The birth and diagnosis of a child with congenital abnormalities can alter parental reproductive patterns, yet its association with subsequent fecundability remains insufficiently explored. We conducted a government-supported matched cohort study in China to evaluate this association and assess whether it varies by the severity of the child’s condition and parental characteristics. A total of 2448 couples from the National Free Preconception Check-up Project between 2012 and 2018 attempting to conceive again were included: 612 exposed couples with children affected by congenital abnormalities and 1836 nonexposed couples with unaffected children and no adverse pregnancy history. Participants were followed via telephone every 3 months for 1 year to track pregnancy outcomes. Cox proportional hazards models with a shared frailty were used to estimate HRs and 95% CIs for fecundability. Overall, exposed couples demonstrated a 28% higher fecundability than nonexposed couples (HR 1.28 [95% CI, 1.10-1.49]). This association was primarily observed among parents with “healthy” characteristics and those whose children had single-system/body part congenital abnormalities (HR 1.27 [95% CI, 1.09-1.48]). These findings highlight the importance of integrated fertility counseling, prenatal screening, and psychological support for families seeking subsequent pregnancies after the birth of a child with congenital abnormalities.

The clinical manifestations of 22q11.2 deletion syndrome (22q11.2 DS) are highly heterogeneous, and the underlying causes of phenotypic variation remain unclear. This study conducted a systematic meta-analysis to evaluate the impact of the deletion position within the 22q11.2 region on phenotypic variability. PubMed, Web of Science, Scopus, Embase, and Cochrane Library databases were searched through 25 September 2024. Literature was screened, and data were extracted based on predefined inclusion and exclusion criteria. A total of 17 articles comprising 4107 subjects were included in this study. Among these, 1296 patients presented with congenital heart malformations, while 220 exhibited psychiatric and behavioral abnormalities. 1. Congenital heart malformations: in the central deletion region, congenital heart malformations were significantly associated with the LCR22B-D deletion [OR (BD/CD): 2.74, 95

China's accession to the ICH has accelerated the advancement of its regulatory science. To foster innovation and improve the efficiency of pharmaceutical research and development, the China National Medical Products Administration (NMPA) encourages the use of real-world evidence (RWE) to support drug regulatory decision-making and has constructed a series of real-world study (RWS) related guidance, reflecting the contribution of the NMPA to the field of RWS in drug clinical development. Based on the four guidelines on RWE, real-world data (RWD), RWS design and protocol development, and communication with regulatory authorities, the guidance has been extended to more specific clinical applications, such as oncology, rare diseases, pediatric drugs, and traditional Chinese medicine. This paper reviews the core content and features of the series of RWS guidelines, presents their role in promoting drug development, and discusses challenges of using RWE in support of drug regulatory decision-making in China.

STUDY QUESTION Do couple's age ranges for optimal fecundability, and the associations with fecundability of couple's age combinations and age differences differ with gravidity? SUMMARY ANSWER The couple's age range of optimal fecundability and age combinations differed with gravidity, and gravidity might modify the associations of age and spousal age difference with couple's fecundability. WHAT IS KNOWN ALREADY Age is one of the strongest determinants of fecundability, but the existing studies have certain limitations in study population, couple's extreme age combinations and age differences, and have not explored whether the association between age and fecundability differs with gravidity. STUDY DESIGN, SIZE, DURATION Retrospective cohort study. 5 407 499 general reproductive-aged couples (not diagnosed with infertility) participated in the National Free Pre-conception Check-up Projects during 2015-2017. They were followed up for pregnancy outcomes through telephone interviews every 3 months until they became pregnant or were followed up for 1 year. PARTICIPANTS/MATERIALS, SETTING, METHODS The main outcome was time to pregnancy, and the fecundability odds ratios and 95% CIs were estimated using the Cox models for discrete survival time. The associations of age and spousal age difference with fecundability were evaluated by restricted cubic splines. MAIN RESULTS AND THE ROLE OF CHANCE In this large cohort of general reproductive-aged population, the age of optimal fecundability of multigravida couples was older than that of nulligravida couples, but their subsequent fecundability declined more sharply with age. The decline in female fecundability was more pronounced with age, with fecundability dropping by ∼30% in both nulligravida and multigravida couples whose female partners aged ≥35 years. In the nulligravida group, the fecundability of couples who were both ≤24 years with the same age was the highest, which decreased steadily with the increase of spousal age difference, and younger male partners did not seem to contribute to improving couple's fecundability. In the multigravida group, couples with female partners aged 25-34 years and a spousal age difference of -5 to 5 years showed higher fecundability, and the effect of spousal age difference on couple's fecundability became suddenly apparent when female partners aged around 40 years. Young male partners were unable to change the decisive effect of female partner's age over 40 years on couple's reduced fecundability, regardless of gravidity. LIMITATIONS, REASONS FOR CAUTION Lacking the time for couples to attempt pregnancy before enrollment, and some couples might suspend pregnancy plans during follow-up because of certain emergencies, which would misestimate the fecundability. Due to the lack of information on sperm quality and sexual frequency of couples, we could not adjust for these factors. Moreover, due to population characteristics, the extrapolation of our results required caution. WIDER IMPLICATIONS OF THE FINDINGS The couple's age range of optimal fecundability, age combinations, and spousal age difference on fecundability varied with gravidity. Female age-related decline in fecundability was more dominant in couple's fecundability. Targeted fertility guidance should be provided to couples with different age combinations and gravidities. STUDY FUNDING/COMPETING INTEREST(S) This research received funding from the Project of National Research Institute for Family Planning (Grant No. 2018NRIFPJ03), the National Key Research and Development Program of China (Grant No. 2016YFC1000307), and the National Human Genetic Resources Sharing Service Platform (Grant No. 2005DKA21300), People's Republic of China. The funders had no role in study design, analysis, decision to publish, or preparation of the manuscript. The authors report no conflict of interest. TRIAL REGISTRATION NUMBER N/A.

OBJECTIVE:To investigate the relationship between ambient fine particulate matter (PM2.5) exposure and fecundability. METHODS:This study included 751,270 female residents from Henan Province who participated in the National Free Pre-conception Check-up Projects during 2015-2017. Ambient cycle-specific PM2.5 exposure was assessed at the county level for each participant using satellite-based PM2.5 concentration data at 1-km resolution. Cox proportional hazards models with time-varying exposure were used to estimate the association between fecundability and PM2.5 exposure, adjusted for potential individual risk factors. RESULTS:During the study period, 568,713 participants were pregnant, monthly mean PM2.5 concentrations varied from 25.5 to 114.0 µg/m3 across study areas. For each 10 µg/m3 increase in cycle-specific PM2.5, the hazard ratio for fecundability was 0.951 (95 % confidence interval: 0.950-0.953). The association was more pronounced in women who were older, with urban household registration, history of pregnancy, higher body mass index (BMI), hypertension, without exposure to tobacco, or whose male partners were older, with higher BMI, or hypertension. CONCLUSION:In this population-based prospective cohort, ambient cycle-specific PM2.5 exposure was associated with reduced fecundability. These findings may support the adverse implications of severe air pollution on reproductive health.

STUDY QUESTION Is there an association between male creatinine levels and time to pregnancy (TTP) in couples planning pregnancy? SUMMARY ANSWER Low and high male creatinine concentrations were associated with reduced couple fecundity. WHAT IS KNOWN ALREADY Abundant evidence suggests male creatinine dysfunction is associated with infertility in males with kidney diseases. However, the association of preconception creatinine levels with reduced fecundity among general reproductive-aged couples lacks evidence from an in-depth population study. STUDY DESIGN, SIZE, DURATION Based on the population-based cohort study from the National Free Preconception Check-up Projects, 4 023 204 couples were recruited and met the inclusion criteria from 1 January 2015 to 31 December 2017. They were planning pregnancy and were followed up every 3 months until achieving pregnancy as detected by gynaecological ultrasonography or were followed up for 1 year for the analysis of TTP. PARTICIPANTS/MATERIALS, SETTING, METHODS Cox regression models were used to estimate hazard ratios (HRs) and 95% CI for creatinine deciles. Restricted cubic spline regression was adopted for the dose-response relationship of creatinine with HRs. R statistical software was used for data analysis. MAIN RESULTS AND THE ROLE OF CHANCE Of the included participants, 2 756 538 (68.52%) couples successfully conceived. The median male serum creatinine was 81.50 mu mol/l. Compared with the reference group (78.00-81.49 mu mol/l) including the median creatinine, fecundity in the first (<= 64.89 mu mol/l), second (64.90-69.99 mu mol/l), third (70.00-73.99 mu mol/l), and tenth (>= 101.00 mu mol/l) deciles decreased by 8%, 5%, 2%, and 1%, respectively (Decile 1 Adjusted HR 0.92, 95% CI 0.91-0.92; Decile 2 Adjusted HR 0.95, 95% CI 0.95-0.96; Decile 3 Adjusted HR 0.98, 95% CI 0.97-0.99; Decile 10 Adjusted HR 0.99, 95% CI 0.98-0.99). An inverse-U-shaped association was consistently presented among males such that non-inferiority for fecundity was shown when creatinine was in the 81.66-104.90 mu mol/l range (P for non-linearity < 0.001). For males over 40 years old, the risk of fecundity impairment was more obvious and the recommended range of creatinine levels for TTP was reduced and more narrow, compared with that for younger males. LIMITATIONS, REASONS FOR CAUTION Not including the time couples spend preparing for pregnancy before enrolment would lead to an overestimation of fecundity; additionally some couples place pregnancy plans on hold due to special emergencies, which would not have been recognized. Due to the lack of information regarding semen quality, psychological factors, sexual intercourse frequencies, and hazardous environmental factors, we could not adjust for these factors. Some variates were self-reported and dichotomized, which were prone to bias. Direct variables reflecting muscle mass and impaired kidney function were lacking. Thus, extrapolation should be done with caution. WIDER IMPLICATIONS OF THE FINDINGS Male creatinine is associated with couples' fecundity and the relationship varied by age. This study provides a better understanding of the potential implications and significance of different creatinine levels and their association with the clinical significance regarding couples' fecundity. STUDY FUNDING/COMPETING INTEREST(S) This research has received funding from the National Natural Science Foundation of China (Grant No. 81872634), the Basic Research Funds of Central Public Welfare Research Institutes of China (Grant No. 2023GJZ03), the National Key Research and Development Program of China (Grant No. 2016YFC1000307), and the Project of National Research Institute for Family Planning (Grant No. 2018NRIFPJ03), People's Republic of China. The authors have no conflicts of interest to declare.

Maternal anaemia is a major public health problem. Developing maternal anaemia prevention and control policies is an important prerequisite for carrying out evidence-based interventions. This article reviews maternal anaemia prevention and control policies in China, identifies gaps, and provides references for other countries. We examined policies concerning maternal nutrition and other related literature in China, identified through key databases and government websites, and conducted a narrative review of the relevant documentations guided by the Smith Policy-Implementing-Process framework. A total of 65 articles and documents were identified for analysis. We found that Chinese government has committed to reducing maternal anaemia at the policy level, with established objectives and a clear time frame. However, most of policies were not accompanied by operational guidelines, standardized interventions, and vigorous monitoring and evaluation mechanisms, and 85% of the policies don't have quantifiable objectives on anaemia. Maternal anaemia prevention and control services offered in clinical settings were primarily nutrition education and anaemia screening. Population-based interventions such as iron fortification have yet to be scaled up. Furthermore, medical insurance schemes in some regions do not cover anaemia prevention and treatment, and in other regions that offer coverage, the reimbursement rate is low. The number and capacity of health professionals is also limited. Policy changes should focus on the integration of evidence-based interventions into routine antenatal care services and public health service packages, standardization of dosages and provision of iron supplementation, streamline of reimbursement for outpatient expenses, and capacity building of health professionals.

Abstract Background The association of genital Mollicutes infection transition with adverse pregnancy outcomes was insignificant among general pregnant women, but there remains a paucity of evidence linking this relationship in gestational diabetes mellitus (GDM) women. The aim was to investigate the association between genital Mollicutes infection and transition and adverse pregnancy outcomes in GDM women, and to explore whether this association still exist when Mollicutes load varied. Methods We involved pregnant women who attended antenatal care in Chongqing, China. After inclusion and exclusion criteria, we conducted a single-center cohort study of 432 GDM women with pregnancy outcomes from January 1, 2018 to December 31, 2021. The main outcome was adverse pregnancy outcomes, including premature rupture of membrane (PROM), fetal distress, macrosomia and others. The exposure was Mollicutes infection, including Ureaplasma urealyticum (Uu) and Mycoplasma hominis (Mh) collected in both the second and the third trimesters, and testing with polymerase chain reaction method. The logistic regression models were used to estimate the relationship between Mollicutes infection and adverse pregnancy outcomes. Results Among 432 GDM women, 241 (55.79%) were infected with genital Mollicutes in either the second or third trimester of pregnancy. At the end of the pregnancy follow-up, 158 (36.57%) participants had adverse pregnancy outcomes, in which PROM, fetal distress and macrosomia were the most commonly observed adverse outcomes. Compared with the uninfected group, the Mollicutes (+/-) group showed no statistical significant increase in PROM (OR = 1.05, 95% CI:0.51 ∼ 2.08) and fetal distress (OR = 1.21, 95% CI: 0.31 ∼ 3.91). Among the 77 participants who were both Uu positive in the second and third trimesters, 38 participants presented a declined Uu load and 39 presented an increased Uu load. The Uu increased group had a 2.95 odds ratio (95% CI: 1.10~8.44) for adverse pregnancy outcomes. Conclusion Mollicutes infection and transition during trimesters were not statistically associated with adverse pregnancy outcomes in GDM women. However, among those consistent infections, women with increasing Uu loads showed increased risks of adverse pregnancy outcomes. For GDM women with certain Mollicutes infection and colonization status, quantitative screening for vaginal infection at different weeks of pregnancy was recommended to provide personalized fertility treatment.

Background: Currently, awareness about platelet count (PC) and its consequences for perinatal outcome have increased, but there is little reliable evidence on fecundability.Methods: Based on the National Free Pre-conception Check-up Projects supported by the Chinese government, 5,524,886 couples met the inclusion criteria were included in this cohort study. Cox regression models were adopted to estimate fecundability ratios (FRs) and their 95% confidence intervals for pre-pregnancy PC quintiles. Restricted cubic splines were used to flexibly model and visualize the relationship of PC with FRs. Microsoft SQL server and R software were used for data management and analysis.Results: The median of pre-pregnancy PC among women was 221.00x10(9)/L. The first (<177.00 x10(9)/L) and second quintile (177.00-207.99 x10(9)/L) of PC showed slightly increased fecundability (Q1: adjusted FR 1.05, 95% CI 1.04-1.06; Q2: adjusted FR 1.04, 95% CI 1.03-1.05), while higher quintals (Q4: 236.00-271.99 x10(9)/L; Q5: >= 272.00 x10(9)/L) were related to reduction of fecundability, when compared with the third quintile of PC (208.00-235.99 x10(9)/L) (Q4: adjusted FR 0.96, 95% CI 0.95-0.97; Q5: adjusted FR 0.88, 95% CI 0.87-0.89). In the first quintiles (<177.00x10(9)/L), only 20.93% women had PC below 129.94x10(9)/L. An inverse-U shape association was consistently observed among women such that the lower PC of normal range (<118.03x10(9)/L) and higher PC (>223.06x10(9)/L) were associated with the risk of reduced female fecundability (P for non-linearity < 0.01).Conclusion: PC is associated with female fecundability. Further classification of PC levels may deepen our understanding of the early warnings and significance of female fecundability.

IMPORTANCE The association of hepatitis B virus (HBV) infection with reduced fecundability among reproductive-aged couples lacks large-population, in-depth study evidence.OBJECTIVE To investigate the association of HBV infection with time to pregnancy in couples planning pregnancy, and to explore whether this association varied by gravidity, health statuses, or lifestyles.DESIGN, SETTING, AND PARTICIPANTS This is a population-based cohort study of Chinese couples participating in the National Free Preconception Check-up Projects during 2015 to 2017. They were planning pregnancy and were followed-up every 3 months until getting pregnant, as confirmed by gynecologic ultrasonography, or were followed-up for 1 year. Data were analyzed between March 1, 2022, and September 30, 2022.MAIN OUTCOMES AND MEASURES The main outcome was time to pregnancy, assessed using fecundability hazard ratios (HRs). The Cox proportional hazards regression models were used to estimate the association of HBV infection with fecundability.RESULTS Among 2 419 848 couples (mean [SD] age, 27.87 [5.20] years for women and 29.58 [5.50] years for men), 126 728 women (5.24%) and 156 572 men (6.47%) were infected with HBV. Compared with the HBV-negative group, the fecundability of both women and men in the HBV-positive group decreased by 5% (HR, 0.95; 95% CI, 0.94-0.95). Compared with couples in which both partners were HBV negative, the fecundability of those in which both partners were HBV positive declined by 6% (HR, 0.94; 95% CI, 0.93-0.96) among all couples, by 3% (HR, 0.97; 95% CI, 0.95-0.99) among nulligravidas couples, and by 7% (HR, 0.93; 95% CI, 0.91-0.95) among multigravidas couples. Both the female-male and couple models suggested that the association of HBV infection with decreased fecundability was more pronounced in couples with multigravidas. The negative association was greater in people with overweight and obesity and was inconsistent in certain subgroups; in particular, it was more pronounced in women with reproductive tract infections, normal fasting plasma glucose, and no alcohol intake and in men with normal blood pressure.CONCLUSIONS AND RELEVANCE In this population-based cohort study, HBV infection was associated with decreased fecundability in a general reproductive-aged population, especially in couples with multigravidas. For women and men with certain health statuses and lifestyles, a comprehensive consideration of this association is recommended to provide personalized fertility guidance.

We thank Zhao and Xu for their valuable comments and recommendations on our study(1). Firstly, we would like to note that both our study and Zhao’s study find that paternal body mass index (BMI) was associated with birth weight(1,2). We agree that a subgroup analysis by offspring sex is necessary to explore the sex-specific rule. We did subgroup analyses according to the infant’s sex in our first revised manuscript. However, we found that the results were similar in subgroup analyses according to the infant’s sex (online Supplementary Tables 1 and 2), and the associations between paternal preconception BMI levels and small-for-gestational age/large-for-gestational age in female/male infants were similar to the results in online Supplementary Table S4 in our previous study(1), respectively. Based on these results, we found no sex-dependent effect of paternal preconception BMI on largefor-gestational age/small-for-gestational age. According to comments of reviewers and space limitations, we deleted subgroup analyses results by the infant’s sex in our revised manuscript. Secondly, information on the paternal history of chronic metabolic diseaseswas collected through face-to-face interviews by trained health staff in the National Free Pre-pregnancy Checkups Project (NFPCP)(3). We also agree that paternal history of chronic metabolic diseases (e.g. diabetes or hypertension) might have an impact on birth outcomes. The couples’ potential confounding variables which were significant in univariate analyses were subsequently adjusted in multivariate-adjusted multinomial logistic regression models. Paternal history of chronic metabolic diseases (e.g. diabetes or hypertension) was not significant in univariate analyses, and we have tried to put these variables into the model for adjustment, but the results showed that there is no difference between adjusting these variables or not. Therefore, paternal history of chronic metabolic diseases was not included in the final models. In conclusion, no sex-dependent effect of paternal preconception BMI on large-for-gestational age/small-for-gestational age was observed in our study. Both our study and Zhao’s study suggest that more efforts should be put on couples’ preconception health. Tonglei Guo123, Ying Yang123, Jiajing Jia123, Yuzhi Deng123, Yuanyuan Wang12, Ya Zhang12, Hongguang Zhang12, Yuan He123, Jun Zhao12, Zuoqi Peng12, Qiaomei Wang4, Haiping Shen4, Yiping Zhang4, Donghai Yan4 and Xu Ma123

目的 搭建全国中老年骨质疏松症分级健康管理平台,加强骨质疏松症患者档案的数字化管理.方法 制定全国中老年骨质疏松症患者基础档案和规范化诊疗的业务流程和数据管理规范,采用企业级应用的技术架构研发由用户层、表示层、应用层、数据层和存储层构成的全国中老年骨质疏松症分级健康管理平台,并进行应用示范.结果 搭建了由患者管理、样本管理、统计管理、参数管理、用户管理、日志管理、信息发布等功能模块组成的全国中老年骨质疏松症分级健康管理平台,并在中心医院和社区医院的应用示范过程中升级完善,为全国中老年骨质疏松症患者的规范化管理提供了技术支持.结论 全国中老年骨质疏松症分级健康管理平台实现了骨质疏松症患者档案的信息化管理,建立了中心医院与社区医院之间的双向转诊模式,有助于提高骨质疏松症患者的诊疗率和依从性,促进我国医疗资源的合理配置.

Background Although sexually transmitted infections are regarded as the main cause of tubal infertility, the association between the common vaginal microbiome and female fecundability has yet to be determined. The objective of this study was to find convincing evidence relating to the impact of the vaginal bacterial structure on the fecundability of women planning pregnancy. Methods We recruited women who took part in the Free Pre-pregnancy Health Examination Project from 13 June 2018 to 31 October 2018 (n = 89, phase I) and from 1 November 2018 to 30 May 2020 (n = 389, phase II). We collected pre-pregnancy vaginal swabs from each subject; then, we followed up each subject to acquire the pregnancy-planning outcome in 1 year. In phase I, 16S rRNA gene sequencing was performed to investigate the vaginal bacterial content between the pregnancy and non-pregnancy groups. These findings were verified in phase II by applying a quantitative real-time polymerase chain reaction for the measurement of the absolute abundance of specific species. Cox models were used to estimate fecundability ratios (FR) for each vaginal microbiome type. Results In phase I, 59.6% (53/89) of women became pregnant within 1 year. The principal coordinate analysis showed that the pre-pregnancy vaginal microbial community structures of the pregnant and non-pregnant groups were significantly different (PERMANOVA test, R-2 = 0.025, P = 0.049). The abundance of the genus Lactobacillus in the pregnancy group was higher than that of the non-pregnant group (linear discriminant analysis effect size (LDA) > 4.0). The abundance of the genus Gardnerella in the non-pregnant group was higher than those in the pregnant group (LDA > 4.0). In phase II, female fecundability increased with higher absolute loads of Lactobacillus gasseri (quartile Q4 vs Q1, FR = 1.71, 95%CI 1.02-2.87) but decreased with higher absolute loads of Fannyhessea vaginae (Q4 vs Q1, FR = 0.62, 95%CI 0.38-1.00). Clustering analysis showed that the vaginal microbiome of type D (characterized by a higher abundance of Lactobacillus iners, a lower abundance of Lactobacillus crispatus and Lactobacillus gassri) was associated with a 55% reduction of fecundability (FR = 0.45, 95%CI 0.26-0.76) compared with type A (featuring three Lactobacillus species, low Gardnerella vaginalis and Fannyhessea vaginae abundance). Conclusions This cohort study demonstrated an association between the pre-pregnancy vaginal microbiome and female fecundability. A vaginal microbiome characterized by a higher abundance of L. iners and lower abundances of L. crispatus and L. gasseri appeared to be associated with a lower fecundability. Further research now needs to confirm whether manipulation of the vaginal microenvironment might improve human fecundability.

This study aimed to demonstrate the relationship between poor sleep quality in early pregnancy and the risk of developing gestational diabetes mellitus (GDM). We conducted a nested case–control study and performed a 1:3 propensity score (PS) matching to match pregnant women with GDM to women without GDM. After PS matching, logistic regressions were carried out to describe the association between sleep quality (assessed by Pittsburgh Sleep Quality Index [PSQI]) and the risk of GDM. We also performed a second analysis to explore the association in groups divided according to maternal age. A total of 535 women were enrolled in this study. Of 456 women with complete data, the incidence of GDM was 12.1

Abstract Evidence of couples’ BMI and its influence on birth weight is limited and contradictory. Therefore, this study aims to assess the association between couple’s preconception BMI and the risk of small for gestational age (SGA)/large for gestational age (LGA) infant, among over 4·7 million couples in a retrospective cohort study based on the National Free Pre-pregnancy Checkups Project between 1 December 2013 and 30 November 2016 in China. Among the live births, 256 718 (5·44 %) SGA events and 506 495 (10·73 %) LGA events were documented, respectively. After adjusting for confounders, underweight men had significantly higher risk (OR 1·17 (95 % CI 1·15, 1·19)) of SGA infants compared with men with normal BMI, while a significant and increased risk of LGA infants was obtained for overweight and obese men (OR 1·08 (95 % CI 1·06, 1·09); OR 1·19 (95 % CI 1·17, 1·20)), respectively. The restricted cubic spline result revealed a non-linear decreasing dose–response relationship of paternal BMI (less than 22·64) with SGA. Meanwhile, a non-linear increasing dose–response relationship of paternal BMI (more than 22·92) with LGA infants was observed. Moreover, similar results about the association between maternal preconception BMI and SGA/LGA infants were obtained. Abnormal preconception BMI in either women or men were associated with increased risk of SGA/LGA infants, respectively. Overall, couple’s abnormal weight before pregnancy may be an important preventable risk factor for SGA/LGA infants.

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.

IMPORTANCE Abundant evidence suggests thyroid dysfunction is associated with adverse pregnancy outcomes. However, associations of preconception thyrotropin levels outside of reference range with reproductive health outcomes are not well characterized. OBJECTIVE To evaluate the associations of preconception thyrotropin levels with time to pregnancy (TTP) and risk of spontaneous abortion (SA). DESIGN, SETTING, AND PARTICIPANTS This population-based cohort study used data from the Chinese National Free Prepregnancy Checkups Project. Female participants aged 20 to 49 years who were trying to conceive were enrolled between January 1, 2013, and December 31, 2016, for the analysis of TTP or SA. Data were analyzed between August 1, 2020, and July 5, 2021. EXPOSURES Levels of thyrotropin within 1 year prior to pregnancy. MAIN OUTCOMES AND MEASURES The main outcomes were TTP, assessed using hazard ratios (HRs), and SA, assessed using odds ratios (ORs), according to preconception thyrotropin levels. Thyrotropin dose-response associations were assessed using restricted cubic spline regression. RESULTS Among 11 194 002 female participants (mean [SD] age, 27.56 [5.10] years) in the TTP cohort, 4 739 421 (42.34%) participants became pregnant within 1 year. Both low and high preconception thyrotropin levels were associated with delayed TTP compared with thyrotropin levels of 0.37 to 2.49 mIU/L (thyrotropin <0.10 mIU/L: HR, 0.90; 95% CI, 0.89-0.92; thyrotropin 4.88-9.99 mIU/L: HR, 0.86; 95% CI, 0.86-0.87; thyrotropin >= 10.00 mIU/L: HR, 0.78; 95% CI, 0.77-0.79). In the SA analysis cohort including 4 678 679 pregnancies, 108 064 SA events (2.31%) were documented. High thyrotropin groups showed an increased risk of SA compared with the group with thyrotropin levels of 0.37 to 2.49 mIU/L (thyrotropin 4.88-9.99 mIU/L: OR, 1.33; 95% CI, 1.28-1.38; thyrotropin >= 10.00 mIU/L: OR, 1.25; 95% CI, 1.14-1.36). Preconception thyrotropin levels showed an inverted J-shaped dose-response association with TTP (chi(2) = 311.29; nonlinear P < .001) and a J-shaped dose-response association with SA (chi(2) = 58.29; nonlinear P < .001). CONCLUSIONS AND RELEVANCE In this cohort study, preconception thyrotropin levels outside of reference range were associated with increased risk of reduced fecundity and SA. These findings may provide insights for the implementation of preconception thyroid function screening and the design of future levothyroxine supplementation trials.

AbstractAnaemia 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.

Ureaplasma genus (including U. urealyticum and U. parvum) and M. hominis are common opportunistic pathogens in vaginal microenvironments, which would lead to bacterial vaginosis, infertility and adverse pregnancy outcomes. Ascertaining associations between these elements and the vaginal microbiome can help us identify pathogenic mechanisms, and target control measures for different colonization levels. 92 childbearing-age, non-pregnant women were included, with vaginal swabs collected. DNA was extracted and 16S rRNA genes were sequenced using the IlluminaHiseq 2500 platform. A quantitative PCR method quantified bacterial loads. The colonization rates for the Ureaplasma genus and M. hominis were 87.0 ​% (80/92) and 29.3 ​% (27/92), respectively. No M. genitalium was detected. There were no statistical differences for Simpson, Shannon and Chao1 indices between Ureaplasma negative and positive groups (P ​> ​0.05). Based on the quartile classification of relative abundance for Ureaplasma, the third quartile group had the highest relative abundance of Lactobacillus. The Simpson index for the M. hominis positive group was statistically lower than the negative group (P ​= ​0.038). The Lactobacillus abundance appeared to decrease when the M. hominis relative abundance was >0.03 ​%. From a microbiome perspective, Ureaplasma vaginal colonization, at low levels appeared to be harmless, whereas M. hominis colonization was associated with vaginal microbiome changes. Further studies are required to confirm the diagnostic and treatment thresholds for Ureaplasma and M. hominis infections, and to explore in-depth associations between these organisms and the vaginal microbiome.

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/m(2) and 22.69-27.74 kg/m(2) 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. ((C) 2020 by American Society for Reproductive Medicine.)