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.

Selective Fetal Growth Restriction in Monochorionic Diamniotic Twins: Diagnosis and Management

Selective fetal growth restriction (sFGR) is a severe condition that complicates 10% to 15% of all monochorionic diamniotic (MCDA) twin pregnancies. Pregnancies complicated with sFGR are at high risk of intrauterine demise or adverse perinatal outcome for the twins. Three clinical types have been described according to the umbilical artery (UA) Doppler pattern observed in the smaller twin: type I, when the UA Doppler is normal;type II, when there is persistent absent or reversed end-diastolic blood flow in the UA Doppler;and type III, when there is intermittent absent and/or reversed end-diastolic blood flow in the UA Doppler. Clinical evolution and management options mainly depend on the type of sFGR. Type I is usually associated with a good prognosis and is managed conservatively. There is no consensus on the management of types II and III, but in earlier and more severe presentations, fetal interventions such as selective laser photocoagulation of placental anastomoses or selective fetal cord occlusion of the smaller twin may be considered. This review aims to provide updated information about the diagnosis, evaluation, follow-up, and management of sFGR in MCDA twin pregnancies.

Complications of Monochorionic Diamniotic Twins: Stepwise Approach for Early Identification, Differential Diagnosis, and Clinical Management

One in three monochorionic twins may develop complications during pregnancy. Monochorionic twins, especially monochorionic diamniotic (MCDA), present specific problems caused by the presence of interfetal placental anastomoses. The first critical step in the management of MCDA twins is identification in the first trimester. Secondly, close follow-up every 2 weeks is mandatory to allow early diagnosis and timely treatment of twin-twin transfusion syndrome. Other potentially severe complications include selective fetal growth restriction, twin anemia polycythemia syndrome or single fetal death. Thirdly, a correct differential diagnosis is critical to establish the best therapy. This may represent a clinical challenge since MCDA twin complications often overlap. A simple diagnostic algorithm may be of great help to establish the right diagnosis and management option. In this review we summarize the main steps for the clinical follow-up, differential diagnosis, and targeted management of MCDA twins complications.

The Controversies and Challenges in the Management of Twin Pregnancy: From the Perspective of International Federation of Gynecology and Obstetrics Guidelines

The rate of multiple pregnancy is increasing, mainly because of the widespread use of assisted reproduction techniques and families’ desire for twins. Twin pregnancy accounts for a higher risk of chromosomal abnormalities, structural malformations, and neonatal adverse events than singleton pregnancy. The presence of artery-vein anastomoses, unbalanced placenta sharing, and abnormal cord insertion in monochorionic twins is associated with twin complications such as twin-to-twin transfusion syndrome, selective intrauterine growth restriction, and twin anemia polycythemia sequence. Although many guidelines and studies have established and improved the processes about the antenatal surveillance and management of twin pregnancy, they also raise more controversies and challenges. This review aims to highlight the international consensus on the antenatal care of twin pregnancies and analyze the controversies and predicaments based on the published International Federation of Gynecology and Obstetrics guidelines and research.