Outcome of prelabor rupture of membranes before or at the limit of viability: systematic review and meta-analysis.

OBJECTIVE: Counseling of pregnancies complicated by pre- and periviable premature rupture of membranes to reach shared decision-making is challenging, and the current limited evidence hampers the robustness of the information provided. This study aimed to elucidate the rate of obstetrical and neonatal outcomes after expectant management for premature rupture of membranes occurring before or at the limit of viability. DATA SOURCES: Medline, Embase, CINAHL, and Web of Science databases were searched electronically up to September 2023. STUDY ELIGIBILITY CRITERIA: Our study included both prospective and retrospective studies of singleton pregnancies with premature rupture of membranes before and at the limit of viability (ie, occurring between 14 0/7 and 24 6/7 weeks of gestation). METHODS: Quality assessment of the included studies was performed using the Newcastle-Ottawa Scale for cohort studies. Moreover, our study used meta-analyses of proportions to combine data and reported pooled proportions. Given the clinical heterogeneity, a random-effects model was used to compute the pooled data analyses. This study was registered with the International Prospective Register of Systematic Reviews database (registration number: CRD42022368029). RESULTS: The pooled proportion of termination of pregnancy was 32.3%. After the exclusion of cases of termination of pregnancy, the rate of spontaneous miscarriage or fetal demise was 20.1%, whereas the rate of live birth was 65.9%. The mean gestational age at delivery among the live-born cases was 27.3 weeks, and the mean latency between premature rupture of membranes and delivery was 39.4 days. The pooled proportion of cesarean deliveries was 47.9% of the live-born cases. Oligohydramnios occurred in 47.1% of cases. Chorioamnionitis occurred in 33.4% of cases, endometritis in 7.0%, placental abruption in 9.2%, and postpartum hemorrhage in 5.3%. Hysterectomy was necessary in 1.2% of cases. Maternal sepsis occurred in 1.5% of cases, whereas no maternal death was reported in the included studies. When focusing on neonatal outcomes, the mean birthweight was 1022.8 g in live-born cases. The neonatal intensive care unit admission rate was 86.3%, respiratory distress syndrome was diagnosed in 66.5% of cases, pulmonary hypoplasia or dysplasia was diagnosed in 24.0% of cases, and persistent pulmonary hypertension was diagnosed in 40.9% of cases. Of the surviving neonates, the other neonatal complications included necrotizing enterocolitis in 11.1%, retinopathy of prematurity in 27.1%, and intraventricular hemorrhage in 17.5%. Neonatal sepsis occurred in 30.2% of cases, and the overall neonatal mortality was 23.9%. The long-term follow-up at 2 to 4 years was normal in 74.1% of the available cases. CONCLUSION: Premature rupture of membranes before or at the limit of viability was associated with a great burden of both obstetrical and neonatal complications, with an impaired long-term follow-up at 2 to 4 years in almost 30% of cases, representing a clinical challenge for both counseling and management. Our data are useful when initially approaching such patients to offer the most comprehensive possible scenario on short- and long-term outcomes of this condition and to help parents in shared decision-making. El resumen está disponible en Español al final del artículo.

Hyperechogenic fetal bowel: Current evidence-based prenatal diagnosis and management.

Echogenic fetal bowel (EB) is a prenatal ultrasound finding (0.2%-1.4% of all pregnancies) defined as bowel of similar or greater echogenicity than surrounding bone. In fact, the ultrasound assessment is strongly subjective with inter-observer variability. The pathophysiology depends on the underlying condition, apparently related with meconium stasis and hypercellularity. It is often an isolated finding, with possible association with other structural anomalies. About the origin, it was observed in fetuses with cystic fibrosis, congenital infections, thalassemia, intraamniotic bleeding, fetal growth restriction. Fetuses with EB are at increased risk of adverse perinatal outcome, such as intrauterine growth restriction, placental dysfunction and perinatal death, highlighting the need for a thorough antenatal management and post-natal follow-up. It seems to be associated with a plenty of conditions, such as a poor fetal outcome, fetal growth restriction and placental dysfunction. Therefore management requires a multidisciplinary approach with different specialties' involvement and the prognosis is influenced by the underlying pathophysiology. In this complex scenario, the present review aims to define the clinical pathway which should be offered to pregnant women in case of finding of fetal EB ultrasound marker, to rule out any suspected pathological cause.

Severe maternal thrombocytopenia and prenatal invasive procedures: still a grey zone.

Management of severe thrombocytopenia, particularly of ITP, in pregnancy is mainly based on expert consensus and clinical experience while there are no clear indications about the minimum platelet count requested for prenatal diagnosis invasive procedures. Since the lack of specific recommendations we reported our clinical management of a patient suffering from severe thrombocytopenia, undergoing amniocentesis. Due to the anecdotic possibility of maternal and fetal bleeding in case of severe thrombocytopenia, prophylaxis with IVIG or even corticosteroids could be considered as a safer strategy to prevent post-procedural adverse outcomes.

Case Series of Acute Meconium Peritonitis Secondary to Perforation of the Ileum in the Antepartum Period.

Perforation of the ileum in the antepartum period resulting in meconial peritonitis is a condition that, although rare, is burdened by several complications. In 80-90% of cases, meconial ileus is the first manifestation of a disease, cystic fibrosis. In the remaining 10-20% of cases, it is caused by other situations, such as prematurity. In most cases, the diagnosis of meconial ileus occurs after birth, although in some cases it can be suspected prenatally, with the finding of a hyperechoic intestine on second trimester ultrasound. The prognosis depends on the gestational age, the location of the obstruction and the presence of fetal abnormalities. Mortality is very high and the recovery of intestinal function in the postoperative course is very high risk. In this case series, we describe two meconial peritonitis and our experience at the center.

Current protocols and clinical efficacy of human fetal liver cell therapy in patients with liver disease: A literature review.

The fetal liver is unique because of the coexistence of cells with endodermal and mesenchymal origins, making it a potential source of hepatic and pancreatic regenerative medicine. The liver appears at about the third week of gestation, growing rapidly from the fifth to the 10th week. We define fetal liver from 10 weeks of gestation, when hematopoietic progenitor cells gradually migrate from the aorta-mesonephros-gonad region to colonize the liver. Indeed, the fetal liver may be the most available source of cell therapy for liver disease. We conducted a review of the literature using Medline and EMBASE (up to May 2021) to identify clinical studies in which patients with liver disease had been given fetal liver cell therapy. This literature review highlighted the heterogeneity of cell isolation and selection protocols, which hinders the ability to pool data and perform a meta-analysis. A limitation of the studies analyzed was the scarcity of reports (n = 8) and the extremely small sample sizes (median sample size of treated patients was two), although there was a fairly long follow-up (median 12 months). The weeks after conception ranged from 16 to 34. There were no randomized controlled trials, and therefore no study was stratified as being of good methodological quality. Cryopreservation may help to circumvent the critical logistic issues that hamper the use of fetal liver cell therapy in clinical practice. To help consolidate the role of the fetal liver in regenerative medicine, good preclinical translational studies are necessary, whereas tracing strategies and biopsy-based endpoints are crucial in the clinic, along with well-designed, large, multicenter, randomized controlled trials using clinically applicable primary outcomes and refined imaging assessment.

Risk of neural tube defects according to maternal body mass index: a systematic review and meta-analysis.

INTRODUCTION: The aim of our systematic review and meta-analysis was to evaluate the risk of neural tube defects (NTDs) according to the pre-pregnancy body mass index. MATERIALS AND METHODS: Electronic databases were searched (MEDLINE, EMBASE, Web of Sciences, Scopus, ClinicalTrial.gov, OVID, and Cochrane Library). Selection criteria included prospective and retrospective cohort studies reporting the prevalence of fetal NTDs in obese, overweight, and underweight pregnant women. Odds ratios (ORs) comparing risk among these subsets of pregnancies with normal weight mothers were determined with 95% confidence intervals (CI). The evaluated outcome was the association between maternal underweight, overweight, and obesity and the risk of NTDs. RESULTS: We included ten studies published between 2000 and 2017, including underweight, overweight, and obese pregnant women with fetal NTD (cases) and pregnant women with recommended BMI with fetal NTD (controls). Compared with normal BMI women, obese mothers were at significantly higher risk of fetal NTDs (0.53 vs. 0.33%; OR 1.62 95% CI 1.32-1.99, p < .0001), while no difference for the risk of NTDs was found when comparing overweight (0.34 vs. 0.32%; OR 1.09 95% CI 0.92-1.3, p = .3) and underweight (0.65 vs. 0.24%; OR 1.34 95% CI 0.73-2.47, p = .34) with normal weight pregnant women. DISCUSSION: Obese pregnant women are at significantly higher risk NTDs, while no significant difference has been found in overweight and underweight pregnant women. Key message Obese pregnant women are at significantly higher risk of NTDs, such as spina bifida compared with normal weight women. No difference was found when comparing overweight and underweight with normal weight women.

Combined vesicouterine rupture during second-trimester medical abortion for fetal abnormality after prior cesarean delivery: A case report.

INTRODUCTION: The use of mifepristone and misoprostol for the induction of a second-trimester abortion is common and effective. However, its safety in women with previous cesarean delivery is still controversial, given the potentially higher risk of uterine rupture. CASE PRESENTATION: We present the case of a 30-year-old woman (G2P1) who experienced vesicouterine rupture with escape of the dead fetus into the bladder during second-trimester induced abortion after prior cesarean delivery. She was successfully managed with conservative surgery. CONCLUSION: This case highlights the challenges of early diagnosis of vesicouterine rupture during second-trimester medical abortion. We argue that a close monitoring of patients with prior cesarean section is mandatory, particularly if uterine contractions suddenly stop or the fetal head fails to descend. A prompt conservative surgical approach allows preservation of fertility.

Fetoscopic laser ablation in twin-to-twin transfusion syndrome: tips for counselling.

Twin-to-twin transfusion syndrome (TTTS) is a serious complication that affects approximately 10-15% of monochorionic twin pregnancies. The most important role for the development of this condition is the presence of an unbalanced flow through the inter-twin vascular anastomoses. Depending on the number, type and direction of the connecting vessels, blood can be transfused disproportionately from one twin (the donor) to the other twin (the recipient). The diagnosis is defined prenatally by ultrasound and involves of two main criteria: the presence of a monochorionic diamniotic (MCDA) pregnancy; and the presence of oligohydramnios in the donor's sac- deep vertical pocket (DVP) 2 cm - and polyhydramnios in the recipient's sac- DVP>8 cm. Once diagnosed, TTTS is usually graded by using the Quintero staging system, that is composed by five stages, from oligohydramnios in the donor and polyhydramnios in the recipient twin to fetal demise in one or both twins. Photocoagulation of the anastomotic vessels, usually followed by equatorial dichorionization, it has currently become the most common fetoscopic operation today and is considered as the gold standard for stage II-IV TTTS. pPROM, chorioamniotic separation and iatrogenic preterm birth are among the most common complications of fetoscopic laser ablation, and the mean gestational age at delivery after laser procedure is about 31 weeks.

When to test fetuses for RASopathies? Proposition from a systematic analysis of 352 multicenter cases and a postnatal cohort.

PURPOSE: Recent studies have identified suggestive prenatal features of RASopathies (e.g., increased nuchal translucency [NT], cystic hygroma [CH], hydrops, effusions, congenital heart diseases [CHD], polyhydramnios, renal anomalies). Our objective is to clarify indications for RASopathy prenatal testing. We compare genotype distributions between pre- and postnatal populations and propose genotype-phenotype correlations. METHODS: Three hundred fifty-two chromosomal microarray-negative cases sent for prenatal RASopathy testing between 2012 and 2019 were collected. For most, 11 RASopathy genes were tested. Postnatal cohorts (25 patients with available prenatal information and 108 institutional database genotypes) and the NSeuroNet database were used for genotypic comparisons. RESULTS: The overall diagnostic yield was 14% (50/352), with rates >20% for effusions, hydrops, and CHD. Diagnostic yield was significantly improved in presence of hypertrophic cardiomyopathy (HCM), persistent or associated CH, any suggestive finding combined with renal anomaly or polyhydramnios, or ≥2 ultrasound findings. Largest prenatal contributors of pathogenic variants were PTPN11 (30%), RIT1 (16%), RAF1 (14%), and HRAS (12%), which considerably differ from their prevalence in postnatal populations. HRAS, LZTR1, and RAF1 variants correlated with hydrops/effusions, and RIT1 with prenatal onset HCM. CONCLUSION: After normal chromosomal microarray, RASopathies should be considered when any ultrasound finding of lymphatic dysplasia or suggestive CHD is found alone or in association.

Adnexal masses in pregnancy: an updated review on diagnosis and treatment.

Adnexal masses are not common in pregnancy. They are often discovered incidentally during routine ultrasound examinations. In general, 24%-40% of the cases are benign tumors; up to 8% are malignant tumors. Adnexal masses are usually asymptomatic, but sometimes can be responsible for abdominal or pelvic pain. Transvaginal and transabdominal ultrasound is essential to define the morphology of pelvic masses and to distinguish between benign and malignant cases. Magnetic resonance imaging can be a complementary examination when ultrasound findings are equivocal and a useful additional examination to better define tissue planes and relations with other organs. Patient counseling can be challenging because there is no clear consensus on the management of adnexal masses during pregnancy. Treatment options consist of observational management (in case of asymptomatic women with reassuring instrumental findings) or surgery (via laparoscopy or laparotomy). Surgery can be offered as a primary tool when cancer is suspected or when acute complications such as ovarian torsion occur.

Obstetrical and perinatal outcomes in fetuses with early versus late sonographic diagnosis of short femur length: A single-center, prospective, cohort study.

OBJECTIVES: The aim of this study was to evaluate obstetrical and perinatal outcomes in fetuses with short femur length diagnosed before or after 24 weeks of gestation. STUDY DESIGN: This was a prospective cohort study on singleton pregnancies with a diagnosis of fetal femur < 5 centile. Included patients were divided into two groups: patients with a first diagnosis of femur length < 5th percentile at 14-24 weeks (group A) and those with the first diagnosis made at > 24 weeks (group B). RESULTS: 147 patients were included for the analysis. Group A and group B included 66 (44.9%) and 81 (55.1%) cases. Abnormal fetal karyotype and skeletal dysplasia rates were significantly higher (27.3% vs 3.7%,P < 0.001 and 19.7% vs 3.7%, P = 0.002) in group A. Women in group B had a higher incidence of small for gestational age and intrauterine growth restriction (7.6% vs 24.7%, P = 0.007 and 19.7% vs 44.4%, P = 0.002). There was a significant higher incidence of live births in group B (34.9% vs 97.5%, P < 0.001), while the rate of termination of pregnancy was increased in group A (56.1% vs 1.2%, P < 0.001). No significant difference was found in perinatal outcomes of live births, when comparing group A and B. CONCLUSIONS: The incidence of abnormal karyotype and skeletal dysplasia is higher when short femur length diagnosed earlier in gestation, while the incidence of small for gestational age, intrauterine growth restriction and the rate of live births are significantly increased when short femur length is diagnosed later during pregnancy.

Obstetrical outcomes in women with history of breast cancer: a systematic review and meta-analysis.

PURPOSE: Potential risk of adverse obstetrical outcomes has been shown among breast cancer survivors. Therefore, the aim of this systematic review and meta-analysis was to evaluate the relationship between history of breast cancer (BC) and obstetrical outcomes. METHODS: PubMed, EMBASE, and Medline were searched from the inception of each database to April 2019. Selection criteria included prospective and retrospective cohort studies of BC pregnant survivors. The meta-analysis was performed by computing odds ratios (ORs) using both fixed and random-effects models. Quality assessment of the included studies was performed using the Newcastle-Ottawa Scale and the review was registered with PROSPERO number CRD42019127716. RESULTS: Four studies, including 1466 cases of BC survivors and 6,912,485 controls, were included. Compared with controls, a higher incidence of obstetrical complication was found in women with history of BC. The incidence of preterm birth (PTB) in the study group was 11.05% compared with 7.79% in the control group (1.68, 95% confidence interval 1.43-1.99). Breast cancer history was also associated with low birth weight (LBW) (study group: 9.26% vs. control group: 5.54%, 1.88, CI 95% 1.55-2.27), cesarean section (CS) (study group: 19.76% vs. control group 10.81%, 1.78, CI 95% 1.39-2.27), intrauterine fetal death (IUFD) (study group: 0.004% vs. control group 0.36%, of 1.25 CI 95% 0.36-4.35), and fetal anomalies (study group: 5.8% vs. control group: 4.26%, 1.45 CI 95% 1.01-2.09). CONCLUSIONS: History of BC was associated with adverse obstetrical outcomes.

Functions and the Emerging Role of the Foetal Liver into Regenerative Medicine.

During foetal life, the liver plays the important roles of connection and transient hematopoietic function. Foetal liver cells develop in an environment called a hematopoietic stem cell niche composed of several cell types, where stem cells can proliferate and give rise to mature blood cells. Embryologically, at about the third week of gestation, the liver appears, and it grows rapidly from the fifth to 10th week under WNT/ß-Catenin signaling pathway stimulation, which induces hepatic progenitor cells proliferation and differentiation into hepatocytes. Development of new strategies and identification of new cell sources should represent the main aim in liver regenerative medicine and cell therapy. Cells isolated from organs with endodermal origin, like the liver, bile ducts, and pancreas, could be preferable cell sources. Furthermore, stem cells isolated from these organs could be more susceptible to differentiate into mature liver cells after transplantation with respect to stem cells isolated from organs or tissues with a different embryological origin. The foetal liver possesses unique features given the co-existence of cells having endodermal and mesenchymal origin, and it could be highly available source candidate for regenerative medicine in both the liver and pancreas. Taking into account these advantages, the foetal liver can be the highest potential and available cell source for cell therapy regarding liver diseases and diabetes.

Update in non-invasive prenatal testing.

Non-invasive prenatal testing (NIPT) has revolutionized the approach to prenatal diagnosis and, to date, it is the most superior screening method for the common autosomal aneuploidies, mostly trisomy 21. This screening is having a significant population-wide impact on the uptake of conventional screening and diagnostic testing. In recent years, emerging genomic technologies, largely based around next generation sequencing, have expanded the analyses to the sub-chromosomal aneuploidies. However, further clinical validation studies are needed to better characterize this technology. These tests bring advantage through providing a higher diagnostic yield, without risks of miscarriage than previously available diagnostic test, but also raise the question of harms related to an increase in uncertain and unknown results. In view of the revolution brought about by the NIPT, numerous scientific societies have published recommendations regarding the appropriate application of cell-free DNA screening in pregnancy. In this review, we discuss the progress that has been made to date in NIPT.

Midtrimester isolated short femur and perinatal outcomes: A systematic review and meta-analysis.

INTRODUCTION: Fetal femur length below the expected value has been described as a marker of aneuploidy, skeletal dysplasia, intrauterine growth restriction and small-for-gestational-age neonate. The aim of this systematic review and meta-analysis was to evaluate the strength of association between isolated short femur length and intrauterine growth restriction or small-for-gestational-age, and perinatal adverse outcomes. MATERIAL AND METHODS: PubMed, EMBASE and Medline were searched from the inception of each database to May 2018. Selection criteria included prospective and retrospective cohort studies of singleton pregnancies between 18 and 28 weeks of gestation, with sonographic finding of isolated short femur length, without any structural chromosomal abnormality. The meta-analysis was performed by computing odds ratios using both fixed and random-effects models. Quality assessment of the included studies was performed using the Newcastle-Ottawa Scale. RESULTS: Six studies including 3078 cases of isolated short femur length (study group) and 222 303 normal femur length (control group) were included. The prevalence of intrauterine growth restriction or small-for-gestational-age in the study group was 14.2%, compared with 5.2% in the control group (odds ratio of 4.04, 95% confidence interval 3.63-4.50). Isolated short femur length was associated with a higher incidence of low birthweight (study group: 22.10% vs control group: 8.57%, odds ratio 3.24, 95% confidence interval 2.34-4.48), Apgar <7 at 5 minutes (study group: 3.98% vs control group: 1.79%, odds ratio 3.56, 95% confidence interval 1.87-6.77), preterm birth (study group: 12.16% vs control group: 8.16%, odds ratio 3.09, 95% confidence interval 1.57-6.08), fetal death (study group: 1.83% vs control group: 0.44%, odds ratio 6.48, 95% confidence interval 3.70-11.35) and neonatal intensive care unit admission (study group: 15.34% vs control group: 14.81%, odds ratio 2.11, 95% confidence interval 0.56-7.93). CONCLUSIONS: There is a significant association between isolated short femur length and intrauterine growth restriction or small-for-gestational-age and poor perinatal outcome.

Pfeiffer syndrome: literature review of prenatal sonographic findings and genetic diagnosis.

PURPOSE: Pfeiffer syndrome (PS) is an autosomal dominant disorder caused by mutations in FGFR1 and FGFR2 genes. Given its wide range of clinical expression and severity, early prenatal diagnosis is difficult and genetic counseling is desirable. We report a literature review of all prenatal diagnosis of PS and a case report, with a focused description of ultrasound findings. METHODS: After literature search, we selected 14 studies of antenatal diagnosis of PS. Prenatal ultrasound findings, outcome, maternal and obstetrical data and genetic tests were recorded and analyzed. RESULTS: A total of 18 cases including the one we present were selected. Among the most frequent sonographic features, skull shape anomalies were evident in 72.2% of cases, nasal abnormalities in 50%, proptosis and hypertelorism in 44.4% and frontal bossing in 22.2%. Thumbs' anomalies were present in 33.3% of cases and toes' abnormalities in 38.9%. In all cases, postnatal or postmortem examination confirmed the prenatal diagnosis of PS. CONCLUSIONS: We provide a literature review of prenatal diagnosis of PS to identify ultrasound features that may be supportive in the diagnosis of this rare disease, helping in making a differential diagnosis with the other possible craniosynostosis syndromes and in suggesting gene molecular testing.

Prenatal diagnosis of proximal focal femoral deficiency: Literature review of prenatal sonographic findings.

Proximal focal femoral deficiency (PFFD) is a rare musculoskeletal malformation that occurs in 0.11-0.2 per 10,000 live births. This congenital anomaly involves the pelvis and proximal femur with widely variable manifestations, from mild femoral shortening and hypoplasia to the absence of any functional femur and acetabular aplasia. Prenatal diagnosis of PFFD is still a challenge, but early recognition of this malformation could provide useful information to both parents and physicians concerning management and therapeutic planning. For this review, we analyzed all the cases of prenatally diagnosed PFFD that were reported in the literature from 1990 to 2014 and provide a description of the most common prenatal sonographic findings.

Numerical model for RF capacitive regional deep hyperthermia in pelvic tumors.

A numerical model based on Finite Element Method (FEM) for the prediction of power density distribution and temperature during RF-capacitive hyperthermia treatment has been presented in the paper and the results are discussed. In particular the models are related to the treatment of pelvic tumors where it is more difficult to localize and focus heat in deep regions. The geometrical and physical model of the patient is reconstructed with a segmentation procedure by means of dedicated software. The geometrical meshed model has been used as input for the solution of coupled electromagnetic and thermal problems. A deep analysis of different configurations derived from specific scientific literature of the last years has been presented in the paper and discussed. The results obtained by FEM analyses have demonstrated the suitability of this method for the prediction of power and temperature distribution during RF capacitive hyperthermia and that the calculation procedure is an efficient mean to evaluate the efficacy of the heating system.