Haiping Shen

Maternal pre-pregnancy infection with hepatitis B virus and the risk of preterm birth: a population-based cohort study

BACKGROUND Preterm birth is the leading cause of child death in children younger than 5 years. Large cohort studies in developed countries have shown that maternal hepatitis B virus infection is associated with preterm birth, but there is little reliable evidence from China and other developing countries, where hepatitis B virus prevalence is intermediate or high. Hence, we designed this study to investigate the association between pre-pregnancy hepatitis B virus infection and risk of preterm and early preterm birth. METHODS Between Jan 1, 2010, and Dec 31, 2012, we did a population-based cohort study using data from 489 965 rural women aged 21-49 years who had singleton livebirths from 220 counties of China who participated in the National Free Preconception Health Examination Project. Participants were divided into three groups according to their pre-pregnancy status of hepatitis B virus infection: women uninfected with hepatitis B virus (control group), women who were HBsAg positive and HBeAg negative (exposure group 1), and women who were both HBsAg and HBeAg positive (exposure group 2). The primary outcome was preterm birth (gestation at less than 37 weeks). We used log-binomial regression to estimate adjusted risk ratios (aRR) of preterm birth for women with pre-pregnancy hepatitis B virus infection, and risk of early preterm birth (gestation less than 34 weeks). FINDINGS 489 965 women met inclusion criteria and were included in this study; of these, 20 827 (4·3%) were infected with hepatitis B virus. Compared with women who were not infected with hepatitis B virus, women who were HBsAg positive and HBeAg negative had a 26% higher risk of preterm birth (aRR 1·26, 95% CI 1·18-1·34) and women who were both HBsAg and HBeAg positive had a 20% higher risk of preterm birth (aRR 1·20, 1·08-1·32). Compared with women who were not infected with hepatitis B virus, women who were HBsAg positive and HBeAg negative manifested an 18% higher risk of early preterm birth (gestation less than 34 weeks; aRR 1·18, 1·04-1·34) and women who were both HBsAg and HBeAg positive had a 34% higher risk of early preterm birth (aRR 1·34, 1·10-1·61). Maternal pre-pregnancy hepatitis B virus infection was independently associated with higher risk of preterm birth and early preterm birth. These associations were similar in subgroups of participants as defined by baseline characteristics. INTERPRETATION Besides mother-to-child transmission, the risk of preterm birth in women infected with hepatitis B virus should not be neglected. Comprehensive programmes that focus on early detection of hepatitis B virus infection before pregnancy and provide appropriate medical intervention for women infected with hepatitis B virus before and during pregnancy would be helpful in improving maternal and neonatal outcomes and reducing child mortality. FUNDING Chinese Association of Maternal and Child Health Studies.

Investigating the association between prepregnancy body mass index and adverse pregnancy outcomes: a large cohort study of 536 098 Chinese pregnant women in rural China

Objective Unhealthy maternal weight before pregnancy increases the risk of various adverse pregnancy outcomes. We conducted a nutrition survey to provide baseline data on the prepregnant nutritional status of mothers in order to better understand the association between prepregnancy maternal body mass index (BMI) and adverse pregnancy outcomes. Design A large, prospective, population-based cohort study. Setting Data from the National Free Preconception Health Examination Project (NFPHEP) in China during 2010–2012. Participants 536 098 pregnant women out of 2 120 131 were evaluated. Primary and secondary outcome measures The primary adverse pregnancy outcomes included preterm birth (PTB), low birth weight (LBW), spontaneous miscarriage (SM), ectopic pregnancy (EP) and stillbirth (SB). A χ2 test was used to compare the prevalence of each BMI category during 2010–2012. Univariable and multiple logistic regression analyses were performed to assess the association between prepregnancy BMI and various adverse pregnancy outcomes. Results Between 2010 and 2012, the average BMI decreased from 21.31 to 21.16, while underweight prevalence increased from 10.40% to 14.14%. An age-stratified subgroup analysis indicated that the underweight prevalence increased from 13.52% to 17.02% among women aged 21–24 and from 10.72% to 13.71% among women aged 25–34. Overweight prevalence increased from 9.84% to 10.75% (25–34 years) and from 17.10% to 19.20% (35–49 years). Obesity prevalence increased from 2.17% to 2.42% and from 4% to 4.2% among women aged 25–34 and 35–49 respectively. Prepregnancy underweight was associated with PTB, LBW and SM; overweight women had an increased risk of LBW; obese women had a higher risk of LBW, SM, EP and SB. Conclusions While the average prepregnancy BMI decreased, the prevalence of underweight individuals in a very large population significantly increased. The abnormal prepregnancy BMIs were associated with increased risks of adverse pregnancy outcomes. Most notably, underweight prepregnant women appeared to be at a greater risk of developing adverse pregnancy outcomes in Chinas rural areas.

A new perspective on universal preconception care in China

Many risk factors associated with adverse pregnancy outcomes can be identified and modified preconceptionally. Despite a broad consensus that preconception care should be provided to all couples of reproductive age, it has not been integrated in routine healthcare. There are several barriers to its implementation, and even in the most resourceful countries, it is only provided to some select high‐risk groups, rather than being an organized healthcare service provision to all. Recently, China seems to be leading the way by implementing preconception care nationwide in all rural areas. Its National Free Preconception Health Examination Project is a unique model of comprehensive preconception care. Advantages of this ambitious project are now becoming evident and benefiting the most vulnerable sections of Chinese society. This commentary provides an overview of National Free Preconception Health Examination Project and highlights the concepts that could be further developed and adapted into a model of preconception care.

Prevalence of Diabetes and Regional Differences in Chinese Women Planning Pregnancy: A Nationwide Population-Based Cross-sectional Study

Diabetes is closely linked with women’s health, and the Endocrine Society recommends that preconception consulting is provided to all women with diabetes who are considering pregnancy (1). However, the prevalence of hyperglycemia in this population is unknown and identifying diabetes before conception remains a challenge. Risk factor–based screening for type 2 diabetes (including in those of advanced age, who are overweight or obese, and with a family history of type 2 diabetes) in adults is recommended by the U.S. Preventive Services Task Force (2). The occurrence of diabetes is rising in China, where the prevalence of diabetes rose from 2.5% in 1994 to 9.7–11.6% in 2014. We hypothesized that there is a substantial prevalence of hyperglycemia (diabetes and prediabetes), with regional differences, in preconceptional women in China. To address this hypothesis, we analyzed data from the National Free Preconception Health Examination Project (NFPHEP) to quantify hyperglycemia among women with conception intention in China and to determine a more appropriate, tailored screening strategy in this population. A population-based, cross-sectional, fasting plasma glucose (FPG) survey of the hyperglycemia rate and its distribution among women planning pregnancy was performed using NFPHEP …

Prevalence of HBsAg/HBeAg amongst 1 936 801 couples preparing for pregnancy in rural China: An observational study

There are few extant studies on the prevalence of HBV infection in couples preparing for pregnancy. We assessed the prevalence of hepatitis B surface antigen (HBsAg) and hepatitis B e antigen (HBeAg) in couples preparing for pregnancy in rural China, and the association between HBV prevalence and the statuses of HBsAg/HBeAg and ALT in the spouses. We performed a nationwide cross‐sectional study, using data from a health check‐up program for 1 936 801 rural couples from 31 provinces preparing for pregnancy between 2010 and 2012. ELISA was used to test serologic samples, and we defined couples who were either discordant or both positive for HBsAg as “POSITIVE COUPLES” (PC). Amongst the 1 936 801 couples, 202 816 (10.47%; 95% CI, 10.43%‐10.51%) were PC. HBeAg (high infectiousness) was detected in 56 474 (27.84%; 95% CI, 27.65%‐28.04%) of 202 816 HBsAg‐positive couples. Multivariate models showed that the prevalence of HBV infection in wives increased along with the positive statuses for HBsAg/HBeAg and alanine aminotransferase (ALT) of their husbands (adjusted odds ratio increased from 2.31 to 4.98), after adjustment for potential confounders. Similarly, the prevalence of HBV infection in husbands was associated with the positive statuses of HBsAg/HBeAg and ALT of their wives (adjusted odds ratio increased from 2.04 to 4.93). The prevalence of POSITIVE COUPLES in couples preparing for pregnancy in rural China was high, and the prevalence of HBV infection was independently associated with the positive statuses of HBsAg/HBeAg and ALT of the spouses. Instead of solely focussing on mothers prior to becoming pregnant, POSITIVE COUPLES should be taken as an important unit of care.

Association of Long-term Exposure to Airborne Particulate Matter of 1 μm or Less With Preterm Birth in China

Importance Airborne particulate matter pollution has been associated with preterm birth (PTB) in some studies. However, most of these studies assessed only populations living near monitoring stations, and the association of airborne particulate matter having a median diameter of 1 &mgr;m or less (PM1) with PTB has not been studied. Objective To evaluate whether PM1 concentrations are associated with the risk of PTB. Design, Setting, and Participants This national cohort study used National Free Preconception Health Examination Project data collected in 324 of 344 prefecture-level cities from 30 provinces of mainland China. In total, 1 300 342 healthy singleton pregnancies were included from women who were in labor from December 1, 2013, through November 30, 2014. Data analysis was conducted between December 1, 2016, and April 1, 2017. Exposures Predicted weekly PM1 concentration data collected using satellite remote sensing, meteorologic, and land use information matched with the home addresses of pregnant women. Main Outcomes and Measures Preterm birth (<37 gestational weeks). Gestational age was assessed using the time since the first day of the last menstrual period. Cox proportional hazards regression analysis was used to examine the associations between trimester-specific PM1 concentrations and PTB after controlling for temperature, seasonality, spatial variation, and individual covariates. Results Of the 1 300 342 singleton live births at the gestational age of 20 to 45 weeks included in this study, 104 585 (8.0%) were preterm. In fully adjusted models, a PM1 concentration increase of 10 &mgr;g/m3 over the entire pregnancy was significantly associated with increased risk of PTB (hazard ratio [HR], 1.09; 95% CI, 1.09-1.10), very PTB as defined as gestational age from 28 through 31 weeks (HR, 1.20; 95% CI, 1.18-1.23), and extremely PTB as defined as 20 through 27 weeks’ gestation (HR, 1.29; 95% CI, 1.25-1.34). Pregnant women who were older (30-50 years) at conception (HR, 1.13; 95% CI, 1.11-1.14), were overweight before pregnancy (HR, 1.13; 95% CI, 1.11-1.15), had a rural household registration (HR, 1.09; 95% CI, 1.09-1.10), worked as farmers (HR, 1.10; 95% CI, 1.09-1.11), and conceived in autumn (HR, 1.48; 95% CI, 1.46-1.50) appeared to be more sensitive to PM1 exposure than their counterparts. Conclusions and Relevance Results from this national cohort study examining more than 1.3 million births indicated that exposure to PM1 air pollution was associated with an increased risk of PTB in China. These findings will provide evidence to inform future research studies, public health interventions, and environmental policies.

Rubella virus immunization status in preconception period among Chinese women of reproductive age: A nation-wide, cross-sectional study

OBJECTIVE Population-based studies on sero-epidemiology of Rubella in women before conception are lacking. The aim of this study was to investigate the sero-prevalence of Rubella in a nationwide survey among Chinese women planning to get pregnant within six months. METHODS This population-based, cross-sectional, sero-survey of Rubella virus infection was a part of the National Free Preconception Health Examination Project covering all 31 provinces in Mainland China. Women intending to get pregnant within six months was enrolled between 2010 and 12. Information on demographic characteristics (age, residence status, race, education and occupation) and vaccination history was obtained by interviews. Rubella virus IgG sero-positivity was determined using venous blood samples. RESULTS Of 2,120,131 women recruited to the study, Rubella virus IgG serology was available in 1,974,188 (99.3%). Participating women were of young age (median=28years), mostly engaged in agricultural activities (78%), and the majority (90%) had high school education or lower. The overall prevalence of Rubella virus IgG sero-positivity was 58.4% (1,161,129); geographical variation ranged from 92.5% in Jilin to 20.1% in Qinghai and 0.0% in Tibet. Only 4.6% (n=91,604) women reported to have had Rubella virus vaccination, and it varied from 18.6% (Guangdong) to 0.2% (Qinghai). Self-reported vaccination status did not correlate with Rubella virus IgG seropositivity. CONCLUSIONS Prevalence of Rubella sero-positivity is low among Chinese women of reproductive age and there are significant regional differences. Over 40% of women being susceptible to Rubella in preconception period calls for a targeted screening and vaccination strategy.

China’s community-based strategy of universal preconception care in rural areas at a population level using a novel risk classification system for stratifying couples´ preconception health status

BackgroundPreconception care (PCC) is recommended for optimizing a woman’s health prior to pregnancy to minimize the risk of adverse pregnancy and birth outcomes. We aimed to evaluate the impact of strategy and a novel risk classification model of China´s “National Preconception Health Care Project” (NPHCP) in identifying risk factors and stratifying couples’ preconception health status.MethodsWe performed a secondary analysis of data collected by NPHCP during April 2010 to December 2012 in 220 selected counties in China. All couples enrolled in the project accepted free preconception health examination, risk evaluation, health education and medical advice. Risk factors were categorized into five preconception risk classes based on their amenability to prevention and treatment: A-avoidable risk factors, B- benefiting from targeted medical intervention, C-controllable but requiring close monitoring and treatment during pregnancy, D-diagnosable prenatally but not modifiable preconceptionally, X-pregnancy not advisable. Information on each couple´s socio-demographic and health status was recorded and further analyzed.ResultsAmong the 2,142,849 couples who were enrolled to this study, the majority (92.36%) were from rural areas with low education levels (89.2% women and 88.3% men had education below university level). A total of 1463266 (68.29%) couples had one or more preconception risk factors mainly of category A, B and C, among which 46.25% were women and 51.92% were men. Category A risk factors were more common among men compared with women (38.13% versus 11.24%; P = 0.000).ConclusionsThis project provided new insights into preconception health of Chinese couples of reproductive age. More than half of the male partners planning to father a child, were exposed to risk factors during the preconception period, suggesting that an integrated approach to PCC including both women and men is justified. Stratification based on the new risk classification model demonstrated that a majority of the risk factors are avoidable, or preventable by medical intervention. Therefore, universal free PCC can be expected to improve pregnancy outcomes in rural China.

Long‐Term Effects of Ambient Particulate Matter (With an Aerodynamic Diameter ≤2.5 μm) on Hypertension and Blood Pressure and Attributable Risk Among Reproductive‐Age Adults in China

Background Epidemiological evidence on the association between long‐term exposure to ambient fine particulate matter (with an aerodynamic diameter ≤2.5 μm; PM 2.5) and hypertension is mixed. We investigated the long‐term association between ambient fine particles and hypertension in reproductive‐age adults. Methods and Results This analysis included 39 348 119 reproductive‐age (20–49 years) participants from the National Free Preconception Health Examination Project from April 22, 2010 to December 31, 2015 across China. The estimation of annual average ambient PM 2.5 concentrations for each community was realized through using satellite‐based spatial statistical models. Linear mixed models and 2‐level logistic regressions adjusted for potential confounders with natural cubic splines were used to investigate the shape of PM 2.5–blood pressure and PM 2.5‐hypertension, respectively. The effect modification by sex, obesity, smoking status, age, diabetes mellitus, urbanity, race, and region was also taken into account. The concentration‐response relationship between PM 2.5 and hypertension was nonlinear, with a threshold concentration of 47.9 μg/m3. The odds ratio of hypertension related to a 10‐μg/m3 increase in PM 2.5 above threshold was 1.010 (95% confidence interval, 1.007–1.012). A 10‐μg/m3 increase in PM 2.5 above threshold corresponded to a 0.569 (95% confidence interval, 0.564–0.573) mm Hg elevation in systolic blood pressure and a 0.384 (95% confidence interval, 0.381–0.388) mm Hg elevation in diastolic blood pressure. There were 2.3% (95% confidence interval, 2.2%–2.4%) of the hypertension cases that could be attributed to PM 2.5 exposures in reproductive‐age adult populations. Conclusions Long‐term exposures to PM 2.5 above certain levels might increase population risk for hypertension and might be responsible for Chinas avoidable hypertension burden in reproductive‐age adults.

Prevalence of chronic kidney disease markers: Evidence from a three-million married population with fertility desire in rural China

We aimed to assess the prevalence of chronic kidney diseases (CKD) markers among the married residents with fertility desire in rural China. Demographic and clinical data were collected from the National Free Pre-Conception Health Examination Project. Estimated glomerular filtration rate (eGFR) < 60 mL/min//1.73 m2, proteinuria, and hematuria were defined as markers of CKD. GFR was evaluated by using serum creatinine level and the Asian-modified CKD epidemiology collaboration equation. Automated urine dry chemical and microscopic analyses were employed to identify proteinuria and hematuria. The prevalence of CKD markers was 2.92% in the 3,091,379 participants. eGFR < 60 mL/min//1.73 m2, hematuria and proteinuria was observed in 0.85%, 1.41% and 0.71%, respectively. The prevalence of CKD markers varied greatly across different geographical locations, which was the highest in the Eastern Region (3.86%; 95% confidence interval [CI]: 3.81–3.91%), moderate in the Central Region (2.80%; 95% CI: 2.77–2.82%), and lowest in the Western Region (2.62%; 95% CI: 2.59–2.65%). Hypertension, obesity, positive hepatitis B virus surface antigen (HBsAg), age (increased by every 5 years), female gender, and living area were potential risk factors for CKD. In rural China, the prevalence of CKD markers in the married couples with fertility desire is low.