The Proteome Landscape of Human Placentas for Monochorionic Twins with Selective Intrauterine Growth Restriction

In perinatal medicine,intrauterine growth restriction(IUGR)is one of the greatest challenges.The etiology of IUGR is multifactorial,but most cases are thought to arise from placental insufficiency.However,identifying the placental cause of IUGR can be difficult due to numerous confounding factors.Selective IUGR(sIUGR)would be a good model to investigate how impaired placentation affects fetal development,as the growth discordance between monochorionic twins cannot be explained by confounding genetic or maternal factors.Herein,we constructed and analyzed the placental proteomic profiles of IUGR twins and normal cotwins.Specifically,we identified a total of 5481 proteins,of which 233 were differentially expressed(57 up-regulated and 176 down-regulated)in IUGR twins.Bioinformatics analysis indicates that these differentially expressed proteins(DEPs)are mainly associated with cardiovascular system development and function,organismal survival,and organismal development.Notably,34 DEPs are significantly enriched in angiogenesis,and diminished placental angiogenesis in IUGR twins has been further elaborately confirmed.Moreover,we found decreased expression of metadherin(MTDH)in the placentas of IUGR twins and demonstrated that MTDH contributes to placental angiogenesis and fetal growth in vitro.Collectively,our findings reveal the comprehensive proteomic signatures of placentas for sIUGR twins,and the DEPs identified may provide in-depth insights into the pathogenesis of placental dysfunction and subsequent impaired fetal growth.

Analysis of the Characteristics of Pregnancy and Delivery before and after Implementation of the Two-child Policy

Background： After the two-child policy is frilly implemented, new challenges regarding pregnancy management and the treatment of pregnancy complications will arise. The aim of this study was to analyze the characteristics of pregnancy and delivery before and after the implementation of the two-child policy to make suggestions on the quality assurance of the new era of obstetrics. Methods： In total, 5895 cases of pregnant women who delivered from April 2016 to March 2017 in Peking University Third Hospital served as the study group and 5103 cases of pregnant women who delivered from January to December 2015 served as the control group. The characteristics of pregnancy and delivery were retrospectively analyzed. Results： In the study group, the percentage of pregnant women who were older （over 40 years） （3.6% vs. 2.2%）, were multipara （30.3% vs. 17.0%）, received irregular prenatal care （ 1.5% vs. 0.9%）, were transferred for treatment from a subordinate hospital （4.4% vs. 2.8%）, and were not residents of Beijing （3.8% vs. 2.2%）, were significantly increased compared with the control group （P 〈 0.05）. In the study group, the rate of a hypertensive disorder complicating pregnancy （6.4% vs. 5.0%）, gestational diabetes mellitus （25.3% vs. 23.1%）, dangerous placenta previa （3.0% vs. 2.3%）, placental implantation （2.4% vs. 1.8%）, and severe postpartum hemorrhage （2.8% vs. 1.9%） was significantly increased compared with the control group （P 〈 0.05）. In the study group, the cesarean section rate during primipara was significantly reduced compared with the control group （42.0% vs. 44.2%）. However, the rate during inultipara was significantly increased compared with the control group （P 〈 0.05）. Indications for cesarean section in the study group as well as the percentages of scared uterus and placenta previa were significantly increased compared with the control group （P 〈 0.05）. Conclusions： According to the current situation, better methods are needed to strengthen pregnancy and delivery management, reduce the rate of cesarean section, and ensure a positive outcome for mothers and babies.

Gut microbiota dysbiosis in preeclampsia patients in the second and third trimesters

Background:Preeclampsia(PE)is a serious complication that affects maternal and perinatal outcomes.However,the mechanisms have not been fully explained.This study was designed to analyze longitudinal gut microbiota alterations in pregnant women with and without PE in the second(T2)and third trimesters(T3).Methods:In this nested case-control study,which was conducted at Nanjing Maternity and Child Health Care Hospital,fecal samples from 25 PE patients(25 fecal samples obtained in T2 and 15 fecal samples obtained in T3)and 25 matched healthy controls(25 fecal samples obtained in T2 and 22 fecal samples obtained in T3)were collected,and the microbiota were analyzed using 16S rRNA gene sequencing.The diversity and composition of the microbiota of PE cases and controls were compared.Results:No significant differences in diversity were found between the PE and control groups(P>0.05).In the control group,from T2 to T3,the relative abundances of Proteobacteria(median[Q1,Q3]:2.25%[1.24%,3.30%]vs.0.64%[0.20%,1.20%],Z=-3.880,P<0.05),and Tenericutes(median[Q1,Q3]:0.12%[0.03%,3.10%]vs.0.03%[0.02%,0.17%],Z=-2.369,P<0.05)decreased significantly.In the PE group,the relative abundance of Bacteroidetes in T2 was lower than in T3(median[Q1,Q3]:18.16%[12.99%,30.46%]vs.31.09%[19.89%,46.06%],Z=-2.417,P<0.05).In T2,the relative abundances of mircrobiota showed no significant differences between the PE group and the control group.However,in T3,the relative abundance of Firmicutes was significantly lower in the PE group than in the control group(mean±standard deviation:60.62%±15.17%vs.75.57%±11.53%,t=-3.405,P<0.05).The relative abundances of Bacteroidetes,Proteobacteria,and Enterobacteriaceae were significantly higher in the PE group than in the control group(median[Q1,Q3]:31.09%[19.89%,46.06%]vs.18.24%[12.90%,32.04%],Z=-2.537,P<0.05;1.52%[1.05%,2.61%]vs.0.64%[0.20%,1.20%],Z=-3.310,P<0.05;0.75%[0.20%,1.00%]vs.0.01%[0.004%,0.023%],Z=-4.152,P<0.05).Linear discriminant analysis combined effect size measurements analysis showed that the relative abundances of the phylum Bacteroidetes,class Bacteroidia and order Bacteroidales were increased in the PE group,while those of the phylum Firmicutes,the class Clostridia,the order Clostridiales,and the genus unidentified Lachnospiraceae were decreased in the PE group;and these differences were identified as taxonomic biomarkers of PE in T3.Conclusion:From T2 to T3,there was an obvious alteration in the gut microbiota.The gut microbiota of PE patients in T3 was significantly different from that of the control group.

Effect of Primary Elective Cesarean Delivery on Placenta Accreta： A Case-Control Study

Background： Cesarean section （CS） is an independent risk factor for placenta accreta. Some researchers think that the timing of primary cesarean delivery is associated with placenta accreta in subsequent pregnancies. The aim of this study was to investigate the risk of placenta accreta following primary CS without labor, also called primary elective CS, in a pregnancy complicated with placenta previa. Methods： A retrospective, single-center, case-control study was conducted at Peking University Third Hospital. Relevant clinical data of singleton pregnancies between January 2010 and September 2017 were recorded. The case group included women with placenta accreta who had placenta previa and one previous CS. Control group included women with one previous CS that was complicated with placenta previa. Maternal age, body mass index, gestational age, fetal birth weight, gravity, parity, induced abortion, the rate of women received assisted reproductive technology, other uterine surgery, and primary elective CS were analyzed between the two groups. Results： The rate of primary elective CS （90.1% vs. 69.9%, P 〈 0.001 ） was higher, and maternal age was younger （32.7 ± 4.7 years vs. 34.6 ± 4.0 years, P 〈 0.001） in case group, compared with control group. Case group also had higher gravity and induced abortions compared with the control group （both P 〈 0.05）. Primary CS without labor was associated with significantly increased risk of placenta accreta in a subsequent pregnancy complicated with placenta previa （odds ratio： 3.32; 95% confidential interval： 1.68-6.58）. Conclusion： Women with a primary elective CS without labor have a higher chance of developing an accreta in a subsequent pregnancy that is complicated with placenta previa.

Chronic Active Hepatitis B with COVID-19 in Pregnancy: A Case Report

Currently,infection with coronavirus disease 2019(COVID-19),caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),during pregnancy is a problem worthy of attention,especially in patients with underlying diseases.In this case report,we present a case of chronic active hepatitis B with COVID-19 in pregnancy.A 31-year-old woman at 29 weeks of gestation who had a history of chronic hepatitis B virus infection discontinued antiviral treatment,was admitted to the hospital with chronic active hepatitis B,and tested positive for SARS-CoV-2 infection.In this case,we applied liver protective and antiviral agents,and low-dose dexamethasone therapy to successfully treat the critically ill pregnant woman suffering from chronic active hepatitis B combined with COVID-19.

A Cohort Analysis of Patients with Stage I Twin-to-Twin Transfusion Syndrome from a Major Referral Hospital in Northern China

Objective:To describe the outcomes of StageⅠtwin-to-twin transfusion syndrome among patients treated with expectant management(EM),amnioreduction(AR),or fetoscopic laser occlusion of chorioangiopagous vessels(FLOC).Methods:A cohort of 89 cases was studied.Based on the initial management strategy,patients were classified into three groups:the EM,AR,and FLOC.We assessed perinatal survival to 28 days of age and categorized pregnancy outcomes as good(twin live birth at≥30.0 weeks),mixed(single fetal demise or delivery between 26.0 and 29.9 weeks),or poor(double fetal demise or delivery at<26.0 weeks).Results:26(29.2%)patients underwent EM,35(39.3%)underwent AR,and 28(31.5%)underwent FLOC therapy.Of those managed expectantly,19.2%experienced spontaneous abortion,50%progressed in stage,and 30.8%remained stable or regressed.After adjusting for potential confounders including maternal age,'null'iparity,placenta location,and recipient maximum vertical pocket,and so on,FLOC therapy and AR were associated with significantly[odds ratio(OR)=0.09]and borderline significantly(OR=0.20)reduced risks of poor pregnancy outcomes and of no survivors to 28 days of age after birth(OR=0.04 and OR=0.20,respectively)compared with EM.Conclusion:About 70%of those treated with EM progressed in stage or experienced fetal loss.Compared to EM,intervention may decrease the risk of poor pregnancy outcomes and improve the perinatal survival rate.

Reply to “Placenta Previa Accreta and Previous Cesarean Section： Some Clarifications”

First, we want to thank the readers for their comments about our study design. Their opinions about the possible reasons why elective （labor ） cesarean section （CS） leads to higher risk of placenta previa accreta are really valuable and make good sense.