Trajectories of lipids around the menopause transition in Chinese women: results of the Kailuan cohort study.

OBJECTIVE: To investigate changes in lipid parameters around the final menstrual period (FMP) in Chinese women. DESIGN: A prospective community-based cohort study. PATIENT(S): Three thousand seven hundred fifty six Chinese women from the Kailuan cohort study who participated in the first examination and reached their FMP by the end of the seventh examination. Health examinations were performed every 2 years. Multivariable piece-wise linear mixed-effect models were used for repeated measures of lipids as a function of time around FMP. INTERVENTION(S): Number of years before or after FMP at each examination. MAIN OUTCOME MEASURE(S): Lipids at each examination, including total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides (TGs). RESULT(S): Total cholesterol, LDL-C, and TGs began to increase in early transition, regardless of baseline age. Moreover, TC and LDL-C had a maximum annual increase from 1 year before to 2 years after FMP; TGs had a maximum annual increase from early transition to the fourth-year after menopause. The trajectories in other postmenopause segments differed across subgroups of different baseline ages. Furthermore, HDL-C remained stable around FMP if baseline age was <45 years, whereas if baseline age was ≥45 years, HDL-C would first decline and then rise during postmenopause. Women with a higher body mass index (BMI) underwent less adverse changes in TC and TGs during postmenopause and had decline in HDL-C before menopause. A later FMP age was associated with less adverse changes in TC, LDL-C, and TGs and greater increase in HDL-C during postmenopause; it was associated with a greater increase in LDL-C during early transition. CONCLUSION(S): This repeated measurement cohort study of indigenous Chinese women demonstrated that, regardless of baseline age, the adverse effect of menopause on lipids was since early transition, and the most adverse change time was from 1 year before to 2 years after FMP; HDL-C decreased first and then increased during postmenopause in older women; BMI and FMP age affected lipid trajectory mainly during postmenopause. We highlighted positive lipid management during menopause to reduce the burden of postmenopausal dyslipidemia. For lipid stratification management in postmenopausal women, BMI and FMP age are important factors.

Association between body mass index and varicocele among 211 989 Chinese reproductive-age males.

OBJECTIVES: To explore the relationship between body mass index and varicocele, the range of body mass index that leads to increased odds of varicocele, and the association between body mass index with the position and grade of varicocele. METHODS: We conducted a cross-sectional study of 211 989 Chinese males aged 18-65 years participated in the National Free Pre-conception Check-up Projects from January 2013 to December 2018. Univariate and multivariate logistic regression models were constructed to assess the association between body mass index and varicocele. RESULTS: Overweight and obese males had 13.1% (odds ratio 0.869, 95% confidence interval 0.838-0.902) and 32.3% (odds ratio 0.677, 95% confidence interval 0.632-0.725) lower odds of varicocele than those with normal body mass index, respectively. The association between them was non-linear, and males with body mass index of 17.74 to 23.09 kg/m2 had an increased odds of varicocele. The overweight and obese males had lower odds of left and bilateral varicocele, but the right varicocele odds was increased by 63.3% in obese males. CONCLUSION: Body mass index was associated with the odds of varicocele among reproductive-age males, but the odds varied by position. The effects of weight management and varicocele on fertility should be taken into account in fertility guidance.

The prevalence and influencing factors of anaemia among pre-pregnant women in mainland China: a large population-based, cross-sectional study.

Anaemia is a global public health problem affecting women worldwide, and reproductive-age women are at increased risk. We conducted a population-based cross-sectional study analysing the prevalence of overall anaemia and anaemia according to severity in Chinese pre-pregnant women to update current knowledge on anaemia epidemiology. Based on the National Free Preconception Check-up Projects supported by the Chinese government, 5 679 782 women participating in this project in 2017 were included in the present study. The cyanmethemoglobin method was applied to assess Hb concentrations. Univariate and multivariate logistic regressions were applied for associated factors. The prevalence of anaemia among Chinese pre-pregnant women was 21·64 % (mild: 14·10 %, moderate: 7·17 % and severe : 0·37 %). The prevalence of overall and severe anaemia was the highest in Tibet and the lowest in Beijing among thirty-one provinces. Women's age, region, ethnic origin, educational level, occupation and pregnancy history were all correlated with anaemia. Women with B blood type (adjusted OR (aOR) = 0·89), higher BMI (overweight: aOR = 0·84; obesity: aOR = 0·70) and alcohol consumption (aOR = 0·69) were less likely to have anaemia, while those with rhesus negative blood type (aOR = 1·10), history of anaemia (aOR = 2·60), older age at menarche (aOR = 1·19), heavy menstrual blood loss (aOR = 1·39), longer menstrual period (aOR = 1·09) and shorter menstrual cycle (aOR = 1·08) were more likely to suffer from anaemia. Meat or egg eaters were not significantly associated with severe anaemia. Anaemia is of moderate public health significance among Chinese pre-pregnant women. Interventions should be considered to prevent anaemia to the greatest extent possible to avoid potential harm in this population.

Couples' prepregnancy body mass index and time to pregnancy among those attempting to conceive their first pregnancy.

OBJECTIVE: To explore the relationship between couples' prepregnancy body mass index (BMI) and time to pregnancy (TTP) among those with no prior gravidity. DESIGN: Retrospective cohort study. SETTING: Local maternal/child health care or family-planning service institutions. PATIENT(S): A total of 2,301,782 eligible couples participating in the National Free Preconception Check-up Projects from January 1, 2015 to December 31, 2017. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Time to pregnancy. RESULT(S): Underweight, overweight, or obese status in women and underweight status in men were associated with couples' prolonged TTP. The optimal BMI levels were 20.61-23.06 kg/m2 and 22.69-27.74 kg/m2 for women and men, respectively. Compared with couples in whom both partners had a normal BMI, the pregnancy rates were reduced by 10% (fecundability odds ratio [FOR] 0.90; 95% confidence interval [CI], 0.88-0.92) and 19% (FOR 0.81; 95% CI, 0.78-0.84) for couples in whom both partners were underweight or obese, respectively. The combination of women with a normal BMI and overweight men had the greatest fertility (FOR 1.03; 95% CI, 1.02-1.03), and the combination of obese women and underweight men had the lowest fertility (FOR 0.70; 95% CI, 0.65-0.76). CONCLUSION(S): Abnormal prepregnancy BMIs in either women or men were associated with prolonged TTP among couples with no prior gravidity. Scientific management of couples' prepregnancy BMI could improve their fertility.

Pre-pregnancy maternal fasting plasma glucose levels in relation to time to pregnancy among the couples attempting first pregnancy.

STUDY QUESTION: What is the relationship between pre-pregnancy maternal glucose levels and fecundability in Chinese couples? SUMMARY ANSWER: Elevated pre-pregnancy maternal glucose levels were associated with fecundability, as reflected by prolonged time to pregnancy (TTP) among the couples with no prior gravidity. STUDY DESIGN, SIZE, DURATION: Based on the National Free Pre-conception Check-up Projects supported by the Chinese government, 2 226 048 eligible couples attempting first pregnancy and participating in the project from 2015 to 2016 were included. They were followed-up for 1 year or until they reported pregnancy. PARTICIPANTS/MATERIALS, SETTINGS, METHODS: The Kaplan-Meier method was used to estimate the cumulative pregnancy rate in each menstrual cycle, and the discrete-time analogue of the Cox models was used to estimate the fecundability odds ratios (FORs) and 95% CIs by different pre-pregnancy maternal glucose levels (impaired fasting glucose (IFG) or diabetes as compared to normal). MAIN RESULTS AND THE ROLE OF CHANCE: The cumulative pregnancy rate for 12 cycles of the normal fasting plasma glucose (FPG) level group was 42.29%, significantly higher than that of the IFG (35.52%) and diabetes groups (31.52%). After adjusting for confounding factors, the FORs were 0.82 (95% CI: 0.81-0.83) and 0.74 (95% CI: 0.72-0.76) for the IFG and diabetes groups, respectively, as compared to the normal group. The association between pre-pregnancy maternal FPG levels and the FORs was non-linear, and the optimal FPG level for greatest fecundability (shortest TTP) was 3.90-4.89 mmol/L. LIMITATIONS, REASONS FOR CAUTION: The findings from this register-based cohort study require cautious interpretation given that information bias would be inevitable for single FPG measurements and for TTP calculations that were based on telephone follow-up information. Additionally, because couples who achieved pregnancy during their first menstrual cycle in the study were excluded, the pregnancy rates reported were low and possibly biased. WIDER IMPLICATIONS OF THE FINDINGS: The current report suggests that elevated pre-pregnancy maternal glucose levels were associated with prolonged TTP. Early evaluation and preventive treatment for female partners with IFG or diabetes in a pre-pregnancy examination are necessary. STUDY FUNDING/COMPETING INTEREST(S): Funding was provided by the National Key Research and Development Program of China (grants No. 2016YFC1000300 and 2016YFC1000307), the National Natural Science Foundation of China (grant No. 81872634), the CAMS Innovation Fund for Medical Sciences (grant No. 2018-I2M-1-004), the National Human Genetic Resources Sharing Service Platform (grant No. 2005DKA21300) and the National Population and Reproductive Health Science Data Center (grant No. 2005DKA32408), People's Republic of China. The authors have no conflicts of interest to declare. TRIAL REGISTRATION NUMBER: N/A.

Preconception blood pressure and time to pregnancy among couples attempting to conceive their first pregnancy.

BACKGROUND: The association of abnormal blood pressure levels (including hypertension and prehypertension) with reduced fecundability among young childbearing-age couples is not yet elucidated completely. OBJECTIVE: The purpose of this study was to investigate the association between abnormal preconception blood pressure level and time to pregnancy among couples who are attempting to conceive their first pregnancy. STUDY DESIGN: A total of 2,234,350 eligible couples (with no previous gravidity and whose female partners were 20-49 years old) participated in the National Free Preconception Check-up Projects from January 1, 2015, to December 31, 2016. Each couples' preconception blood pressure levels were measured, and time to pregnancy was recorded. Cox models for discrete survival time were used to estimate fecundability odds ratios and their corresponding 95% confidence intervals after adjustment for age, ethnicity, educational level, occupation, household registration, region, tobacco exposure, alcohol intake, body mass index, duration of marriage of the couples, and fasting plasma glucose levels of the female partner. RESULTS: Compared with normotensive women, those women with hypertension (systolic blood pressure ≥140 mm Hg or diastolic blood pressure ≥90 mm Hg) had a 21% lower pregnancy rate (fecundability odds ratio, 0.79; 95% confidence interval, 0.78-0.81). A similar finding was found among men (fecundability odds ratio, 0.89; 95% confidence interval, 0.88-0.90). Prehypertension (systolic blood pressure between 120 and 139 mm Hg, and/or a diastolic blood pressure between 80 and 89 mm Hg) in both male and female partners was associated slightly with reduced fecundability odds ratios. Compared with couples in which both partners were normotensive, the pregnancy rate was reduced by 27% (fecundability odds ratio, 0.73; 95% confidence interval, 0.69-0.77) among couples in which both partners had hypertension. CONCLUSION: Abnormal preconception blood pressure levels were associated with prolonged time to pregnancy among couples who were attempting to conceive their first pregnancy; the mechanism is worth further investigation.

Paired eye-control study of unilateral opaque bubble layer in femtosecond laser assisted laser in situ keratomileusis.

AIM: To investigate the predictive factors of the opaque bubble layer (OBL) compared to the fellow eye of same patients in FS200 femtosecond laser assisted laser in situ keratomileusis (FS-LASIK). METHODS: This study consisted of 60 consecutive patients (120 eyes) with unilateral OBL during FS-LASIK. Eyes were divided into OBL (the OBL eyes) and OBL-free groups (the fellow eyes) based on the occurrence of OBL. The preoperative demographic data, refraction, keratometry, corneal astigmatism, pachymetry, intraocular pressure and intraoperative data including the outlet location of gas diffusing canal were collected. Conditional logistic regression analysis was performed to find the associated factors with OBL in the two groups by determining odds ratios (OR) and 95%CI. RESULTS: The preoperative demographic data, mean spherical errors, mean K value, suction time, intraocular pressure and central cornea thickness were not significantly different between the two groups. The outlet location of gas diffusing canal (P<0.01, OR 7.16, 95%CI 2.53-20.32) and the corneal astigmatism (P=0.013, OR 0.13, 95%CI 0.03-0.65) were significantly associated with the incidence of OBL by multivariate logistic regression analysis. Visual acuity, efficacy, and safety were comparable between the two groups two months after surgery except for a slightly lower predictability value for the hard OBL eyes. CONCLUSION: The reduction of the incidence of OBL is obvious when the outlet of gas diffusing canal located at the posterior border of the corneoscleral limbus. This is probably consequent to more effectiveness of gas diffusing canal. Corneal astigmatism is also an independent protective factor for OBL formation.

The association between low glucose-6-phosphate dehydrogenase activity level and hepatitis B virus infection among pre-pregnant reproductive-age Chinese females.

The relationship between females with low glucose-6-phosphate dehydrogenase activity level (LG6PD) and HBV infection is unclear. We conducted a cross sectional study of 124 406 reproductive-age Chinese females who participated in the National Free Pre-conception Check-up Projects to investigate the risk of HBV infection among females with LG6PD and its effect on liver enzyme. Based on HBV serological test results, the participants were divided into the susceptible, immunized, and HBV infected groups. The multivariable-adjusted odds ratios (ORs) for HBV infection in LG6PD participants were 1.71 (95% confidence interval (CI): 1.45-2.01) and 1.41 (95% CI: 1.23-1.62), respectively with the susceptible and immunized participants as references, compared to those without LG6PD. Participants with HBV infection only and combined with HBV infection and LG6PD had 184% and 249% significantly higher risks of elevated alanine transaminase (ALT) (susceptible participants as reference). If the immunized participants were used as reference, significant higher odds of elevated ALT occurred (3.48 (95% CI: 3.18-3.80), 4.28 (95% CI: 2.92-6.28)). Thus, reproductive-age females with LG6PD had a higher prevalence of HBV infection, and LG6PD might exacerbate ALT elevation in HBV infected females. Our findings underscore the need to explore collaborative management approaches for these two diseases among reproductive-age females for maternal and child health.

The association between glucose-6-phosphate dehydrogenase deficiency and abnormal blood pressure among prepregnant reproductive-age Chinese females.

The morbidity of hypertension is increasing among young adults worldwide, and glucose-6-phosphate dehydrogenase (G6PD) deficiency is a high-prevalence genetic disease. We investigated whether G6PD deficiency was associated with abnormal blood pressure (including elevated blood pressure and hypertension) among prepregnant reproductive-age females. We conducted a cross-sectional study in Shenzhen, which included 154 917 females aged 20-49 who participated in the National Free Pre-conception Check-up Projects supported by the Chinese government. After adjusting for confounding factors, the odds ratios (ORs) for the effects of G6PD deficiency on elevated blood pressure and hypertension were 1.18 (95% confidence interval (CI): 1.03-1.35) and 1.11 (95% CI: 1.00-1.23), respectively. Moreover, the association between G6PD deficiency and abnormal blood pressure was statistically significant for systolic blood pressure (SBP) but not significant for diastolic blood pressure (DBP). The multivariable-adjusted ORs for females with G6PD deficiency in the SBP 120-139 mm Hg and SBP ≥ 140 mm Hg groups were 1.10 (95% CI: 1.00-1.21) and 1.75 (95% CI: 1.25-2.42), respectively, while the multivariable-adjusted ORs for females with G6PD deficiency in the DBP 80-89 mm Hg and DBP ≥ 90 mm Hg groups were 1.09 (95% CI: 0.98-1.21) and 0.89 (95% CI: 0.66-1.19), respectively. Subgroup analyses showed similar results. The findings of this study underscored that reproductive-age females with a G6PD deficiency had a higher risk of elevated blood pressure and hypertension. Therefore, females with G6PD deficiency combined with elevated blood pressure or hypertension were high-risk populations during prepregnancy and pregnancy periods. Early intervention and collaborative management approaches should be explored to reduce the burden of these two diseases and improve maternal and child health.

Paternal smoking and spontaneous abortion: a population-based retrospective cohort study among non-smoking women aged 20-49 years in rural China.

BACKGROUND: To comprehensively evaluate the association of paternal smoking and spontaneous abortion. METHODS: We conducted a population-based retrospective cohort study among 5 770 691 non-smoking rural Chinese women, along with their husbands, participating in the National Free Pre-Pregnancy Checkups Project, regarding outcome events that occurred in 2010-2016. The main outcome was spontaneous abortion (SA). Multivariable logistic regression was used to estimate OR and 95% CI, and restricted cubic spline was used to estimate the non-linear relationship. RESULTS: The multivariable-adjusted OR of exposure to paternal smoking for SA was 1.17 (95% CI 1.16 to 1.19), compared with women without exposure to paternal smoking; and corresponding OR of exposure to preconception paternal smoking for SA was 1.11 (95% CI 1.08 to 1.14), compared with women without exposure to preconception paternal smoking. The ORs of preconception paternal smoking also increased with increases in paternal smoking (pnonlinear<0.05, almost linearly shaped) and preconception paternal smoking (pnonlinear>0.05). In addition, periconception paternal smoking cessation was associated with an 18% (15%-22%) lower risk of SA. CONCLUSION: Paternal smoking was associated with SA. The importance of tobacco control, specifically pertaining to paternal smoking, should be emphasised during preconception and pregnancy counselling.

Correction: A Meta-Analysis of the Association between ESR1 Genetic Variants and the Risk of Breast Cancer.

[This corrects the article DOI: 10.1371/journal.pone.0153314.].

Association of Husband Smoking With Wife's Hypertension Status in Over 5 Million Chinese Females Aged 20 to 49 Years.

BACKGROUND: The effect of second-hand smoking, especially husband smoking, on wife's hypertension has not been well studied. The current study was aimed to assess the association of husband smoking with wife's hypertension among females aged 20 to 49 years. METHODS AND RESULTS: This study included 5 027 731 females along with their husbands from the National Free Pre-pregnancy Checkup Projects conducted across 31 provinces in China in 2014. Smoking/passive smoking status was collected by a standard questionnaire and blood pressure was measured by an electronic device after 10 minutes rest. Odds ratios and their corresponding 95% CIs for female hypertension were estimated according to smoking status of husband and wife, husbands' smoking amount, and cumulative exposure to husband smoking. Compared with neither-smoker group, the multivariable-adjusted odds ratio for female hypertension was 1.28 (1.27-1.30), 1.53 (1.30-1.79), and 1.50 (1.36-1.67) in husband-only, wife-only, and mixed group, respectively. Furthermore, a higher risk of having hypertension was associated with amount and cumulative exposure of husband smoking. For example, compared with neither-smoker, the multivariate-adjusted odds ratio was 1.22 (1.19-1.25), 1.24 (1.21-1.26), 1.32 (1.26-1.37), 1.37 (1.34-1.41), and 1.75 (1.64-1.87) for females whose husband smoked 1 to 5, 6 to 10, 11 to 15, 16 to 20, and ≥21 cigarettes per day, respectively (Pfor trend<0.001). Subgroup analyses identified similar results. CONCLUSIONS: There were associations of husband smoking with female hypertension prevalence. A family-based smoking restriction strategy may reduce smoking in males and improve hypertension control in females.

MicroRNA biogenesis pathway genes polymorphisms and cancer risk: a systematic review and meta-analysis.

MicroRNAs (miRNAs) may promote the development and progression of human cancers. Therefore, components of the miRNA biogenesis pathway may play critical roles in human cancer. Single nucleotide polymorphisms (SNPs) or mutations in genes involved in the miRNA biogenesis pathway may alter levels of gene expression, affecting disease susceptibility. Results of previous studies on genetic variants in the miRNA biogenesis pathway and cancer risk were inconsistent. Therefore, a meta-analysis is needed to assess the associations of these genetic variants with human cancer risk. We searched for relevant articles from PubMed, Web of Science, CNKI, and CBM through Jun 21, 2016. In total, 21 case-control articles met all of the inclusion criteria for the study. Significant associations were observed between cancer risk and the DGCR8polymorphism rs417309 G >A (OR 1.22, 95% CI [1.04-1.42]), as well as the DICER1 polymorphism rs1057035 TT (OR 1.13, 95% CI [1.05-1.22]). These SNPs exhibit high potential as novel diagnostic markers. Future studies with larger sample sizes and more refined analyses are needed to shed more light on these findings.

Apolipoprotein E Gene Variants and Risk of Coronary Heart Disease: A Meta-Analysis.

Objectives. Apo E genes involved in lipoprotein synthesis and metabolism are considered one of the candidates to CHD. However, the results remain conflicting. Methods. We performed this meta-analysis based on 30 published studies including 11,804 CHD patients and 17,713 controls. Results. Compared with the wild genotype E3/3, the variant genotypes ApoEE3/4 and E4/4 were associated with 22% and 45% increased risk of CHD, respectively (E3/4 versus E3/3: OR = 1.22, 95% CI = 1.15-1.29; E4/4 versus E3/3: OR = 1.45, 95% CI = 1.23-1.71). Besides, compared with ε3 allele, carriers with the ε4 allele had a 46% increased risk of CHD (OR = 1.46, 95% CI = 1.28-1.66), while the ε2 had no significantly decreased risk of CHD. In the subgroup analysis by ethnicity, ε4 had a 25% increased risk of CHD in Caucasians (OR = 1.25, 95% CI = 1.11-1.41), and the effects were more evident in Mongolians (OR = 2.29, 95% CI = 1.89-2.77). The ε2 allele had a decreased risk of CHD in Caucasians (OR = 0.84, 95% CI = 0.74-0.96), but not in Mongolians. Conclusions. The analysis suggested that ApoEε4 mutation was associated with the increased risk of CHD, while ApoEε2 allele had a decreased risk of CHD just in Caucasians.

The TOMM40 gene rs2075650 polymorphism contributes to Alzheimer's disease in Caucasian, and Asian populations.

Largescale genome-wide association studies (GWAS) showed that the TOMM40 rs2075650 polymorphism is significantly associated with Alzheimer's disease (AD) in Caucasian ancestry and Asian population. Here, we evaluated this association with large-scale samples from selected 12 studies (N=28,515; 10,358 cases and 18,157 controls) through the PubMed, AlzGene, and Google Scholar. We identified a significant association between rs2075650 and AD with P=0.000, OR=4.178 and 95% CI 1.891-9.228. In subgroup analysis, we identified significant association between rs2075650 polymorphism and AD in both Asian and Caucasians but not mixed populations. Collectively, our analysis shows TOMM40 rs2075650 polymorphism is associated with AD susceptibility in Asian, Caucasian, and mixed populations. We believe that our analysis will be helpful for future genetic researches on AD.

A Meta-Analysis of the Association between ESR1 Genetic Variants and the Risk of Breast Cancer.

BACKGROUND: Single nucleotide polymorphisms (SNPs) in the estrogen receptor gene (ESR1) play critical roles in breast cancer (BC) susceptibility. Genome-wide association studies have reported that SNPs in ESR1 are associated with BC susceptibility; however, the results of recent studies have been inconsistent. Therefore, we performed this meta-analysis to obtain more accurate and credible results. METHODS: We pooled published literature from PubMed, EMBASE, and Web of Science and calculated odds ratios (ORs) with 95% confidence intervals (CIs) to assess the strength of associations using fixed effects models and random effects models. Twenty relevant case-control and cohort studies of the 3 related SNPs were identified. RESULTS: Three SNPs of the ESR1 gene, rs2077647:T>C, rs2228480:G>A and rs3798577:T>C, were not associated with increased BC risk in our overall meta-analysis. Stratified analysis by ethnicity showed that in Caucasians, the rs2228480 AA genotype was associated with a 26% decreased risk of BC compared with the GG genotype (OR = 0.740, 95% CI: 0.555-0.987). The C allele of the rs3798577:T>C variant was associated with decreased BC risk in Asians (OR = 0.828, 95% CI: 0.730-0.939), while Caucasians with this allele were found to experience significantly increased BC risk (OR = 1.551, 95% CI: 1.037-2.321). A non-significant association between rs2077647 and BC risk was identified in all of the evaluated ethnic populations. CONCLUSION: Rs3798577 was associated with an increased risk of BC in Caucasian populations but a decreased risk in Asians. Rs2228480 had a large protective effect in Caucasians, while rs2077647 was not associated with BC risk.