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.

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.

Preconception folic acid supplementation for the prevention of birth defects: a prospective, population-based cohort study in mainland China.

BACKGROUND: Folic acid supplementation is recommended for reducing the risk of birth defects. We aimed to assess the protective association of periconception folic acid supplements with birth defects in real-world setting. METHODS: This prospective, population-based cohort study utilized national preconception registered data of married Chinese couples planning a pregnancy within 6 months between 2010 and 2012 in Mainland China. Participated women are freely provided folic acid starting 3 months before conception till 3 months after conception. Birth defects were self-reported at 42 days postpartumn followup. R software (v4.0.2) was applied for statistical analyses. RESULTS: Complete data of 567,547 couples with pregnancy outcomes and folic acid supplementation were extracted for final analysis. A total of 74.7% women were with folic acid supplementation, and 599 birth defects were self-reported. The odd of birth defects was lower among women taking folic acid compared to their counterparts not taking (0.102% vs 0.116%, P < 0.001). In the multiple logistic regression analyses, the odd of birth defects was lower among couples with maternal folic acid supplementation (OR = 0.78, 95%CI: 0.66-0.95, P = 0.011), especially decreased odd of neural tube defects (NTDs) (OR = 0.56, 95%CI: 0.39-0.82, P = 0.003). This association was confirmed by 1:4 and 1:10 case control analysis. Odds of birth defects were significantly lower among women with folic acid supplementation more than 3 months before pregnancy (P < 0.001), and moreover, the odds of cleft (P = 0.007) and NTDs (P = 0.007) were of notable decrease. CONCLUSION: This retrospective case cohort study provides programmatic evidence for public health strategy-making to for reducing the risk of NTDs and clefts.

Detection method of micro and macro scale defects in silicon carbide castings.

Aiming at challenges such as low efficiency, high missing rate, difficulty in identifying contour defects, and difficulty in extracting tiny defects, a defect detection method for extracting micro and macro scale defects is proposed in this paper. After preprocessing the image, contour detection is performed to identify the contours. Subsequently, a contour complementation algorithm is employed to complement the unclosed contours. Finally, the detection of micro scale defects is conducted based on the grayscale variation of the center of the micro scale defects. The experimental results show that compared with the traditional method, the proposed algorithm can accurately detect the bubble defects of different scales in silicon carbide castings and can identify the complex defects better.

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.

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.

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.

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.

Preconception paternal/maternal BMI and risk of small/large for gestational age infant in over 4·7 million Chinese women aged 20-49 years: a population-based cohort study in China.

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.

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.

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.

The association between serum alanine aminotransferase and hypertension: A national based cross-sectional analysis among over 21 million Chinese adults.

BACKGROUND: Inconsistent results were found in the association between serum alanine aminotransferase (ALT) and hypertension among population-based studies. This study evaluated the association between ALT and hypertension among Chinese reproductive-age population by utilizing registration data from National Free Pre-pregnancy Checkups Project in 2016-2017. METHODS: The 21,103,790 registered participants were eligible for analysis, including women who were 20-49 years old and men who were 20-59 years old with available data for ALT and blood pressure (BP). Logistic regression was conducted to estimate odds ratio (OR) for the association between ALT and hypertension as a binary outcome. Linear regression was used to examine the association between ALT and BP as a continuous outcome. RESULTS: In total, 4.21% of the participants were hypertensive, and 11.67% had elevated ALT (> 40 U/L). Hypertension prevalence was 3.63% and 8.56% among participants with normal and elevated ALT levels. A strong linear relationship was found between serum ALT levels and the odds of hypertension after adjustment for potential confounders. The multivariable-adjusted ORs for hypertension were 1, 1.22 (1.21, 1.22), 1.67 (1.65 1.68), 1.78 (1.76, 1.80), and 1.92 (1.90, 1.94) in participants with ALT levels of ≤ 20, 20.01-40, 40.01-60, 60.01-80, and > 80 U/L, respectively. Systolic and diastolic BPs rose by 1.83 and 1.20 mmHg on average, for each 20 U/L increase in ALT (P for trend < 0.001). The association was consistent among subgroups and tended to be stronger among populations who are overweight (body mass index ≥ 24 kg/m2) (χ2 = 52,228, P < 0.001), alcohol drinking (χ2 = 100,730, P < 0.001) and cigarette smoking (χ2 = 105,347, P < 0.001). CONCLUSIONS: Our cross-sectional analysis suggested a linear association between serum ALT and hypertension or BP, which indicated that abnormal liver metabolism marked by elevated serum ALT could play a role in hypertension or elevated BP condition.

Association between air particulate matter pollution and blood cell counts of women preparing for pregnancy: Baseline analysis of a national birth cohort in China.

BACKGROUND: Limited evidence is known about whether long-term exposures to air borne particulate matters of 2.5 µm or less (PM2.5) impact human hematologic index for women preparing for pregnancy. No study assessed the effect of PM1, which is small enough to reach the blood circulation. OBJECTIVE: To evaluate whether exposure to PM1 and PM2.5 is associated with blood cell count of woman preparing for pregnancy. METHOD: Based on the baseline data of a national birth cohort in China, we analysed the white blood cell (WBC), red blood cells (RBC) and thrombocyte counts of 1,203,565 women who are aged 18-45 years, being Han ethnicity, had no chronic disease and preparing for pregnancy. We matched their home addresses and examination date with daily concentrations of PM1 and PM2.5 which were estimated by a machine learning method with remote sensing, meteorological and land use information. Generalized additive mixed model to examine the associations between exposure to one-year average exposure to PMs prior to the health examination and the blood cells counts, after adjustment for potential individual variables. RESULTS: A 10 µg/m3 PM1 increment was associated with -1.49% (95%CI: 1.56%, -1.42%) difference in WBC count; with 0.33% (95%CI: 0.30%, 0.36%) difference of RBC count; and with 1.08% (95%CI: 1.01%, 1.15%) difference of thrombocyte count. For PM2.5, the corresponding difference was -0.47% (95%CI: 0.54%, -0.39%) for WBC; was 0.06% (95%CI: 0.03%, 0.09%) for RBC; and was 1.10% (95%CI: 1.02%, 1.18%) for thrombocyte. Women working as workers, being overweight and with tobacco smoking exposure had higher associations between PMs and hematologic index than their counterparts (p < 0.05 for interaction test). CONCLUSION: Long-term exposure to PMs were associated with decrement in WBC, as well as increment in RBC and thrombocytes among Han Chinese women preparing for pregnancy. Measures such as using air purifiers and wearing a mask in polluted areas should be improved to prevent women from the impact of PMs.

The trend of caesarean birth rate changes in China after 'universal two-child policy' era: a population-based study in 2013-2018.

BACKGROUND: The universal two-child policy in China which was announced in October 2015 might affect the caesarean birth rate. Few studies reported the caesarean birth rate affected by the policy especially after the universal two-child policy period. This study aimed to demonstrate the caesarean birth rate changes before and after the universal two-child policy and further elaborate the underlying influencing factors. METHODS: This nationwide, retrospective, population-based study was based on National Free Pre-Pregnancy Check-ups Project (NFPCP). Couples planning to conceive in next 6 months were encouraged to participate in NFPCP. Baseline information was collected using a standardized questionnaire with a face-to-face interview, and medical examinations were conducted. Two rounds of follow-up interviews were then conducted by trained nurses to update pregnancy status and outcomes. NFPCP participants who completed deliveries before December 31, 2018, were included in the current study. We used marginal effect of year to examine the trend of caesarean birth rate over time and interrupted time series (ITS) analysis to determine impacts of the universal two-child policy on the trend of caesarean birth rate. RESULTS: A total of 9,398,045 participants were included in the final analysis. High-risk factors to increase caesarean birth rate were identified. In the current study, the standardized caesarean birth rate declined from 34.1% in 2013 to 31.8% in 2015 and increased to 35.6% in 2018. ITS analysis showed the caesarean birth rate decreased by 0.1% (95% CI 0.1-0.1) per month before the release of universal two-child policy, 1.3% (95% CI 0.6-2.1%) absolute drop during the policy release month, and increased by 0.2% (95% CI 0.1-0.2%) per month after the policy implementation. For the period after the policy release, the increasing trends were observed in rural participants and urban primiparas. The prevalence of caesarean birth rates within China varied regionally. CONCLUSIONS: The decreasing trend of caesarean birth rate was reported after immediate release of the universal two-child policy. An increasing trend of caesarean birth rate was observed 2-3 years after the policy. It reminds us that the caesarean birth rate control is a long-lasting process and all the strategies need to be continually reinforced.

Long-term exposure to airborne particulate matter of 1 µm or less and blood pressure in healthy young adults: A national study with 1.2 million pregnancy planners.

No evidence exists concerning the effect of airborne particulate matter of 1 µm or less (PM1) on blood pressure of young adults planning for pregnancy. We collected health examination information of about 1.2 million couples (aged 18-45 years) from a national birth cohort in China from Jan 1, 2013 to Oct 1, 2014 and matched their home address to daily PM1 and PM2.5 concentrations, which were predicted by remote sensing information. Generalized additive mixed models were used to analyze associations between long-term exposure to PM and blood pressure, after controlling for individual factors. A 10 µg/m3 increase in PM1 was associated with increased systolic blood pressure (SBP) for 0.26 (95%CI: 0.24, 0.29) mmHg in females and 0.29 (95%CI: 0.26, 0.31) mmHg in males, respectively. PM1 was also associated with increased DBP for 0.22 (95%CI: 0.20, 0.23) mmHg in females and 0.17 (95%CI: 0.15, 0.19) mmHg in males, respectively. Similar effects on blood pressure were found for PM2.5, meanwhile, the effect of PM2.5 on SBP increased with the scale of PM1 included in PM2.5 (p for interaction term <0.01). In summary, long-term exposure to PM1 as well as PM2.5 was associated with increased SBP and DBP of Chinese young adults planning for pregnancy.

Preconception Hb concentration with risk of spontaneous abortion: a population-based cohort study in over 3·9 million women across rural China.

OBJECTIVE: Evidence on the relationship between maternal Hb concentration and spontaneous abortion (SA) risk is limited and conflicting. The purpose of the study was to evaluate whether maternal preconception anaemia or high Hb concentration is associated with risk of SA. DESIGN: A population-based cohort study established between 2013 and 2017. SETTINGS: Local maternal and child care service centres in each county. PARTICIPANTS: In total, 3 971 428 women aged 20-49 years, who participated in National Free Pre-Pregnancy Checkups Project from 2013 to 2016 and successfully got pregnant before 2017 in rural China. RESULTS: A total of 101 700 (2·56 %) women were recorded having SA, with highest SA rate in women with severe anaemia (4·58 %). Compared with women with Hb of 110-149 g/l, the multivariable-adjusted OR for SA was 1·52 (95 % CI: 1·25, 1·86) for women with Hb < 70 g/l, 0·92 (0·84, 1·01) for 70-99 g/l, 0·80 (0·77, 0·83) for 100-109 g/l, 1·11 (1·08, 1·15) for 150-159 g/l, 1·12 (1·04, 1·20) for 160-169 g/l and 1·02 (0·93, 1·12) for ≥ 170 g/l, respectively. An approximate U-shaped curve for the risk of SA with Hb concentrations was observed when Hb concentrations less than 145 g/l, above which the association plateaued (Pnon-linear < 0·001). CONCLUSIONS: Severe anaemia and high Hb concentration before pregnancy were associated with an increased risk of SA. Women with mild anaemia prior to pregnancy had lower risk of SA. Underlying mechanisms need to be further studied.

Preconception diabetes mellitus and adverse pregnancy outcomes in over 6.4 million women: A population-based cohort study in China.

BACKGROUND: Diabetes mellitus (DM) increases the risk of adverse maternal and neonatal outcomes, and optimization of glycemic control during pregnancy can help mitigate risks associated with diabetes. However, studies seldom focus precisely on maternal blood glucose level prior to pregnancy. We aimed to evaluate the associations between preconception blood fasting plasma glucose (FPG) level and subsequent pregnancy outcomes. METHODS AND FINDINGS: We conducted a population-based retrospective cohort study among 6,447,339 women aged 20-49 years old who participated in National Free Pre-Pregnancy Checkups Project and completed pregnancy outcomes follow-up between 2010 and 2016 in China. During the preconception health examination, serum FPG concentration was measured, and self-reported history of DM was collected. Women were classified into three groups (normal FPG group: FPG < 5.6 mmol/L and no self-reported history of DM; impaired fasting glucose [IFG]: FPG 5.6-6.9 mmol/L and no self-reported history of DM; and DM: FPG ≥ 7.0 mmol/L or self-reported history of DM). The primary outcomes were adverse pregnancy outcomes, including spontaneous abortion, preterm birth (PTB), macrosomia, small for gestational age infant (SGA), birth defect, and perinatal infant death. Logistic regression model was used to calculate odds ratio (OR) and 95% confidence interval (CI) after adjusting for confounding variables. The mean age of women was 25.24 years, 91.47% were of Han nationality, and 92.85% were from rural areas. The incidence of DM and IFG was 1.18% (76,297) and 13.15% (847,737), respectively. Only 917 (1.20%) women reported a history of DM (awareness of their DM status), of whom 37.28% (337) had an elevated preconception FPG level (≥ 5.6 mmol/L), regarded as noncontrolled DM. A total of 1,005,568 (15.60%) women had adverse pregnancy outcomes. Compared with women with normal FPG, women with IFG had higher risks of spontaneous abortion (OR 1.08; 95% CI 1.06-1.09; P < 0.001), PTB (1.02; 1.01-1.03; P < 0.001), macrosomia (1.07; 1.06-1.08; P < 0.001), SGA (1.06; 1.02-1.10; P = 0.007), and perinatal infant death (1.08; 1.03-1.12; P < 0.001); the corresponding ORs for women with DM were 1.11 (95% CI 1.07-1.15; P < 0.001), 1.17 (1.14-1.20; P < 0.001), 1.13 (1.09-1.16; P < 0.001), 1.17 (1.04-1.32; P = 0.008), and 1.59 (1.44-1.76; P < 0.001). Women with DM also had a higher risk of birth defect (OR 1.42; 95% CI 1.15-1.91; P = 0.002). Among women without self-reported history of DM, there was a positive linear association between FPG levels and spontaneous abortion, PTB, macrosomia, SGA, and perinatal infant death (P for trend <0.001, <0.001, <0.001, 0.001, <0.001). Information about hypoglycemic medication before or during pregnancy was not collected, and we cannot adjust it in the analysis, which could result in underestimation of risks. Data on 2-hour plasma glucose level and HbA1c concentration were not available, and the glycemic control status was evaluated according to FPG value in women with DM. CONCLUSIONS: Women with preconception IFG or DM had higher risk of adverse pregnancy outcomes, including spontaneous abortion, PTB, macrosomia, SGA, and perinatal infant death. Preconception glycemic control through appropriate methods is one of the most important aspects of preconception care and should not be ignored by policy makers.

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.

Seroepidemiological map of Toxoplasma gondii infection and associated risk factors in preconception period in China: A nationwide cross-sectional study.

AIM: The aims of this study were to investigate the regional differences in seroepidemiology of toxoplasmosis in preconception period among Chinese women of reproductive age and to evaluate associated risk factors. METHODS: This national, population-based, cross-sectional serosurvey covered all 31 provinces and province-level municipalities in Mainland China. Married women intending to get pregnant within 6 months between 2010 and 2012 were recruited. Information on demographic characteristics (age, place of residence, occupation, dietary habits and exposure to cat) was obtained using interviews, and venous blood samples were collected to screen for Toxoplasma gondii infection. RESULTS: Of 2 008 561 women recruited to the study, 45 405 (2.3%) were Toxoplasma gondii IgG positive, and 6884 (0.3%) were IgM positive. Geographical variation for seropositivity ranged from 0.2% in Heilongjiang to 11.2% in Tianjing for IgG and from 0% in Tibet to 0.9% in Anhui for IgM. Advanced maternal age, occupation of a farmer, vegetarian diet and exposure to cat was significantly associated with Toxoplasma gondii IgM seropositivity, and its association with occupation of farmer and exposure to cat was significant after adjusting for province of residence (P < 0.05). CONCLUSION: There were significant regional variations in Toxoplasma gondii seropositivity and associated risk factors among Chinese women of reproductive age during preconception period. This calls for a targeted primary prevention strategy. Screening and treatment before conception and preconception health education may have potential for reducing congenital Toxoplasmosis in China.