Publications by authors named "Shaoping Yang"

26 Publications

  • Page 1 of 1

Early childhood body mass index trajectory and overweight/obesity risk differed by maternal weight status.

Eur J Clin Nutr 2021 Sep 17. Epub 2021 Sep 17.

Department of Maternal and Child Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.

Objectives: To evaluate the associations of maternal prepregnancy body mass index (pp-BMI) and gestational weight gain (GWG) with the childhood BMI z-score (BMI-z) trajectories from birth to 2 years old and the risk of overweight/obesity (OWO) at 2 years of age.

Subjects/methods: Mother-child dyads (23,617) were involved in the analysis. They were followed up from early pregnancy to 2 years postpartum with their healthcare data recorded in the Wuhan Maternal and Child Health Management Information System (WMCHMIS). The OWO in children was defined as BMI-z > 1. Linear mixed models (LMM) and unconditional logistic regression were used to evaluate the independent and joint associations of pp-BMI and GWG with the BMI-z trajectory of children per their anthropometric measurements at 0, 1, 3, 6, 9, 12, 18, and 24 months old and the risk of OWO at 2 years of age.

Results: Maternal overweight/obesity and excessive GWG independently and jointly increased the risks of their offspring falling into high BMI-z trajectories of birth to 2 years (p < 0.001). In addition, the children whose mothers were overweight/obese before pregnancy and gained excessive weight during pregnancy independently and jointly increased the OWO risk in children at age 2, with adjusted odds ratios (adjOR) of 1.36 (95% CI, 1.22-1.53), 1.28 (95% CI, 1.18-1.39), and 1.76 (95% CI: 1.52-2.03), respectively.

Conclusions: Maternal prepregnancy overweight/obesity and excessive GWG can independently and jointly increase the risks of their children falling into high BMI-z trajectories from birth to 2 years of age and becoming overweight/obese at age 2. Maternal overweight/obesity and excessive gestational weight should be the prime targets for early obese prevention efforts.
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http://dx.doi.org/10.1038/s41430-021-00975-6DOI Listing
September 2021

What Links Maternal Prepregnancy BMI to Early Childhood BMI: A Serial Mediation Analysis.

Obesity (Silver Spring) 2021 07 14;29(7):1164-1170. Epub 2021 May 14.

Department of Maternal and Child Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Objective: The aim of this study was to explore the potential impact of maternal gestational weight gain (GWG), infant birth weight, and postnatal weight change (ΔWAZ) on the relationship between maternal prepregnancy BMI (ppBMI) and childhood BMI.

Methods: This retrospective cohort study analyzed a data set from Wuhan, China. The mediation effect of targeted mediators on the association between maternal BMI and childhood BMI at the age of 2 years was analyzed.

Results: In the mediation model comprising maternal GWG, infant birth weight, and the first-6-month ΔWAZ as mediators of the association between ppBMI and children's BMI, the per unit increase in ppBMI resulted in a 0.01-kg/m increase in children's BMI, through all three mediators. For the model comprising infant birth weight and the first-6-month ΔWAZ as mediators but maternal GWG as a moderator, the indirect effects of the first-6-month ΔWAZ on the relationship between ppBMI and childhood BMI was 0.0018 higher when maternal GWG increased from average values to 1 SD above the average values.

Conclusions: Maternal GWG, infant birth weight, and the first-6-month ΔWAZ mediated the effects of maternal ppBMI on children's BMI. Interventions targeting these factors can mitigate the risk of childhood obesity.
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http://dx.doi.org/10.1002/oby.23176DOI Listing
July 2021

Association between maternal outdoor physical exercise and the risk of preterm birth: a case-control study in Wuhan, China.

BMC Pregnancy Childbirth 2021 Mar 12;21(1):206. Epub 2021 Mar 12.

Department of Epidemiology and Biostatistics, College for Public Health & Social Justice, Saint Louis University, 3545 Lafayette Avenue, Saint Louis, MO, 63104, USA.

Background: China had the second largest proportion of preterm birth (PTB) internationally. However, only 11% of pregnant women in China meet international guidelines for maternal physical activity, a significantly lower proportion than that in Western countries. This study aims to examine the association between outdoor physical exercise during pregnancy and PTB among Chinese women in Wuhan, China.

Methods: A case-control study was conducted among 6656 pregnant women (2393 cases and 4263 controls) in Wuhan, China from June 2011 to June 2013. Self-reported measures of maternal physical exercise (frequency per week and per day in minutes) were collected. Adjusted odds ratios were estimated using Bayesian hierarchical logistic regression and a generalized additive mixed model (GAMM).

Results: Compared to women not involved in any physical activity, those who participated in physical exercise 1-2 times, 3-4 times, and over five times per week had 20% (aOR: 0.80, 95% credible interval [95% CI]: 0.68-0.92), 30% (aOR: 0.70, 95% CI: 0.60-0.82), and 32% (aOR: 0.68, 95% CI: 0.59-0.78) lower odds of PTB, respectively. The Bayesian GAMM showed that increasing physical exercise per day was associated with lower risk of PTB when exercise was less than 150 min per day; however, this direction of association is reversed when physical exercise was more than 150 min per day.

Conclusion: Maternal physical exercise, at a moderate amount and intensity, is associated with lower PTB risk. More data from pregnant women with high participation in physical exercise are needed to confirm the reported U-shape association between the physical exercise and risk of preterm birth.
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http://dx.doi.org/10.1186/s12884-021-03678-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7955628PMC
March 2021

Association and potential mediators between socioeconomic status and childhood overweight/obesity.

Prev Med 2021 05 20;146:106451. Epub 2021 Feb 20.

Department of Maternal and Child Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. Electronic address:

The associations between socioeconomic status and childhood overweight/obesity are inconsistent, and potential underlying factors are unclear. In China, Hukou status is an important attribute of individual's socioeconomic circumstances, but previously received less consideration as a socioeconomic indicator. This study aimed to investigate the association between comprehensive socioeconomic status and childhood overweight/obesity. Using data from Wuhan Maternal and Child Health Management Information System (2009-2018, N = 209,500), clustering analysis was used to create comprehensive socioeconomic groups with indicator components such as parental education level, occupation, and maternal Hukou. The associations between the determined socioeconomic status and childhood overweight/obesity at age 1 and 2 were examined by log-binomial model. Parallel and serial mediation analyses were performed to test the indirect effects of potential mediators, including maternal pre-pregnancy body mass index, gestational weight gain, and infant birth weight, in the association between socioeconomic status and childhood overweight/obesity. Four clusters, defined as low, low-medium, medium-high, and high socioeconomic groups, were identified through clustering analysis. Hukou, among five socioeconomic components, contributed the most to the development of childhood overweight/obesity. Children in the low-medium socioeconomic group have a greater risk of overweight/obesity than the low socioeconomic group. Indirect effects of maternal pre-pregnancy body mass index, gestational weight gain, and infant birth weight were identified for the association. In conclusion, socioeconomic status may impact childhood obesity through maternal pre-pregnancy body mass index, gestational weight gain, and infant birth weight. Hukou should be considered in the evaluation of socioeconomic status in China.
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http://dx.doi.org/10.1016/j.ypmed.2021.106451DOI Listing
May 2021

Prenatal exposure to air pollutants and early childhood growth trajectories: A population-based prospective birth cohort study.

Environ Res 2021 03 17;194:110627. Epub 2020 Dec 17.

School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, No. 13 Hangkong Road, Qiaokou District, Wuhan, 430030, Hubei, China. Electronic address:

Background: Air pollution exposure during pregnancy has been documented to be associated with impaired fetal growth and adverse birth outcomes, but the evidence regarding the effects of air pollution on early childhood growth is still limited.

Objective: We aimed to explore the associations of exposure to air pollutants during pregnancy with childhood growth trajectories from birth to age of 6 years.

Methods: A prospective cohort study based on the administrative registration system was conducted covering 62,540 births in Wuhan, China between January 1, 2011 and December 31, 2013 and followed for 6 years. Inverse distance weighted method was used to estimate the concentrations of air pollutants exposure for pregnant women. Group-based trajectory models (GBTM) were used to identify growth patterns of children: slow growth, normal growth, and rapid growth. Multinomial logistic regression models were used to examine the associations between prenatal exposure to air pollutants and childhood growth trajectories with adjustment for maternal age, educational status, pre-pregnancy BMI, residential areas, gestational diabetes, birth type, gender of infant, and breastfeeding duration.

Results: The mean (SD) of prenatal exposure concentrations for PM, SO, NO, CO, and O were 107.9 (30.4), 32.8(12.6), 55.8(13.1), 1081.2(293.1), and 81.6(31.0) μg/m respectively. Compared with normal growth trajectory, increased PM and CO exposure were significantly associated with higher risk of slow growth trajectory but lower risk of rapid growth trajectory. An increase in prenatal exposure to NO significantly increased both the risk of slow growth trajectory and rapid growth trajectory. Increased prenatal SO exposure was significantly associated with rapid growth trajectory and was not associated with low growth trajectory. With O exposure levels increased, risk to be rapid growth trajectory decreased. Prenatal air pollutants exposure had a greater impact on childhood growth of children who were girls, and those mothers lived in rural areas and were normal weight before pregnancy.

Conclusions: High levels of air pollutants exposure during pregnancy were associated with the risk of being in a trajectory with the deviation of BMI gain from birth to 6 years old. These findings suggest that efforts to identify children at risk of growth deviation in early childhood should pay attention to environmental exposure during pregnancy for their mothers.
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http://dx.doi.org/10.1016/j.envres.2020.110627DOI Listing
March 2021

Crocin induces autophagic cell death and inhibits cell invasion of cervical cancer SiHa cells through activation of PI3K/AKT.

Ann Transl Med 2020 Sep;8(18):1180

Department of Obstetrics and Gynecology, Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, Chengdu, China.

Background: Cervical cancer is a prevalent tumor mainly induced by Human Papilloma Virus (HPV). Autophagy was inactivated with HPV to promote cancer progression. Here we explored the effects of crocin on cervical cancer cells, mainly on autophagy and apoptosis.

Methods: SiHa cells were treated with crocin, and proliferation, metastases, apoptosis and autophagy were measured using a CCK-8 assay, transwell migration assay, flow cytometry and immunofluorescence. Protein levels were measured using western blotting. The antitumor effects of crocin were validated in female BALB/c nude mice injected with SiHa cells.

Results: The result showed that 2, 4, 8 and 16 mM of crocin significantly reduced the viability of SiHa cells within 24 h. Subsequently, 0, 1, 2 and 4 mM crocin concentrations were used in later experiments. Treatment with crocin reduced invasive cells, while increasing autophagic and apoptotic cells dose-dependently. The enhanced apoptosis and autophagy were partly validated by an increase in cleaved caspase-3/caspase-3, cleaved caspase-9/caspase9, LC3B II/I, Beclin1 and ATG7. AMPK and mTOR were inactivated with crocin treatment, while PI3K was activated. These results indicated that crocin might promote autophagy and apoptosis by inactivating AMPK and mTOR signaling. Tumor progression was inhibited in mice treated with 50 mg/kg/d of crocin, which was demonstrated by smaller tumor volumes, less VEGF expression, more intense caspase-3 staining and increased LC3B II/I in the tumor tissues.

Conclusions: Crocin inhibited the progression of cervical cancer and , possibly through inactivation of AMPK and mTOR, inhibition of proliferation and invasion, and promotion of autophagy and apoptosis. These results support the potential therapeutic value of crocin in treating cervical cancer.
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http://dx.doi.org/10.21037/atm-20-5882DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7576020PMC
September 2020

Associations of exposure to green space with problem behaviours in preschool-aged children.

Int J Epidemiol 2020 06;49(3):944-953

Key Laboratory of Environment and Health, Ministry of Education & Ministry of Environmental Protection, and State Key Laboratory of Environmental Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, People's Republic of China.

Background: Limited evidence is available regarding the association of green-space exposure with childhood behavioural development. This study aimed to investigate the associations of exposure to green space with multiple syndromes of behavioural development in preschool children.

Methods: This cross-sectional study was conducted in Wuhan, China from April 2016 to June 2018. We recruited a sample of 6039 children aged 5-6 years from 17 kindergartens located in five urban districts of the city. We measured the greenness using average Normalized Difference Vegetation Index (NDVI) within a circular buffer area of 100 metres surrounding the central point of residences and kindergartens. We calculated the residence-kindergarten-weighted greenness by assuming that children spent 16 hours per day at home and 8 hours at kindergarten. The problem behaviours of children were evaluated at kindergarten using the Childhood Behavioral Checklist (CBCL) and standardized into problem behavioural T scores. Linear mixed-effect models and linear-regression models were used to estimate the associations.

Results: We observed decreases in problem behaviours associated with kindergarten and residence-kindergarten-weighted surrounding greenness in preschool children. For example, a one-interquartile range increase in kindergarten and residence-kindergarten-weighted NDVI was associated with decreased T scores for total behaviour by -0.61 [95% confidence interval (CI): -1.09, -0.13) and -0.49 (95% CI -0.85, -0.12), anxiety and depression by -0.65 (95% CI: -1.13, -0.17) and -0.46 (95% CI: -0.82, -0.10), aggressive behaviour by -0.53 (95% CI: -1.01, -0.05) and -0.38 (95% CI: -0.75, -0.02) and hyperactivity and attention deficit by -0.54 (95% CI: -1.01, -0.07) and -0.48 (95% CI: -0.83, -0.12), respectively. Stratified analyses indicated that the associations of green-space exposure with problem behaviours were stronger in boys than in girls.

Conclusions: Children attending kindergartens with higher levels of surrounding green space exhibited better behavioural development. The mechanisms underlying these associations should be explored further.
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http://dx.doi.org/10.1093/ije/dyz243DOI Listing
June 2020

Risks of maternal prepregnancy overweight/obesity, excessive gestational weight gain, and bottle-feeding in infancy rapid weight gain: evidence from a cohort study in China.

Sci China Life Sci 2019 Dec 18;62(12):1580-1589. Epub 2019 Nov 18.

Wuhan Children's Hospital (Wuhan Maternal and Child Healthcare Hospital), Tongji Medical College, Huazhong University of Science & Technology, Wuhan, 430014, China.

Rapid weight gain (RWG) in infants is associated with numerous health problems, and its risk factors are still unclear. We assessed 98,097 maternal-infant pairs from a population-based cohort study and followed up with them until the infants were 6 months old. We assessed the associations between maternal prepregnancy weight status; gestational weight gain; feeding pattern; and infants' RWG at 0-1, 0-3, 1-3, and 3-6 months using multivariate unconditional logistic regression models, with controlled confounders. We found that maternal prepregnancy weight status, gestational weight gain, and feeding pattern at the 1st, 3rd, and 6th months had significant impacts on the infants' RWG at each time period (P<0.05). Infants with overweight/obese mothers had a higher risk of RWG after birth, whereas those of mothers who experienced excessive gestational weight gain had higher risks of RWG from birth than the other groups (P<0.01). Infants who were formula-fed had a higher risk of RWG than breastfed infants at the same time point (P<0.01). In conclusion, maternal prepregnancy obesity, excessive gestational weight gain, and formula-feeding were risk factors for infants' RWG during the first 6 months of life.
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http://dx.doi.org/10.1007/s11427-018-9831-5DOI Listing
December 2019

Antagonistic effect of epigallocatechin-3-gallate on neurotoxicity induced by formaldehyde.

Toxicology 2019 01 3;412:29-36. Epub 2018 Nov 3.

Hubei Key Laboratory of Genetic Regulation and Integrative Biology, School of Life Sciences, Central China Normal University, Wuhan, 430079, Hubei, China. Electronic address:

The toxicity of formaldehyde (FA) has always been of great concern, particularly since its use is unavoidable. On the other hand, epigallocatechin-3-gallate (EGCG), an active substance in tea polyphenols, has been shown to demonstrate physiological protective functions by in both epidemiological and zoological studies, particularly in the nervous system. The study described here, aims to explore whether EGCG can alleviate the neurotoxic effects induced by formaldehyde. After 14 days of exposure to 3 mg/m formaldehyde, mice exhibited significant cognitive impairment. In the FA group, a significant increase in iNOS level compared with the control group was observed. The reduced GSH level was significantly decreased. The levels of IL-1β, TNF-α and Caspase-3 were obviously raised, while H&E and Nissl staining illustrated significant neuronal damage. After administering EGCG as a protective agent, all the above observed changes were reversed, and the protective effect of EGCG became gradually evident in the 20-500 mg/kg range. Immunohistochemistry results showed that EGCG could activate the Nrf2 signaling pathway, thus alleviating the oxidative damage caused by formaldehyde.
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http://dx.doi.org/10.1016/j.tox.2018.10.022DOI Listing
January 2019

Perinatal risk factors for obstructive sleep apnea syndrome in children.

Sleep Med 2018 12 17;52:145-149. Epub 2018 Sep 17.

Wuhan Children's Hospital (Wuhan Maternal and Child Healthcare Hospital), Tongji Medical College, Huazhong University of Science & Technology, No. 100 Hongkong Road, Jiangan District, Wuhan, China. Electronic address:

Objective: The aim of this study was to determine whether specific perinatal factors are associated with obstructive sleep apnea syndrome (OSAS) in children.

Methods: A retrospective case-control study was conducted. All cases of OSAS were obtained from a tertiary pediatric hospital between April 2013 and April 2016. A total of 823 children who had been diagnosed with OSAS were designated as the case group, and 823 children without OSAS were selected with strict criteria to match with the case group by age, gender and body mass index. Logistic regression models were used to determine the perinatal factors associated with childhood OSAS.

Results: Preterm birth (adjusted odds ratio (aOR): 1.87, 95% confidence interval (CI): 1.13-3.08) and cesarean section (aOR: 1.32, 95% CI: 1.03-1.68) were significantly associated with OSAS. Exposure of the mother to smoke (aOR: 2.59, 95% CI: 1.57-4.26) was also associated with an increased risk of childhood OSAS. Mothers aged 35 years and above, performing manual labor, and living in suburban areas significantly increased the risk of childhood OSAS. Multiparous mothers decreased the risk of childhood OSAS (aOR: 0.59, 95% CI: 0.42-0.83). Maternal education, gravidity, prenatal care times, pregnancy-induced hypertension, multiple pregnancies, sex of the child and birth weight were not significantly associated with OSAS in children.

Conclusion: Perinatal risk factors are important for predicting childhood OSAS. Our findings provide evidence regarding several potentially useful factors for recognizing OSAS in children, which could be important in diagnosis of pediatric OSAS by physicians.
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http://dx.doi.org/10.1016/j.sleep.2018.08.018DOI Listing
December 2018

Maternal exposure to ambient air pollutant and risk of oral clefts in Wuhan, China.

Environ Pollut 2018 Jul 31;238:624-630. Epub 2018 Mar 31.

Department of Maternal and Child Health, School of Public Health, Tongji Medical College, Huazhong University of Science & Technology, Wuhan, China. Electronic address:

Maternal exposure to ambient air pollution has been related to oral clefts in offspring; however, the epidemiologic evidence is equivocal. Especially, the association between high levels of exposure to ambient air pollution during pregnancy and oral clefts remains unclear. The objective of this study was to evaluate whether high levels of maternal exposure to PM, PM, O, CO and SO are related to increased risk of oral clefts in Wuhan, China. A population-based study was conducted using cohort of 105,927 live-born infants, fetal deaths, and stillbirths during a two-year period from 2011 to 2013. For each participant, weekly and monthly averages of daily mean concentrations for each pollutant were estimated. Multiple logistic regression analyses were constructed to quantify the adjusted odds ratios (aORs) for the relationship between each air pollutant and oral clefts while controlling for key covariates. Using monthly averages, a cleft lip with or without cleft palate (CLP) was associated with PM (aORs  = 1.34, CI:1.19-1.49; aORs 1.14, CI:1.02-1.28), PM (aORs  = 1.11, CI:1.00-1.23) and CO (aORs  = 1.31, CI:1.14-1.51; aORs  = 1.17, CI:1.03-1.33). A cleft palate only (CPO) was associated with PM (aORs  = 1.24, CI: 1.03-1.48), and O (aORs  = 1.21, CI: 1.03-1.42; aORs  = 1.18, CI: 1.02-1.37). Our findings reveal an association between air pollutants exposure and the risk of oral clefts. Future studies are needed to confirm these associations, and clarify the causality related to specific pollutants during the most relevant vulnerable exposure time windows for oral clefts during pregnancy.
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http://dx.doi.org/10.1016/j.envpol.2018.03.053DOI Listing
July 2018

Ambient air pollution the risk of stillbirth: A prospective birth cohort study in Wuhan, China.

Int J Hyg Environ Health 2018 04 13;221(3):502-509. Epub 2018 Feb 13.

Wuhan Children's Hospital (Wuhan Maternal and Child Healthcare Hospital), Tongji Medical College, Huazhong University of Science & Technology, No. 100 Hongkong Road, Jiangan District, Wuhan, China. Electronic address:

Background: Recent studies suggest that ambient air pollution exposure during pregnancy is associated with stillbirth occurrence. However, the results on the associations between ambient air pollutants and stillbirths are inconsistent and little is known about the gestational timing of sensitive periods for the effects of ambient air pollutants exposure on stillbirth.

Objective: This study aimed to examine whether exposure to high levels of ambient air pollutants in a Chinese population is associated with an increased risk of stillbirth, and determine the gestational period when the fetus is most susceptible.

Methods: We conducted a population-based cohort study in Wuhan, China, involving 95,354 births between June 10, 2011 and June 9, 2013. The exposure assessments were based on the daily mean concentrations of air pollutants obtained from the exposure monitor nearest to the pregnant women's residence. Logistic regression analyses were performed to determine the associations between stillbirths and exposure to each of the air pollutants at different pregnancy periods with adjustment for confounding factors.

Results: Stillbirth increased with a 10 μg/m increase in particulate matter 2.5 (PM) in each stage of pregnancy, and a significant association between carbon monoxide (CO) exposure and stillbirth was found during the third trimester (adjusted odds ratio (aOR): 1.01, 95% confidence interval (CI): 1.00-1.01) and in the entire pregnancy (aOR: 1.18, 95% CI: 1.04-1.34). Furthermore, an increased risk of stillbirth in the third trimester was associated with a 10 μg/m increase in PM (aOR: 1.08, 95% CI: 1.04-1.11), nitrogen dioxide (NO) (aOR: 1.13, 95% CI: 1.07-1.21) and sulfur dioxide (SO) (aOR: 1.26, 95% CI: 1.16-1.35). However, no positive association was observed between ozone exposure and stillbirth. In the two-pollutant models, PM and CO exposures were found to be consistently associated with stillbirth.

Conclusions: Our study revealed that exposure to high levels of PM, PM, SO, NO and CO increases the risk of stillbirth and the most susceptible gestational period to ambient air pollution exposure was in the third trimester. Further toxicological and prospective cohort studies with improved exposure assessments are needed to confirm the causal link between air pollutants and stillbirth.
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http://dx.doi.org/10.1016/j.ijheh.2018.01.014DOI Listing
April 2018

The Wuhan Twin Birth Cohort (WTBC).

Twin Res Hum Genet 2017 08 27;20(4):355-362. Epub 2017 Jun 27.

Wuhan Children's Hospital (Wuhan Maternal and Child Healthcare Hospital,Tongji Medical College,Huazhong University of Science & Technology,Wuhan,Hubei Province,China.

The Wuhan Pre/Post-Natal Twin Birth Registry (WPTBR) is one of the largest twin birth registries with comprehensive medical information in China. It recruits women from the first trimester of pregnancy and their twins from birth. From January 2006 to May 2016, the total number of twins enrolled in WPTBR is 13,869 twin pairs (27,553 individuals). The WPTBR initiated the Wuhan Twin Birth Cohort (WTBC). The WTBC is a prospective cohort study carried out through incorporation of three samples. The first one comprises 6,920 twin pairs, and the second one, 6,949 twin pairs. Both are population-based samples linked to the WPTBR and include pre- and post-natal information from WPTBR. The second sample includes neonatal blood spots as well. Using a hospital-based approach, we recently developed a third sample with a target enrolment of 1,000 twin pairs and their mothers. These twins are invited, via their parents, to participate in a periodic health examination from the first trimester of pregnancy to 18 years. Biological samples are collected initially from the mother, including blood, urine, cord blood, cord, amniotic fluid, placenta, breast milk and meconium, and vaginal secretions, and later from the twins, including meconium, stool, urine, and blood. This article describes the design, recruitment, follow-up, data collection, and measures, as well as ongoing and planned analyses at the WTBC. The WTBC offers a unique opportunity to follow women from prenatal to postnatal, as well as follow-up of their twins. This cohort study will expand the understanding of genetic and environmental influences on pregnancy and twins' development in China.
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http://dx.doi.org/10.1017/thg.2017.24DOI Listing
August 2017

Symptoms of anxiety and depression during pregnancy and their association with low birth weight in Chinese women: a nested case control study.

Arch Womens Ment Health 2017 04 24;20(2):283-290. Epub 2016 Dec 24.

Wuhan Medical and Health Center for Women and Children, 100 Hongkong Road, Wuhan, Hubei, 430015, China.

This study is a nested case control study from a population-based cohort study conducted in Wuhan, China. The aim is to estimate the association between symptoms of depression during pregnancy (DDP), anxiety during pregnancy(ADP), and depression with anxiety during pregnancy (DADP) and low birth weight (LBW) and to examine the extent to which preterm birth (PTB) moderates these associations. Logistic regression analyses were used to model associations between DDP, ADP, and DADP and LBW. Models were stratified by the presence or absence of PTB to examine moderating effects. From the cohort study, 2853 had a LBW baby (cases); 5457 pregnant women served as controls. Women with DDP or ADP only were not at higher risk of having a LBW baby, but DADP was associated with increased risk of LBW (crude OR 1.41, 95% CI 1.17-1.70; adjusted OR 1.29, 95% CI 1.07-1.57), and the significant association was particularly evident between DADP and LBW in PTB, but not in full-term births. Our data suggests that DADP is related to an increased risk of LBW and that this association is most present in PTBs.
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http://dx.doi.org/10.1007/s00737-016-0697-2DOI Listing
April 2017

Ozone and Other Air Pollutants and the Risk of Congenital Heart Defects.

Sci Rep 2016 10 18;6:34852. Epub 2016 Oct 18.

Wuhan Medical &Healthcare Center for Women and Children, Wuhan, Hubei Province 430030, China.

The objective of this study was to evaluate whether high levels of maternal exposure to O, SO, NO, CO are related to increased risk of congenital heart defects (CHDs) in Wuhan, China. The study included mothers living in the central districts of Wuhan during pregnancy over the two-year period from June 10, 2011 to June 9, 2013. For each study participant, we assigned 1-month averages of O, SO, NO and CO exposure based on measurements obtained from the nearest exposure monitor to the living residence of mothers during their early pregnancy period. In one-pollutant model, we observed an increased risk of CHDs, ventricular septal defect (VSD), and tetralogy of fallot (TF) with increasing O exposure. In two-pollutant model, associations with all CHDs, VSD, and TF for O were generally consistent compared to the models that included only O, with the strongest aORs observed for exposures during the third month of pregnancy. We also observed a positive association between CO exposures during the third month of pregnancy and VSD in two pollution model.Our results contribute to the small body of evidence regarding air pollution exposure and CHDs, but confirmation of these associations will be needed in future studies.
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http://dx.doi.org/10.1038/srep34852DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5067649PMC
October 2016

Maternal Prepregnancy Body Mass Index and Small for Gestational Age Births in Chinese Women.

Paediatr Perinat Epidemiol 2016 11 1;30(6):550-554. Epub 2016 Sep 1.

College for Public Health and Social Justice, Saint Louis University, Saint Louis, MO.

Background: Both high and low prepregnancy body mass index (BMI) has been associated with small for gestational age births (SGA; birthweight below the population specific 10th centile for the gestational age), but results remain inconsistent. We examined the association between maternal BMI and SGA, and evaluated if the associations were modified by preterm birth (being born prior to 37 weeks) status.

Methods: A population-based cohort study was conducted in Wuhan, China from June 2011, to June 2013. Women who delivered a non-malformed livebirth (n = 76 695) were included using the Wuhan Maternal and Child Health Management Information System. Log-binomial regression models were used to analyse the associations between prepregnancy BMI, categorized using thresholds adapted to the Chinese population, and SGA. Stratified analyses were used to examine the relationship of prepregnancy BMI to preterm-SGA and term-SGA.

Results: Of the 76 695 live births, 3058 (4.0%) were delivered preterm. For babies born at term, prepregnancy underweight (<18.5 kg/m ) was associated with an increased risk of SGA, the adjusted risk ratio (RR) was 1.41 (95% confidence interval (CI) 1.33, 1.49), whereas, being overweight (24.0-27.9 kg/m ) was associated with a decreased risk (RR 0.84, 95% CI 0.74, 0.94). For babies born preterm, prepregnancy underweight was not associated with risk of SGA, but being overweight was associated with an increased risk (RR 1.57, 95% CI 1.04, 2.35).

Conclusions: These data suggest that the association of overweight and underweight prepregnancy BMI and SGA differs depending on whether the baby is full term or preterm.
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http://dx.doi.org/10.1111/ppe.12315DOI Listing
November 2016

Ambient Air Pollution and Adverse Pregnancy Outcomes in Wuhan, China.

Res Rep Health Eff Inst 2016 09(189):1-65

Background: Several recent studies have suggested that maternal exposures to air pollution and temperature extremes might contribute to low birth weight (LBW), preterm birth (PTB), and other outcomes that can adversely affect infant health. At the time the current study began, most other studies had been conducted in the United States or Europe. Dr. Zhengmin Qian proposed to extend work he had done on ambient particulate air pollution and daily mortality in Wuhan, China (Qian et al. 2010), as part of the HEIsponsored Public Health and Air Pollution in Asia program, to study adverse birth outcomes. Wuhan is the capital city of Hubei province, has a large population of about 6.4 million within the urban study area, experiences temperature extremes, and generally has higher air pollution levels than those observed in the United States and Europe, thus providing a good opportunity to explore questions about air pollution and health.

Approach: Qian and colleagues planned a cohort and nested case–control design with four specific aims, examining whether increased exposures to air pollutants (PM2.5, PM10, SO2, NO2, O3, and CO) during vulnerable pregnancy periods were associated with increased rates of PTB, LBW (<2500 g), or intrauterine growth retardation (IUGR, defined as having a birth weight below the 10th percentile of singleton live births in Wuhan) after adjusting for major risk factors and whether the associations were confounded by copollutant exposures, affected by residual confounding, or modified by temperature extremes, socioeconomic status (SES), or secondhand smoke (SHS) exposure. The cohort study included 95,911 births that occurred from June 10, 2011, to June 9, 2013, and met typical prespecified inclusion criteria used in other birth outcome studies. The case–control study included 3146 cases (PTB, LBW, or both, but not IUGR) and 4263 controls (matched to the cases by birth month) for whom investigators were able to complete home visits and questionnaires. The investigators obtained air pollution and daily weather data for August 2010 to June 2013 from nine monitoring stations representing background air pollution sites in seven Wuhan inner-city districts. Only two of these stations provided PM2.5 data. For the cohort study, the investigators assigned exposures to mothers according to the daily mean concentrations from the monitor nearest the residential community in which the mother lived at the time of the birth. For the case–control study, they assigned exposures based on the inverse distance weighted average of daily mean concentrations from the three nearest monitors, for all but PM2.5 for which the method was not specified. They also collected data on various factors that might confound or modify the impact of the pollutants on the adverse outcomes, including data collected in the cohort from mothers at the time of delivery and, in the case–control study, from questionnaires administered to mothers. In the case–control study, covariates representing SES (as indicated by the mother’s educational attainment and household income) and SHS exposures were of particular interest. The primary statistical analyses of the pollutant associations with PTB, LBW, and IUGR were conducted using logistic regression models. In the cohort study, exposures during the pregnancy period of interest (full term, trimesters, and selected months) were included as continuous variables. In the case–control study, the exposures were modeled as binary variables (i.e., above or below the median pollutant concentrations). Numerous sensitivity analyses were conducted.

Results And Interpretation: Although originally planning a nested case–control study, the investigators encountered challenges that led them to analyze the cohort and case–control studies using different ways of assigning exposures and characterizing them in their statistical models. These decisions precluded direct comparisons between the sets of results, making it difficult to answer the questions about residual confounding that nested case–control studies are designed to answer. The odds ratios from the two study designs using different exposures also have different interpretations. Still, one can ask whether the sets of findings were qualitatively consistent with each other or with those of similar studies. There were some similarities. Both studies suggested that increased PM(2.5), PM(10), CO, and O(3) exposures over the full pregnancy were associated with small increases in the odds of PTB (the case–control study also showed an association with NO2) and that increased PM(2.5) exposures were associated with significantly increased odds of LBW. However, most of the other pollutants had no effect on LBW, except CO in the cohort study and O(3) in the case–control study, both of which increased the odds of LBW. The exposures over the entire pregnancy were generally associated with decreased odds of IUGR. Adjustments for potential confounders were greatest for the delivery covariates. The investigators found no systematic association of any of these outcomes with particular trimesters or months, another result that differed from those of some other studies. They found little evidence that their main results were confounded or modified by the presence of copollutants, although with the exception of O3, most of the pollutants were highly correlated, making it difficult to disentangle the effects of individual pollutants. Could the two sets of data be analyzed in a more comparable way, as in a standard nested case–control study? At the Committee’s request, the investigators reanalyzed the case–control data using the same exposures and models as in the cohort study. The results were strikingly different from those using the inverse distance weighted exposures, modeled as binary variables — the pollutants had either no effect or an apparent beneficial effect on PTB and LBW. The Committee was not convinced by the explanations offered for these differences, leaving the reasons for them unresolved.

Conclusions: This study set out to answer important questions about the effects of air pollution exposure on three measures of adverse birth outcomes — LBW, PTB, and IUGR — in a large cohort of mothers and newborns in Wuhan, China. Given the cohort size, high pollution levels and temperatures, and detailed covariate data, the investigators were well poised to address these questions. They sought to pattern their work on other studies of birth outcomes, were very responsive to Committee questions, and provided many additional analyses and explanations. In the Committee’s view, however, the study was unable to address with confidence several of its specific aims. Most important, the differences in results when the case–control data were analyzed with different exposure metrics remain unexplained, raising concerns about the ability to draw conclusions from subsequent analyses assessing residual confounding and effect modification by temperature extremes, SES, and SHS exposure. Consequently, any individual findings from the cohort and case–control studies should be considered suggestive rather than conclusive, and should be interpreted carefully together.
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September 2016

Relationship Between Common Mental Disorder Symptoms During Pregnancy and Preterm Birth Among Chinese Women in Wuhan.

Matern Child Health J 2016 10;20(10):2121-9

Department of Epidemiology, College for Public Health and Social Justice, Saint Louis University, 3545 Lafayette Avenue, Saint Louis, MO, 63104, USA.

Objectives Few studies focus on the symptoms of common mental disorders during pregnancy (CMDP) and risk of preterm birth subtypes (PTB). The purpose of this study was to estimate the association between CMDP and PTB, and to examine whether or not the association between CMDP and PTB varies with the subtype of PTB in Chinese. Methods This population-based case control study, conducted in Wuhan, China, defined cases as every pregnant woman who had a PTB among all births in Wuhan, from June 10, 2011, to June 9, 2013. The same number of pregnant women who had term births was randomly selected as controls. The Electronic Perinatal Health Care Information System, a questionnaire designed for the study, provided data about the participants. Logistic regression analyses were used to model associations between CMDP and PTB, and to test associations between CMDP and two subtypes of PTB. Results The study recruited 8616 cases and an equal number of controls. We successfully collected maternal information on 6656 cases and controls for a response rate of 77.3 %. The incidence of PTB in Wuhan was 4.5 %. Spontaneous preterm births (SPTB) accounted for 60.1 %, and medically induced preterm births (IPTB) accounted for 39.9 % of preterm births. The prevalence rate of CMDP was 15.8 %. CMDP was slightly associated with PTB (crude OR 1.16, 95 % CI 1.01-1.32; adjusted OR 1.15, 95 % CI 1.00-1.32), further analyses showed CMDP was associated with IPTB (aOR 1.25, 95 % CI 1.04-1.50), but not with SPTB. Conclusion Our data suggest that CMDP is related to an increased risk of PTB, and that this association is primarily due to IPTB rather than SPTB.
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http://dx.doi.org/10.1007/s10995-016-2042-9DOI Listing
October 2016

Maternal exposure to air pollutant PM2.5 and PM10 during pregnancy and risk of congenital heart defects.

J Expo Sci Environ Epidemiol 2016 06 17;26(4):422-7. Epub 2016 Feb 17.

Guidance Department for General Staff, Wuhan Women and Children Health Care Center, Wuhan, Hubei Province, China.

Maternal exposure to ambient air pollution has increasingly been linked to congenital heart defects (CHDs). The objective of this study was to evaluate whether high levels of maternal exposure to PM2.5 and PM10 are related to increased risk of CHDs in Wuhan, China. We conducted a cohort study with a total of 105,988 live-born infants, stillbirths, and fetal deaths. The study included mothers living in the urban district of Wuhan during pregnancy over the 2-year period from 10 June 2011 to 9 June 2013. For each study participant, we assigned 1-month and 1-week averages of PM10 and PM2.5 exposure based on measurements obtained from the nearest exposure monitor to the living residence of mothers during their early pregnancy period. Logistic regression analyses were conducted to calculate the adjusted odds ratios (aORs) and 95% confidence intervals (CI) for the association between exposure to these ambient air pollutants during early pregnancy and CHDs. We observed an increased risk of CHDs, particularly ventricular septal defect (VSD), with increasing PM2.5 exposure. Using 1-week averages, we also observed significant monotonically increasing associations between PM2.5 exposure during weeks 7-10 of pregnancy and risk of VSD, with aORs ranging from 1.11 to 1.17 (95% CI: 1.02-1.20, 1.03-1.22, 1.05-1.24, and 1.08-1.26 separately) per a 10 μg/m(3) change in PM2.5 concentration. Our study contributes to the small body of knowledge regarding the association between in utero exposure to air pollution and CHDs, but confirmation of these associations will be needed in future studies.
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http://dx.doi.org/10.1038/jes.2016.1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4913168PMC
June 2016

Ambient air pollution and preterm birth: A prospective birth cohort study in Wuhan, China.

Int J Hyg Environ Health 2016 Mar 19;219(2):195-203. Epub 2015 Nov 19.

Wuhan Medical and Health Center for Women and Children, 100 Hongkong Road, Jiangan District, Wuhan 430015, China. Electronic address:

Importance: Although studies in western countries suggest that ambient air pollution is positively associated with adverse pregnancy outcomes, the upper levels of pollutant exposures have been relatively low, thus eroding confidence in the conclusions. Meanwhile, in Asia, where upper levels of exposure have been greater, there have been limited studies of the association between air pollution and adverse pregnancy outcomes.

Objective: The primary objective was to evaluate whether high levels of pollution, including particulate matter pollution with a mass median aerodynamic diameter of less than 2.5 μm (PM2.5) and 10 μm (PM10), sulfur dioxide (SO2), nitrogen dioxide (NO2), ozone (O3), and carbon monoxide (CO) are related to increased occurrence of preterm birth (PTB).

Methods: We conducted a population-based study in Wuhan, China in a cohort of 95,911 live births during a two-year period from 2011 to 2013. The exposure was estimated based on daily mean concentrations of pollutants estimated using the pollutants' measurements from the nine closest monitors. Logistic regressions were performed to determine the relationships between exposure to each of the pollutants during different pregnancy periods and PTB while controlling for key covariates.

Results: We found 3% (OR=1.03; 95% CI: 1.02, 1.05), 2% (OR=1.02; 95% CI: 1.02, 1.03), 15% (OR=1.15; 95% CI: 1.11, 1.19), and 5% (OR=1.05; 95% CI: 1.02, 1.07) increases in risk of PTB with each 5-μg/m(3) increase in PM2.5 and PM10 concentrations, 100-μg/m(3) increase in CO concentrations, and 10-μg/m(3) increase in O3 concentrations, respectively. There was negligible evidence for associations for SO2 and NO2. The effects from two-pollutant models were similar to the estimated effects from single pollutant models. No critical exposure windows were identified consistently: the strongest effect for PTB was found in the second trimester for PM2.5, PM10, and CO, but for SO2 it was in the first trimester, second month, and third month. For NO2 it was in the first trimester and second month, and for O3, the third trimester.

Conclusion: Findings reveal an association between air pollutants and PTB. However, more toxicological studies and prospective cohort studies with improved exposure assessments are needed to establish causality related to specific pollutants.
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http://dx.doi.org/10.1016/j.ijheh.2015.11.003DOI Listing
March 2016

Pre-Pregnancy BMI, Gestational Weight Gain, and the Risk of Hypertensive Disorders of Pregnancy: A Cohort Study in Wuhan, China.

PLoS One 2015 25;10(8):e0136291. Epub 2015 Aug 25.

Wuhan Women and Children Health Care Center, Wuhan, Hubei, People's Republic of China.

Background: Hypertensive disorders of pregnancy (HDP) are major causes of maternal death worldwide and the risk factors are not fully understood. Few studies have investigated the risk factors for HDP among Chinese women. A cohort study involving 84,656 women was conducted to investigate pre-pregnancy BMI, total gestational weight gain (GWG), and GWG during early pregnancy as risk factors for HDP among Chinese women.

Methods: The study was conducted between 2011-2013 in Wuhan, China, utilizing data from the Maternal and Children Healthcare Information Tracking System of Wuhan. A total of 84,656 women with a live singleton pregnancy were included. Multiple unconditional logistic regression was conducted to evaluate associations between putative risk factors and HDP.

Results: Women who were overweight or obese before pregnancy had an elevated risk of developing HDP (overweight: OR = 2.66, 95% CI = 2.32-3.05; obese: OR = 5.53, 95% CI = 4.28-7.13) compared to their normal weight counterparts. Women with total GWG above the Institute of Medicine (IOM) recommendation had an adjusted OR of 1.72 (95% CI = 1.54-1.93) for HDP compared to women who had GWG within the IOM recommendation. Women with gestational BMI gain >10 kg/m2 during pregnancy had an adjusted OR of 3.35 (95% CI = 2.89-3.89) for HDP, compared to women with a gestational BMI gain <5 kg/m2. The increased risk of HDP was also observed among women with higher early pregnancy (up to 18 weeks of pregnancy) GWG (>600g/wk: adjusted OR = 1.48, 95% CI = 1.19-1.84).

Conclusion: The results from this study show that maternal pre-pregnancy BMI, early GWG, and total GWG are positively associated with the risk of HDP. Weight control efforts before and during pregnancy may help to reduce the risk of HDP.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0136291PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4548954PMC
May 2016

Parental Body Mass Index, Gestational Weight Gain, and Risk of Macrosomia: a Population-Based Case-Control Study in China.

Paediatr Perinat Epidemiol 2015 Sep 30;29(5):462-71. Epub 2015 Jul 30.

Healthcare Department, Wuhan Women and Children Medical and Healthcare Center, Wuhan, Hubei, China.

Background: The prevalence of macrosomia has risen markedly worldwide, including in China, during the past two decades. Few epidemiological studies, however, have investigated the risk factors for macrosomia in China. This study was designed to investigate the associations between parental anthropometric characteristics, gestational weight gain (GWG), and risk of macrosomia in China.

Methods: This population-based, case-control study in Wuhan, China, included a total of 6341 subjects (870 cases and 5471 controls). Multivariable logistic regression was conducted to calculate odds ratios (OR) and 95% confidence intervals (CI).

Results: Mothers or fathers who were overweight or obese before pregnancy had an elevated risk of giving birth to a macrosomic infant compared with their normal weight counterparts. Women with GWG above the Institute of Medicine (IOM) recommendation had an adjusted OR of 6.09 [95% CI 5.04, 7.35] for delivering a macrosomic infant compared with women who had GWG within the IOM recommendation. When stratified by maternal pre-pregnancy body mass index (BMI), women who were underweight or normal weight before pregnancy were observed to have a higher risk of macrosomia birth associated with greater GWG.

Conclusions: Parental pre-pregnancy overweight/obesity and excessive GWG during pregnancy were highly associated with macrosomia. The association with GWG was most pronounced in mothers who had a normal or underweight pre-pregnancy BMI. Weight control efforts before pregnancy for mothers and fathers as well as control of maternal gain during pregnancy may reduce the risk of macrosomia.
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http://dx.doi.org/10.1111/ppe.12213DOI Listing
September 2015

Pre-Pregnancy Body Mass Index, Gestational Weight Gain, and Birth Weight: A Cohort Study in China.

PLoS One 2015 26;10(6):e0130101. Epub 2015 Jun 26.

Department of Primary Guidance, Wuhan Women and Children Health Care Center, Wuhan, Hubei Province, 430015, China.

Objective: To assess whether pre-pregnancy body mass index (BMI) modify the relationship between gestational weight gain (GWG) and child birth weight (specifically, presence or absence of low birth weight (LBW) or presence of absence of macrosomia), and estimates of the relative risk of macrosomia and LBW based on pre-pregnancy BMI were controlled in Wuhan, China.

Methods: From June 30, 2011 to June 30, 2013. All data was collected and available from the perinatal health care system. Logistic regression models were used to estimate the independent association among pregnancy weight gain, LBW, normal birth weight, and macrosomia within different pre-pregnancy BMI groups. We built different logistic models for the 2009 Institute of Medicine (IOM) Guidelines and Chinese-recommended GWG which was made from this sample. The Chinese-recommended GWG was derived from the quartile values (25th-75th percentiles) of weight gain at the time of delivery in the subjects which comprised our sample.

Results: For LBW children, using the recommended weight gain of the IOM and Chinese women as a reference, the OR for a pregnancy weight gain below recommendations resulted in a positive relationship for lean and normal weight women, but not for overweight and obese women. For macrosomia, considering the IOM's recommended weight gain as a reference, the OR magnitude for pregnancy weight gain above recommendations resulted in a positive correlation for all women. The OR for a pregnancy weight gain below recommendations resulted in a negative relationship for normal BMI and lean women, but not for overweight and obese women based on the IOM recommendations, significant based on the recommended pregnancy weight gain for Chinese women. Of normal weight children, 56.6% were above the GWG based on IOM recommendations, but 26.97% of normal weight children were above the GWG based on Chinese recommendations.

Conclusions: A GWG above IOM recommendations might not be helpful for Chinese women. We need unified criteria to classify adult BMI and to expand the sample size to improve representation and to elucidate the relationship between GWG and related outcomes for developing a Chinese GWG recommendation.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0130101PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4482572PMC
April 2016

Progress on the maternal mortality ratio reduction in Wuhan, China in 2001-2012.

PLoS One 2014 21;9(2):e89510. Epub 2014 Feb 21.

Department of Primary Guidance, Wuhan Women and Children Health Care Center, Wuhan, Hubei Province, China.

Background: Most maternal deaths occur in developing countries and most maternal deaths are avoidable. China has made a great effort to reduce MMR by three quarters to meet the fifth Millennium Development Goal (MDG5).

Methods: This retrospective study reviewed and analyzed maternal death data in Wuhan from 2001 to 2012. Joinpoint regression and multivariate Poisson regression was conducted using the log-linear model to measure the association of the number of maternal deaths with time, cause of death, where the death occurred, and cognitive factors including knowledge, attitude, resource, and management stratified.

Results: The MMR declined from 33.41 per 100,000 live births in 2001 to 10.63 per 100,000 live births in 2012, with a total decline of 68.18% and an average annual decline of 9.89%. From 2001-2012, the four major causes of maternal death were obstetric hemorrhage (35.16%), pregnancy complications (28.57%), amniotic fluid embolism (16.48%) and gestational hypertension (8.79%). Multivariate Poisson regression showed on average the MMR decreased by.17% each year from 2001-2006 and stayed stagnant since 2007-2012.

Conclusions: With the reduction in MMR in obstetric death (e.g. obstetric hemorrhage), there had been a remarkable reduction in MMR in Wuhan in 2001-2012, which may be due to (1) the improvement in the obstetric quality of perinatal care service on prevention and treatment of obstetric hemorrhage and emergency care skills, and (2) the improvement in the maternal health management and quality of prenatal care. Interventions to further reduce the MMR include several efforts such as the following: (1) designing community-based interventions, (2) providing subsidies to rural women and/hospitals for hospital delivery, (3) screening for pregnancy complications, and (4) establishing an emergency rescue system for critically ill pregnant women.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0089510PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3931783PMC
October 2014

Identification and control of metal-chelating chromatographic artifacts in the analysis of a malonohydrazide derivative drug compound.

J Pharm Biomed Anal 2010 Nov 24;53(3):371-5. Epub 2010 Apr 24.

Product Development Group, Pharmaceutical Development, GlaxoSmithKline, USA.

Two unusual chromatographic artifact peaks were detected in the HPLC analysis for content of a malonohydrazide derivative drug and drug-related impurities. The artifacts were identified as the copper(II) chelating complexes with the drug compound and one of the process impurities. Our investigations suggested that built-up of Cu(2+) contamination in the HPLC system was the primary source for formation of the chelating artifacts. A rinse procedure using diluted EDTA solution was developed, and demonstrated to effectively purge trace level of heavy metals including Cu(2+) from the system, and therefore inhibited the formation of both chelates. Furthermore, the rinse was shown to introduce no detrimental impact on the response accuracy of the active drug compound and related impurities.
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http://dx.doi.org/10.1016/j.jpba.2010.04.021DOI Listing
November 2010

[Study on mathematical model of optimum fertilizer application to Pinellia ternate cultivation].

Zhongguo Zhong Yao Za Zhi 2009 Mar;34(6):669-73

College of Agriculture, Gansu Agricultural University, Lanzhou 730070, China.

Objective: To study the mathematical model of optimum fertilizer application to Pinellia by field experiments.

Method: Three factors and 5 levels quadratic rotational combination design was applied to study the effects of N, P and K.

Result And Conclusion: N, P and K combination application can achieve the maximum yield of 29,921.4 kg x hm(-2), the amount of N, P2O5, K2O were 413.79, 224.79, 164.01 kg x hm(-2), respectively. The effects of the 3 factors were in following orders: P > N > K.
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March 2009
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