[Latest Findings on Prediction and Prevention of Preeclampsia].

Preeclampsia, a progressive disease involving multiple systems, afflicts pregnancy specifically. It contributes to severe maternal and perinatal morbidity and mortality. It has been reported that preeclampsia initiates from a mismatch between the utero-placental supply and demand, which subsequently triggers the release of placental syncytiotrophoblast stress-derived factors and an imbalance of proangiogenic/antiangiogenic factors, eventually causing maternal systemic endothelial lesions and systemic inflammatory response. Currently, treatments available for preeclampsia are very limited in number. Hence, prediction and prevention carry special significance. Herein, we reviewed the current understanding of preeclampsia, especially findings on the prediction and prevention of preeclampsia published within the past 5 years. We discussed the Fetal Medicine Foundation (FMF) screening model based on placental growth factor (PlGF) and the effects of aspirin, calcium, exercise, and termination of pregnancy in preventing preeclampsia. The efficacy and safety of other new preventive measures still need further validation.

Optimized cutoff maternal age for adverse obstetrical outcomes: a multicenter retrospective cohort study in Urban China during 2011 to 2012.

BACKGROUND: China's two-child policy has led to a trend of aging in pregnancy which was associated with adverse outcomes. This study aimed to identify the clinically cutoff maternal age for adverse obstetric outcomes in China. METHODS: This secondary analysis of a multicenter retrospective cohort study included data of childbearing women from 39 hospitals collected in urban China during 2011 to 2012. Logistic regression was used to assess the adjusted odds ratios (aOR) of adverse outcomes in different age groups in comparison to women aged 20 to 24 years. The adjustments included the location of the hospital, educational level, and residence status. Clinically cutoff age was defined as the age above which the aOR continuously become both statistically (P < 0.05) and clinically (aOR > 2) significant. RESULTS: Overall, 108,059 women were recruited. In primiparae, clinically cutoff maternal ages for gestational diabetes (aOR: 2.136, 95% confidence interval [CI]: 1.856-2.458, P < 0.001), placenta previa (aOR: 2.400, 95% CI: 1.863-3.090, P < 0.001), cesarean section (aOR: 2.511, 95% CI: 2.341-2.694, P < 0.001), hypertensive disorder (aOR: 2.122, 95% CI: 1.753-2.569, P < 0.001), post-partum hemorrhage (aOR: 2.129, 95% CI: 1.334-3.397, P < 0.001), and low birth weight (aOR: 2.174, 95% CI: 1.615-2.927, P < 0.001) were 27, 31, 33, 37, 41, and 41 years, respectively. In multiparae, clinically cutoff ages for gestational diabetes (aOR: 2.977, 95%CI: 1.808-4.904, P < 0.001), hypertensive disorder (aOR: 2.555, 95% CI: 1.836-3.554, P < 0.001), cesarean section (aOR: 2.224, 95% CI: 1.952-2.534, P < 0.001), post-partum hemorrhage (aOR: 2.140, 95% CI: 1.472-3.110, P < 0.001), placenta previa (aOR: 2.272, 95% CI: 1.375-3.756, P < 0.001), macrosomia (aOR: 2.215, 95% CI: 1.552-3.161, P < 0.001), and neonatal asphyxia (aOR: 2.132, 95% CI: 1.461-3.110, P < 0.001) were 29, 31, 33, 35, 35, 41, and 41 years, respectively. CONCLUSIONS: Early cutoff ages for gestational diabetes and cesarean section highlight a reasonable childbearing age in urban China. The various optimized cutoff ages for different adverse pregnancy outcomes should be carefully considered in childbearing women.

A Comparison of Prediction of Adverse Perinatal Outcomes between Hadlock and INTERGROWTH-21st Standards at the Third Trimester.

Little is known about the clinical value of the Hadlock and INTERGROWTH-21st EFW standards for predicting adverse perinatal outcomes (APOs) in the third trimester. The purpose of this study was to study the association between low estimated fetal weight percentile (EFWc) in the third trimester and the risk of APOs and compare predictions of APOs between Hadlock and INTERGROWTH-21st EFW standards. A prospective cohort of 690 singleton pregnancies with ultrasonography performed in the third trimester between March 2015 and March 2016 in China was conducted. EFW and the corresponding EFWc were measured using the Hadlock and INTERGROWTH-21st standards, respectively. Cox proportional hazard models were used to assess the relationship between low EFWc (i.e., <5 percentile, P5) and the risk of APOs. Compared with fetuses with ≥P5 of the EFWc, fetuses with

Preeclampsia is associated with hypermethylation of IGF-1 promoter mediated by DNMT1.

Previous studies have demonstrated a dynamic epigenetic regulation of genes expression in placenta trophoblasts and a dynamic imbalance of DNA methylation and hydroxymethylation. Reduced IGF-1 has been observed in preeclampsia. This study was to investigate the interactive roles between IGF-1 and the global DNA methylation/hydroxymethylation, and the status of DNA methylation/hydroxymethylation and associated enzymes such as DNMTs and TETs in peeeclamptic placentas and hypoxic trophoblasts. It was found that IGF-1 was decreased in preeclamptic placentas and hypoxic trophoblasts when compared to the control group using immunohistochemisty, western blot, qRT-PCR and ELISA. Pyrophosphate sequencing showed IGF-1 promoter was significantly hypermethylated in preeclamptic placentas, which was responsible for reduced IGF-1 expression. Preeclamptic placentas and hypoxic trophoblasts were hypermethylated and hypohydroxymethylated accompanied by remarkably higher 5mC, DNMT1 and DNMT3b, and lower DNMT3a, 5hmC, TET1, TET2 and TET3 detected by immunohistochemisty, western blot, qRT-PCR and ELISA. Pearson's correlation confirmed a statistically significant negative correlation between IGF-1 and DNMT1. Furthermore, both treatment with 5-Aza-dc and DNMT1-siRNA significantly increased the expression of IGF-1 in HTR8 cells, indicating the potential mechanism of DNMT1-mediated DNA methylation in IGF-1 regulation. However, IGF-1 didn't change DNA methylation or hydroxymethylation. These findings suggest that preeclampsia is associated with hypermethylation of IGF-1 promoter mediated by DNMT1 and provide new insights into the diagnosis and treatment of preeclampsia.