Vasa previa: prenatal diagnosis and management

PURPOSE AND VIEW: Vasa previa is a rare disorder of placentation associated with a high rate of perinatal morbidity and mortality when undetected before delivery. We have evaluated the recent evidence for prenatal diagnosis and management of vasa previa. RECENT FINDINGS: Around 85% of cases of vasa previa have one or more identifiable risk factors including in-vitro fertilization, multiple gestations, bilobed, succenturiate or low-lying placentas, and velamentous cord insertion. The development of standardized prenatal targeted scanning protocols may improve perinatal outcomes. There is no clear consensus on the optimal surveillance strategy including the need for hospitalization, timing of corticosteroids administration and the value of transvaginal cervical length measurements. Outpatient management is possible if there is no evidence of cervical shortening on ultrasound and there are no symptoms of bleeding or uterine contractions. Recent national guidelines and expert reviews have recommended scheduled cesarean section of all asymptomatic women presenting with vasa previa between 34 and 36 weeks’ gestation. SUMMARY: Prenatal diagnosis of vasa previa is pivotal to prevent intrapartum fetal death. Although there is insufficient evidence to support the universal mid-gestation ultrasound screening for vasa previa, recent evidence indicates the need for standardized prenatal targeted screening protocols of pregnancies at high-risk of vasa previa

Prenatal diagnosis and management of vasa previa in twin pregnancies: a case series and systematic review

BACKGROUND: Twin pregnancies are at higher risks of velamentous cord insertion and vasa previa. In vitro fertilization is an additional risk factor of abnormal cord insertion and thus the incidence of vasa previa is likely to increase over the next decades. OBJECTIVE: We sought to evaluate the role of ultrasound imaging in optimizing the management of twins diagnosed with vasa previa antenatally. STUDY DESIGN: We searched our database for twin pregnancies diagnosed with vasa previa and managed antenatally using measurements of cervical length and performed a systematic review of articles that correlated prenatal diagnosis of vasa previa in twins and pregnancy outcome. PubMed and MEDLINE were searched for studies published from 1987 through October 20, 2016, using specific medical subject heading terms, key words, and their combination. The primary eligibility criteria were articles that correlated prenatal ultrasound imaging of vasa previa and pregnancy outcome in twins. The secondary eligibility criteria was the use of cervical length in the management of twin pregnancies diagnosed antenatally with vasa previa. Two authors independently assessed inclusion criteria, data extraction, and analysis. The final selection included 3 case report series, 9 retrospective cohort studies, and 1 retrospective case-control study of vasa previa diagnosed prenatally and confirmed at birth in twin pregnancies. RESULTS: The search of our databases identified 6 cases of dichorionic-diamniotic twins and 1 case of monochorionic-diamniotic twins diagnosed prenatally with vasa previa between 22-29 weeks and managed using cervical length. Two cases were delivered by emergency because of rapid changes in cervical length in one and bleeding on placenta previa in the other at 33 and 30 weeks, respectively. The systematic review identified data on 56 cases. The incidence of twin pregnancies diagnosed antenatally with vasa previa in the cohort and case-control studies was 11.0%. Data on chorionicity were available in only 34 cases and cervical length measurements were used by only the authors of 2 case reports and 4 cohort studies. Velamentous cord insertion was the most common additional ultrasound findings in twins presenting with vasa previa in both our series and the systematic review. CONCLUSION: Vasa previa is associated with specific prenatal and obstetric complications with different outcomes in singletons compared to twins. Data on the diagnosis and management of vasa previa in twin pregnancies are limited but there is enough evidence to warrant guidelines for targeted screening. To enable the development of efficient management protocols tailored to the need of individual cases, future studies of the screening, diagnosis, and management of vasa previa should be prospective and multicentric with detailed data on twins including chorionicity and use of cervical length

Prospective Evaluation of the Ultrasound Signs Proposed for the Description of Uterine Niche in Nonpregnant Women

OBJECTIVES: To evaluate the new ultrasound-based signs for the diagnosis of post-cesarean section uterine niche in nonpregnant women. METHODS: We investigated prospectively a cohort of 160 consecutive women with one previous term cesarean delivery (CD) between December 2019 and 2020. All women were separated into two subgroups according to different stages of labor at the time of their CD: subgroup A (n = 109; 68.1%) for elective CD and CD performed in latent labor at a cervical dilatation (≤4 cm) and subgroup B (n = 51; 31.9%); for CD performed during the active stage of labor (>4 cm). RESULTS: Overall, the incidence of a uterine niche was significantly (P  3 mm in subgroup A than in subgroup B and a significant negative relationship was found between the RMT and the cervical dilatation at CD (r = -0.22; P = .008). CONCLUSIONS: Sonographic cesarean section scar assessment indicates that the type of CD and the stage of labor at which the hysterotomy is performed have an impact on the location of the scar and the scarification process including the niche formation and RMT

Comparison between a prenatal sonographic scoring system and a clinical grading at delivery for Placenta Accreta Spectrum disorders

OBJECTIVE: Placenta Accreta Spectrum (PAS) disorders have become a major iatrogenic obstetric complication worldwide. Data on the accuracy of ultrasound examination diagnosis are limited by incomplete confirmation and variability in the description of the different grades of PAS at delivery. The aim of this study was to compare our prenatal routine sonographic screening and diagnostic scoring system with a standardized clinical grading system at birth in patient at risk of PAS. STUDY DESIGN: This is a retrospective cohort study of 607 pregnant patients with at least one prior cesarean delivery between December 2013 and December 2018. All patients were assessed for PAS using our institutional prenatal sonographic scoring system and the corresponding ultrasound findings were compared with those of a standardized clinical intra-operative macroscopic grading system of the degree of accreta placentation at vaginal birth or laparotomy. RESULTS: PAS was diagnosed clinically at birth in 50 (8.2%) cases, 17 of which were confirmed by histopathology. A low (score ≤ 5), medium (score 6-7), high (score ≥ 8) probability for PAS was reported in 502, 61 and 44 cases, respectively. The probability score increased significantly (p < .001) in women ≥2 prior cesarean deliveries, with an anterior low-lying/placenta previa, with absent clear space, increased in retroplacental vascularity and with the size and numbers of lacunae. The number of cases classified clinically as grade 1 (non-PAS) and 3 (adherent PAS) was significantly (p < .001) lower in women with a high probability score whereas the rates of the other grades was significantly (p < .001) higher. The widest discrepancy between ultrasound probability score and clinical grade was found for grade 2 which, describes a partial placental adherence and grades 4 and 5 which, refer to placental percreta which describes tissue having invade trough the uterine serosa and beyond. CONCLUSIONS: Both ends of the spectrum of accreta placentation remain difficult to diagnose antenatal and clinically at birth, in particular when no histopathologic confirmation is available. There is a need to develop ultrasound accuracy score systems that can differentiate between the different grades of PAS and which are validated by standardized clinical and pathology protocols

Second-trimester levels of fetoplacental hormones among women with placenta accreta spectrum disorders

Maternal serum human chorionic gonadotropin could be a useful biomarker in the prenatal diagnosis of placenta accreta spectrum disorders

Evaluation of the impact of vasa previa on feto-placental hormonal synthesis and fetal growth

Introduction A vasa previa (VP) refers to aberrant chorionic vessels which can either connect the chorionic plate to a velamentous cord (type I) or a succenturiate or accessory lobe to the main placental mass (type II). Methods We performed retrospective cohort study of 32 singleton pregnancies diagnosed with VP. The levels of maternal serum alpha-fetoprotein (AFP), human chorionic gonadotropin (hCG) and unconjugated estriol (uE3) were measured at 15–18 weeks as part of the triple test screening for Trisomy 21. The data were subdivided according to the type of VP and compared with those of a control group with central cord insertion and no succenturiate or accessory placental lobe. Results Twenty one (65.6%) parturient women presented with VP type I and 11 (34.4%) with VP type II. The mean birthweight and placental weight was significantly higher in pregnancies with VP type II than in pregnancies with VP with VP type I (3037.3 ± 400.9 gr vs 2493.5 ± 491.6 gr; p = 0.004 and 511.0 ± 47.2 gr vs 367.1 ± 64.3 gr; p < 0.0001; respectively). The mean hCG level in VP type II was significantly (p < 0.001) higher than those with type I (2.38 MoM vs 1.17 MoM) and compared to controls (2.38 MoM vs 0.99 MoM). Conclusions There is no obvious impact on both placental and fetal growth in VP type II. By contrast, VP type I is associated with slower feto-placental growth secondary to impaired development and biological functions of the placenta during the first half of pregnancy

Impact of targeted scanning protocols on perinatal outcomes in pregnancies at risk of placenta accreta spectrum or vasa previa

Background Placenta accreta spectrum and vasa previa (VP) are congenital disorders of placentation associated with high morbidity and mortality for both mothers and newborns when undiagnosed before delivery. Prenatal diagnosis of these conditions is essential to allow multidisciplinary management and thus improve perinatal outcomes. Objective The objective of the study was to compare perinatal outcome in women with placenta accreta spectrum or vasa previa before and after implementation of targeted scanning protocols. Study Design This retrospective study included 2 nonconcurrent cohorts for each condition before and after implementation of the corresponding protocols (2004–1012 vs 2013–2016 for placenta accreta spectrum and 1988–2007 vs 2008–2016 for vasa previa). Clinical reports of women diagnosed with placenta accreta spectrum and vasa previa during the study periods were reviewed and outcomes were compared. Results In total, there were 97 cases of placenta accreta spectrum and 51 cases with vasa previa, all confirmed at delivery. In both cohorts, the prenatal detection rate increased after implementation of the scanning protocols (28 of 65 cases [43.1%] vs 31 of 32 cases [96.9%], P < .001, for placenta accreta spectrum and 9 of 18 cases [50%] vs 29 of 33 cases [87.9%], 87.9%, P < .01 for vasa previa). The perinatal outcome improved also significantly in both cohorts after implementation of the protocols. In the placenta accreta spectrum cohort, the estimated blood loss and the postoperative hospitalization stay decreased between periods (1520 ± 845 vs 1168 ± 707 mL, P < .01, and 10.9 ± 14.1 vs 5.7 ± 2.2 days, P < .05, respectively). In the vasa previa cohort, the number of 5 minute Apgar score ≤5 and umbilical cord pH <7 decreased between periods (5 of 18 cases [27.8%] vs 1 of 33 cases [3%]; P < .05, and 4 of 18 cases [22.2%] vs 1 of 33 cases [3%], P < .05, respectively). Conclusion The implementation of standardized prenatal targeted scanning protocols for pregnant women with risk factors for placenta accreta spectrum and vasa previa was associated with improved maternal and neonatal outcomes. The continuous increases in the rates of caesarean deliveries and use of assisted reproductive technology highlights the need to develop training programs and introduce targeted scanning protocols at the national and international levels

Nicotinamide Protects against Ethanol-Induced Apoptotic Neurodegeneration in the Developing Mouse Brain

BACKGROUND: Exposure to alcohol during brain development may cause a neurological syndrome called fetal alcohol syndrome (FAS). Ethanol induces apoptotic neuronal death at specific developmental stages, particularly during the brain-growth spurt, which occurs from the beginning of third trimester of gestation and continues for several years after birth in humans, whilst occuring in the first two postnatal weeks in mice. Administration of a single dose of ethanol in 7-d postnatal (P7) mice triggers activation of caspase-3 and widespread apoptotic neuronal death in the forebrain, providing a possible explanation for the microencephaly observed in human FAS. The present study was aimed at determining whether nicotinamide may prevent ethanol-induced neurodegeneration. METHODS AND FINDINGS: P7 mice were treated with a single dose of ethanol (5g/kg), and nicotinamide was administered from 0 h to 8 h after ethanol exposure. The effects of nicotinamide on ethanol-induced activation of caspase-3 and release of cytochrome-c from the mitochondria were analyzed by Western blot ( n = 4–7/group). Density of Fluoro-Jade B–positive cells and NeuN-positive cells was determined in the cingulated cortex, CA1 region of the hippocampus, and lateral dorsal nucleus of the thalamus ( n = 5–6/group). Open field, plus maze, and fear conditioning tests were used to study the behavior in adult mice ( n = 31–34/group). Nicotinamide reduced the activation of caspase-3 (85.14 ± 4.1%) and the release of cytochrome-c (80.78 ± 4.39%) in postnatal mouse forebrain, too. Nicotinamide prevented also the ethanol-induced increase of apoptosis. We demonstrated that ethanol-exposed mice showed impaired performance in the fear conditioning test and increased activity in the open field and in the plus maze. Administration of nicotinamide prevented all these behavioral abnormalities in ethanol-exposed mice. CONCLUSIONS: Our findings indicate that nicotinamide can prevent some of the deleterious effects of ethanol on the developing mouse brain when given shortly after ethanol exposure. These results suggest that nicotinamide, which has been used in humans for the treatment of diabetes and bullous pemphigoid, may hold promise as a preventive therapy of FAS

Discordant Gene Expression Signatures and Related Phenotypic Differences in Lamin A- and A/C-Related Hutchinson-Gilford Progeria Syndrome (HGPS)

Hutchinson-Gilford progeria syndrome (HGPS) is a genetic disorder displaying features reminiscent of premature senescence caused by germline mutations in the LMNA gene encoding lamin A and C, essential components of the nuclear lamina. By studying a family with homozygous LMNA mutation (K542N), we showed that HGPS can also be caused by mutations affecting both isoforms, lamin A and C. Here, we aimed to elucidate the molecular mechanisms underlying the pathogenesis in both, lamin A- (sporadic) and lamin A and C-related (hereditary) HGPS. For this, we performed detailed molecular studies on primary fibroblasts of hetero- and homozygous LMNA K542N mutation carriers, accompanied with clinical examinations related to the molecular findings. By assessing global gene expression we found substantial overlap in altered transcription profiles (13.7%; 90/657) in sporadic and hereditary HGPS, with 83.3% (75/90) concordant and 16.7% (15/90) discordant transcriptional changes. Among the concordant ones we observed down-regulation of TWIST2, whose inactivation in mice and humans leads to loss of subcutaneous fat and dermal appendages, and loss of expression in dermal fibroblasts and periadnexial cells from a LMNAK542N/K542N patient further confirming its pivotal role in skin development. Among the discordant transcriptional profiles we identified two key mediators of vascular calcification and bone metabolism, ENPP1 and OPG, which offer a molecular explanation for the major phenotypic differences in vascular and bone disease in sporadic and hereditary HGPS. Finally, this study correlates reduced TWIST2 and OPG expression with increased osteocalcin levels, thereby linking altered bone remodeling to energy homeostasis in hereditary HGPS

Characterization of lamin Mutation Phenotypes in Drosophila and Comparison to Human Laminopathies

Lamins are intermediate filament proteins that make up the nuclear lamina, a matrix underlying the nuclear membrane in all metazoan cells that is important for nuclear form and function. Vertebrate A-type lamins are expressed in differentiating cells, while B-type lamins are expressed ubiquitously. Drosophila has two lamin genes that are expressed in A- and B-type patterns, and it is assumed that similarly expressed lamins perform similar functions. However, Drosophila and vertebrate lamins are not orthologous, and their expression patterns evolved independently. It is therefore of interest to examine the effects of mutations in lamin genes. Mutations in the mammalian lamin A/C gene cause a range of diseases, collectively called laminopathies, that include muscular dystrophies and premature aging disorders. We compared the sequences of lamin genes from different species, and we have characterized larval and adult phenotypes in Drosophila bearing mutations in the lam gene that is expressed in the B-type pattern. Larvae move less and show subtle muscle defects, and surviving lam adults are flightless and walk like aged wild-type flies, suggesting that lam phenotypes might result from neuromuscular defects, premature aging, or both. The resemblance of Drosophila lam phenotypes to human laminopathies suggests that some lamin functions may be performed by differently expressed genes in flies and mammals. Such still-unknown functions thus would not be dependent on lamin gene expression pattern, suggesting the presence of other lamin functions that are expression dependent. Our results illustrate a complex interplay between lamin gene expression and function through evolution