence of the greatest changes on AMS and IIEF-5 scores in the 61-70 age group prompts the importance of early intervention to postpone the degradation of reproductive health. STRENGTH & LIMITATIONS: Compared with cross-sectional data, longitudinal data can provide a more natural progression trajectory of reproductive health of aging male individuals. The low follow-up rate might affect the parameter estimation to some extent. CONCLUSION: Cohort data over 4 years' follow-up showed more abrupt changes on AMS and IIEF-5 scores in the 61-70 age group than in other age groups. Zheng J-B, Liang Q-F, Li J-H, et al. Longitudinal Trends of AMS and IIEF-5 Scores in Randomly-Selected Community Men 40 to 80 Years Old: Preliminary Results. J Sex Med 2019;16:1567-1573.

Puberty timing associated with obesity and central obesity in Chinese Han girls.

BACKGROUND: There is growing scientific evidence supports a link between increased childhood adiposity and early onset of puberty in girls worldwide in recent decades. However, the data from Chinese girls remain ambiguous. The aims of this study were to estimate the puberty milestones and examine attainment of puberty associated with obesity and central obesity in Chinese Han schoolgirls. METHODS: The cross-sectional school-based study examined 2996 Han schoolgirls aged 9 to 19 years from 6 provinces in China. Trained clinicians assessed  the girls for height, weight, waist circumference, Tanner stages of breast and pubic hair development, and menarcheal status. We classified girls as normal weight, overweight, or obese based on BMI, and as normal weight or central obese based on the waist-height ratio, then estimated and compared median age at a given Tanner stage or greater by weight class using Probit models. RESULTS: The median age at menarche was 12.36 years. The median ages at breast stages(B) 2 through 5 were 10.03, 11.38, 13.39, and 15.79 years, respectively, and at pubic hair stages(PH) 2 through 5 were 11.62, 12.70, 14.38, and 16.92 years, respectively. Girls from urban areas experienced menarche, B3 and B4 stages, and PH3 through PH5 stages earlier. Girls with central obesity and overweight/obesity reached puberty earlier at almost every Tanner stage of breast and pubic hair than normal girls. Girls with obesity developed PH2 and PH3 earlier than their overweight peers. However, we did not find any significant differences between girls with overweight and obesity at all stages of breast development. CONCLUSIONS: Childhood obesity, including both overweight/obesity and central obesity, is associated with earlier attainment of puberty in Chinese Han schoolgirls.

The impact of age, BMI and sex hormone on aging males' symptoms and the international index of erectile function scores.

OBJECTIVE: To analyze the impact of age, BMI and sex hormone on aging males' symptoms (AMS) and the 5-item version of the international index of erectile function (IIEF-5) scores in middle-aged and elderly Chinese men. METHODS: A population-based cross-sectional study was conducted in Jiashan County. A total of 969 men, aged between 40 and 80 years old, were admitted. Physical examination and the sex hormones were measured, and AMS and IIEF-5 scores were assessed. RESULTS: The oneway ANOVA analysis indicated older age groups had higher AMS total-scores, somatic and sexual sub-scores, and lower IIEF5 scores (all p < .01). Pairwise correlation (rpairwise) analyses showed the significant associations between AMS and age or sex hormone (cFT, Bio-T, SHBG, and LH) levels, and similar for IIEF5. However, when age was adjusted, the correlation coefficients (rpartial) weakened, and correlation significance disappeared, except LH (for AMS: rpartial = 0.096, p = .009; for IIEF-5: rpartial = -0.140, p = .001). Multiple linear regressions confirmed the influence of increased age and LH on the AMS and IIEF5 scores. CONCLUSION: CFT, Bio-T and SHBG failed to yield any additional predicting information when age was adjusted. To improve the male reproductive health, future research should pay more attention on aging-related comorbidities and how to improve general wellness.

Anorexia nervosa, depression and suicidal thoughts among Chinese adolescents: a national school-based cross-sectional study.

BACKGROUND: Although there is much literature on adolescent suicide, combined effects of depression and anorexia nervosa on suicide were rarely investigated. The aims of this study are to examine the association between anorexia nervosa and suicidal thoughts and explore the interaction between anorexia nervosa and depression. METHODS: This is a cross-sectional study, in the study, a sample of 8,746 Chinese adolescents was selected by multistage stratified method in 2012/2013 from 20 middle schools in 7 provinces across China Mainland. Multilevel logistic model was introduced to explore association between anorexia nervosa and suicidal thoughts. And subgroup analyses were conducted on participants with or without depression. RESULTS: Multilevel logistic model revealed that demographic variables, including academic achievement, were not the predictive risk factors of suicidal thoughts. Those who suffered from worse severity of perceived anorexia nervosa were at increased risk of thinking about suicide. The interaction between depression and anorexia nervosa was significant, however, subgroup analyses showed that the associations were significant only among the adolescents without depression. CONCLUSIONS: Our results indicate that all levels of anorexia nervosa serve as predictable indicators of suicidal thoughts in Chinese adolescents, and the effects of anorexia nervosa are modified by depression status.

Single or double semen samples: the dilemma in epidemiological studies on semen quality.

STUDY QUESTION: Is it necessary to collect more than one semen sample from each individual in epidemiological studies? SUMMARY ANSWER: Single semen samples can be used in model construction as long as the model adjusts for major relevant covariates. WHAT IS KNOWN ALREADY: If a series of semen samples are taken from one individual at different times, significant intra-individual variation may exist. STUDY DESIGN, SIZE, DURATION: A population-based cross-sectional study was conducted from 1 December 2000 to 20 November 2002. A total of 1010 volunteers, aged between 20 and 60 years old, were recruited. PARTICIPANTS/MATERIALS, SETTING, METHODS: A total of 998 subjects were included for statistical analysis. Of these, 332 men provided single semen samples (group 1) and 666 men provided two samples (group 2). Semen parameters, including semen volume, sperm concentration, total sperm number, progressive motility, vitality, and sperm morphology, were analyzed with standardized methods according to the World Health Organization (WHO) laboratory manual for the examination of human semen and sperm-cervical mucus interaction (3rd edition). MAIN RESULTS AND THE ROLE OF CHANCE: Rapidly progressive motility of semen from group 1 was lower than that of group 2, but other parameters were not significantly different. The differences in mean values between the double samples were small on all semen parameters. The correlations between the two ejaculates were high, but the agreements were poor except for sperm vitality and normal morphology. Model selection and validation analysis supported the premise that the regression model from the first samples was applicable for the second samples. The large sample size with extensive quality control provides robust parameter estimation and promises good applicability for model selection and validation. LIMITATIONS, REASONS FOR CAUTION: The results are valid for healthy men in China, not for subfertile or infertile men. WIDER IMPLICATIONS OF THE FINDINGS: The overall semen quality of a given group of healthy men will not vary significantly in the short term. Single semen samples can be used in model building as long as major relevant covariates are considered. Utilizing multiple semen donations may actually cause the samples to be less representative. STUDY FUNDING/COMPETING INTERESTS: This research was supported by a grant from Shanghai Science and Technical Committee (02DJ14053) and a grant from Ministry of Science and Technology, China (9902). All authors have no competing interests.

Prenatal exposure to antidepressants and risk of epilepsy in childhood.

PURPOSE: This study aimed to estimate the association between prenatal exposure to antidepressants and risk of epilepsy in childhood, taking maternal depression into account. METHODS: We conducted a population-based cohort study including all Danish singletons born alive between 1997 and 2008 (n = 734 237). Information on antidepressant medication and diagnosis of depression and epilepsy was obtained from Danish National Registers. The exposed group comprised children of mothers who used antidepressants from 30 days before pregnancy until the date of birth. The reference group comprised children of mothers who used no antidepressants from 6 months before pregnancy to birth. We estimated the hazard ratios (HR) of epilepsy and 95% confidence intervals (CI) using Cox proportional hazard models. RESULTS: We identified 12 438 (1.7%) children exposed to antidepressants during pregnancy (including 30 days before pregnancy) and 5829 (0.8%) children diagnosed with epilepsy in the follow-up time (mean: 6.7 years). Children exposed to antidepressants during pregnancy had a 27% higher risk of epilepsy (aHR: 1.27; 95%CI: 1.05-1.54) than children in the reference group. The estimate of this association was 1.71 (95%CI: 1.10-2.66) if their mothers also had a registry-based hospital diagnosis of depression in the 6 months before pregnancy or during pregnancy and 1.14 (95%CI: 0.91-1.43) if their mothers had no registry-based hospital diagnosis of depression. Children of mothers who used antidepressants from 2 to 6 months before pregnancy (but not during pregnancy) had an increased risk of epilepsy (aHR: 1.36; 95%CI: 1.07-1.73). CONCLUSIONS: Antidepressant use during pregnancy was associated with a higher risk of epilepsy among children whose mothers had also a registry-based hospital diagnosis of depression during pregnancy. Copyright © 2016 John Wiley & Sons, Ltd.

Association between environmental exposure to cadmium and human semen quality.

Cadmium (Cd) is a heavy metal with toxicant to reproductive functions. The aim of this study was to explore the effects of environmental exposure to Cd on human semen quality. A total of 587 men from the general population, aged from 20 to 59 years old, and without occupational exposure to Cd were recruited from three provinces in China to participate in the study. The median of serum Cd was 1.9 µg/L (P25-P75:1.1-2.9). In case Cd was less than or equal to 6.3 µg/L (P95) and the semen parameters were logarithmically transformed, the inverse associations between Cd and semen volume (-0.03 ± 0.007), progressive motility (-0.01 ± 0.004), and sperm morphology (-0.04 ± 0.004) were found across the whole group, after adjusting for age group, occupation, season of semen sample collection, abstinence intervals, smoking, alcohol drinking, and body mass index. Our findings indicate that higher Cd may reduce the semen volume, progressive motility, and morphology among men without occupational exposure to Cd.

Another functional frame-shift polymorphism of DEFB126 (rs11467497) associated with male infertility.

DEFB126 rs140685149 mutation was shown to cause sperm dysfunction and subfertility. Indel rs11467497 is another 4-nucleotide frame-shift mutation (151bp upstream of rs140685149) that leads to the premature termination of translation and the expression of peptide truncated at the carboxyl terminus. In the present study, we performed a comprehensive association study to check the contribution of rs140685149 and rs11467497 to male infertility. Our results confirmed the previous findings that there was no association between rs140685149 and sperm motility. In contrast, we found a significant association of another indel rs11467497 with male infertility. Moreover, rs11467497 was shown to be associated with higher number of round cells in the infertile males with low sperm motility. Surprisingly, the two mutations commonly existed in the sperm donors (n = 672), suggesting a potential application of the two indels in the screening for eligible sperm donors. Western blotting assays showed the sperms with rs140685149 2-nt deletion tended to have unstable DEFB126 protein in contrast of no DEFB126 protein expressed in the sperms with rs11467497 4-nt deletion, suggesting a more severe consequence caused by rs11467497 mutation. In conclusion, our study presented a significant contribution of another functional frame-shift polymorphism of DEFB126 (rs11467497) to male infertility.

Altered microRNAs expression profiling in cumulus cells from patients with polycystic ovary syndrome.

BACKGROUND: Polycystic ovary syndrome (PCOS) is a common endocrine disorder in women of reproductive age, and oocyte developmental competence is altered in patients with PCOS. In recent years microRNAs (miRNAs) have emerged as important regulators of gene expression, the aim of the study was to study miRNAs expression patterns of cumulus cells from PCOS patients. METHODS: The study included 20 patients undergoing in vitro fertilization (IVF) and intra-cytoplasmic sperm injection (ICSI): 10 diagnosed with PCOS and 10 matching controls. We used deep sequencing technology to identify the miRNAs differentially expressed in the cumulus cells of PCOS. RESULTS: There were 17 differentially expressed miRNAs in PCOS cumulus cells, including 10 miRNAs increase and 7 miRNAs decrease. These miRNAs were predicted to target a large set of genes with different functions, including Wnt- and MAPK- signaling pathways, oocyte meiosis, progesterone-mediated oocyte maturation and cell cycle. Unsupervised hierarchical clustering analysis demonstrated that there was a specific miRNAs expression pattern in PCOS cumulus cells. CONCLUSION: We found that the miRNAs expression profile was different in cumulus cells isolated from PCOS patients compared with control. This study provided new evidence for understanding the pathogenesis of PCOS.

The Ser680Asn polymorphism in the follicle-stimulating hormone receptor gene is associated with the ovarian response in controlled ovarian hyperstimulation.

OBJECTIVE: Polymorphisms in the follicle-stimulating hormone receptor (FSHR) gene are reported to be associated with the ovarian response in controlled ovarian hyperstimulation (COH), although there remains some discordance between studies. Here, using the largest patient sample to date, we evaluated the association of the p.Ser680Asn (S(680)N) polymorphism in the FSHR gene with the outcome of COH. DESIGN: Cohort study. SETTING: Medical academy and hospital. PATIENTS: A total of 1250 infertile Chinese women undergoing IVF/ICIS-ET treatment were included. MEASURES: The association between an FSHR polymorphism (S(680)N) and the ovarian response was analysed. Genotyping was performed by utilizing direct sequencing and the Sequenom MassARRAY iPLEX platform. Follicular fluid oestradiol (E2) and follicle-stimulating hormone (FSH) concentrations were determined using electrochemiluminesence immunoassays. The ovarian response parameters were analysed based on the FSHR genotypes. The odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated for the risk genotypes and alleles. RESULTS: There were linear correlations between the basal FSH level, exogenous gonadotropin consumption, and oocytes retrieved and the Ser680 alleles. Patients in the homozygous SS group demonstrated higher basal FSH levels, required more dosage of exogenous gonadotropin for ovarian stimulation, and had fewer numbers of oocytes retrieved compared with patients in the homozygous NN and heterozygous groups. Logistic regression analysis revealed that the OR of a poor ovarian response for the NS genotype was 1·79 (95% CI 1·28-2·61; P < 0·001), whereas that for the SS genotype was 2·25 (95% CI 1·40-3·58; P < 0·001) after adjusting for age, BMI and basal FSH level. The concentration of E2 in the follicular fluid was significantly higher in subjects with the NN genotype than the SS genotype (772 ± 545 ng/ml vs. 1299 ± 504 ng/ml). CONCLUSIONS: Follicle-stimulating hormone receptor gene polymorphism at position 680 is associated with different ovarian responses to controlled ovarian hyperstimulation.

Relative validity and reproducibility of a food frequency questionnaire used in pregnant women from a rural area of China.

OBJECTIVE: Food frequency questionnaires are relatively inexpensive, easy and quick to administer, but the construction of a food frequency questionnaire that can capture Chinese food habits is challenging given the diverse lifestyle and eating habits in different parts of the country. The aim of this study was to assess the validity and reproducibility of a self-administered food frequency questionnaire against a 3-day dietary recall in a rural region of western China. DESIGN: Prospective cohort study. SETTING: Chinese maternal and child healthcare hospital. POPULATION: A total of 168 healthy pregnant women. METHODS: Pregnant women completed a food frequency questionnaire at 16-24 weeks gestation, and again at 29-31 weeks; during weeks 26-27 they completed a 3-day dietary recall. RESULTS: In general, mean intake was higher when assessed with food frequency questionnaires compared with dietary recall. Spearman and intra-class correlation coefficients between the two food frequency questionnaires ranged from 0.31 to 0.69 and from 0.27 to 0.79, respectively. For the second food frequency questionnaire and the dietary recall, the crude and de-attenuated Spearman correlations ranged from 0.12 to 0.55 and 0.14 to 0.58, respectively. The correlation both between the two food frequency questionnaires and between the second food frequency questionnaire and the dietary recall decreased after adjustment for energy. Ranking women, 31-57% and 1-8% were classified into the same and the opposite quartile, respectively, by both food frequency questionnaires; 30-45% and 1-11% were classified into the same and the opposite quartile respectively for the second food frequency questionnaire and dietary recall. CONCLUSION: The food frequency questionnaire showed good reproducibility and correlations with dietary recall; it is useful for ranking study participants according to dietary intake, which is of great importance to future etiological studies in this cohort.

Navigating the gut-bone axis: The pivotal role of Coprococcus3 in osteoporosis prevention through Mendelian randomization.

Osteoporosis (OP) constitutes a notable public health concern that significantly impacts the skeletal health of the global aging population. Its prevalence is steadily escalating, yet the intricacies of its diagnosis and treatment remain challenging. Recent investigations have illuminated a profound interlink between gut microbiota (GM) and bone metabolism, thereby opening new avenues for probing the causal relationship between GM and OP. Employing Mendelian randomization (MR) as the investigative tool, this study delves into the causal rapport between 211 varieties of GM and OP. The data are culled from genome-wide association studies (GWAS) conducted by the MiBioGen consortium, in tandem with OP genetic data gleaned from the UK Biobank, BioBank Japan Project, and the FinnGen database. A comprehensive repertoire of statistical methodologies, encompassing inverse-variance weighting, weighted median, Simple mode, Weighted mode, and MR-Egger regression techniques, was adroitly harnessed for meticulous analysis. The discernment emerged that the genus Coprococcus3 is inversely associated with OP, potentially serving as a deterrent against its onset. Additionally, 21 other gut microbial species exhibited a positive correlation with OP, potentially accentuating its proclivity and progression. Subsequent to rigorous scrutiny via heterogeneity and sensitivity analyses, these findings corroborate the causal nexus between GM and OP. Facilitated by MR, this study successfully elucidates the causal underpinning binding GM and OP, thereby endowing invaluable insights for deeper exploration into the pivotal role of GM in the pathogenesis of OP.