The impact of cesarean delivery on infant DNA methylation.

BACKGROUND: Mounting evidence suggests that cesarean delivery may have a long-lasting effect on infant health. But the underlying mechanisms remain unclear. This study aims to examine whether cesarean delivery on maternal request without any medical indications (CDMR) impacts DNA methylation status in the umbilical cord blood of the infant. METHODS: A cross-sectional study was conducted in Shanghai, China. A total of 70 CDMR and 70 vaginal deliveries (VD) were recruited in 2012. The cord blood DNA methylation status was measured in 30 CDMR and 30 VD newborns using Illumina Infinium Human Methylation 450 K BeadChip. To validate the results, the cord blood DNA methylation status was measured in another 40 CDMR and 40 VD newborns using targeted bisulfite sequencing assay. A total of 497 CpG sites from 40 genes were included in the analysis. RESULTS: A total of 165 differentially methylated positions (DMPs) exhibited differences in DNA methylation by 10% or more between the CDMR and VD groups, many of which were related to the development of the immune system. Based on the targeted bisulfite sequencing assay, 16 genes (16/22, 72.7%) had higher methylation level in the CDMR group than the VD group. Among them, 5 genes were related to the immune system. After considering the estimation of cell type proportions, there was few significant differences in DNA methylation between CDMR and VD groups. CONCLUSIONS: The DMPs identified between CDMR and VD groups might be largely explained by the cell type proportions. Further studies are needed to examine DNA methylation in each cell type separately.

A cluster-randomized field trial to reduce cesarean section rates with a multifaceted intervention in Shanghai, China.

BACKGROUND: Cesarean section (CS) rate has risen dramatically and stayed at a very high level in China over the past two to three decades. Given the short- and long-term adverse effects of CS, effective strategies are needed to reduce unnecessary CS. We aimed to evaluate whether a multifaceted intervention would decrease the CS rate in China. METHODS: We carried out a cluster-randomized field trial with a multifaceted intervention in Shanghai, China, from 2015 to 2017. A total of 20 hospitals were randomly allocated into an intervention or a control group. The intervention consisted of more targeted health education to pregnant women, improved hospital CS policy, and training of midwives/doulas for 8 months. The study included a baseline survey, the intervention, and an evaluation survey. The primary outcome was the changes of overall CS rate from the pre-intervention to the post-intervention period. A subgroup analysis stratified by the Robson classification was also conducted to examine the CS change among women with various obstetric characteristics. RESULTS: A total of 10,752 deliveries were randomly selected from the pre-intervention period and 10,521 from the post-intervention period. The baseline CS rates were 42.5% and 41.5% in the intervention and control groups, respectively, while the post-intervention CS rates were 43.4% and 42.4%, respectively. Compared with the control group, the intervention did not significantly reduce the CS rate (adjusted OR = 0.92; 95% CI 0.73, 1.15). Similar results were obtained in subgroup analyses stratified by the risk level of pregnancy, maternal age, number of previous CS, or parity. Scarred uterus and maternal request remained the primary reasons for CS after the interventions in both groups. The intervention did not alter the perinatal outcomes (adjusted change of risk score = - 0.06; 95%CI - 0.43, 0.31). CONCLUSIONS: A multifaceted intervention including more targeted prenatal health education, improved hospital CS policy, and training of midwives/doulas, did not significantly reduce the CS rate in Shanghai, China. However, our experience in implementing a multifaceted intervention may provide useful information to other similar areas with high CS use. TRIAL REGISTRATION: This trial was registered at the Chinese Clinical Trial Registry (www.chictr.org.cn) (ChiCTR-IOR-16009041) on 17 August 2016.

Is age and socioeconomic status associated with preference for birth mode in nulliparous women in China?

PURPOSE: To examine the association between sociodemographic factors and preference for birth mode in nulliparous women in China. METHODS: A total of 4606 women before or in early pregnancy were recruited from 2013 to 2016 in the Shanghai Birth Cohort Study. Generalized linear regression was used to examine the association of sociodemographic characteristics with preferred birth mode and actual cesarean section (CS) without clinical indications in 2713 nulliparous women, and the changes from preference of vaginal birth to actual CS without clinical indications in 2369 nulliparous women. RESULTS: After controlling for potential confounders, preference for CS was associated with older maternal age [31-34 years: adjusted risk ratio (ARR) 2.73, 95% confidence interval (CI) 1.56-4.78; ≥ 35 years: 6.27, 3.28-12.01, p for trend < 0.0001] and lower level of education (below junior college vs college or above: 1.51, 1.10-2.09). Older maternal age (≥ 35 years: 3.37, 1.74-6.50), born in city or township (city vs countryside: 3.18, 1.93-5.24; township vs countryside: 1.97, 1.06-3.66), and lower level of education (below junior college vs college or above: 1.38, 1.01-1.88) were significantly associated with a CS without clinical indications. Women who preferred vaginal birth but had an actual CS without clinical indications were more likely to be older (≥ 35 years: 4.30, 1.44-12.83) and born in city (city vs countryside: 2.89, 1.33-6.30). CONCLUSIONS: Older age, lower education level, and being born in city or township were risk factors for CS without clinical indication in China.

Epidemiology of placenta accreta spectrum disorders in Chinese pregnant women: A multicenter hospital-based study.

INTRODUCTION: Placenta accreta spectrum disorder (PASD) is a life-threatening obstetric complication. China still lacks high-quality data on the epidemiology of PASD. We intend to examine the major risk factors for PASD, explore the association of PASD with severe adverse perinatal outcomes and describe the geographical variations in China. METHODS: We used data from the China Labor and Delivery Survey, which included a total of 75,132 births from 96 hospitals in 24 provinces in China in 2015 and 2016. Each participating hospital randomly selected 6-10 weeks within a 12-month period. In the selected weeks, all births with gestational age ≥24 weeks or birth weight ≥500 g were included. We analyzed the demographic characteristics and prevalence of PASD in pregnant women. Multivariable logistic regression was used to examine the association of previous caesarean section (CS) and repeated surgical abortion with PASD. We explored the association of PASD with severe adverse perinatal outcomes, which indicated by Weighted Adverse Outcome Score (WAOS) ≥ 20. Multivariable logistic regression was used to examine the association of PASD with WAOS. We also calculated and compared the prevalence of PASD in different regions of China. RESULTS: The weighted prevalence of PASD was 2.20% (95% CI 0.76 to 4.95) in our population，and there was a substantial difference in the prevalence of PASD by geographic regions in China. Two or more previous CS (adjusted OR 2.34, 95%CI 1.41 to 3.88) and repeated surgical abortion (twice: 2.16, 1.20 to 3.92; 3 times: 4.31, 1.70 to 10.96; ≥4 times: 4.76, 3.12 to 7.26) were significant risk factors for PASD. PASD (adjusted OR 3.77, 95% CI 2.80 to 5.06) was a significant risk factor for severe adverse perinatal outcomes indicated by WAOS score. DISCUSSION: The prevalence of PASD in China appeared higher than that in other countries, and varied substantially by geographic regions. Two or more previous CS and repeated surgical abortion were major risk factors for PASD. Pregnant women with PASD had more severe adverse pregnancy outcomes. Reducing primary cesarean section and repeated surgical abortion are the key to decreasing PASD.

Epidemiology and region-specific risk factors for low Apgar scores in China: a nationwide study.

BACKGROUND: Neonatal asphyxia is a serious public health issue. This study aimed to determine the epidemiology and region-specific risk factors for low Apgar scores, an important proxy for neonatal asphyxia, in China from 2015 to 2016. METHODS: The China Labor and Delivery Survey was a multicenter cross-sectional study including 96 hospitals distributed in 24 (out of 34) provinces. Logistic regression analysis was performed to examine the risk factors for a low Apgar score (< 7). Correspondence analyses were performed among neonates with low Apgar scores to explore the relationship between risk factors and geographical regions. The population attributable risk percentage (PAR%) was calculated for each region-specific risk factor. RESULTS: A total of 72,073 live births, including 320 births with low Apgar scores, were used for the analysis, giving a weighted rate of 3.9/1000 live births. There was a substantial difference in the incidence of low Apgar scores by geographic region, from 2.3/1000 live births in East China to 10.9/1000 live births in Northeast China. Maternal and obstetric factors are the major region-specific risk factors. In Southwest China, hypertensive disorders in pregnancy were more important contributors, with PAR% being 74.47%; in North and Northwest China, pre-pregnancy underweight was a more significant factor, with PAR% of 62.92%; in East China, infants born between 0:00 a.m. and 7:59 a.m. were a key factor, with PAR% of 80.44%. CONCLUSION: Strategies based on region-specific risk factors should be considered to reduce the burden of low Apgar scores in China.

Dissecting the current caesarean section rate in Shanghai, China.

The high caesarean section (CS) rate has been of great public concern around the world. Yet, large-scale studies of dissecting such a high CS rate are few in the Chinese population. We carried out a cross-sectional survey randomly selecting 10,855 births from 20 hospitals in Shanghai from January to June, 2016. Labor and delivery information was extracted from medical records. The Robson classification system for CS was used to classify all women into ten groups. The overall CS rate was 41.5%. Prelabor CS in nulliparous, term singleton vertex women was the predominant contributor (37.4%) to the total CS and accounted for the second highest proportion of total births (15.5%) in all hospital types. The vast majority of women with a previous CS had a repeat CS (96.6%). CS rate was still high in Shanghai. Nulliparous women in low risk and having CS before labour, often without any medical indication, was a major contributor to the high CS rate.