Perfluorononanoic Acid Induces Neurotoxicity via Synaptogenesis Signaling in Zebrafish.

Perfluorononanoic acid (PFNA), commonly used as an alternative polyfluorinated compound (PFC) of perfluorooctanoic acid (PFOA), has been widely detected in the aquatic environment. Previous ecotoxicological and epidemiological results suggested that some neurobehavioral effects were associated with PFC exposure; however, the ecological impacts and underlying neurotoxicity mechanisms remain unclear, particularly in aquatic organisms during sensitive, early developmental stages. In this study, zebrafish embryos were exposed to environmentally relevant concentrations of PFNA for 120 h, and the neurological effects of PFNA were comprehensively assessed using transcriptional, biochemical, morphological, and behavioral assays. RNA sequencing and advanced bioinformatics analyses predicted and characterized the key biological processes and pathways affected by PFNA exposure, which included the synaptogenesis signaling pathway, neurotransmitter synapse, and CREB signaling in neurons. Neurotransmitter levels (acetylcholine, glutamate, 5-hydroxytryptamine, γ-aminobutyric acid, dopamine, and noradrenaline) were significantly decreased in zebrafish larvae, and the Tg(gad67:GFP) transgenic line revealed a decreased number of GABAergic neurons in PFNA-treated larvae. Moreover, the swimming distance, rotation frequency, and activity degree were also significantly affected by PFNA, linking molecular-level changes to behavioral consequences.

Effects of fine ambient particulate matters on de novo hypertensive disorders of pregnancy and blood pressure before 20 weeks.

The effects of fine particulate matter (PM) on de novo hypertensive disorders of pregnancy (HDP) were inconsistent during the first and second trimesters. This study aimed to assess the trimester-specific effects of PM2.5 and PM1 prior to diagnosis of de novo HDP. The exposure of fine PM was predicted by satellite remote sensing data according to maternal residential addresses. De novo HDP was defined as gestational hypertension and preeclampsia during the current pregnancy. A logistic regression model was performed to assess the association of PM2.5 and PM1 with HDP during the first and early second trimesters (0-13 weeks and 14-20 weeks). The generalized estimating equation model was conducted to assess the effect of PM2.5 and PM1 on blood pressure. The present study included 22,821 pregnant women (mean age, 29.1 years) from 2013 to 2017. PM2.5 and PM1 were significantly associated with an increased risk of de novo HDP during the first trimester (OR = 1.070, 95% CI: 1.013-1.130; OR = 1.264, 95% CI: 1.058-1.511 for per 10 µg/m3) and early second trimester (OR = 1.045, 95% CI: 1.003-1.088; OR = 1.170, 95% CI: 1.002-1.366 for per 10 µg/m3). Significant trends of increased de novo HDP risk was also observed with the increment of PM (all P for trend <0.05). The stratified analyses demonstrated that the associations between exposure to fine PM and the risk of HDP were more pronounced among the pregnant women with maternal age above 35 and low maternal education level (all OR >1.047). Each 10 µg/m3 increase of PM1 and PM2.5 before diagnosis of de novo HDP elevated 0.204 (95% CI: 0.098-0.310) and 0.058 (95%CI: 0.033-0.083) mmHg of systolic blood pressure. Exposure to PM2.5 and PM1 during the first and early second trimester were positively associated with the risk of de novo HDP. The fine PM before diagnosis of de novo HDP elevated the systolic blood pressure.

Effect of levothyroxine treatment on fetal growth among women with mild subclinical hypothyroidism and thyroid peroxidase antibody negative: a cohort study.

BACKGROUND: Some clinicians used levothyroxine (LT4) treatment for mild subclinical hypothyroidism (SCH) pregnant women (2.5 < thyroid-stimulating hormone (TSH) ≤ the pregnancy-specific reference range with normal free thyroxine (FT4) level) with thyroid peroxidase antibody negative (TPOAb-), although the recent clinical guideline did not recommend it. It is unknown whether LT4 treatment for pregnant women with mild SCH and TPOAb- have impact on fetal growth. Therefore, the aim of the study was to investigate the effect of LT4 treatment on fetal growth and birth weight among mild SCH pregnant women with TPOAb-. METHODS: This was a birth cohort study including 14,609 pregnant women between 2016 and 2019 in Tongzhou Maternal and Child Health Hospital of Beijing, China. Pregnant women were divided into 3 groups as follows: Euthyroid (n = 14,285, 0.03 ≤ TSH ≤ 2.5mIU/L, normal FT4), TPOAb-; Untreated mild SCH with TPOAb- (n = 248, 2.5 < TSH ≤ 2.9mIU/L, normal FT4, without LT4 treatment); Treated mild SCH with TPOAb- (n = 76, 2.5 < TSH ≤ 2.9mIU/L, normal FT4, with LT4 treatment). The main outcome measures were Z-scores of fetal growth indicators (abdominal circumference (AC), biparietal diameter (BPD), femur length (FL), head circumference (HC), estimated fetal weight (EFW)), fetal growth restriction (FGR) and birth weight. RESULTS: There was no difference in fetal growth indicators and birth weight between the untreated mild SCH women with TPOAb- and the euthyroid pregnant women. But the HC Z-score was lower in the LT4 treated mild SCH women with TPOAb-, compared with the euthyroid pregnant women (ß = -0.223, 95%CI: -0.422, -0.023). The LT4 treated mild SCH women with TPOAb- had lower fetal HC Z-score (ß = -0.236, 95%CI: -0.457, -0.015), compared with the untreated mild SCH women with TPOAb-. CONCLUSIONS: We observed that LT4 treatment for mild SCH with TPOAb- was associated with decreased fetal HC, which was not observed for untreated mild SCH women with TPOAb-. The adverse effect of LT4 treatment for mild SCH with TPOAb- provided new evidence for the recent clinical guideline.

Enrofloxacin Induces Intestinal Microbiota-Mediated Immunosuppression in Zebrafish.

The immunosuppressive effects of antibiotics and the potential associations with the intestinal microbiota of the host have been increasingly recognized in recent years. However, the detailed underlying mechanisms of immune interference of antibiotics in environmental organisms remain unclear, particularly at the early life stage of high sensitivity. To better understand the gut microbiome and immune function interactions, the vertebrate model, zebrafish, was treated with environmentally relevant concentrations of a frequently detected antibiotic, enrofloxacin (ENR), ranging from 0.01 to 100 µg/L. 16S ribosomal RNA sequencing indicated diminished diversity, richness, and evenness of intestinal flora following ENR treatment. Twenty-two taxa of gut bacteria including Rickettsiales, Pseudomonadales, and Flavobacteriales were significantly correlated with immunosuppressive biomarkers, including a significant decrease in the abundance of macrophages and neutrophils. To validate the immunomodulatory effects due to altered intestinal microbial populations, zebrafish reared under sterile and non-sterile husbandry conditions were compared after ENR treatment. A significant inhibitory effect was induced by ENR treatment under non-sterile conditions, while the number of macrophages and neutrophils, as well as biomarkers of immunosuppressive effects, were significantly salved in zebrafish under sterile conditions, confirming for the first time that immunosuppression by ENR was closely mediated through alterations of the intestinal microbiome in fish.

Individual and joint effects of prenatal green spaces, PM2.5 and PM1 exposure on BMI Z-score of children aged two years: A birth cohort study.

BACKGROUND: Few studies examined the association of prenatal exposure to green spaces with children's body mass index (BMI) Z-score, and no study evaluated the joint effect of prenatal green spaces and PM2.5 or PM1 exposure on children's BMI Z-score. We aimed to assess the individual and joint effects of prenatal green spaces, PM2.5, and PM1 exposure on BMI Z-score of children aged two years. METHODS: The study was based on a birth cohort in Beijing, China, in which 13,253 mothers (LMP from 2014 to 2017) and their children were included. We estimated prenatal green spaces exposure by calculating average normalized difference vegetation index with 500 m buffers (NDVI-500), prenatal PM2.5 and PM1 exposure based on maternal residential addresses. Weight and height of children were measured at 2 years old. We calculated children's BMI Z-score based on the WHO Standards. Generalized linear regression was used to examine the individual and joint effects of prenatal NDVI-500, PM2.5 and PM1 exposure on children's BMI Z-score. RESULTS: A 0.1 increase in prenatal NDVI-500 exposure, a 10 µg/m3 decrease in PM2.5, a 10 µg/m3 decrease in PM1 were associated with 0.185 [95% confidence interval (95%CI): 0.155, 0.216], 0.034 (95%CI: 0.015, 0.052) and 0.041 (95%CI: 0.020, 0.061) increase of children's BMI Z-score, respectively. Compared with those exposed to low-level NDVI-500 (not greater than median) and high-level PM2.5 (greater than median), the BMI Z-score was higher in children whose mother exposed to high-level of NDVI-500 and low-level PM2.5 [ß:0.172 (95%CI: 0.131, 0.214), Pinteraction = 0.003]. Compared with those exposed to low-level NDVI-500 and high-level PM1, the BMI Z-score was higher in children whose mother exposed to high-level of NDVI-500 and low-level PM1 [ß:0.169 (95%CI: 0.127, 0.210), Pinteraction<0.001]. In the trimester-specific analysis, NDVI-500 and PM exposure during the second trimester have a consistent individual effect, together with a joint effect, on child growth. CONCLUSION: The study suggested the beneficial effect of prenatal exposure to green spaces on child growth and its interaction with PM2.5 and PM1, especially in the second trimester. The findings call for developing public health policy to improve green infrastructure and control PM2.5 and PM1 concentrations, in order to promote child growth.

The association between maternal fat-soluble vitamin concentrations during pregnancy and infant birth weight in China.

Fat-soluble vitamins during pregnancy are important for fetal growth and development. The present study aimed at exploring the association between vitamin A, E and D status during pregnancy and birth weight. A total of 19 640 women with singleton deliveries from a retrospective study were included. Data were collected by the hospital electronic information system. Maternal serum vitamin A, E and D concentrations were measured during pregnancy. Logistic regression was performed to estimate the association between the vitamin status and low birth weight (LBW) or macrosomia. Women with excessive vitamin E were more likely to have macrosomia (OR 1·30, 95 % CI 1·07, 1·59) compared with adequate concentration. When focusing on Z scores, there was a positive association between vitamin E and macrosomia in the first (OR 1·07, 95 % CI 1·00, 1·14), second (OR 1·27, 95 % CI 1·11, 1·46) and third (OR 1·28, 95 % CI 1·06, 1·54) trimesters; vitamin A was positively associated with LBW in the first (OR 1·14, 95 % CI 1·01, 1·29), second (OR 1·31, 95 % CI 1·05, 1·63) and third (OR 2·00, 95 % CI 1·45, 2·74) trimesters and negatively associated with macrosomia in the second (OR 0·79, 95 % CI 0·70, 0·89) and third (OR 0·77, 95 % CI 0·62, 0·95) trimesters. The study identified that high concentrations of vitamin E are associated with macrosomia. Maintaining a moderate concentration of vitamin A during pregnancy might be beneficial to achieve optimal birth weight. Further studies to explore the mechanism of above associations are warranted.

Maternal mortality ratios in 2852 Chinese counties, 1996-2015, and achievement of Millennium Development Goal 5 in China: a subnational analysis of the Global Burden of Disease Study 2016.

BACKGROUND: As one of only a handful of countries that have achieved both Millennium Development Goals (MDGs) 4 and 5, China has substantially lowered maternal mortality in the past two decades. Little is known, however, about the levels and trends of maternal mortality at the county level in China. METHODS: Using a national registration system of maternal mortality at the county level, we estimated the maternal mortality ratios for 2852 counties in China between 1996 and 2015. We used a state-of-the-art Bayesian small-area estimation hierarchical model with latent Gaussian layers to account for space and time correlations among neighbouring counties. Estimates at the county level were then scaled to be consistent with country-level estimates of maternal mortality for China, which were separately estimated from multiple data sources. We also assessed maternal mortality ratios among ethnic minorities in China and computed Gini coefficients of inequality of maternal mortality ratios at the country and provincial levels. FINDINGS: China as a country has experienced fast decline in maternal mortality ratios, from 108·7 per 100 000 livebirths in 1996 to 21·8 per 100 000 livebirths in 2015, with an annualised rate of decline of 8·5% per year, which is much faster than the target pace in MDG 5. However, we found substantial heterogeneity in levels and trends at the county level. In 1996, the range of maternal mortality ratios by county was 16·8 per 100 000 livebirths in Shantou, Guangdong, to 3510·3 per 100 000 livebirths in Zanda County, Tibet. Almost all counties showed remarkable decline in maternal mortality ratios in the two decades regardless of those in 1996. The annualised rate of decline across counties from 1996 to 2015 ranges from 4·4% to 12·9%, and 2838 (99·5%) of the 2852 counties had achieved the MDG 5 pace of decline. Decline accelerated between 2005 and 2015 compared with between 1996 and 2005. In 2015, the lowest county-level maternal mortality ratio was 3·4 per 100 000 livebirths in Nanhu District, Zhejiang Province. The highest was still in Zanda County, Tibet, but the fall to 830·5 per 100 000 livebirths was only 76·3%. 26 ethnic groups had population majorities in at least one county in China, and all had achieved declines in maternal mortality ratios in line with the pace of MDG 5. Intercounty Gini coefficients for maternal mortality ratio have declined at the national level in China, indicating improved equality, whereas trends in inequality at the provincial level varied. INTERPRETATION: In the past two decades, maternal mortality ratios have reduced rapidly and universally across China at the county level. Fast improvement in maternal mortality ratios is possible even in less economically developed places with resource constraints. This finding has important implications for improving maternal mortality ratios in developing countries in the Sustainable Development Goal era. FUNDING: National Health and Family Planning Commission of the People's Republic of China, China Medical Board, WHO, University of Washington Center for Demography and Economics of Aging, Bill & Melinda Gates Foundation.

The individual and joint effects of maternal 25(OH)D deficiency and gestational diabetes on infant birth size.

BACKGROUND AND AIMS: To examine the independent effect of maternal serum 25-hydroxyvitamin D [25(OH)D] deficiency and its joint effect with gestational diabetes mellitus (GDM) on infant birth size. METHODS AND RESULTS: This retrospective cohort study was conducted in 15,724 mother-offspring dyads in Beijing, China between 2016 and 2017. Outcomes included infant birth weight Z-score (adjusted for gestational age and sex) and large for gestational age (LGA). Exposures were maternal 25(OH)D concentrations. Linear and logistic regression models were used to assess the associations of exposures with continuous and binary outcomes, respectively. Exposure-outcome associations were not observed when analyzing 25(OH)D concentrations continuously or in quartiles (P > 0.05); however, mothers with severely deficient 25(OH)D concentrations (n = 307) had a decreased risk of LGA compared with those with sufficient 25(OH)D concentrations (≥30.0 ng/mL; n = 5400) (adjusted odds ratio (OR): 0.63; 95% confidence interval (CI): 0.42, 0.93). Compared to mothers with no 25(OH)D deficiency (≥20.0 ng/mL) and no GDM (n = 7975), those with both 25(OH)D deficiency and GDM (n = 1090) had 0.15 (95% CI: 0.09, 0.21) higher infant birth weight Z-score and a higher risk of LGA (OR: 1.29; 95% CI: 1.09, 1.52). Maternal 25(OH)D deficiency and GDM had additive interaction on the risk of LGA (relative risk due to interaction: 0.18). CONCLUSION: Mothers with severely deficient 25(OH)D might have a decreased risk of LGA. However, the joint effect of maternal 25(OH)D deficiency and GDM might increase the risk of LGA. Our findings have clinical and public health implications and provide potential directions for future studies.

CAREGIVER'S DEPRESSIVE SYMPTOMS AND YOUNG CHILDREN'S SOCIOEMOTIONAL DEVELOPMENT DELAYS: A CROSS-SECTIONAL STUDY IN POOR RURAL AREAS OF CHINA.

Poverty and its associated factors put people at risk for depression. The aims of this study were to describe the prevalence of depressive symptoms (DS) of primary caregivers and socioemotional development (SED) delays of young children in poor rural areas of China, and to explore the association between them. Cross-sectional data of 2,664 children aged 3 to 35 months and their primary caregivers were used for analysis. Characteristics of the child, caregiver, and family were collected through face-to-face caregiver interviews. DS were assessed by the Zung Self-Rating Depression Scale (W.W. Zung, 1965, as cited in World Health Organization, ), and SED was evaluated by the Ages and Stage Questionnaires: Social-Emotional (J. Squires, D. Bricker, & L. Potter, 1997). The χ2 test, stratification analysis, and logistic regression analyses were used to explore the association. Among the caregivers, 40.3% (95% confidence interval [CI] [38.4, 42.1]), reported DS. Caregivers who were male, older and ethnic minorities as well as had a low level of education, a low family income, or more children were more likely to have DS. Of the children, 24.4% (95% CI [22.8, 26.0]) were recognized with SED delays. Older children displayed more delays than did younger children, but no significant differences between males and females were found. SED delays were significantly associated with mother outmigrating, male caregivers, older age, ethnic minorities, and low education or families with a single parent, low-income, and having more children. Caregivers having DS, odds ratio (OR) = 2.40, 95% CI [1.99, 2.88], was a significant predictor of increased odds of SED delays; other factors were single-parent family, OR = 1.99, 95% CI [1.37, 2.89], inadequate care, OR = 1.69, 95% CI [1.30, 2.21], physical punishment, OR = 1.61, 95% CI [1.33, 1.95], ethnic minorities, OR = 1.41, 95% CI [1.17, 1.71], and child age in months, OR = 1.03, 95% CI [1.02, 1.04], according to the logistic regression analysis. DS are prevalent among caregivers with young children in poor rural areas. Interventions to improve the mental health of caregivers and their parenting behaviors are needed to improve children's SED.

Under-5 mortality in 2851 Chinese counties, 1996-2012: a subnational assessment of achieving MDG 4 goals in China.

BACKGROUND: In the past two decades, the under-5 mortality rate in China has fallen substantially, but progress with regards to the Millennium Development Goal (MDG) 4 at the subnational level has not been quantified. We aimed to estimate under-5 mortality rates in mainland China for the years 1970 to 2012. METHODS: We estimated the under-5 mortality rate for 31 provinces in mainland China between 1970 and 2013 with data from censuses, surveys, surveillance sites, and disease surveillance points. We estimated under-5 mortality rates for 2851 counties in China from 1996 to 2012 with the reported child mortality numbers from the Annual Report System on Maternal and Child Health. We used a small area mortality estimation model, spatiotemporal smoothing, and Gaussian process regression to synthesise data and generate consistent provincial and county-level estimates. We compared progress at the county level with what was expected on the basis of income and educational attainment using an econometric model. We computed Gini coefficients to study the inequality of under-5 mortality rates across counties. FINDINGS: In 2012, the lowest provincial level under-5 mortality rate in China was about five per 1000 livebirths, lower than in Canada, New Zealand, and the USA. The highest provincial level under-5 mortality rate in China was higher than that of Bangladesh. 29 provinces achieved a decrease in under-5 mortality rates twice as fast as the MDG 4 target rate; only two provinces will not achieve MDG 4 by 2015. Although some counties in China have under-5 mortality rates similar to those in the most developed nations in 2012, some have similar rates to those recorded in Burkina Faso and Cameroon. Despite wide differences, the inter-county Gini coefficient has been decreasing. Improvement in maternal education and the economic boom have contributed to the fall in child mortality; more than 60% of the counties in China had rates of decline in under-5 mortality rates significantly faster than expected. Fast reduction in under-5 mortality rates have been recorded not only in the Han population, the dominant ethnic majority in China, but also in the minority populations. All top ten minority groups in terms of population sizes have experienced annual reductions in under-5 mortality rates faster than the MDG 4 target at 4.4%. INTERPRETATION: The reduction of under-5 mortality rates in China at the country, provincial, and county level is an extraordinary success story. Reductions of under-5 mortality rates faster than 8.8% (twice MDG 4 pace) are possible. Extremely rapid declines seem to be related to public policy in addition to socioeconomic progress. Lessons from successful counties should prove valuable for China to intensify efforts for those with unacceptably high under-5 mortality rates. FUNDING: National "Twelfth Five-Year" Plan for Science and Technology Support, National Health and Family Planning Commission of The People's Republic of China, Program for Changjiang Scholars and Innovative Research Team in University, the National Institute on Aging, and the Bill & Melinda Gates Foundation.

Inequality in early childhood neurodevelopment in six poor rural counties of China: a decomposition analysis.

BACKGROUND: Previous studies about inequality in children's health focused more on physical health than the neurodevelopment. In this study, we aimed to evaluate the inequality in early childhood neurodevelopment in poor rural China and explore the contributions of socioeconomic factors to the inequality. METHOD: Information of 2120 children aged 0 to 35 months and their households in six poor rural counties of China was collected during July - September, 2013. Age and Stages Questionnaire-Chinese version, concentration index and decomposition analysis were used to assess the neurodevelopment of early childhood, measure its inequality and evaluate the contributions of socioeconomic factors to the inequality, respectively. RESULT: The prevalence of suspected developmental delay in children under 35 months of age in six poor rural counties of China was nearly 40%, with the concentration index of -0.0877. Household economic status, caregivers' depressive symptoms, learning material and family support for learning were significantly associated with children's suspected developmental delay, and explained 34.1, 14.1, 8.9 and 7.0% of the inequality in early childhood neurodevelopment, respectively. CONCLUSION: The early childhood neurodevelopment in the surveyed area is poor and unfair. Factors including household economic status, caregivers' depressive symptoms, learning material and family support for learning are significantly associated with children's suspected developmental delay and early developmental inequality. The results highlight the urgent need of monitoring child neurodevelopment in poor rural areas. Interventions targeting the caregivers' depressive symptoms, providing learning material and developmental appropriate stimulating activities may help improve early childhood neurodevelopment and reduce its inequality.

Geographic Variations and Temporal Trends in Cesarean Delivery Rates in China, 2008-2014.

Importance: The increasing use of cesarean delivery is an emerging global health issue. Prior estimates of China's cesarean rate have been based on surveys with limited geographic coverage. Objective: To provide updated information about cesarean rates and geographic variation in cesarean use in China. Design, Setting, and Data Sources: Descriptive study, covering every county (n = 2865) in mainland China's 31 provinces, using county-level aggregated information on the number of live births, cesarean deliveries, maternal deaths, and perinatal deaths, collected by the Office for National Maternal & Child Health Statistics of China, from 2008 through 2014. Exposures: Live births. Main Outcomes and Measures: Annual rate of cesarean deliveries. Results: Over the study period, there were 100 873 051 live births, of which 32 947 229 (32.7%) were by cesarean delivery. In 2008, there were 13 160 634 live births, of which 3 788 029 (28.8%) were by cesarean delivery and in 2014 there were 15 123 276 live births, of which 5 280 124 (34.9%) were by cesarean delivery. Rates varied markedly by province, from 4.0% to 62.5% in 2014. Despite the overall increase, by 2014 rates of cesarean delieries in 14 of the nation's 17 "super cities" had declined by 4.1 to 17.5 percentage points from their earlier peak values (median, 11.4; interquartile range, 6.3-15.4). In 4 super cities with the largest decreases, there was no increase in maternal or perinatal mortality. Conclusions and Relevance: Between 2008 and 2014, the overall annual rate of cesarean deliveries increased in China, reaching 34.9%. There was major geographic variation in rates and trends over time, with rates declining in some of the largest urban areas.

Identification, Quantification, and Site Localization of Protein Posttranslational Modifications via Mass Spectrometry-Based Proteomics.

Posttranslational modifications (PTMs) are important biochemical processes for regulating various signaling pathways and determining specific cell fate. Mass spectrometry (MS)-based proteomics has been developed extensively in the past decade and is becoming the standard approach for systematic characterization of different PTMs on a global scale. In this chapter, we will explain the biological importance of various PTMs, summarize key innovations in PTMs enrichment strategies, high-performance liquid chromatography (HPLC)-based fractionation approaches, mass spectrometry detection methods, and lastly bioinformatic tools for PTMs related data analysis. With great effort in recent years by the proteomics community, highly efficient enriching methods and comprehensive resources have been developed. This chapter will specifically focus on five major types of PTMs; phosphorylation, glycosylation, ubiquitination/sumosylation, acetylation, and methylation.

[Secular trends of premarital medical examination in China during 1996 and 2013].

OBJECTIVE: To describe the secular trends of premarital medical examination (PME) in China during 1996 and 2013 and to assess the impacts of national health policies on the PME rate. METHODS: The information on marriage and PME for districts and counties in 31 provinces of China was annually collected by the Office for National Maternal & Child Health Statistics of China, and the information on the health policies was from official governmental websites. According to the main health policies, the calendar years were categorized into 3 periods: 1996 to 2003 was mandatory PME period; 2004 to 2008 was encouraged voluntary PME period; and 2009 to 2013 was free-paid voluntary PME period. RESULTS: During the 18-year period, 284 242 719 people were registered for a marriage in which 107 198 795 were examined, giving the PME rate of 37.7%. During the mandatory PME period, the rate ranged 52.7%-67.7% with an average of 60.9% (urban 71.5%, and rural 51.7%). In 2004, the first year when the PME became voluntary, the rate was abruptly dropped to 2.6%, and thereafter gradually increased to 11.5% in 2008. As the policies of the free-paid voluntary PME were subsequently issued, the rate was quickly increased to 52.3% (urban 49.8%, and rural 54.6%) in 2013. The increasing trend was consistently observed both in urban and rural areas, and across East, Middle, West, and Northeast economical regions. However, the rates differed greatly among provinces. In 2013, 5 provinces had rates of >90% (Guangxi 97.5%, Fujian 96.0%, Ningxia 95.4%, Zhejiang 93.4% and Anhui 90.1%), whereas some provinces were stuck at a low rate, including developed and underdeveloped provinces/cities. The PME rate in 2013 was 27.4% for Shanghai, 25.5% for Guangdong, 12.4% for Chongqing, 5.8% for Beijing and 4.6% for Tianjin. Underdeveloped provinces were Guizhou (6.4%) and Qinghai (1.8%). CONCLUSION: As various national policies to promote voluntary PME were issued, the PME rate was significantly increased after a sharp decline, though it varied greatly by provinces. For provinces with high PME rate, PME-related health benefits need to be evaluated; for provinces with low rate, it is of important practical significance to explore a cost-effective health service model that is likely incorporated with pre-pregnancy examination.

Pyrene degradation accelerated by constructed consortium of bacterium and microalga: effects of degradation products on the microalgal growth.

Abundant microbes including bacteria, fungi, or algae are capable of biodegrading polycyclic hydrocarbons (PAHs). However, pure cultures never occur in the contaminated environments. This study aimed to understand the general potential mechanisms of interactions between microbes under pollution stress by constructing a consortium of PAH-degrading microalga (Selenastrum capricornutum) and bacterium (Mycobacterium sp. strain A1-PYR). Bacteria alone could grow on the pyrene, whereas the growth of algae alone was substantially inhibited by the pyrene of 10 mg L(-1). In the mixing culture of algae and bacteria, the growth rate of algae was significantly increased from day 4 onward. Rapid bacterial degradation of pyrene might mitigate the toxicity of pyrene to algae. Phenolic acids, the bacterial degradation products of pyrene, could serve as the phytohormone for promoting algal growth in the coculture of algae and bacteria. In turn, bacterial growth was also enhanced by the algae presented in the mixing culture. Consequently, the fastest degradation of pyrene among all biodegradation systems was achieved by the consortium of algae and bacteria probably due to such interactions between the two species by virtue of degradation products. This study reveals that the consortium containing multiple microbial species is high potential for microbial remediation of pyrene-contaminated environments, and provides a new strategy to degrade the recalcitrant PAHs.

[The method and efficacy for screening neonatal tetanus in high risk areas in China].

OBJECTIVES: To establish a method for screening neonatal tetanus (NT) in high risk areas in China using multi-sources data. METHODS: We adopted six NT-related indicators from National Notifiable Disease Report System (NNDRS) and National Maternal and Child Health Annual Report System, to calculate weighted high-risk score at prefecture level in 2010 and 2011. And we selected the top 30 high risk cities, and compared the scores with the actual NT incidence ranking and WHO scoring. RESULTS: The highest areas distributed in the Southwest of China with poor and minority population, and the Southeast part with high density of migrants. In the leading 30 prefectures with high score between the methods of weighted high-risk scoring and reported NT incidence ranking, there were 8 different. In comparison of the results of the methods of weighed high-risk scoring and WHO scoring, 276 prefectures in 340 distributed were divided into the same ranking groups, with Kappa coefficient 0.56 (P < 0.01). The Chi-Square association coefficient was 0.74 (P < 0.01), which showed a high correlation. But there were 10 different prefectures in the leading 36 prefectures between the two methods. CONCLUSION: The weighted scoring method included several possible factors influencing NT incidence and took their weights into consideration. Thereby, compared with WHO scoring method, this method could be more appropriate for the reality in China.

Individual and joint effect of indoor air pollution index and ambient particulate matter on fetal growth: a prospective cohort study.

BACKGROUND: Limited studies have examined the effect of prenatal exposure to particulate matter with diameter of <2.5 µm (PM2.5) and <1 µm (PM1) on fetal growth using ultrasound measurements with inconsistent results. No study has evaluated the joint effect of the indoor air pollution index and ambient particulate matter on fetal growth. METHODS: We conducted a prospective birth cohort study in Beijing, China in 2018, including 4319 pregnant women. We estimated prenatal PM2.5 and PM1 exposure using a machine-learning method and calculated the indoor air pollution index based on individual interviews. Gender- and gestational age-adjusted Z-score of the abdominal circumference (AC), head circumference (HC), femur length (FL) and estimated fetal weight (EFW) was calculated and then undergrowth was defined. A generalized estimating equation was used to evaluate the individual and joint effect of indoor air pollution index, PM2.5 and PM1 on fetal Z-score and undergrowth parameters. RESULTS: One unit increase in the indoor air pollution index was associated with -0.044 (95% CI: -0.087, -0.001) and -0.050 (95% CI: -0.094, -0.006) decrease in the AC and HC Z-scores, respectively. PM1 and PM2.5 were associated with decreased AC, HC, FL and EFW Z-scores, and higher risk of undergrowth. Compared with exposure to lower PM1 (≤ median) and no indoor air pollution, those exposed to higher PM1 (> median) and indoor air pollution had decreased EFW Z-scores (ß = -0.152, 95% CI: -0.230, -0.073) and higher risk of EFW undergrowth (RR = 1.651, 95% CI: 1.106, 2.464). Indoor air pollution and ambient PM2.5 exposure had a similar joint effect on the Z-scores and undergrowth parameters of fetal growth. CONCLUSIONS: This study suggested that indoor air pollution and ambient PM exposure had individual and joint negative effects on fetal growth.

Risk of De Novo Hypertensive Disorders of Pregnancy After Exposure to PM1 and PM2.5 During the Period From Preconception to Delivery: Birth Cohort Study.

BACKGROUND: Particulate matter (PM) is detrimental to the respiratory and circulatory systems. However, no study has evaluated the lag effects of weekly exposure to fine PM during the period from preconception to delivery on the risk of hypertensive disorders of pregnancy (HDPs). OBJECTIVE: We set out to investigate the lag effect windows of PM on the risk of HDPs on a weekly scale. METHODS: Data from women with de novo HDPs and normotensive pregnant women who were part of the Peking University Retrospective Birth Cohort, based on the hospital information system of Tongzhou district, were obtained for this study. Meteorological data and data on exposure to fine PM were predicted by satellite remote sensing data based on maternal residential address. The de novo HDP group consisted of pregnant women who were diagnosed with gestational hypertension or preeclampsia. Fine PM was defined as PM2.5 and PM1. The gestational stage of participants was from preconception (starting 12 weeks before gestation) to delivery (before the 42nd gestational week). A distributed-lag nonlinear model (DLNM) was nested in a Cox regression model to evaluate the lag effects of weekly PM exposure on de novo HDP hazard by controlling the nonlinear relationship of exposure-reaction. Stratified analyses by employment status (employed or unemployed), education level (higher or lower), and parity (primiparity or multiparity) were performed. RESULTS: A total of 22,570 pregnant women (mean age 29.1 years) for whom data were available between 2013 and 2017 were included in this study. The prevalence of de novo HDPs was 6.7% (1520/22,570). Our findings showed that PM1 and PM2.5 were significantly associated with an elevated hazard of HDPs. Exposure to PM1 during the 5th week before gestation to the 6th gestational week increased the hazard of HDPs. A significant lag effect of PM2.5 was observed from the 1st week before gestation to the 6th gestational week. The strongest lag effects of PM1 and PM2.5 on de novo HDPs were observed at week 2 and week 6 (hazard ratio [HR] 1.024, 95% CI 1.007-1.042; HR 1.007, 95% CI 1.000-1.015, respectively, per 10 µg/m3 increase). The stratified analyses indicated that pregnant women who were employed, had low education, and were primiparous were more vulnerable to PM exposure for de novo HDPs. CONCLUSIONS: Exposure to PM1 and PM2.5 was associated with the risk of de novo HDPs. There were significant lag windows between the preconception period and the first trimester. Women who were employed, had low education, and were primiparous were more vulnerable to the effects of PM exposure; more attention should be paid to these groups for early prevention of de novo HDPs.

Interpretable machine learning to identify important predictors of birth weight: A prospective cohort study.

Background: Predicting birth weight and identifying its risk factors are clinically important. This study aims to use interpretable machine learning to predict birth weight and identity important predictors. Methods: This prospective cohort study was conducted in Tongzhou Maternal and Child Health Care Hospital of Beijing, China, recruiting pregnant women between June 2018 and February 2019. We used 24 features to predict infant birth weight, including gestational age, mother's age, parity, history of macrosomia delivery, pre-pregnancy body mass index (BMI), height, father's BMI, lifestyle (diet, physical activity, smoking), and biomarker (fasting glucose and lipids) features. Study outcome was birth weight of infant. We used 8 supervised learning models including 4 individual [linear regression, ridge regression, lasso regression, support vector machines regression (SVR)], and 4 ensemble estimators (random forest, AdaBoost, gradient boosted trees, and voting ensemble for regression) to predict birth weight. Model accuracy was measured by root mean squared error (RMSE) of 10-fold cross validation on the training set and RMSE of prediction on the test set. We used permutation importance algorithm to understand the prediction from the models and what affected them. Result: This study included 4,754 mother-child dyads. RMSEs were lower in voting ensemble for regression, linear regression, and SVR than random forest, AdaBoost, and gradient boosted tree. The 5 most important predictors for infant birth weight were gestational age, fetal sex, preterm birth, mother's height, and pre-pregnancy BMI. After adding ultrasound-measured indicators of fetal growth into predictors, mother's height and pre-pregnancy BMI remained the most important predictors in predicting the outcome. Conclusion: Mother's height and pre-pregnancy BMI were identified as important predictors for infant birth weight. Interpretable machine learning is a promising tool in the prediction of birth weight.

The First-Trimester Gestational Weight Gain Associated With de novo Hypertensive Disorders During Pregnancy: Mediated by Mean Arterial Pressure.

The relationship between first-trimester GWG ( T1GWG) and risk of hypertensive disorders of pregnancy (HDP) remained uncertain. This study aimed to investigate the association between T1GWG and risk of de novo HDP. Meanwhile, we explored the mediated effect and constructed an early GWG category to evaluate the predictive capacity for HDP. T1GWG was defined as the weight difference between 13 ± 1 gestational weeks and pre-conception. HDP group was defined as having diagnosis of de novo HDP, including gestational hypertension or de novo pre-eclampsia (PE) during the current pregnancy. Early GWG category was constructed according to the risk of HDP within each pre-pregnancy body mass index (BMI) group. Cox regression model was utilized to check the association between the T1GWG and HDP. Serial mediation model was adopted to evaluate the potential mediators including mean arterial pressure (MAP) at 13th and 20th week. The logistic regression model with bootstrap was performed to assess the predictive capacity of Early GWG category and MAP for the risk of HDP. A total of 17,901 pregnant women (mean age, 29.0 years) were recruited from 2013 to 2017 at the Tongzhou Maternal and Child Health Hospital in Beijing, China. Compared to women in Class 1 of early GWG category, women in the Class 2, 3, 4 have increased risks of HDP by 1.42, 4.27, and 4.62 times, respectively (hazard ratio [HR] = 2.42, 95% CI: 2.11-2.77; HR = 5.27, 95% CI: 4.05-6.86; HR = 5.62, 95% CI: 4.05-7.79). The MAP measured at 13th and 20th week totally mediated 33.1 and 26.7% of association between T1GWG GWG and HDP in total participants and overweight/obesity pregnancies, respectively. The area under receiver operator characteristic curve for predictive model utilizing early GWG category and MAP measured at 13th and 20th week for the risk of HDP is 0.760 (95% CI: 0.739-0.777). The T1GWG was associated with de novo HDP, which was partially mediated by MAP measured at 13th and 20th week. Early GWG category showed a better predictive capacity for the risk of HDP compared to the National Academy of Medicine criteria for T1GWG.