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.

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.

Echocardiographic features and outcome of restrictive foramen ovale in fetuses with and without cardiac malformations: Literature review.

Foramen ovale is a small communication between the left and the right atrium and its restriction is a rare congenital heart anomaly. There is no consensus on diagnosis and management of fetal restrictive foramen ovale (RFO). In our paper we included 11 studies about fetuses affected by isolated RFO, RFO with D-Transposition of the Great Arteries (dTGA) and RFO with hypoplastic left heart syndrome (HLHS). While fetuses affected from HLHS and dTGA with RFO have a poor prognosis, premature RFO in an otherwise structurally normal heart, if found in later gestation, have an overall good outcome.

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.

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.

Pregnant women's knowledge and behaviour to prevent cytomegalovirus infection: an observational study.

OBJECTIVES: Congenital cytomegalovirus (cCMV) infection can negatively affect pregnancy outcomes, but may be prevented by simple precautions. Literature suggests that gynaecologists do not always adequately inform about preventive behaviour and most pregnant women have a low-level knowledge regarding cCMV infection. The aim of this study is to evaluate knowledge and risk behaviours related to cCMV infection in an unselected group of pregnant women. METHODS: An institutional based cross-sectional study was conducted in three Maternal and Fetal Divisions in Rome between November and February 2019 on 296 pregnant women, their knowledge on cCMV was measured using six cytomegalovirus (CMV) related questions. RESULTS: Out of the 296 respondents, 59.1% had heard, read or seen information about cCMV infection. Regarding the way of transmission, 96/296 (32.4%) correctly recognize children as a potential source of the infection but only 25/296 (8.44%) knew all prevention practices, 28/296 (9.5%) of women reported that they have never performed cCMV test during pregnancy. CONCLUSIONS: The results of this survey show that knowledge on cCMV infection among pregnant women is poor. This highlights the need to improve counselling on all preventive practices for cCMV infection during perinatal care consultation.

Hypoplasia of the Corpus Callosum: A Single Center Experience and a Concise Literature Review.

AimCorpus callosum hypoplasia is described as a fully formed corpus callosum with reduced thickness. Our purpose is to evaluate the current knowledge about this anomaly including it's effect on the neurodevelopmental outcome and to report our single center experience. Methods: PubMed, Medline and reference lists were searched using combinations of these terms: "Hypoplasia of corpus callosum and prenatal diagnosis" and "neurodevelopmental outcome". Results: Eleven studies were included, with a final population of 48 patients (45 cases from literature plus 3 of our own cases). Hypoplasia of the corpus callosum was detected by ultrasound scan alone in 77% of cases: magnetic resonance confirmed the ultrasound suspicion in the remaining 23% of cases. Isolated form was detected in 31% cases. Adverse fetal outcomes occurred in 62% of cases, while 38% of cases were born alive. The neurodevelopmental outcome was found to be normal in 33% of cases. Conclusion: Antenatal detection of corpus callosum hypoplasia remains challenging. Counseling is difficult because neurodevelopmental outcomes are variable.

An observational study to assess Italian obstetrics providers' knowledge about preventive practices and diagnosis of congenital cytomegalovirus.

OBJECTIVES: Congenital cytomegalovirus (cCMV) infection can be easily prevented by hygienic measures. Up to date the majority of the studies in literature highlighted a reduction in cCMV antenatal counseling and its prevention. Our purpose was to evaluate obstetrics providers' knowledge about cCMV infection, management and the behavioral practices to avoid it. METHODS: This is a cross-sectional survey carried out in Umberto I Hospital, "Sapienza" University of Rome between November 2019 and January 2020. We recruited 148 specialists and residents in Obstetrics and Gynecology through online anonymous multiple-choice 13-questions, 10 min-survey comparing responses between the two groups. RESULTS: A total of 94.6% of all participants said they always prescribe cytomegalovirus (CMV) serum screening: 73.6% of them regularly counsel about preventive practices, with specialists recording higher percentages (85.4 vs. 65.1%, p<0.005). We identified a good knowledge about the diagnostic pathway, but only 58.1% of our population knows the correct time of late amniocentesis. 12.2% of providers do not consider magnetic resonance (MRI) as a complementary exam. CONCLUSIONS: Prevention of maternal seroconversion is crucial: even if our data show an acceptable knowledge about antenatal counseling, we encourage clinicians to firmly inform and educate women about behavioral measures.

Fetal tongue posture associated with micrognathia: An ultrasound marker of cleft secondary palate?

Cleft lip and cleft palate (CP) are the most common facial malformations. Two-dimensional (2D) ultrasound (US) is the first-line examination in the prenatal diagnosis of CP. Three-dimensional, four-dimensional US and MRI provide a better detection of facial clefts. We present two fetuses with micrognathia and suspected secondary CP on 2D US: fetal tongue appeared in an unusual position (low tip and high dorsum position) and showed uncoordinated movements. MRI did not confirm the US suspicion, but at birth the two fetuses were affected by Pierre Robin sequence.

Clinical and functional characterization of a novel RASopathy-causing SHOC2 mutation associated with prenatal-onset hypertrophic cardiomyopathy.

SHOC2 is a scaffold protein mediating RAS-promoted activation of mitogen-activated protein kinase (MAPK) signaling in response to extracellular stimuli. A recurrent activating mutation in SHOC2 (p.Ser2Gly) causes Mazzanti syndrome, a RASopathy characterized by features resembling Noonan syndrome and distinctive ectodermal abnormalities. A second mutation (p.Met173Ile) supposed to cause loss-of-function was more recently identified in two individuals with milder phenotypes. Here, we report on the third RASopathy-causing SHOC2 mutation (c.807_808delinsTT, p.Gln269_His270delinsHisTyr), which was found associated with prenatal-onset hypertrophic cardiomyopathy. Structural analyses indicated a possible impact of the mutation on the relative orientation of the two SHOC2's leucine-rich repeat domains. Functional studies provided evidence of its activating role, revealing enhanced binding of the mutant protein to MRAS and PPP1CB, and increased signaling through the MAPK cascade. Differing from SHOC2 S2G , SHOC2 Q269_H270delinsHY is not constitutively targeted to the plasma membrane. These data document that diverse mechanisms in SHOC2 functional dysregulation converge toward MAPK signaling upregulation.

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.

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.

Congenital jugular vein phlebectasia or aneurysma: A rare entity in prenatal diagnosis.

Vascular malformations arising from the wall of the external jugular vein are rare and appeared most commonly in pediatric population. Here, we present a case of vascular malformation in the left external jugular vein diagnosed in a fetus during third trimester ultrasound. This is the first described case in prenatal diagnosis.

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.

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.

Use of non-steroidal anti-inflammatory drugs in pregnancy and oligohydramnios: a review.

OBJECTIVE: The aim of this review is to evaluate the relationship between the use of non-steroidal anti-inflammatory drugs (NSAIDs) during last trimesters of the pregnancy and the reduction of amniotic fluid. METHODS: Electronic databases were searched (PubMed, Medline, and Scopus). Selection criteria included studies reporting the relationship between oligohydramnios and use of NSAID during pregnancy. We analyzed the median age of women, weeks of pregnancy at the beginning of the drug administration, kind of medication, period of exposure and dosage, deepest vertical pocket (DVP), and amniotic fluid index (AFI). RESULTS: Of the 68 records identified, we analyzed 29 studies investigating the administration of NSAIDs, including 11 studies examined the administration of the Indomethacin, four articles have focused on the use of Nimesulide, and only two manuscripts considered the use of Diclofenac. We found a strict correlation between the development of oligohydramnios and the use of NSAIDs. The oligohydramnios is reversible, and the normal amount of amniotic fluid is restored after the interruption of the treatment. CONCLUSIONS: The use of NSAIDs should be considered when maternal benefits outweigh the potential fetal risk, at the lowest effective dose for shortest duration. Beyond 48 h of NSAIDs treatment, we consider ultrasound monitoring of amniotic fluid, and we suggest stopping therapy if a decline AFI is present.

Removal versus retention of cervical cerclage with preterm prelabor rupture of membranes: Systematic review and meta-analysis.

OBJECTIVE: To evaluate maternal and perinatal outcomes of removal versus retention of cervical cerclage after premature preterm rupture of membranes (pPROM). STUDY DESIGN: Medline, Embase and Cochrane databases were searched electronically on February 2023 utilizing combinations of the relevant medical subject heading (MeSH) terms, keywords, and word variants that were considered suitable for the topic. Either prospective or retrospective trials were considered suitable for the inclusion. The coprimary outcome of this study were pregnancy latency >7 days from pPROM and pregnancy latency >48 h from pPROM. Random effect head to-head meta-analyses were performed to directly compare each outcome, expressing the results as summary odds ratio (OR) for dichotomous outcomes and as mean difference (MD) for continuous outcomes, plus relative 95% confidence interval (CI). Quality assessment of the included studies was performed using the Newcastle-Ottawa Scale. RESULTS: Six studies involving a total of 377 women (169 in the "removal" and 208 in the "retention" group) were included. The rate of pregnancy prolongation >48 h was significantly lower in the removal compared to retention group (OR 0.15, 95% CI 0.07-0.31; p < 0.0001), as well as the rate of pregnancy prolongation >7 days (OR 0.30 95% CI 0.11-0.83; p = 0.02) and pregnancy latency expressed in days (MD -2.84 days, 95% CI -5.40 to -0.29; p = 0.03). The rate of chorioamnionitis was significantly lower in the removal compared to the retention group (OR 0.57 95% CI 0.34-0.96p = 0.03) as was the rate of Apgar score < 7 at 5 min (OR 0.22 95% CI 0.08-0.56; p = 0.002). There was no difference between removal and retention groups for all the other maternal and perinatal outcomes. CONCLUSIONS: The decision whether to remove or retain cerclage in case of pPROM should balance the prematurity-related risks with that of infectious complications, thus highlighting the need for tailored management based on gestational age at occurrence of pPROM.

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.