National Free Pre-pregnancy Checkups Research Articles

Evaluating the progression to abnormal thyrotropin in euthyroid preconception women: a population-based study

Background Abnormal preconception thyrotropin levels were associated with fecundability and adverse fetomaternal outcomes, however, little is known regarding the natural change of serum thyrotropin in euthyroid preconception women. Thus, we performed a population-based study to evaluate the progression to abnormal thyrotropin in euthyroid preconception women.Methods This retrospective cohort study used data from the National Free Prepregnancy Checkups Project (NFPCP) collected between 2010 and 2020. Female Han Chinese participants aged 20–49 years who had two repeated NFPCP participations with a time interval of 1.5–3.0 years, confirmed non-pregnant status within this duration, and normal thyrotropin levels during their first participation were included for the analysis of thyrotropin abnormalities during the second NFPCP examination. Data were analyzed between June 1 and October 1, 2023.ResultsThis study included 186,095 euthyroid women of reproductive age (mean ± SD, 26.72 ± 4.70 years) whose preconception thyrotropin levels were between 0.37 and 4.87 mIU/L. The median follow-up time was 2.13 (IQR, 1.85–2.54) years. A total of 8,497 (4.57%) women developed abnormal thyrotropin, including 4,118 (2.21%) subnormal thyrotropin and 4,379 (2.35%) supranormal thyrotropin. Compared with the reference group (thyrotropin 1.01–2.00 mIU/L), the lower baseline thyrotropin group had greater risk of developing subnormal thyrotropin, and the higher baseline thyrotropin group had greater risk of developing supranormal thyrotropin. Moreover, the restricted cubic spline analysis revealed a U-shaped dose–response association of baseline thyrotropin levels or thyrotropin multiples of the median (MOM) levels against risk of subnormal thyrotropin in the follow-up, and a J-shaped dose–response association against risk of supranormal thyrotropin levels in the follow-up. We further found that baseline thyrotropin outside of 1.43–1.93 mIU/L or baseline thyrotropin MOM outside 0.59–1.36 would hava a higher risk of developing of abnormal thyrotropin.ConclusionsBoth low and high baseline thyrotropin were associated with a significantly increased risk of developing abnormal thyrotropin outcomes. The optimal preconception baseline thyrotropin levels may be between 1.43 mIU/L and 1.93 mIU/L or baseline thyrotropin MoM between 0.59 and 1.36 to minimize progression toward abnormal thyrotropin after 1.5–3.0 years. These findings may help with counseling of preconception thyroid function monitoring.

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

BackgroundThe 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.MethodsThis 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.ResultsLate 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.ConclusionsStructural 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.

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

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. To evaluate the associations of preconception thyrotropin levels with time to pregnancy (TTP) and risk of spontaneous abortion (SA). 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. Levels of thyrotropin within 1 year prior to pregnancy. 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. 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). 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.

Paternal smoking and preterm birth: a population-based retrospective cohort study among non-smoking women aged 20\u201349\xa0years in rural China

BackgroundTo comprehensively evaluate the association of paternal smoking and preterm birth (PTB).MethodsWe 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.ResultsCompared 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).ConclusionsPaternal 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.

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, 256718 (5·44 %) SGA events and 506495 (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.

Increased Risk of Stillbirth among Women whose Partner Has Tuberculosis.

Background The relationship between tuberculosis (TB) and adverse pregnancy outcomes remains unclear. The aim of our study was to investigate whether TB is a risk factor for adverse pregnancy outcomes including premature birth, low birth weight, and stillbirth. Method We conducted a population-based retrospective cohort study in mainland China. A total of 3,668,004 Chinese women, along with their partners, were included in this study, within the National Free Pre-Pregnancy Checkups Project, during 2015–2018. Propensity score matching was used to balance the two groups (cases: women or partners with TB; controls: women and partners without TB). Multivariable logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs). Results Multivariate logistic regression showed that the OR of stillbirth for cases was 1.89 (95% CI: 1.09–3.16), in comparison with the control group. In the subgroup analysis, women whose partner had TB had a higher risk of stillbirth (OR: 2.13, 95% CI: 1.10–3.86) than women whose partner did not have TB. There was no significant difference in adverse pregnancy outcomes, including preterm birth, low birth weight, and stillbirth, between women with and without TB. Conclusions Women whose partner had TB were more likely to have stillbirth than women whose partners did not have TB.

Maternal Pre-conception Body Mass Index and Fasting Plasma Glucose With the Risk of Pre-term Birth: A Cohort Study Including 4.9 Million Chinese Women.

Background: To evaluate the associations of pre-conception body mass index (BMI), fasting plasma glucose (FPG) alone and their combination with pre-term birth (PTB) risk.Methods: We conducted a population-based retrospective cohort study with 4,987,129 reproductive-aged women, who participated in National Free Pre-Pregnancy Checkups Project in 2013–2016 and had a singleton delivery before December 2017 in China. All data analyses were conducted in 2018–2021.Results: A total of 339,662 (6.81%) women had pre-term deliveries. Compared with women with normal weight and normal glucose, underweight and normal weight were associated with PTB among hypoglycemia women, the adjusted odd ratios (aORs) were 1.24 (95% CI: 1.05–1.48) and 1.16 (95% CI: 1.07–1.25), respectively; underweight, overweight and obesity were associated with PTB among women with normal glucose, the aORs were 1.09 (95% CI: 1.08–1.10), 1.06 (95% CI: 1.05–1.07) and 1.08 (95% CI: 1.05–1.12), respectively; all the BMI groups were significantly associated with PTB among women with pre-diabetes or diabetes (P < 0.05). The dose-response relationships of BMI with PTB varied in different FPG level, with U-shaped curve in normal glucose and pre-diabetes women, J-shaped in diabetes women, L-shaped in hypoglycemia women. For FPG with PTB, the dose-response relationships were U-shaped in normal weight, overweight, and obesity women, and L-shaped in underweight women.Conclusion: We found that the associations of PTB with BMI varied with levels of FPG, and associations of PTB with FPG varied with levels of BMI. There was a synergistic effect on PTB risk due to abnormal weight and glycemia besides a conventional main effect derived from either of them. Achieving desirable weight and glucose control before conception should be advised.

Preconception Thyrotropin Levels and Risk of Adverse Pregnancy Outcomes in Chinese Women Aged 20 to 49 Years

Maternal thyrotropin levels during gestation have a profound effect on pregnancy outcomes; however, few studies to date have evaluated the importance of preconception thyrotropin levels. To investigate the associations between preconception thyrotropin levels and pregnancy outcomes. This population-based cohort study enrolled Chinese women aged 20 to 49 years from the National Free Prepregnancy Checkups Project in China. Participants conceived within 6 months after the thyrotropin examination and completed follow-up for pregnancy outcomes between January 1, 2013, and December 31, 2017. Data were analyzed between May 1, 2019, and March 31, 2020. Levels of thyrotropin within 6 months before pregnancy, measured as less than 0.10 mIU/L, 0.10 to 0.36 mIU/L, 0.37 to 2.49 mIU/L, 2.50 to 4.87 mIU/L, 4.88 to 9.99 mIU/L, and 10.00 mIU/L or greater. The association of maternal preconception thyrotropin levels with the 4 primary adverse pregnancy outcomes was assessed, including preterm birth (PTB), small for gestational age (SGA), birth defect, and perinatal infant death. Logistic regression analyses were used to evaluate the association between preconception maternal thyrotropin levels and risk of adverse pregnancy outcomes. The dose-response associations were assessed using restricted cubic spline regression. This study enrolled 5 840 894 women (mean [SD] age, 26.30 [4.10] years) in the primary analysis. The median (interquartile range [IQR]) thyrotropin level was 1.60 (1.06-2.37) mIU/L. The cumulative incidences for the adverse pregnancy outcomes were as follows: PTB, 6.56%; SGA, 7.21%; birth defect, 0.02%; and perinatal infant death, 0.33%. Compared with the reference group (thyrotropin range, 0.37-2.49 mIU/L), both low (<0.10 mIU/L and 0.10-0.36 mIU/L) and high (4.88-9.99 mIU/L and ≥10.00 mIU/L) maternal preconception thyrotropin levels were associated with higher risk of PTB (low: odds ratio [OR], 1.23 [95% CI, 1.19-1.27] and OR, 1.15 [95% CI, 1.13-1.18] vs high: OR, 1.13 [95% CI, 1.10-1.15] and OR, 1.14 [95% CI, 1.08-1.20]), SGA (low: OR, 1.37 [95% CI, 1.33-1.40] and OR, 1.14 [95% CI, 1.12-1.17] vs high: OR, 1.05 [95% CI, 1.03-1.08] and OR, 1.17 [95% CI, 1.11-1.23]), and perinatal infant death (low: OR, 1.26 [95% CI, 1.10-1.43] and OR, 1.14 [95% CI, 1.05-1.24] vs high: OR, 1.31 [95% CI, 1.20-1.43] and OR, 1.47 [95% CI, 1.21-1.80]). J-shaped associations between preconception thyrotropin levels and PTB (χ2 = 1033.45; nonlinear P < .001), SGA (χ2 = 568.90; nonlinear P < .001), and perinatal infant death (χ2 = 38.91; nonlinear P < .001) were identified. In this cohort study, both low and high maternal thyrotropin levels were associated with a significantly increased risk of adverse pregnancy outcomes. Results suggest that the optimal preconception thyrotropin levels may be between 0.37 mIU/L and 2.50 mIU/L to prevent adverse pregnancy outcomes.

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

BackgroundInconsistent 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.MethodsThe 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.ResultsIn 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).ConclusionsOur 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.

The trend of caesarean birth rate changes in China after \u2018universal two-child policy\u2019 era: a population-based study in 2013\u20132018

BackgroundThe 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.MethodsThis 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.ResultsA 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.ConclusionsThe 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.

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

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. A population-based cohort study established between 2013 and 2017. Local maternal and child care service centres in each county. 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. 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). 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.

Women’s preconception health patterns in traditional Chinese medicine as a predictor of fertility outcomes

ObjectiveTo examine the association between traditional Chinese medicine (TCM), preconception health patterns and fertility outcomes. MethodsA community-based prospective cohort study was conducted in China. A total of 3012 newly married women who were willing to conceive within 2 years were enrolled in the study and took National Free Prepregnancy Checkups (NFPC). A reliably structured self-rating scale was used to measure the TCM preconception health patterns of the enrolled women. A 3-year follow-up was conducted to obtain the fertility outcomes, including pregnancy rate, time to pregnancy, spontaneous miscarriage and newborn status. Statistical analyses were conducted using Chi-square or Fisher’s exact tests, logistic regression models, general linear models and the Cox proportional hazard model. ResultsThe fertility outcomes showed no statistic correlations to the terms of NFPC in this population. Approximately a half of the women (46.66%) had unhealthy patterns. Women with qi & blood-deficiency (odds ratio [OR] = 35.19, 95% confidence interval [CI] = 1.55–801.15) or qi-stagnation (OR = 4.55, 95% CI = 0.90–23.06) pattern took a longer time to get pregnant, and those with qi-stagnation (OR = 2.05, 95% CI = 1.1–3.82) or yang-deficiency (OR = 1.91, 95% CI = 1.12–3.25) pattern had a higher risk of spontaneous miscarriage. ConclusionThree unhealthy TCM patterns during the preconception period might be risk factors for low fecundity or poor pregnancy outcomes. The TCM preconception pattern identification may provide a convenient and effective way to screen for potential pregnancy risks beyond the NFPC. Further, appropriate interventions based on the TCM preconception health patterns are needed to improve quality in women’s fecundability and birth outcomes.

The association of husbands' smoking with wives' dysglycemia status: A cross-sectional study among over 10 million Chinese women aged 20-49.

We comprehensively evaluated the association between husbands' smoking amount and wives' dysglycemia status. We conducted a cross-sectional study which recruited 12 023 714 reproductive couples who participated in the National Free Pre-Pregnancy Checkups Project (NFPCP) between 2015 and 2016 in China. Multivariable logistic models were used to estimate odds ratio (OR) and 95% CI. Subgroup analysis and stratified analysis were further performed to investigate potential effect modification. Compared to the neither-smoker group, the multivariable-adjusted ORs for diabetes mellitus (DM) among women was 1.09 (95% CI, 1.07-1.10), 1.04 (95% CI, 0.87-1.23), and 1.28 (95% CI, 1.17-1.41) in the husband-smoker, wife-smoker, and both-smokers groups, respectively. An increased risk of DM was also observed for women whose husbands smoke 1 to 10 (OR, 1.06; 95% CI, 1.04-1.07), 11 to 20 (OR, 1.13; 95% CI, 1.11-1.15), and over 20 cigarettes per day (OR, 1.25; 95% CI, 1.17-1.31). The prevalence of wives' DM showed significant linear trends with husbands' smoking amount (Pfor trend < .001). A similar growth tendency was also observed between husband smoking amount and impaired fasting glucose (IFG) prevalence with ORs of 1.04 (95% CI, 1.04-1.05), 1.05 (95% CI, 1.04-1.06), and 1.09 (95% CI, 1.06-1.11) for 1-10, 11-20, and over 20 cigarettes per day, respectively. The relationship between husbands' smoking amount and wives' IFG/DM prevalence appear to be modified by body mass index (BMI). This study shows significant relationships between husbands' smoking and wives' risk of IFG/DM, and this result exists in both a categorical and dose-response manner. This association is modified by BMI. Family-oriented smoking interventions may both reduce husbands' active smoking and wives' risk of DM.

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

BackgroundDiabetes 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 findingsWe 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.ConclusionsWomen 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.

The association between air pollution and preterm birth and low birth weight in Guangdong, China

BackgroundA mountain of evidence has shown that people’s physical and mental health can be affected by various air pollutions. Poor pregnancy outcomes are associated with exposure to air pollution. Therefore, this study aims to investigate the association between air pollutions (PM2.5, PM10, SO2, NO2, CO, and O3) and preterm birth/low birth weight in Guangdong province, China.MethodAll maternal data and birth data from January 1, 2014 to December 31, 2015 were selected from a National Free Pre-pregnancy Check-ups system, and the daily air quality data of Guangdong Province was collected from China National Environmental Monitoring Center. 1784 women with either preterm birth information (n = 687) or low birth weight information (n = 1097) were used as experimental group. Control group included 1766 women with healthy birth information. Logistic regression models were employed to evaluate the effects of air pollutants on the risk of preterm birth and low birth weight.ResultsThe pollution levels of PM2.5, PM10, SO2, NO2, CO, and O3 in Guangdong province were all lower than the national air pollution concentrations. The concentrations of PM2.5, PM10, SO2, NO2 and CO had obvious seasonal trends with the highest in winter and the lowest in summer. O3 concentrations in September (65.72 μg/m3) and October (84.18 μg/m3) were relatively higher. After controlling for the impact of confounding factors, the increases in the risk of preterm birth were associated with each 10 μg/m3 increase in PM2.5 (OR 1.043, 95% CI 1.01–1.09) and PM10 (OR 1.039, 95% CI 1.01~1.14) during the first trimester and in PM2.5 (OR 1.038, 95% CI 1.01~1.12), PM10 (OR 1.024, 95% CI 1.02~1.09), SO2 (OR 1.081, 95% CI 1.01~1.29), and O3 (OR 1.016, 95% CI 1.004~1.35) during the third trimester. The increase in the risk of low birth weight was associated with PM2.5, PM10, NO2, and O3 in the first month and the last month.ConclusionThis study provides further evidence for the relationships between air pollutions and preterm birth/low birth weight. Pregnant women are recommended to reduce or avoid exposure to air pollutions during pregnancy, especially in the early and late stages of pregnancy.

Preconception alanine aminotransferase concentrations and risk of preterm birth in rural Chinese women aged 20–49 years: a population-based cohort study

BackgroundPrevious studies have shown maternal hepatitis B virus infection is associated with preterm birth. However, whether liver dysfunction caused by hepatitis B virus infection or other factors can lead to preterm delivery needs further exploration. Serum alanine aminotransferase (ALT) is a sensitive indicator of liver function, but few studies have investigated the association between serum ALT concentrations and preterm birth. We aimed to examine the relationship between maternal preconception ALT concentration and risk of preterm birth. MethodsWe did a population-based cohort study of 4832887 women aged 20–49 years old, who participated in the National Free Pre-pregnancy Checkups Project (NFPCP) in 2013–16, and delivered a livebirth before Dec 31, 2017, in rural China. We collected information about demographic characteristics, history of pregnancy and diseases, serum ALT concentration, hepatitis B surface antigen (HBsAg) status, and other variables. We divided participants into five groups according to serum ALT concentration (≤20 U/L, 21–40 U/L, 41–60 U/L, 61–80 U/L, and ≥ 81 U/L). The primary outcome was preterm birth (gestational age 28 to <37 weeks). We used logistic models to estimate odds ratios (ORs) and 95% CIs, after adjusting for confounding variables. We applied restricted cubic splines to investigate the dose-response relationship. The study was approved by the Institutional Research Review Board at the National Health Commission, and all participants gave written consent. FindingsBy Dec 31, 2017, 324207 (6·71%) preterm birth events were documented in the 4832887 participants. Incidence of preterm birth was lowest in women with ALT concentrations of 21–40 U/L (93685 [6·42%] of 1 458 233 women), whereas the preterm birth incidence was highest in women with ALT concentrations of 81 U/L or higher (3302 [7·52%] of 43912 women). There was a non-linear dose-response relationship between serum ALT concentration and risk of preterm birth (U-shaped, p<0·001). In women who were HBsAg negative, the multivariable-adjusted OR for preterm birth was 1·07 (95% CI 1·06–1·08) for ALT concentrations of 20 U/L or less, 1·19 (1·16–1·22) for concentrations of 41–60 U/L, 1·16 (1·11–1·20) for concentrations of 61–80 U/L, and 1·16 (1·12–1·21) for concentrations of 81 U/L or higher, when compared to women with ALT concentrations of 21–40 U/L. In women who were HBsAg positive, there were significant associations between preterm birth and ALT concentrations of 61–80 U/L (OR 1·17, 95% CI 1·05–1·29), and 81 U/L or higher (1·21, 1·11–1·31). InterpretationOur study identified a U-shaped relationship between maternal preconception ALT concentration and risk of preterm birth. The association between ALT concentration and risk of preterm birth was independent of hepatitis B virus infection. The surveillance of ALT among women planning pregnancy should be warranted, given the increased risk of preterm birth. FundingThis study was supported by the National Key Research and Development Program (number 2016YFC10003007).

Preconception Hb concentration and risk of preterm birth in over 2·7 million Chinese women aged 20-49 years: a population-based cohort study.

Evidence on the association between maternal Hb concentration and preterm birth (PTB) risk is inconclusive. This paper aimed to explore whether women with anaemia or high Hb level before pregnancy would be at higher risk of PTB. We conducted a population-based cohort study with 2 722 274 women aged 20-49 years, who participated in National Free Pre-Pregnancy Checkups Project between 2013 and 2015 and delivered a singleton before 2016 in rural China. Logistic models were used to estimate OR and 95 % CI after adjusting for confounding variables. Restricted cubic spline models were applied to evaluate the dose-response relationships. A total of 192 819 (7·08 %) women had preterm deliveries. Compared with women with Hb of 110-149 g/l, the multivariable-adjusted OR for PTB was 1·19 (95 % CI 0·98, 1·44) for women with Hb<70 g/l, 1·01 (95 % CI 0·97, 1·03) for 70-99 g/l, 0·96 (95 % CI 0·95, 0·98) for 100-109 g/l, 1·04 (95 % CI 1·01, 1·06) for 150-159 g/l, 1·11 (95 % CI 1·05, 1·17) for 160-169 g/l and 1·19 (95 % CI 1·11, 1·27) for ≥170 g/l, respectively. The multivariable-adjusted OR for very PTB (VPTB) was 1·07 (95 % CI 1·03, 1·12) and 1·06 (95 % CI 1·01, 1·12) for women with Hb <110 and ≥150 g/l, compared with those with Hb of 110-149 g/l, respectively. Our study identified a U-shaped relationship between maternal preconception Hb concentration and PTB risk. Both preconception anaemia and high Hb level can significantly increase VPTB risk. Appropriate intervention for women with abnormal Hb levels before pregnancy is very necessary.

The association between ambient PM2.5 exposure and the risk of preterm birth in China: A retrospective cohort study

BackgroundThe relationship between PM2.5 exposure and preterm birth remains unclear. ObjectivesTo explore the effect of exposure to PM2.5 on preterm birth in China. MethodsThe birth outcomes of 426,246 pregnant women enrolled between January 2014 and December 2014 in NFPCP (National Free Pre-pregnancy Checkups Project) were collected, and their individual PM2.5 exposure values were estimated from the China National Environmental Monitoring Centre. The time of gestational exposure to PM2.5 was divided into four periods (the first trimester, the second trimester, the third trimester and the entire pregnancy). The average concentration and the corresponding quartiles of PM2.5 were calculated in these periods by the daily average PM2.5 data. Cox proportional hazards regression was used and he effects of maternal age, education level, occupation, second-hand smoking, alcohol use, pre-pregnancy BMI, baby's sex, number of previous pregnancies, coastal areas and season of conception were adjusted for. ResultsA total of 426,246 singleton births were included, among which 35,261 (8.3%) were preterm birth. Effect of each 10μg/m3 increase of PM2.5 on preterm birth was most significant during the third trimester (HR, 1.06; 95%CI, 1.06–1.07), and also significant during the first trimester (HR, 1.04; 95%CI, 1.03–1.04), the second trimester (HR, 1.02; 95%CI, 1.02–1.02) and the entire pregnancy (HR, 1.06; 95%CI, 1.05–1.06). Compared with the lowest quartile of PM2.5, other quartiles increased the risk of preterm birth, and were most significant during the third trimester (HR, 1.87; 95%CI, 1.69–2.06). Subgroup analysis showed that compared with other subgroups, women who were older than 30years, had low education level, worked as farmers, had male baby, had previous pregnancies, not live in coastal areas and pregnant in winter were more sensitive to PM2.5 exposure. ConclusionsAmbient PM2.5 exposure during pregnancy played an important role in the pregnancy process and increased the risk of preterm birth.

Association between PM2·5 exposure and the risk of preterm birth in Henan, China: a retrospective cohort study

BackgroundIn recent years, air pollution has become an important global public health problem and has received extensive attention, but its association with preterm birth is still unclear. The aim of this study was to explore the effect of PM2·5 exposure on preterm births in China. MethodsIn this retrospective cohort study, we used data from the National Free Pre-pregnancy Checkups Project (NFPCP). The NFPCP is a national health service that has been supported by the National Health and Family Planning Commission and the Ministry of Finance of the People's Republic of China since 2010, aiming to provide free pre-pregnancy medical examinations and follow-up pregnancy outcomes for couples of childbearing age throughout the country. We investigated the birth outcomes of 244 305 pregnant women and their individual PM2·5 exposure values in the Henan province from 2014 to 2015 from NFPCP and the Ministry of Environmental Protection of the People's Republic of China. In this research, the PM2·5 exposure time was divided into three periods (1 day before delivery, 1 week before delivery, and 4 weeks before delivery) according to the previous research. We calculated the average concentration and the corresponding quartiles of PM2·5 in these three periods. We used logistic regression to explore the association between PM2·5 exposure and preterm birth in different periods, and compared the effects of different quartiles of levels of PM2·5 exposure on preterm birth in each exposure phase. The effects were adjusted for maternal age, body-mass index (BMI) before pregnancy, month at delivery, second-hand smoking, drinking, sex of infants, and number of pregnancies. This study was approved by the Institutional Research Review Board at the National Health and Family Planning Commission. Informed consent was obtained from all the NFPCP participants. FindingsWe included 244 305 singleton births, among which 6709 (2·7%) were preterm. Each 10 μg/m3 increase of PM2·5 was associated with increases in the risk of preterm birth of 1·99% (95% CI 1·52–2·47) in the period of 1 day before delivery, 4·01% (3·30–4·73) in the period of 1 week before delivery, and 5·94% (5·00–6·88) in the period of 4 weeks before delivery. We found that PM2·5 exposure during 4 weeks before delivery had the highest significant increase in the risk of preterm birth, and we then explored the dose association between preterm birth and PM2·5 exposure based on quartiles. Compared with the lowest quartile of PM2·5, the exposure of the second, third, and fourth quartile PM2·5 during 4 weeks before delivery increased the risk of preterm birth (adjusted ORs were 1·42 [95% CI 1·32–1·53] for the second quartile, 1·51 [1·41–1·63] for the third quartile, and 1·80 [1·66–1·96] for the fourth quartile). InterpretationWe observed that short-term acute PM2·5 exposure before delivery played an important role in the pregnancy process and could increase the risk of preterm birth. FundingNational Key Research and Development Program of China (2016YFC1000300, 2016YFC1000307).