Maohua Miao

Exposure to bisphenol-A and reproductive hormones among male adults

BACKGROUND Bisphenol A (BPA) is a suspected human endocrine disruptor which is widely used. METHODS In order to determine whether urine BPA level is associated with serum reproductive hormone levels among male adults, we carried out a cross-sectional study in China. We recruited 592 male workers and collected their urine samples for BPA measurement. We also collected blood samples and examined serum reproductive hormones. We used multiple linear regression and log-binomial model to examine associations between urine BPA level and hormone levels after controlling for age and smoking status. RESULTS An increased urine BPA level was associated with increased prolactin (p<0.001), estradiol (p<0.001), sex hormone-binding globulin level (p=0.001), and a reduced androstenedione (p<0.001) and free androgen index level (p=0.021). Males, whose urine BPA level was in the 2nd, 3rd and highest quartiles, had respectively 1.58, 1.33 and 3.09-fold increased prevalence of having a high prolactin level (>P75 level). The highest quartile of BPA level was associated with 1.63 and 1.50-fold increased prevalence of having a high estradiol and elevated sex hormone-binding globulin level. Males with higher quartile of BPA level had a lower inhibin B level. CONCLUSION High BPA exposure is associated with increased prolactin, estradiol and sex hormone-binding globulin level in males, and may contribute to male infertility.

Associations between Bisphenol A Exposure and Reproductive Hormones among Female Workers.

The associations between Bisphenol-A (BPA) exposure and reproductive hormone levels among women are unclear. A cross-sectional study was conducted among female workers from BPA-exposed and unexposed factories in China. Women’s blood samples were collected for assay of follicle-stimulating hormone (FSH), luteinizing hormone (LH), 17β-Estradiol (E2), prolactin (PRL), and progesterone (PROG). Their urine samples were collected for BPA measurement. In the exposed group, time weighted average exposure to BPA for an 8-h shift (TWA8), a measure incorporating historic exposure level, was generated based on personal air sampling. Multiple linear regression analyses were used to examine linear associations between urine BPA concentration and reproductive hormones after controlling for potential confounders. A total of 106 exposed and 250 unexposed female workers were included in this study. A significant positive association between increased urine BPA concentration and higher PRL and PROG levels were observed. Similar associations were observed after the analysis was carried out separately among the exposed and unexposed workers. In addition, a positive association between urine BPA and E2 was observed among exposed workers with borderline significance, while a statistically significant inverse association between urine BPA and FSH was observed among unexposed group. The results suggest that BPA exposure may lead to alterations in female reproductive hormone levels.

Effects of maternal folic acid supplementation on gene methylation and being small for gestational age

BACKGROUND Being small for gestational age (SGA), a foetal growth abnormality, has a long-lasting impact on childhood health. Its aetiology and underlying mechanisms are not well understood. Underlying epigenetic changes of imprinted genes have emerged as a potential pathological pathway because they may be associated with growth, including SGA. As a common methyl donor, folic acid (FA) is essential for DNA methylation, synthesis and repair, and FA supplementation is widely recommended for women planning pregnancy. The present study aimed to investigate the inter-relationships among methylation levels of two imprinted genes [H19 differentially methylated regions (DMRs) and MEST DMRs], maternal FA supplementation and SGA. METHODS We conducted a case-control study. Umbilical cord blood was taken from 39 SGA infants and 49 controls whose birth weights are appropriate for gestational age (AGA). DNA methylation levels of H19 and MEST DMRs were determined by an analysis of mass array quantitative methylation. RESULTS Statistically significantly higher methylation levels were observed at sites 7.8, 9 and 17.18 of H19 (P = 0.030, 0.016 and 0.050, respectively) in the SGA infants compared to the AGA group. In addition, the association was stronger in male births where the mothers took FA around conception at six H19 sites (P = 0.004, 0.005, 0.048, 0.002, 0.021 and 0.005, respectively). CONCLUSIONS Methylation levels at H19 DMRs were higher in SGA infants compared to AGA controls. It appears that the association may be influenced by maternal peri-conception FA supplementation and also be sex-specific.

Urine bisphenol A and pubertal development in boys

BACKGROUND Bisphenol A (BPA) is an environmental endocrine disruptor and is found in many consumer products. Animal studies suggest that BPA may perturb pubertal development in males, although studies in humans are limited. OBJECTIVE This study investigated the association between BPA exposure and pubertal onset and progression among school-aged boys in Shanghai, China. METHODS A total of 671 boys aged 9-18 years from three schools (one elementary, one middle, and one high school) in Shanghai were enrolled in a cross-sectional study. Tanner stages for genital and pubic hair development and testicular volume were assessed by a specifically trained physician. Information concerning spermarche was self-reported. Urine samples were collected to examine peripubertal BPA exposure levels. Associations between BPA exposure and pubertal development, as indicated by the presence of different milestones in early puberty, mid-puberty and late puberty, were assessed using Poisson multivariate regression to derive adjusted prevalence ratios (PRs) and 95% confidence intervals (CIs). RESULTS Earlier onset of genital and pubic hair development was observed in boys with moderate BPA exposure compared with those exposed to the least BPA; the adjusted PRs were 1.31 (95%CI:1.03, 1.68) and 1.28 (95%CI:1.02, 1.60) for onset of genital maturation and pubic hair development, respectively. A similar trend was seen for onset of testicular development, although the association was not statistically significant. Conversely, compared with the lowest level of BPA exposure, moderate BPA exposure was associated with delayed presence of the late stage of genital development, with an adjusted PR of 0.78 (95%CI: 0.65, 0.92). A suggestive inverse association was also observed between BPA exposure and late progression of testicular development. CONCLUSIONS Our findings indicate an association between peripubertal BPA exposure and earlier pubertal onset, but delayed pubertal progression, in boys. Longitudinal studies of male pubertal development with periodic follow-up are needed to verify these results.

Couple's infertility in relation to male smoking in a Chinese rural area.

Smoking is a well-known risk factor of reproductive health. However, the effect of paternal smoking on fertility has been less extensively examined. We conducted a cross-sectional study in a mountainous area of South-West China to assess the effect of male smoking on couples′ fertility. A total of 8200 couples aged 18-49 years in the study area were invited to participate in the study. An in-person interview was performed to collect demographic characteristics of the couples, and husbands′ life style factors including smoking and drinking habits. Information on time to pregnancy (TTP) was collected retrospectively. Infertility was defined as failure to achieve clinical pregnancy after regular unprotected intercourse for ≥12 months. Logistic regression model was used to estimate the association between male smoking and infertility. A total of 7025 couples were included in the final analysis. After adjusting for potential confounders, the couples were more likely to suffer from infertility if the husbands smoked (adjusted odds ratio [aOR] =1.28, 95% CI: 1.08-1.52) before the first pregnancy. After the analyses were performed according to husbands′ smoking duration, an increased risk started at a relatively longer smoking duration of 5-10 years (aOR = 1.58, 95% CI: 1.26-1.99) and a stronger association (aOR = 3.34, 95% CI: 2.45-4.56) was observed in the group of ≥10 years. Similar patterns were found for the number of cigarettes smoked per day and the total amount of cigarettes smoked. From our findings, we conclude that male smoking may have an adverse impact on couples′ infertility.

The relationship between age at menarche and infertility among Chinese rural women

OBJECTIVE To explore the relationship between age at menarche and infertility. STUDY DESIGN The cross-sectional study investigated 6906 couples from the communities in Sandu Shui Autonomous County of Guizhou Province, China. Face to face interviews were conducted to collect information on age at menarche and time to first pregnancy, as well as demographic characteristics and lifestyle factors. Infertility was defined as being unable to become pregnant after attempting for ≥12 months. Poisson regression was used to assess the relationship between age at menarche and infertility of first attempt. RESULTS The prevalence rate of infertility for the first pregnancy attempt of the study population was 11.87%. There is an obvious monotonic, almost linear, trend of prevalence rate of infertility with increasing age at menarche (P for trend: <0.001). Compared with wives with age at menarche of 13 years, the prevalence ratios of infertility were 0.71 (95%CI: 0.42, 1.20), 1.33 (95%CI: 1.05, 1.68), 1.47 (95%CI: 1.17, 1.85), 1.57 (95%CI: 1.20, 2.04), 1.41 (95%CI: 1.00, 1.99) and 1.73 (95%CI: 1.18, 2.52) for wives with age at menarche of ≤12, 14, 15, 16, 17 and ≥18 years, respectively, after adjusting for wifes year at birth, age at marriage, ethnic group, education and occupation, and husbands smoking and drinking habits before marriage. CONCLUSIONS The present community-based study indicated that increasing age at menarche was associated with an increased risk of infertility in the study population.

Mifepristone-induced abortion and duration of third stage labour in a subsequent pregnancy

To evaluate the impact of mifepristone-induced abortion (MA) on the duration of third stage labour in a subsequent pregnancy, an observational cohort study was conducted from 1998 to 2001 at antenatal clinics in Shanghai, Beijing and Chengdu, China. A total of 4925 pregnant women with no history of induced abortion (NA) and 4931 pregnant women with one previous MA were enrolled and followed until delivery. Of these, 5139 women who delivered singletons vaginally were used in the present analyses, including 2614 with NA and 2525 with a history of MA. Maternal characteristics, labour duration and other obstetric and gynaecological information were obtained. The incidence rates of prolonged third stage of labour were 1.55% and 1.49% in NA and MA, respectively. After adjusting for age at delivery, maternal education, maternal occupation, area of residence, duration of gestational, type of delivery and pregnancy-induced hypertension, MA was not associated with the risk of prolonged third stage of labour (odds ratios = 0.92, 95% confidence interval 0.58, 1.44). Subgroup analysis of women with MA showed similar results regardless of gestational age at abortion, womans age at abortion, subsequent curettage/complications and the interpregnancy interval. In conclusion, the data did not provide evidence that one MA was associated with the risk of prolonged third stage of labour in a subsequent pregnancy in primiparae.

Gestational Weight Gain Trend and Population Attributable Risks of Adverse Fetal Growth Outcomes in Ohio.

BACKGROUND The trend of gestational weight gain (GWG) in relation to the Institute of Medicine (IOM) guidelines and the population attributable risks (PARs) of GWG on fetal growth outcomes remain unclear. METHODS We analysed Ohio birth certificates from 2006 to 2012 to examine GWG trend by prepregnancy body mass index, to calculate the risk of small- and large-for-gestational age (SGA and LGA), and macrosomia (birthweight >4000 g or >4500 g) infants, and to estimate the PARs of GWG below or above the guidelines. RESULTS Of 869,531 women who delivered singleton live births at 22-44 weeks of gestation, 4.5% were underweight, 48.9% were normal weight, 23.9% were overweight, and 22.7% were obese before pregnancy. About 36.5% of underweight, 52.6% of normal weight, 72.5% of overweight, and 62.4% of obese women gained weight above the guidelines, with only slight changes from 2006 to 2012. Also, 34.9% of underweight, 20.1% of normal weight, 16.3% of overweight, and 27.0% of obese women gained weight below the guidelines. The PAR of GWG below or above the guidelines was -13% for SGA, 32.6% for LGA, 28.1% for macrosomia >4000 g, and 48.3% for macrosomia >4500 g, mostly driven by currently GWG above the guidelines in normal weight, overweight, and obese women. CONCLUSIONS A high percentage of pregnant women gained weight outside of the current IOM GWG guidelines; however, changes from 2006 to 2012 were small. GWG above the IOM guidelines significantly contributed to a large proportion of LGA and macrosomic infants in the general population.

Effect of interpregnancy interval after a mifepristone-induced abortion on neonatal outcomes in subsequent pregnancy

BACKGROUND The study evaluated effects of interpregnancy interval (IPI) on neonatal outcomes after mifepristone-induced abortion in the first pregnancy. STUDY DESIGN This observational cohort study, conducted from 1998 to 2001 at antenatal clinics in Shanghai, Beijing, and Chengdu, China, included 4682 nulliparous women with one mifepristone-induced abortion in their first pregnancy, who were enrolled and followed up until delivery. We compared neonatal outcomes among women with different IPIs between their mifepristone-induced abortion and subsequent pregnancy. RESULTS When compared to IPI of 18-24 months, there was an increased risk of the neonate being small for gestational age (SGA) [adjusted odds ratio (aOR): 2.01; 95% confidence interval (CI): 1.04-3.88] when IPI was <6 months; this risk was greater among women without a curettage history after abortion (aOR: 2.49; 95% CI: 1.13-5.50). The associations between IPI and preterm delivery (<37 weeks), low birth weight (<2500 g), mean birth weight and ponderal index were not statistically significant. CONCLUSIONS The results indicate that an IPI <6 months after one mifepristone-induced abortion in first pregnancy is associated with an increased risk of SGA in the subsequent pregnancy.

Risk of autism spectrum disorder in offspring following paternal use of selective serotonin reuptake inhibitors before conception: a population-based cohort study

Objective The present study aimed to examine the association between paternal selective serotonin reuptake inhibitor (SSRI) use before conception and the risk of autism spectrum disorder (ASD) in offspring. Design A population-based cohort study. Methods We conducted a cohort study of 669 922 children born from 1998 to 2008, with follow-up throughout 2013. Based on Danish national registers, we linked information on paternal use of SSRIs, ASD diagnosed in children and a range of potential confounders. The children whose fathers used SSRIs during the last 3 months prior to conception were identified as the exposed. Cox regression model was used to estimate the HR for ASD in children. Results Compared with unexposed children, the exposed had a 1.62-fold higher risk of ASD (95% CI 1.33 to 1.96) and the risk attenuated after adjusting for potential confounders, especially fathers’ psychiatric conditions (HR=1.43, 95% CI 1.18 to 1.74). When extending the exposure window to 1 year before conception, the increased risk persisted in children of fathers using SSRIs only from the last year until the last 3 months prior to conception (HR=1.54, 95% CI 1.21 to 1.94) but not in children of fathers using SSRIs only during the last 3 months prior to conception (HR=1.17, 95% CI 0.75 to 1.82). We also performed stratified analyses according to paternal history of affective disorders and observed no increased ASD risk among children whose father had affective disorders. Besides, the sibling analysis showed that the ASD risk did not increase among exposed children compared with their unexposed siblings. Conclusions The mildly increased risk of ASD in the offspring associated with paternal SSRI use before conception may be attributable to paternal underlying psychiatric indications related to SSRI use or other unmeasured confounding factors.