Maternal Preconception Serum Alanine Aminotransferase Levels and Risk of Preterm Birth among Reproductive-Aged Women - China, 2013-2017.

What is already known about this topic?: The significance of maternal liver health concerning preterm birth (PTB) is well recognized; however, there is a gap in understanding the precise influence of preconception serum alanine aminotransferase (ALT) levels on the risk of PTB. What is added by this report?: In this retrospective cohort study, a J-shaped relationship between preconception serum ALT levels and risk of PTB was observed, indicating that both significantly elevated and decreased ALT levels may contribute to the risk. What are the implications for public health practice?: Maintaining optimal preconception serum ALT levels may reduce the risk of PTB, thereby informing specific preventive measures for women of reproductive age.

Husband smoking is associated with Wife's thyrotropin abnormality: A population-based cohort study among Chinese reproductive-aged women.

OBJECTIVES: To comprehensively assess the association of husband smoking with wives' thyrotropin abnormality. METHODS: This population-based retrospective cohort study included 2 406 090 Chinese reproductive-aged women who had participated twice in the National Free Pre-pregnancy Checkups Project between 2010 and 2020. Multivariate-adjusted odds ratios and 95% confidence intervals for subnormal and supranormal thyrotropin were estimated according to the husband's smoking status. RESULTS: Husband smoking at the first visit was associated with a 17% (15%-20%) and 26% (24%-28%) increased odds of subnormal thyrotropin and supranormal thyrotropin respectively compared to participants in neither-smoker group. In non-smoking participants with normal thyrotropin levels at the first visit, the corresponding increased risk of subnormal thyrotropin and supranormal thyrotropin at the second visit were 15% (12%-18%) and 19% (16%-21%) in contrast to participants without husband-smoking exposure. In non-smoking participants with abnormal thyrotropin levels at their first visit, husband smoking cessation was associated with 27% (17%-35%) and 36% (31%-40%) reduced odds of subnormal thyrotropin and supranormal thyrotropin at the second visit compared with the participants whose husband still smoking at the second visit. CONCLUSION: Husband smoking was associated with wives' subnormal thyrotropin and supranormal thyrotropin, and cessation of husband smoking could reduce the odds of thyrotropin abnormality. Couple-focused smoking intervention should be developed to reduce the burden of asymptomatic thyroid disease in females.

An immune window of opportunity to prevent spontaneous abortion: prepregnancy peripheral leukocytes and subsets were associated with a decreased risk of spontaneous abortion.

STUDY QUESTION: Do prepregnancy peripheral leukocytes (PPLs) and their subsets influence the risk of spontaneous abortion (SAB)? SUMMARY ANSWER: PPLs and their subsets are associated with the risk of SAB. WHAT IS KNOWN ALREADY: Compelling studies have revealed the crucial role of maternal peripheral leukocytes in embryo implantation and pregnancy maintenance. Adaptive changes are made by PPLs and their subsets after conception. STUDY DESIGN, SIZE, DURATION: This population-based retrospective cohort study was based on data from the National Free Pre-pregnancy Check-up Project (NFPCP) in mainland China. Couples preparing for pregnancy within the next six months were provided with free prepregnancy health examinations and counseling services for reproductive health. The current study was based on 1 310 494 female NFPCP participants aged 20-49 who became pregnant in 2016. After sequentially excluding 235 456 participants lost to follow-up, with multiple births, and who failed to complete blood tests, a total of 1 075 038 participants were included in the primary analysis. PARTICIPANTS/MATERIALS, SETTING, METHODS: PPLs and their subset counts and ratios were measured. The main outcome was SAB. A multivariable logistic regression model was used to estimate the odds ratio (OR) and 95% CI of SAB associated with PPLs and their subsets, and restricted cubic spline (RCS) was used to estimate the nonlinear exposure-response relationship. MAIN RESULTS AND ROLE OF CHANCE: Of the included pregnant participants, a total of 35 529 SAB events (3.30%) were recorded. Compared to participants with reference values of PPLs, the ORs (95% CIs) of leukopenia and leukocytosis for SAB were 1.14 (1.09-1.20) and 0.74 (0.69-0.79), respectively. The RCS result revealed a monotonous decreasing trend (Pnonlinear < 0.05). Similar relationships were observed for the neutrophil count and ratio, monocyte count, and middle-sized cell count and ratio. The lymphocyte ratio showed a positive and nonlinear relationship with the risk of SAB (Pnonlinear < 0.05). Both eosinophils and basophils showed positive relationships with the risk of SAB (eosinophil Pnonlinear > 0.05 and basophil Pnonlinear < 0.05). LIMITATIONS, REASONS FOR CAUTION: Chemical abortion events and the cause of SAB were not collected at follow-up. Whether women with abnormal PPLs had recovered during periconception was not determined. WIDER IMPLICATIONS OF THE FINDINGS: PPLs and their subsets are associated with the risk of SAB. Leukopenia and neutropenia screening in women preparing for pregnancy and developing a feasible PPL stimulation approach should be emphasized to utilize the immune window of opportunity to prevent SAB. STUDY FUNDING/COMPETING INTEREST(S): This study was approved by the Institutional Research Review Board of the National Health and Family Planning Commission. This study was supported by the National Key Research and Development Program of China (grants 2021YFC2700705 [Y.Y.] and 2016YFC100307 [X.M.]) and the National Natural Science Foundation of China (grant no. 82003472 [L.W.]). The funding source was not involved in the study design, data collection, analysis and interpretation of the data, writing the report, or the decision to submit this article for publication. No competing interests. TRIAL REGISTRATION NUMBER: N/A.

Association between short-term air pollution exposure and perturbation in thyrotropin levels in 1.38 million Chinese women: A national longitudinal analysis, 2014-2019.

Prevalence of subclinical hypothyroidism substantially increased during the last decade in China, which has been commonly/clinically diagnosed as elevation in thyrotropin (thyroid-stimulating hormone [TSH]). Tobacco smoke containing toxic substances has been linked to thyroid dysfunction; however, data on perturbation of TSH following air pollution exposure in human has not been assessed at nationwide population level. We investigated the longitudinal impact of daily ambient air pollution estimated at residential level on serum TSH in 1.38 million women from China's 29 mainland provinces between 2014 and 2019. We observed that particulate matter with aerodynamic diameter ≤ 10 and ≤ 2.5 µm (PM10, PM2.5) and nitrogen dioxide (NO2) at cumulative lag 0-7 days of exposure were associated with percent elevations in TSH (0.88% [95% CI: 0.71, 1.05] per [interquartile range, IQR: 54.8 µg/m3] of PM10; 0.89% [95% CI, 0.71, 1.07] per IQR [40.3 µg/m3] of PM2.5; 2.01% [95% CI: 1.81, 2.22] per IQR [27.4 µg/m3] of NO2). Greater associations were observed in participants living in areas with ≥adequate iodine intake and those with low BMI levels and high inflammation status. Our results suggest that increased concentrations of recent ambient air pollutants at exposure ranges commonly encountered in Asia were associated with increases in TSH, supporting disturbing role of short-term air pollution exposure on the regulation of thyroid hormone homeostasis.

Gravidity modifies the associations of age and spousal age difference with couple's fecundability: a large cohort study from 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.

Evaluating the Impact of Maternal Exposure to Ozone on Twin Fetal Growth in China.

Unlike singletons, twins require attention not only to the birth weight of the fetuses but also to discordance (i.e., the differences between weights) because twin growth discordance is a significant factor contributing to perinatal mortality and morbidity in twin pregnancies. However, the impact of maternal air pollution exposure on twin growth discordance has rarely been investigated. We examined the association of long-term ozone exposure during preconception and pregnancy with the birth weight of twins and twin growth discordance among 35,795 twins from the National Free Preconception Health Examination Project between January 2010 and December 2019. Linear mixed-effect models and random-effect logistic regression models were used to examine the associations of ozone exposure with the birth weight-related outcomes (i.e., birth weight of twins and within-pair birth weight difference) and risk of twin growth discordance, respectively, after adjustment for demographic characteristics and lifestyle. We found that an interquartile range (IQR) increase (15 µg/m3) in ozone exposure during the entire pregnancy was associated with a reduction (-28.96g, 95% confidence interval [CI]: -46.37, -11.56) in the total birth weight of twins, and ozone had a more pronounced impact on the birth weight of the smaller fetuses (-18.28 g, 95% CI: -27.22, -9.34) compared to the larger fetuses (-9.88 g, 95% CI: -18.84, -0.92) in twin pregnancies. An IQR increase in ozone exposure during the entire pregnancy was associated with a significant increase (8.41 g, 95% CI: 4.13, 12.69) in the within-pair birth weight difference; the odds ratio (OR) of twin growth discordance related to ozone exposure increased by 9% (OR = 1.09, 95% CI: 1.01, 1.18). However, no consistently significant associations were observed for ozone exposure during prepregnancy. Male-male twin pairs and those who were born prematurely appeared to be more susceptible to ozone exposure than their counterparts. Long-term ozone exposure during pregnancy was associated with twin growth discordance, and our findings provide reference data for future studies.

Structural transition of parenthood among Chinese nulliparous couples with planned pregnancies, 2013-2019.

BACKGROUND: The postponement of parenthood is a global public health issue that has received attention of many public health experts. However, few studies have investigated the postponement in marriage age, marriage and conception interval, and pregnancy age in terms of demographic and regional heterogenicities. METHODS: This is a cross-sectional, registry-based study, and a total of 13 894 601 nulliparous couples who participated in the National Free Pre-Pregnancy Check-ups Project and became pregnant during 2013-2019 were included. We calculated annual percentage change and forest plots for marriage age, marriage and conception interval, and pregnancy age. RESULTS: Late marriage (marriage age ≥ 35 years), long marriage and conception interval (marriage and conception interval ≥ 2 years), and advanced pregnancy (pregnancy age ≥ 35 years) increased from 1.20%, 22.01%, and 1.88% in 2013 to 1.69%, 32.75%, and 2.79% in 2019, respectively. The corresponding annual percentage changes were 6.55%, 8.44%, and 8.17%. Participants without higher education had a higher annual percentage change, but comparable prevalence for long marriage and conception interval with participants with higher education. Participants residing in second- or new first-tier cities, and the northeast of China who had a higher prevalence of parenthood postponement also had higher corresponding annual percentage changes. CONCLUSIONS: Structural postponement of parenthood with demographic and regional heterogenicities was observed among Chinese nulliparous couples with planned pregnancies during 2013-2019. Inclusive and comprehensive parenting support should be developed and implemented in mainland China to minimize the negative health effects arising from the postponement, especially for couples without higher education and living in new first/second-tier cities or the northeast China.

The association between the maternal pre-pregnancy platelet count and fecundability in mainland China: a population-based cohort study.

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 221.00×109/L. The first (<177.00 ×109/L) and second quintile (177.00-207.99 ×109/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 ×109/L; Q5: ≥272.00 ×109/L) were related to reduction of fecundability, when compared with the third quintile of PC (208.00-235.99 ×109/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 (<177.00×109/L), only 20.93% women had PC below 129.94×109/L. An inverse-U shape association was consistently observed among women such that the lower PC of normal range (<118.03×109/L) and higher PC (>223.06×109/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.

Declined prevalence, improved awareness and control of hypertension are associated with spousal educational attainment: A mega-data study.

Cardiovascular diseases, including hypertension, have posed a serious threat to human health in recent decades. Family-centered health promotion and disease control for the management of hypertension is gaining attention. In this study, we assessed the association between spousal educational attainment (SEA) and hypertension prevalence, awareness, and control, intending to provide new directions for family health care. A total of 71 211 191 reproductive-aged participants from the National Free NFPCP during 2013-2019 were included in the current study. Inverse probability weighting (IPW) via propensity models were used to adjust for the imbalance by SEA. Both multivariable-adjusted ORs and inverse-probability-weighted ORs were used to assess the association between SEA and the prevalence, awareness, and control of hypertension. ORs of prevalence, awareness, and control of hypertension with SEA stratified by sex, age, and residency type were also reported. Compared with participants with SEA of compulsory education, the inverse-probability-weighted ORs for hypertension were 0.97 (0.96-0.97), 0.99 (0.98-1.00), and 0.91 (0.88-0.93) for participants with SEA of senior high, college, and postgraduate, respectively. The corresponding ORs for hypertension awareness were 1.12 (1.10-1.13), 1.15 (1.13-1.16), and 1.38 (1.34-1.41). The increment of hypertension control associated with SEA was only identified in urban areas. Modification analyses revealed that urban participants were observed to have more healthy benefits associated with SEA; additional decreased prevalent hypertension and increased hypertension awareness associated with SEA were observed in wives and husbands respectively. Thus, SEA was associated with decreased prevalent hypertension and increased awareness and control of hypertension. Our findings call for increased participation of spouses in family-centered healthcare, with consideration of modified effects by gender, age, and residency type, to improve chronic disease prevention and control including hypertension.

Assessment of Prior Infection With Hepatitis B Virus and Fecundability in Couples Planning Pregnancy.

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.

Association of Fine Particulate Matter and Its Components with Macrosomia: A Nationwide Birth Cohort Study of 336 Chinese Cities.

To examine the associations between macrosomia risk and exposure to fine particulate matter (PM2.5) and its chemical components during pregnancy, we collected birth records between 2010 and 2015 in mainland China from the National Free Preconception Health Examination Project and used satellite-based models to estimate concentrations of PM2.5 mass and five main components, namely, black carbon (BC), organic carbon (OC), nitrate (NO3-), sulfate (SO42-), and ammonium (NH4+). Associations between macrosomia risk and prenatal exposure to PM2.5 were examined by logistic regression analysis, and the sensitive subgroups were explored by stratified analyses. Of the 3,248,263 singleton newborns from 336 cities, 165,119 (5.1%) had macrosomia. Each interquartile range increase in concentration of PM2.5 during the entire pregnancy was associated with increased risk of macrosomia (odds ratio (OR) = 1.18; 95% confidence interval (CI), 1.17-1.20). Among specific components, the largest effect estimates were found on NO3- (OR = 1.36; 95% CI, 1.35-1.38) followed by OC (OR = 1.23; 95% CI, 1.22-1.24), NH4+ (OR = 1.22; 95% CI, 1.21-1.23), and BC (OR = 1.21; 95% CI, 1.20-1.22). We also that found boys, women with a normal or lower prepregnancy body mass index, and women with irregular or no folic acid supplementation experienced higher risk of macrosomia associated with PM2.5 exposure.

Metabolomic and transcriptomic analyses reveal the biosynthetic mechanisms of pigments and main taste compounds in an albino tea cultivar.

Significant variations in leaf colours, pigment contents, and main taste compounds in young shoots from albino tea plants (Camellia sinensis) influence tea flavour. However, the seasonal metabolic pattern and molecular regulatory mechanism of these metabolites remain largely elusive. Herein, we conducted morphological, biochemical, metabolomic and transcriptomic analyses between an albino tea cultivar 'Zhonghuang 3' ('ZH3') and a green strain 'Tai cha 15' ('TC15') at four-time points (April 12, May 31, July 14, and August 17) to elucidate dynamic changes in these compounds and predict the relationships among transcription factors (TFs), target genes (TGs), and metabolite abundance. Generally, leaf colours and pigment contents were significantly lighter and lower, respectively, in 'ZH3' than in 'TC15' from spring to summer, but were subsequently similar. Compared to 'TC15', 'ZH3' had a lower and broader phenol/ammonia ratio as well as stable caffeine content and showed more significantly different metabolites and differentially expressed genes. The relationship between pigments, main taste compounds, and their biosynthetic genes, as well as TFs and their TGs, had genetic specificity. These results suggested that the biosynthesis of these compounds was probably both season- and variety-dependent. In total, 12 models of the TF-TG-metabolite regulatory network were proposed to uncover the biosynthetic and regulatory mechanisms of these metabolites in tea plants. A high correlation was observed between some structural genes and TFs with the accumulation of these metabolites. These findings provide novel insights into the regulatory mechanisms underlying accumulation of pigments and main taste compounds in tea plants.

Maternal Preconception Hepatitis B Virus Infection and Risk of Congenital Heart Diseases in Offspring Among Chinese Women Aged 20 to 49 Years.

Importance: Maternal hepatitis B virus (HBV) infection during early pregnancy has been related to congenital heart diseases (CHDs) in offspring. However, no study to date has evaluated the association of maternal preconception HBV infection with CHDs in offspring. Objective: To explore the association of maternal preconception HBV infection with CHDs in offspring. Design, Setting, and Participants: This retrospective cohort study used nearest-neighbor (1:4) propensity score matching of 2013 to 2019 data from the National Free Preconception Checkup Project (NFPCP), a national free health service for childbearing-aged women who plan to conceive throughout mainland China. Women aged 20 to 49 years who got pregnant within 1 year after preconception examination were included, and those with multiple births were excluded. Data were analyzed from September to December 2022. Exposures: Maternal preconception HBV infection statuses, including uninfected, previous, and new infection. Main Outcomes and Measures: The main outcome was CHDs, which were prospectively collected from the birth defect registration card of the NFPCP. Logistic regression with robust error variances was used to estimate the association between maternal preconception HBV infection status and CHD risk in offspring, after adjusting for confounding variables. Results: After matching with a 1:4 ratio, there were 3 690 427 participants included in the final analysis, where 738 945 women were infected with HBV, including 393 332 women with previous infection and 345 613 women with new infection. Approximately 0.03% (800 of 2 951 482) of women uninfected with HBV preconception and women newly infected with HBV carried an infant with CHDs, whereas 0.04% (141 of 393 332) of women with HBV infection prior to pregnancy carried an infant with CHDs. After multivariable adjustment, women with HBV infection prior to pregnancy had a higher risk of CHDs in offspring compared with women who were uninfected (adjusted relative risk ratio [aRR], 1.23; 95% CI, 1.02-1.49). Moreover, compared with couples who were uninfected with HBV prior to pregnancy (680 of 2 610 968 [0.026%]), previously infected women with uninfected men (93 of 252 919 [0.037%]) or previously infected men with uninfected women (43 of 95 735 [0.045%]) had a higher incidence of CHDs in offspring and were significantly associated with a higher risk of CHDs in offspring (previously infected women with uninfected men: aRR, 1.36; 95% CI, 1.09-1.69; previously infected men with uninfected women: aRR, 1.51; 95% CI, 1.09-2.09) with multivariable adjustment, while no significant association was observed between maternal new HBV infection and CHDs in offspring. Conclusions and Relevance: In this matched retrospective cohort study, maternal preconception previous HBV infection was significantly associated with CHDs in offspring. Moreover, among women with HBV-uninfected husbands, significantly increased risk of CHDs was also observed in previously infected women prior to pregnancy. Consequently, HBV screening and getting HBV vaccination-induced immunity for couples prior to pregnancy are indispensable, and those with previous HBV infection prior to pregnancy should also be taken seriously to decrease the CHDs risk in offspring.

Burden and Trend of Macrosomia and Large-for-Gestational-Age Neonates Attributable to High Pre-Pregnancy Body Mass Index in China, 2013-2017: A Population-Based Retrospective Cohort Study.

Background: The world is transitioning to an obese future, but few studies have measured the burden of increased maternal body mass index (BMI) on pathological fetal overgrowth, especially the trends in this burden and its heterogeneity in populations with different characteristics. Methods: A population-based retrospective cohort study was conducted with 7,998,620 Chinese females who had participated in the National Free Pre-Pregnancy Check-ups Project and became pregnant during 2013-2017. The proportions of macrosomic and LGA neonates attributable to high BMI (population attributable fraction, PAF) and annual percent change of yearly PAFs were estimated. Results: We found that the burden of macrosomic and LGA (large-for-gestational-age) neonates attributable to high pre-pregnancy BMI increased among Chinese females with planned pregnancies during 2013-2017. The PAF of macrosomia attributable to high BMI increased from 3.16% (95% confidence interval: 2.97-3.35%) to 7.11% (6.79-7.42%) by 23.60% (16.76-30.85%) annually, and the PAF of LGA increased from 2.35% (2.21-2.48%) to 5.00% (4.79-5.21%) by 21.98% (16.14-28.11%) annually. Our study identified that participants with disadvantaged socioeconomic status (including those without higher education, living in provinces with GDP per capita < 40,000 CNY, tier IV, and tier V cities) and residing in northern and southwestern China were at high risk of a rapidly expanding burden. Conclusions: Government authorities should control pre-pregnancy BMI through nationwide intervention programs and direct more resources to focus on the unfair burden on females with disadvantaged socioeconomic status.

Association of Preconception Thyrotropin Levels With Fecundability and Risk of Spontaneous Abortion in China.

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 (χ2 = 311.29; nonlinear P < .001) and a J-shaped dose-response association with SA (χ2 = 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.

Effects of greenness on preterm birth: A national longitudinal study of 3.7 million singleton births.

Exposure to greenness may lead to a wide range of beneficial health outcomes. However, the effects of greenness on preterm birth (PTB) are inconsistent, and limited studies have focused on the subcategories of PTB. A total of 3,751,672 singleton births from a national birth cohort in mainland China were included in this study. Greenness was estimated using the satellite-based Normalized Difference Vegetation Index (NDVI) and Enhanced Vegetation Index with 500-m and 1,000-m buffers around participants' addresses. The subcategories of PTB (20-36 weeks) included extremely PTB (EPTB, 20-27 weeks), very PTB (VPTB, 28-31 week), and moderate-to-late PTB (MPTB, 32-36 weeks). Gestational age (GA) was included as another birth outcome. We used logistic regression models and multiple linear regression models to analyze these associations throughout the entire pregnancy. We found inverse associations between greenness and PTB and positive associations between greenness and GA. Specifically, an increase of 0.1 NDVI exposure within a 500-m buffer throughout the entire pregnancy was significantly associated with decreases in PTB (odds ratio [OR], 0.930; 95% confidence interval [CI], 0.927-0.932), EPTB (OR, 0.820; 95% CI, 0.801-0.839), VPTB (OR, 0.913; 95% CI, 0.908-0.919), MPTB (OR, 0.934; 95% CI, 0.931-0.936), and an increase in GA (ß = 0.050; 95% CI, 0.049-0.051 weeks). These results suggest the potential protective effects of greenness on PTB and its subcategories: MPTB, VPTB, and EPTB in China.

Physiological attributes and transcriptomics analyses reveal the mechanism response of Helictotrichon virescens to low temperature stress.

BACKGROUND: Helictotrichon virescens is a perennial grass that is primarily distributed in high altitude areas of 2000 ~ 4500 m. It is widely cultivated in the Qinghai-Tibet Plateau of China, strongly resistant to cold, and an essential part of the wild herbs in this region. However, the molecular mechanism of the response of H. virescens to low temperature stress and the key regulatory genes for specific biological processes are poorly understood. RESULTS: Physiological and transcriptome analyses were used to study the cold stress response mechanism in H virescens. During the low temperature stress period, the content of chlorophyll a and b decreased more and more with the delay of the treatment time. Among them, the difference between the controls was not significant, and the difference between the control and the treatment was significant. At the same time, the expression of related differential genes was up-regulated during low temperature treatment. In addition, the plant circadian pathway is crucial for their response to cold stress. The expression of differentially expressed genes that encode LHY and HY5 were strongly up-regulated during cold stress. CONCLUSIONS: This study should help to fully understand how H. virescens responds to low temperatures. It answers pertinent questions in the response of perennial herbs to cold stress, i.e., how light and low temperature signals integrate to regulate plant circadian rhythms and Decrease of content of chlorophylls (which can be also accompanied with decrease of total quantity of reaction centers) leads to an increase in photosynthetic damage.

Paternal smoking and preterm birth: 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 preterm birth (PTB). METHODS: We performed a population-based retrospective cohort study in rural areas of China among 5,298,043 reproductive-aged couples who participated in the National Free Pre-Pregnancy Checkups Project (NFPCP), regarding outcome events that occurred in 2010-2016. Multivariate Cox proportional regression was used to estimate hazard ratio (HR) and 95% confident intervals (95%CI), and restricted cubic spline (RCS) were used to estimate the dose-response relationship. RESULTS: Compared to neither-smoker couples, the fully adjusted HR for PTB was 1.04 (95% CI, 1.03-1.04), 1.08 (0.96-1.22), and 1.11 (1.03-1.19) in the couples where only the female smoked, only the male smoked and both, respectively. HR of PTB for paternal smoking was 1.07 (1.06-1.07), compared with women without paternal smoking. Consistent with paternal smoking, preconception paternal smoking showed 1.07-fold higher risk of PTB (95%CI, 1.06-1.09). The multivariable-adjusted HRs of PTB were 1.05 (1.03-1.06), 1.04 (1.03-1.05), 1.05 (1.04-1.07), 1.07 (1.05-1.10) and 1.13 (1.12-1.14) for participants whose husband smoked 1-4, 5-9, 10-14, 15-19, and ≥ 20 cigarettes/day respectively, compared with participants without paternal smoking. The HRs of PTB also increased with the increment of paternal smoking and preconception paternal smoking categories (Plinear < 0.05). CONCLUSIONS: Paternal smoking and preconception paternal smoking was independently positively associated with PTB risk. The importance of tobacco control, should be emphasized during preconception and pregnancy counselling should be towards not only women but also their husband.

Preterm birth (PTB) is the leading cause of neonatal morbidity and mortality, as well as other system immaturity problem. But as one of important environmental tobacco smoking sources of maternal secondhand smoking in the family, paternal smoking is worthy for deep exploring of its potential impacts on PTB. Moreover, evidence on the independent role of preconception paternal smoking is still lacking. Thus, we conducted a population-based retrospective cohort study to evaluate the association between paternal smoking and risk of PTB among among 5,298,043 reproductive-aged couples who participated in the National Free Pre-Pregnancy Checkups Project (NFPCP), regarding outcome events that occurred in 2010­2016.We found a significant association between paternal smoking and PTB. Smoking reduction should not only be advised to pregnant women but also to their partners to reduce PTB in their fetal. In addition, supporting patients to continue smoking reduction will be crucial when considering the adverse health outcome of smoking. Intervention of tobacco use before and during pregnancy, are critical for prevention of PTB. Avoiding both maternal and paternal smoking during pregnancy will benefit the developing fetus.