Mechanisms underlying the role of endoplasmic reticulum stress in the placental injury and fetal growth restriction in an ovine gestation model

Background Exposure to bisphenol A(BPA),an environmental pollutant known for its endocrine-disrupting properties,during gestation has been reported to increase the risk of fetal growth restriction(FGR)in an ovine model of pregnancy.We hypothesized that the FGR results from the BPA-induced insufficiency and barrier dysfunction of the placenta,oxidative stress,inflammatory responses,autophagy and endoplasmic reticulum stress(ERS).However,precise mechanisms underlying the BPA-induced placental dysfunction,and subsequently,FGR,as well as the potential involvement of placental ERS in these complications,remain to be investigated.Methods In vivo experiment,16 twin-pregnant(from d 40 to 130 of gestation)Hu ewes were randomly distributed into two groups(8 ewes each).One group served as a control and received corn oil once a day,whereas the other group received BPA(5 mg/kg/d as a subcutaneous injection).In vitro study,ovine trophoblast cells(OTCs)were exposed to 4 treatments,6 replicates each.The OTCs were treated with 400μmol/L BPA,400μmol/L BPA+0.5μg/m L tunicamycin(Tm;ERS activator),400μmol/L BPA+1μmol/L 4-phenyl butyric acid(4-PBA;ERS antagonist)and DMEM/F12 complete medium(control),for 24 h.Results In vivo experiments,pregnant Hu ewes receiving the BPA from 40 to 130 days of pregnancy experienced a decrease in placental efficiency,progesterone(P4)level and fetal weight,and an increase in placental estrogen(E2)level,together with barrier dysfunctions,OS,inflammatory responses,autophagy and ERS in type A cotyledons.In vitro experiment,the OTCs exposed to BPA for 24 h showed an increase in the E2 level and related protein and gene expressions of autophagy,ERS,pro-apoptosis and inflammatory response,and a decrease in the P4 level and the related protein and gene expressions of antioxidant,anti-apoptosis and barrier function.Moreover,treating the OTCs with Tm aggravated BPA-induced dysfunction of barrier and endocrine(the increased E2 level and decreased P4 level),OS,inflammatory responses,autophagy,and ERS.However,treating the OTCs with 4-PBA reversed the counteracted effects of Tm mentioned above.Conclusions In general,the results reveal that BPA exposure can cause ERS in the ovine placenta and OTCs,and ERS induction might aggravate BPA-induced dysfunction of the placental barrier and endocrine,OS,inflammatory responses,and autophagy.These data offer novel mechanistic insights into whether ERS is involved in BPA-mediated placental dysfunction and fetal development.

Associations of serum D-dimer and glycosylated hemoglobin levels with third-trimester fetal growth restriction in gestational diabetes mellitus

BACKGROUND Gestational diabetes mellitus(GDM)is a special type of diabetes that commonly occurs in women during pregnancy and involves impaired glucose tolerance and abnormal glucose metabolism;GDM is diagnosed for the first time during pregnancy and can affect fetal growth and development.AIM To investigate the associations of serum D-dimer(D-D)and glycosylated hemoglobin(HbA1c)levels with third-trimester fetal growth restriction(FGR)in GDM patients.METHODS The clinical data of 164 pregnant women who were diagnosed with GDM and delivered at the Obstetrics and Gynecology Hospital of Fudan University from January 2021 to January 2023 were analyzed retrospectively.Among these women,63 whose fetuses had FGR were included in the FGR group,and 101 women whose fetuses had normal body weights were included in the normal body weight group(normal group).Fasting venous blood samples were collected from the elbow at 28-30 wk gestation and 1-3 d before delivery to measure serum D-D and HbA1c levels for comparative analysis.The diagnostic value of serum D-D and HbA1c levels for FGR was evaluated by receiver operating characteristic analysis,and the influencing factors of third-trimester FGR in GDM patients were analyzed by logistic regression.RESULTS Serum fasting blood glucose,fasting insulin,D-D and HbA1c levels were significantly greater in the FGR group than in the normal group,while the homeostasis model assessment of insulin resistance values were lower(P<0.05).Regarding the diagnosis of FGR based on serum D-D and HbA1c levels,the areas under the curves(AUCs)were 0.826 and 0.848,the cutoff values were 3.04 mg/L and 5.80%,the sensitivities were 81.0%and 79.4%,and the specificities were 88.1%and 87.1%,respectively.The AUC of serum D-D plus HbA1c levels for diagnosing FGR was 0.928,and the sensitivity and specificity were 84.1%and 91.1%,respectively.High D-D and HbA1c levels were risk factors for third-trimester FGR in GDM patients(P<0.05).CONCLUSION D-D and HbA1c levels can indicate the occurrence of FGR in GDM patients in the third trimester of pregnancy to some extent,and their combination can be used as an important index for the early prediction of FGR.

Long-term implications of fetal growth restriction

Fetal growth restriction(FGR),or intrauterine growth restriction(IUGR),is a complication of pregnancy where the fetus does not achieve its genetic growth potential.FGR is characterized by a pathological retardation of intrauterine growth velocity in the curve of intrauterine growth.However,the FGR definition is still debated,and there is a lack of a uniform definition in the literature.True IUGR,compared to constitutional smallness,is a pathological condition in which the placenta fails to deliver an adequate supply of oxygen and nutrients to the developing fetus.Infants with IUGR,compared to appropriately grown gestational age infants,have a significantly higher risk of mortality and neonatal complications with long-term consequences.Several studies have demonstrated how suboptimal fetal growth leads to long-lasting physiological alterations for the developing fetus as well as for the newborn and adult in the future.The long-term effects of fetal growth retardation may be adaptations to poor oxygen and nutrient supply that are effective in the fetal period but deleterious in the long term through structural or functional alterations.Epidemiologic studies showed that FGR could be a contributing factor for adult chronic diseases including cardiovascular disease,metabolic syndrome,diabetes,respiratory diseases and impaired lung function,and chronic kidney disease.In this review we discussed pathophysiologic mechanisms of FGR-related complications and potential preventive measures for FGR.

Effect of Bushen Yiqi Huoxue Recipe on Placental Vasculature in Pregnant Rats with Fetal Growth Restriction Induced by Passive Smoking

Interactions of vascular endothelial growth factor （VEGF） with receptors VEGFR1/Fltl and VEGFR2/Flk1, and those of angiopoietins （Ang-1, Ang-2） with receptor Tie2 play important roles in placental angiogenesis. This study investigated vascular morphology and expression of these angiogenic factors in rat placenta on the day 15, 18, 21 of gestation （D 15, D 18 and D21）. The rats were randomly assigned into 3 groups： normal group, model group [fetal growth restriction （FGR） model], and Bushen Tqi Huoxue （BYHR） recipe treatment group （BYHR group, the pregnant rats with FGR were treated with BYHR recipe）. Morphological analysis indicated that during initial villous formation, fetal nucle- ated erythrocytes （FNEs） appeared in maternal blood sinus （MBS）. Subsequently, FNEs were sur- rounded by endothelial cells to form fetal capillary （FC） and then by trophoblast cells to form villi. As pregnancy proceeded, FC density increased progressively with increasing endothelial identification staining （EIS） in normal and BYHR groups. Whereas, villous formation was suppressed, normal in- crease in FC density was impaired and EIS was weakened in model group. Quantitative PCR analysis showed that VEGF and Flkl mRNA increased over gestation in all groups, indicating that VEGF might play a pivotal role in FC growth during late gestation. VEGF mRNA was increased on D15, while de- creased on D21 in model group as compared with normal group and BYHR group. Immunohistochemi- cally, Ang-2 protein was highly expressed in FNEs, gradually disappeared as villi matured, and decreased over gestation in all groups, indicating that Ang-2 might play a pivotal role in villous formation, which was further supported by decreased Ang-2 mRNA and protein expression in model group on D 15. Ang-1 mRNA, Tie2 mRNA and Ang-1/Ang-2 ratio increased from D15 to D18 in all groups as placenta matured. Ang-1 mRNA, Tie2 mRNA and Ang-1/Ang-2 ratio were decreased on D18 in model group as compared with normal and BYHR groups, indicating delayed maturity of FGR placenta. Alterations in angiogenic factors may result in altered placental vasculature and cause placental insufficiency. BYHR recipe could balance the angiogenic factors to promote the formation and maturation of FGR placental vasculature.

Concentrations of Polybrominated Diphenyl Ethers in Maternal Blood,Placental Size,and Risk for Fetal Growth Restriction:A Nested Case-control Study

Objective To explore the effects of prenatal exposure to polybrominated diphenyl ethers(PBDEs)on placental size and birth outcomes.Methods Based on the perspective Wenzhou Birth Cohort,this nested case-control study included 101 fetal growth restriction(FGR)and 101 healthy newborns.Maternal serum samples were collected during the third trimester and measured for PBDEs by gas chromatography tandem mass spectrometry.The basic information of mother-newborn pairs was collected from questionnaires,whereas the placental size and birth outcomes of newborns were obtained from hospital records.Results A total of 19 brominated diphenyle ether(BDE)congeners were detected in maternal serum samples.Higher concentrations of BDE-207,-208,-209,and∑19PBDEs were detected in FGR cases than in controls.Increased BDE-207,-208,-209,and∑19PBDEs levels in maternal serum were related to decreased placental length,breadth,surface area,birth weight,birth length,gestational age,and Quetelet index of newborns.After adjusting for confounders,BDE-207 and∑19PBDE concentrations in maternal serum were significantly associated with an increased risk of FGR.Conclusion A negative association was found between PBDE levels in maternal serum and placental size and birth outcomes.Prenatal PBDE exposure may be associated with elevated risk of the incidence of FGR birth.

Impairments of spatial learning and memory in rat offspring with fetal growth restriction

Objective： Throughout the world, fetal growth restriction（FGR） is one of the most severe complications occurring during pregnancy. It is subsequently associated with neurologic abnormalities in chldren. Our aim was to investigate the spatial learning and memory ability of rat offspring born With FGR. Methods：A rat model of FGR was constructed using the method of passive smoking. Spatial learning and memory were studied in rat offspring born with FGR by assessing the animals＇ performance using the Morris water maze task. Results： At 1- and 2- months of age, both female and male offspring rats showed impairment of performance, while at 4 months of age, only female rats showed impaired performance. The FGR offspring spent a longer time swimming and used inefficient strategies（P〈 0.05, respectively）. However, there were no significant maze performance FGR effects in the 4 month old male rats. In all groups of FGR offspring, irrespective of age or sex, the time spent in the platform quadrant by the rat was significantly less than that in the control group（P〈 0.05）. Conclusion： The Morris water maze performance decreased in rat offspring born with FGR. It is suggested that FGR can cause impairments of spatial learning and memory in young animals.

Fetal Growth Restriction: Mechanisms, Epidemiology, and Management

Fetal growth restriction(FGR)is the condition in which a fetus does not reach its intrinsic growth potential and in which the shortterm and long-term risks of severe complications are increased.FGR is a frequent complication of pregnancy with a complex etiology and limited management options,other than timely delivery.The most common pathophysiological mechanism is placental insufficiency,due to many underlying causes such as maternal vascular malperfusion,fetal vascular malperfusion and villitis.Identifying truly growth restricted fetuses remains challenging.To date,FGR is often defined by a cut-off of the estimated fetal weight below a certain percentile on a population-based standard.However,small fetal size as a single marker does not discriminate adequately between fetuses or newborns that are constitutionally small but healthy and fetuses or newborns that are growth restricted and thus at risk for adverse outcomes.In 2016,the consensus definition of FGR was internationally accepted to better pinpoint the FGR population.In this review we will discuss the contemporary diagnosis and management issues.Different diagnostic markers are considered,like Doppler measurements,estimated fetal growth,interval growth,fetal movements,biomarkers,and placental markers.

A Summary of Chinese Expert Consensus on Fetal Growth Restriction (An Update on the 2019 Version)

Fetal growth restriction(FGR)is a common complication of pregnancy associated with higher rates of perinatal mortality and morbidity,as well as a variety of long-term adverse outcomes.To standardize the clinical practice for the management of FGR in China,Fetal Medicine Subgroup,Chinese Society of Perinatal Medicine,Chinese Medical Association and Maternal-Fetal Medicine Committee,Chinese Society of Obstetrics and Gynecology,Chinese Medical Association organized an expert committee to provide official consensus-based recommendations on FGR.We evaluated the evidence provided by relevant high-quality literature,performed a three-round Delphi study and organized face-to-face meetings with experts from multidisciplinary backgrounds.The consensus includes the definition,prenatal screening,prevention,diagnosis,monitoring and management of FGR.

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.

The Update of Fetal Growth Restriction Associated with Biomarkers

Fetal growth restriction(FGR)has a prevalence of about 10%worldwide and is associated with an increased risk of perinatal mortality and morbidity.FGR is commonly caused by placental insufficiency and can begin early(<32 weeks)or in late(≥32 weeks)gestational age.A false positive antenatal diagnosis may lead to unnecessary monitoring and interventions,as well as cause maternal anxiety.Whereas a false negative diagnosis exposes the fetus to an increased risk of stillbirth and renders the pregnancy ineligible from the appropriate care and potential treatments.The clinical management of FGR pregnancies faces a complex challenge of deciding on the optimal timing of delivery as currently the main solution is to deliver the baby early,but iatrogenic preterm delivery of infants is associated with adverse short-and long-term outcomes.Early and accurate diagnosis of FGR could aid in better stratification of clinical management,and the development and implementation of treatment options,ultimately benefiting clinical care and potentially improving both short-and long-term health outcomes.The aim of this review is to present the new insights on biomarkers of placenta insufficiency,including their current and potential value of biomarkers in the prediction and prevention for FGR,and highlight the association between biomarkers and adverse outcomes in utero to explore the specific mechanism of impaired fetal growth that establish the basis for disease later in life.

Incidence and Clinical Features of Fetal Growth Restriction in 4 451 Women with Hypertensive Disorders of Pregnancy

Objective:To assess the clinical features of fetal growth restriction(FGR)in women with hypertensive disorders of pregnancy in China.Methods:This is a retrospective cohort study.The clinical data of 4451 women with hypertensive disorders of pregnancy were retrospectively collected from 11 tertiary hospitals across ten provinces in China during January 2015 to December 2015.The mean maternal age was(31.0±5.4)years old.Participants were divided into FGR group(n=670)and non-FGR group(n=3781).The incidence and clinical features of FGR,and its correlation with gestational age,previous FGR history,24-hour urinary protein excretion,and hemolysis,elevated liver enzyme and low platelet count(HELLP)syndrome were analyzed.Student’s t-test and Chi-square test were used when comparing clinical features between FGR and non-FGR groups.Results:The overall incidence of FGR was 15.1%(670/4451).The FGR incidence was 22.4%(433/1937)in women with severe preeclampsia and 18.6%(68/365)in women with chronic hypertension with superimposed preeclampsia,respectively.FGR was more prevalent in women who had preterm births than those who had term births(22.8%(432/1898)vs.9.3%(238/2553),P<0.001).It was also more prevalent in women with early-onset preeclampsia than those with late-onset preeclampsia(18.4%(189/1025)vs.14.0%(481/3426),P=0.001).Women with a previous FGR history had a significantly higher FGR incidence than those without an FGR history(66.7%(4/6)vs.15.7%(250/1596),P=0.007).The presence of abnormal results of the umbilical artery Doppler(13%(87/670)vs.2.4%(89/3781),P<0.001)and the middle cerebral artery Doppler(3.3%(22/670)vs.0.4%(15/3781),P<0.001)was higher in the FGR group compared with the non-FGR group,while the presence of increased uterine artery resistance was not statistically different(1.5%(10/670)vs.0.8%(29/3781),P=0.072).The FGR group delivered earlier than the non-FGR group((35.3±3.0)weeks vs.(36.4±4.3)weeks,P<0.001)with lower birth weight(1731.0±574.5)g vs.(2753.9±902.1)g,P<0.001,higher fetal or neonatal death(9.4%(63/670)vs.4.2%(157/3781),P<0.001),and higher cesarean section rate(82.5%(553/670)vs.70.2%(2656/3781),P<0.001).In the FGR group,more neonates had 5-minute Apgar score≤7(7.9%(53/670)vs.3.9%(149/3780),P<0.001),with higher neonatal intensive care unit admission rate(48.1%(322/670)vs.23.3%(881/3781),P<0.001).More cases of HELLP syndrome occurred in the FGR group(6.9%(46/670)vs.3.2%(122/3781),P<0.001).Women with FGR had heavier 24-hour urinary protein excretion than those without FGR((3.9±3.7)g vs.(3.1±4.2)g,P=0.005).Conclusion:In pregnancies with hypertensive disorders,increased risks of FGR are associated with preterm birth,birth before 34 weeks,and a previous FGR history.FGR is related to higher occurrence of abnormal uterine artery Doppler and umbilical artery Doppler.When hypertensive disorders is complicated by FGR,there appears to be higher maternal morbidity including higher rate of HELLP syndrome,cesarean section,and heavier proteinuria,as well as worse neonatal outcomes.

Association of an Increased Risk of Pre-eclampsia and Fetal Growth Restriction in Singleton and Twin Pregnancies with Female Fetuses

Objective: To investigate whether the fetal gender affects the incidence of pre-eclampsia (PE) and fetal growth restriction (FGR) in singleton and twin pregnancies.Methods: This was a 10-year single-center, retrospective, cohort study from January 2009 to January 2019. A total of 57,129 singleton and 3699 twin pregnancies aged between 18-55 years old were recruited at the Third Affiliated Hospital of Guangzhou Medical University, China. We used multivariable logistic regression to analyze the effect of fetal gender on the incidence of PE and FGR.Results: In singleton pregnancies, the incidence rates of PE and FGR with a female fetus were higher than those with a male fetus (6.4% (1713/26,793)vs. 5.9% (1803/30,336),P < 0.05 and 3.5% (932/26,793)vs. 2.4% (745/30,336),P < 0.05, respectively). A female fetus was an independent risk factor for either PE or FGR (adjusted odds ratio: 1.169 or 1.563;95% confidence interval: 1.036-1.319 or 1.349-1.810, respectively). In twin pregnancies, the incidence of early-onset PE was greater in pregnancies with two females compared with two males or one male plus one female (4.6% (46/1003)vs. 4.1% (54/1305)vs. 2.4% (33/1391),P < 0.05). Female-female twins was an independent risk factor for PE (adjusted odds ratio: 1.367, 95% confidence interval: 1.011-1.849), especially early-onset PE.Conclusion: The female fetus was associated with PE in both singleton and twin pregnancies and was also a risk factor of FGR in singleton pregnancies.

Genetics Etiologies Associated with Fetal Growth Restriction

Fetal growth restriction(FGR)is associated with multiple adverse perinatal outcomes,such as increased risk of intrauterine death,neonatal morbidity and mortality,and long-term adverse outcomes.Genetic etiological factors are critical in fetuses with intrauterine growth restriction,including chromosomal abnormalities,copy number variants,single gene disorders,uniparental disomy,epigenetic changes,and confined placental mosaicism.This paper aims to provide an overview of genetic defects related to FGR and to highlight the importance of prenatal genetic counseling and testing for precise diagnosis and management of FGR.

Expression of Lung Surfactant Proteins SP-B and SP-C and Their Modulating Factors in Fetal Lung of FGR Rats

This study investigated the expression of lung surfactant proteins SP-B and SP-C, and their modulating factors TTF-1 and PLAGL2 in the fetal lung of rats with fetal growth restriction（FGR）. The rat FGR model was established by prenatal hypoxia in the first stage of pregnancy, 180 rats for experiment served as hypoxia group, and 197 healthy rats served as normal control group. The FGR incidence in hypoxia was compared with that in normal control group. The histological changes in the fetal lung were observed under the light microscope and electronic microscope in two groups. The SP-B, SP-C, TTF-1 and PLAGL2 proteins were determined in the fetal lung of two groups immunohistochemically. The expression levels of SP-B, SP-C, TTF-1 and PLAGL2 protein and m RNA in the fetal lung of two groups were detected by using Western blotting and RT-PCR respectively. The FGR rat model was successfully established by using hypoxia. Pathologically the fetal lung developed slowly, and the expression levels of SP-B, SP-C, TTF-1 and PLAGL2 protein and mR NA in the fetal lung were significantly reduced in hypoxia group as compared with those in normal control group. It was suggested that maternal hypoxia in the first stage of pregnancy could induce FGR, and reduce the expression of SP-B and SP-C, resulting in the disorder of fetal lung development and maturation.

Helicobacter pylori infection in pregnant women:Gastrointestinal symptoms and pregnancy-related disorders

Helicobacter pylori(H.Pylori)is a gram-negative,flagellated and spiral-shaped bacterial pathogen that impacts approximately 46%among pregnant women globally and has been associated with various maternal-fetal complications.Iron deficiency anemia,fetal growth restriction,cardiovascular diseases,and insufficient nutrient absorption can be observed in pregnant women,as well as miscarriages and pregnancy-specific hypertensive disease,such as pre-eclampsia.Thus,the evidence supports the influence of H.pylori infection on fetal implantation/placentation failure,and positive strains of the cytotoxin-associated gene A of H.Pylori were reported as the most prevalent in these conditions.However,current knowledge indicates a relationship between this infection and the occurrence of hyperemesis gravidarum,characterized by frequent nausea and vomiting.Regarding the diagnosis of this bacterial infection,non-invasive approaches such as stool antigen test,urea breath test,and serological tests are more accepted during pregnancy,as they are easy to carry out and cost-effective.Finally,the bacteria eradication therapy should consider the risks and benefits for the pregnant woman and her child,with pharmacological intervention depending on the clinical presentation.

Multiple Sclerosis in Pregnancy—A Practical Guide for the Obstetrician

Technological advances, a deeper understanding of disease processes and increased sophistication of therapeutic methods have all led to better outcomes in rare diseases which previously had devastating effects on many women’s lives. The inevitable result of this progress is that women, who in the past did not contemplate pregnancy because of significant morbidity, now get to adulthood and are reasonably “disease free” enough to have their own families. The ever expanding, but relatively new specialty of Obstetric medicine seeks to further improve the outcome in pregnant women with intercurrent disease by enhancing the literature base, thereby contributing to the creation of appropriate guidance in the management of these patients. This article is a brief but useful guide for the busy obstetrician who may have limited experience in dealing with multiple sclerosis in pregnant women.

Effectiveness of Scutellaria baicalensis Georgi root in pregnancy-related diseases:A review

The root of Scutellaria baicalensis Georgi,also called Huangqin,is frequently used in traditional Chinese medicine.In ancient China,S.baicalensis root was used to clear heat,protect the fetus,and avoid a miscarriage for thousands of years.In modern times,pregnancy-related diseases can seriously affect maternal and fetal health,but few systematic studies have explored the mechanisms and potential targets of S.baicalensis root in the treatment of pregnancy-related diseases.Flavonoids(baicalein,wogonin and oroxylin A)and flavonoid glycosides(baicalin and wogonoside)are the main chemical components in the root of S.baicalensis.This study presents the current understanding of the major chemical components in the root of S.baicalensis,focusing on their traditional uses,potential therapeutic effects and ethnopharmacological relevance to pregnancy-related disorders.The mechanisms,potential targets and experimental models of S.baicalensis root for ameliorating pregnancy-related diseases,such as recurrent spontaneous abortion,preeclampsia,preterm birth,fetal growth restriction and gestational diabetes mellitus,are highlighted.

The Application of Aspirin in Pregnancy-Related Complications

Aspirin,one of the most widely applied medicines,not only possesses the effects on reducing fever,anti-vascular hyperplasia,and anti-inflammation,but also has the capacity of preventing platelet aggregation.So far,it is acceptable to adopt aspirin,especially low-dose aspirin(LDA),to prevent pregnancy-related complications,such as pregnancy complicated by antiphospholipid syndrome,systemic lupus erythematosus,or preeclampsia;unexplained recurrent spontaneous abortion;fetal growth restriction;and preterm birth.In this article,we reviewed the possible mechanism of action and applications of aspirin in these pregnancy-related complications.

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.

Preventing Stillbirth:A Review of Screening and Prevention Strategies

Stillbirth is a devastating pregnancy complication that still affects many women,particularly from low and middle-income countries.It is often labeled as“unexplained”and therefore unpreventable,despite the knowledge that placental dysfunction has been identified as a leading cause of antepartum stillbirth.Currently,screening for pregnancies at high-risk for placental dysfunction relies on checklists of maternal risk factors and serial measurement of symphyseal-fundal height to identify small for gestational age fetuses.More recently,the first-trimester combined screening algorithm developed by the Fetal Medicine Foundation has emerged as a better tool to predict and prevent early-onset placental dysfunction and its main outcomes of preterm preeclampsia,fetal growth restriction and stillbirth by the appropriate use of Aspirin therapy,serial growth scans and induction of labour from 40 weeks for women identified at high-risk by such screening.There is currently no equivalent to predict and prevent late-onset placental dysfunction,although algorithms combining an ultrasound-based estimation of fetal weight,assessment of maternal and fetal Doppler indices,and maternal serum biomarkers show promise as emerging new screening tools to optimize pregnancy monitoring and timing of delivery to prevent stillbirth.In this review we discuss the strategies to predict and prevent stillbirths based on firsttrimester screening as well as fetal growth and wellbeing assessment in the second and third trimesters.