Recurrent Metastatic Pulmonary Synovial Sarcoma during Pregnancy: A Case Report and Literature Review.

Primary pulmonary synovial sarcoma is a rare type of soft tissue tumor. Exceptionally it can occur during pregnancy, representing a challenge in management and treatment given its notable aggressiveness and the not infrequent incidence of maternal death. We report our case of metastatic recurrence of pulmonary synovial sarcoma during pregnancy, with the aim to emphasize the decision-making, diagnostic, and therapeutic multidisciplinary processes and the evolution of the pathology. Besides, we focused on the analysis of the limited literature data available on the topic.

Ultrasound Features and Clinical Outcome of Patients with Ovarian Masses Diagnosed during Pregnancy: Experience of Single Gynecological Ultrasound Center.

(1) Background: The number of adnexal masses detected during pregnancy has increased due to the use of first-trimester screening and increasingly advanced maternal age. Despite their low risk of malignancy, other risks associated with these masses include torsion, rupture and labor obstruction. Correct diagnosis and management are needed to guarantee both maternal and fetal safety. Adnexal masses may be troublesome to classify during pregnancy due to the increased volume of the uterus and pregnancy-related hormonal changes. Management should be based on ultrasound examination to provide the best treatment. The aim of this study was to describe the ultrasound features of ovarian masses detected during pregnancy and to optimize and personalize their management with the expertise of gynecologists, oncologists and sonographers. (2) Methods: Clinical, ultrasound, histological parameters and type of management (surveillance vs. surgery) were retrospectively retrieved. Patient management, perinatal outcomes and follow-up were also evaluated. (3) Results: according to the literature, these masses are most frequently benign, ultrasound follow-up is the best management, and obstetric outcomes are not considerably influenced by the presence of adnexal masses. (4) Conclusions: the management of patients with ovarian masses detected during pregnancy should be based on ultrasound examination, and a centralization in referral centers for ovarian masses should be considered.

Pre-Eclampsia: From Etiology and Molecular Mechanisms to Clinical Tools-A Review of the Literature.

Pre-eclampsia is a severe pregnancy-related complication that manifests as a syndrome with multisystem involvement and damage. It has significantly grown in frequency during the past 30 years and could be considered as one of the major causes of maternal and fetal morbidity and mortality. However, the specific etiology and molecular mechanisms of pre-eclampsia are still poorly known and could have a variety of causes, such as altered angiogenesis, inflammations, maternal infections, obesity, metabolic disorders, gestational diabetes, and autoimmune diseases. Perhaps the most promising area under investigation is the imbalance of maternal angiogenic factors and its effects on vascular function, though studies in placental oxidative stress and maternal immune response have demonstrated intriguing findings. However, to determine the relative importance of each cause and the impact of actions aiming to significantly reduce the incidence of this illness, more research is needed. Moreover, it is necessary to better understand the etiologies of each subtype of pre-eclampsia as well as the pathophysiology of other major obstetrical syndromes to identify a clinical tool able to recognize patients at risk of pre-eclampsia early.

Conservative management of preterm premature rupture of membranes < 30 weeks of gestational age: Effectiveness of clinical guidelines implementation strategies.

Objective: To compare obstetrical and neonatal outcomes in patients with p-PROM (preterm premature rupture of membranes) at less than 30 weeks of gestational age before and after the application of protocols developed on the basis of international guidelines and to identify local barriers and strategies for their implementation. Study design: Single and twin pregnancies with p-PROM < 30 weeks of gestation without signs of infection were retrospectively collected. The population was divided in two groups. Group A contained patients treated before the introduction of the protocol, hospitalized from the day of the p-PROM to delivery and treated according to clinicians' practice. Group B included patients managed according to a standardized protocol, treated with home care management under strict surveillance, after 48 h of hospitalization. Results: 19 women with 21 newborns in group A and 22 women with 26 newborns in group B were enrolled. Maternal characteristics and p-PROM gestational age were comparable. In group A we observed minor latency time from diagnosis to delivery (1.6 vs 6.5 weeks, p < 0.001) with lower gestational age at delivery (25.8 ± 2 vs 30.7 ± 4.2 weeks, p = 0.00) and lower newborn weight (859 ± 268 vs 1511 ± 917 g, p = 0.002). Concerning neonatal outcomes, in group A there were lower Apgar score at 1 min (4.0 ± 2.1vs 6.3 ± 2, p = 004), longer hospitalization (42 ± 38 vs 68 ± 38 days, p = 0.05) and, even if non statistically significant, major rate of neonatal mortality (11,5% vs 19%, p = 1.00) and of neonatal complications (need of neonatal intensive care unit, sepsis, bronchopulmonary dysplasia, retinopathy of prematurity, mechanical ventilation). Postnatal follow-up showed comparable outcomes at 24 months of correct age. Conclusions: Educational and interdisciplinary meetings, along with group performance audit and standardization of procedures are successful strategies to implement guidelines application. Applying this strategy, we developed a protocol according to international guidelines for the treatment of early onset p-PROM based on a standardized conservative management at home, achieving better results compared to hospital management in terms of latency, gestational age at delivery, neonatal weight and neonatal hospitalization.

Obliterated cavum septi pellucidi: is it always a benign finding? A case report and narrative review of the literature.

OBJECTIVE: The septum pellucidum is a virtual cavity located at the anterior part of the brain midline, which only in fetal life has a certain amount of fluid inside. The presence of an obliterated cavum septi pellucidi (oCSP) in the prenatal period is poorly described in the literature but, nevertheless, it constitutes an important clinical dilemma for the fetal medicine specialist in terms of significance and prognosis. Moreover, its occurrence is increasing maybe because of the widespread of high-resolution ultrasound machine. The aim of this work is to review the available literature regarding the oCSP along with the description of a case-report of oCSP with an unexpected outcome. METHODS: A search of the literature through Pubmed was performed up to December 2022 with the aim to identify all cases of oCSP previously described, using as keywords "cavum septi pellucidi," "abnormal cavum septi pellucidi," "fetus," and "septum pellucidum." Along with the narrative review, we describe a case-report of oCSP. RESULTS: A 39 years old woman was diagnosed with a nuchal translucency between the 95° and 99° centile in the first trimester and an oCSP and "hookshaped" gallbladder at 20 weeks. Left polymicrogyria was found at fetal magnetic resonance imaging (MRI). Standard karyotype and chromosomal microarray analysis (CMA) were normal. After birth, the newborn presented signs of severe acidosis, untreatable seizures and multiorgan failure leading to death. A targeted gene analysis of the epilepsy panel revealed the presence of a de novo pathogenic variant involving the PTEN gene. The literature review identified four articles reporting on the oCSP of which three were case report and one was a case-series. The reported rate of associated cerebral findings is around 20% and the rate of adverse neurological outcome is around 6%, which is higher than the background risk of the general population. CONCLUSIONS: This case-report and review of the literature shows that oCSP is a clinical entity poorly described so far and that, despite the generally good prognosis, it requires caution in counseling. The diagnostic work-up should include neurosonography while fetal MRI may be always indicated for non-isolated cases only, depending on local facilities. Targeted gene analysis or whole exome sequencing may be indicated for non-isolated cases.

The clinical impact of the first-trimester nuchal translucency between the 95th-99th percentiles.

OBJECTIVES: To evaluate the clinical significance of nuchal translucency (NT) between the 95th-99th percentile in terms of typical and atypical chromosomal abnormalities (ACAs), associated fetal congenital defects and postnatal outcome. METHODS: A retrospective cohort study of fetuses with NT between the 95th-99th percentile. Data regarding the rate of associated fetal defects, genetic abnormalities and postnatal outcome were collected. RESULTS: A total of 306 cases of fetuses with an NT between the 95th-99th percentiles were included. The overall rate of genetic abnormalities was 12.1% (37/306). Chromosomal abnormalities were found in 10.1% (31/306) of cases and 2% were ACA (6/306). Within this group, two were pathogenic Copy Number Variants (CNVs) and four were single gene disorders. The overall rate of fetal congenital defects was 13.7% (42/306). All ACAs were found in fetuses with congenital defects. Postnatally, a new diagnosis of a single gene disorder was made in 0.85% of cases (2/236). CONCLUSIONS: The presence of an NT between the 95th-99th percentiles carries a 10-fold increased risk of fetal defects, representing an indication for referral for a detailed fetal anatomy evaluation. The risk of ACA is mainly related to the presence of fetal defects, irrespective of the combined test risk.

Umbilical Vein Blood Flow in Uncomplicated Pregnancies: Systematic Review of Available Reference Charts and Comparison with a New Cohort.

The objectives of the study were (1) to perform a systematic review of the available umbilical vein blood flow volume (UV-Q) reference ranges in uncomplicated pregnancies; and (2) to compare the findings of the systematic review with UV-Q values obtained from a local cohort. Available literature in the English language on this topic was identified following the PRISMA guidelines. Selected original articles were further grouped based on the UV sampling sites and the formulae used to compute UV-Q. The 50th percentiles, the means, or the best-fitting curves were derived from the formulae or the reported tables presented by authors. A prospective observational study of uncomplicated singleton pregnancies from 20+0 to 40+6 weeks of gestation was conducted to compare UV-Q with the results of this systematic review. Fifteen sets of data (fourteen sets belonging to manuscripts identified by the research strategy and one obtained from our cohort) were compared. Overall, there was a substantial heterogeneity among the reported UV-Q central values, although when using the same sampling methodology and formulae, the values overlap. Our data suggest that when adhering to the same methodology, the UV-Q assessment is accurate and reproducible, thus encouraging further investigation on the possible clinical applications of this measurement in clinical practice.

Obliterated cavum septi pellucidi: Clinical significance and role of fetal magnetic resonance.

INTRODUCTION: The objective of this study was to describe a cohort of fetuses with an ultrasound prenatal diagnosis of obliterated cavum septi pellucidi (oCSP) with the aim to explore the rate of associated malformations, the progression during pregnancy and the role of fetal magnetic resonance imaging (MRI). MATERIAL AND METHODS: This was a retrospective multicenter international study of fetuses diagnosed with oCSP in the second trimester with available fetal MRI and subsequent ultrasound and/or fetal MRI follow-up in the third trimester. Where available, postnatal data were collected to obtain information on neurodevelopment. RESULTS: We identified 45 fetuses with oCSP at 20.5 weeks (interquartile range 20.1-21.1). oCSP was apparently isolated at ultrasound in 89% (40/45) and fetal MRI found additional findings in 5% (2/40) of cases, including polymicrogyria and microencephaly. In the remaining 38 fetuses, fetal MRI found a variable amount of fluid in CSP in 74% (28/38) and no fluid in 26% (10/38). Ultrasound follow-up at or after 30 weeks confirmed the diagnosis of oCSP in 32% (12/38) while fluid was visible in 68% (26/38). At follow-up MRI, performed in eight pregnancies, there were periventricular cysts and delayed sulcation with persistent oCSP in one case. Among the remaining cases with normal follow-up ultrasound and fetal MRI findings, the postnatal outcome was normal in 89% of cases (33/37) and abnormal in 11% (4/37): two with isolated speech delay, and two with neurodevelopmental delay secondary to postnatal diagnosis of Noonan syndrome at 5 years in one case and microcephaly with delayed cortical maturation at 5 months in the other. CONCLUSIONS: Apparently isolated oCSP at mid-pregnancy is a transient finding with the visualization of the fluid later in pregnancy in up to 70% of cases. At referral, associated defects can be found in around 11% of cases at ultrasound and 8% at fetal MRI indicating the need for a detailed evaluation by expert physicians when oCSP is suspected.

Changes in preterm birth and stillbirth during COVID-19 lockdowns in 26 countries.

Preterm birth (PTB) is the leading cause of infant mortality worldwide. Changes in PTB rates, ranging from -90% to +30%, were reported in many countries following early COVID-19 pandemic response measures ('lockdowns'). It is unclear whether this variation reflects real differences in lockdown impacts, or perhaps differences in stillbirth rates and/or study designs. Here we present interrupted time series and meta-analyses using harmonized data from 52 million births in 26 countries, 18 of which had representative population-based data, with overall PTB rates ranging from 6% to 12% and stillbirth ranging from 2.5 to 10.5 per 1,000 births. We show small reductions in PTB in the first (odds ratio 0.96, 95% confidence interval 0.95-0.98, P value <0.0001), second (0.96, 0.92-0.99, 0.03) and third (0.97, 0.94-1.00, 0.09) months of lockdown, but not in the fourth month of lockdown (0.99, 0.96-1.01, 0.34), although there were some between-country differences after the first month. For high-income countries in this study, we did not observe an association between lockdown and stillbirths in the second (1.00, 0.88-1.14, 0.98), third (0.99, 0.88-1.12, 0.89) and fourth (1.01, 0.87-1.18, 0.86) months of lockdown, although we have imprecise estimates due to stillbirths being a relatively rare event. We did, however, find evidence of increased risk of stillbirth in the first month of lockdown in high-income countries (1.14, 1.02-1.29, 0.02) and, in Brazil, we found evidence for an association between lockdown and stillbirth in the second (1.09, 1.03-1.15, 0.002), third (1.10, 1.03-1.17, 0.003) and fourth (1.12, 1.05-1.19, <0.001) months of lockdown. With an estimated 14.8 million PTB annually worldwide, the modest reductions observed during early pandemic lockdowns translate into large numbers of PTB averted globally and warrant further research into causal pathways.

The accuracy of cell-free DNA screening for fetal segmental copy number variants: A systematic review and meta-analysis.

BACKGROUND: The performance of cell-free DNA (cfDNA) screening for microscopic copy number variants (CNVs) is unclear. OBJECTIVES: This was a systematic review and meta-analysis to investigate the sensitivity, specificity and positive predictive value (PPV) of cfDNA screening for CNVs. SEARCH STRATEGY: Articles published in EMBASE, PubMed or Web of Science before November 2022 were screened for inclusion. This protocol was registered with PROSPERO (23 March 2021, CRD42021250849) prior to initiation. SELECTION CRITERIA: Articles published in English, detailing diagnostic outcomes for at least 10 high-risk CNV results with cfDNA were considered for inclusion. DATA COLLECTION AND ANALYSIS: The PPV was calculated and pooled with random-effects models for double-arcsine transformed proportions, using cases with diagnostic confirmation. Overall sensitivity, specificity and a summary receiver-operating characteristics (ROC) curve were calculated using bivariate models. The risk of bias was assessed using QUADAS-2. MAIN RESULTS: In all, 63 articles were included in the final analysis, detailing 1 591 459 cfDNA results. The pooled PPV was 37.5% (95% confidence interval [CI] 30.6-44.8), with substantial statistical heterogeneity (I2  = 93.9%). Bivariate meta-analysis estimated sensitivity and specificity to be 77.4% (95% CI 65.7-86.0) and 99.4% (95% CI 98.0-99.8), respectively, with an area under the summary ROC curve of 0.947 (95% CI 0.776-0.984). CONCLUSIONS: Approximately one-third of women who screen high-risk for CNVs with cfDNA will have an affected fetus. This value is of importance for screening counselling.

The accuracy of prenatal cell-free DNA screening for sex chromosome abnormalities: A systematic review and meta-analysis.

OBJECTIVE: Although cell-free DNA screening for sex chromosome abnormalities is increasingly used in clinical practice, its diagnostic accuracy and clinical utility remain unclear. This systematic review and meta-analysis aimed to determine the performance of cell-free DNA in the detection of sex chromosome abnormalities. DATA SOURCES: Medline and PubMed, Embase, and Web of Science were searched from inception to January 2022 for articles relating to cell-free DNA screening for sex chromosome abnormalities. STUDY ELIGIBILITY CRITERIA: Original articles, randomized control trials, conference abstracts, cohort and case-control studies, and case series with more than 10 cases with diagnostic confirmation were considered for inclusion. METHODS: Quality assessment of each included publication was performed using the Quality Assessment of Diagnostic Accuracy Studies 2 tool. The positive predictive value was calculated as the proportion of true positive cases among those who tested positive and underwent diagnostic testing. Sensitivity and specificity were pooled, and a summary receiver operating characteristic curve was produced using bivariate models that included studies that had diagnostic confirmation for high- and low-risk women. RESULTS: The search identified 7553 results. Of these, 380 proceeded to the full-text screening, of which 94 articles were included in the meta-analysis with a total of 1,531,240 women tested. All studies reported a confirmatory genetic test. The pooled positive predictive value was 49.4% (95% confidence interval, 45.8-53.1). The pooled positive predictive value was 32.0% (95% confidence interval, 27.0%-37.3%) for monosomy X, 67.6% (95% confidence interval, 62.5%-72.5%) for XXY, 57.5% (95% confidence interval, 51.7%-63.1%) for XXX, and 70.9% (95% confidence interval, 63.9%-77.1%) for XYY. The pooled sensitivity and specificity of cell-free DNA for sex chromosome abnormalities were 94.1% (95% confidence interval, 90.8%-96.3%) and 99.5% (95% confidence interval, 99.0%-99.7%), respectively, with an area under the summary receiver operating characteristic curve of 0.934 (95% confidence interval, 0.907-0.989). CONCLUSION: Although the sensitivity and specificity of cell-free DNA for sex chromosome abnormalities are high, the positive predictive value was approximately 50%. The positive predictive value was higher for sex chromosome abnormalities with a supernumerary Y chromosome and lower for monosomy X. Clinicians should inform couples about these findings when offering cell-free DNA for sex chromosome abnormalities.

The predictive value of prenatal cell-free DNA testing for rare autosomal trisomies: a systematic review and meta-analysis.

OBJECTIVE: The diagnostic accuracy of cell-free fetal DNA in screening for rare autosomal trisomies is uncertain. We conducted a systematic review and meta-analysis aiming to determine the predictive value of cell-free DNA in screening for rare autosomal trisomies. DATA SOURCES: PubMed, Embase, and Web of Science were searched from inception to January 2022. STUDY ELIGIBILITY CRITERIA: All studies that reported on the diagnostic accuracy of cell-free DNA in the detection of rare autosomal trisomies were included. Case series were included if they contained at least 10 cases with diagnostic test results or postnatal genetic testing. METHODS: Study appraisal was completed using the Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2) tool. Statistical analysis was performed using random-effects meta-analysis of double-arcsine transformed proportions of confirmed results in the fetus out of the positive tests to obtain a pooled estimate of the positive predictive value. RESULTS: The search identified 7553 studies, of which 1852 were duplicates. After screening 5701 titles and abstracts, 380 studies proceeded to the full-text screen; 206 articles were retrieved for data extraction, of which another 175 articles were excluded. A total of 31 studies, with a total of 1703 women were included for analysis. The pooled positive predictive value of cell-free DNA for the diagnosis of rare autosomal trisomies was 11.46% (95% confidence interval, 7.80-15.65). Statistical heterogeneity was high (I2=82%). Sensitivity analysis restricted to 5 studies at low risk of bias demonstrated a pooled positive predictive value of 9.13% (95% confidence interval, 2.49-18.76). There were insufficient data to provide accurate ascertainment of sensitivity and specificity because most studies only offered confirmatory tests to women with high-risk results. CONCLUSION: The positive predictive value of cell-free DNA in diagnosing rare autosomal trisomies is approximately 11%. Clinicians should provide this information when offering cell-free DNA for screening of conditions outside of common autosomal trisomies.

Current practice in the diagnosis and management of fetal growth restriction: An international survey.

INTRODUCTION: The aim of this survey was to evaluate the current practice in respect of diagnosis and management of fetal growth restriction among obstetricians in different countries. MATERIAL AND METHODS: An e-questionnaire was sent via REDCap with "click thru" links in emails and newsletters to obstetric practitioners in different countries and settings with different levels of expertise. Clinical scenarios in early and late fetal growth restriction were given, followed by structured questions/response pairings. RESULTS: A total of 275 participants replied to the survey with 87% of responses complete. Participants were obstetrician/gynecologists (54%; 148/275) and fetal medicine specialists (43%; 117/275), and the majority practiced in a tertiary teaching hospital (56%; 153/275). Delphi consensus criteria for fetal growth restriction diagnosis were used by 81% of participants (223/275) and 82% (225/274) included a drop in fetal growth velocity in their diagnostic criteria for late fetal growth restriction. For early fetal growth restriction, TRUFFLE criteria were used for fetal monitoring and delivery timing by 81% (223/275). For late fetal growth restriction, indices of cerebral blood flow redistribution were used by 99% (250/252), most commonly cerebroplacental ratio (54%, 134/250). Delivery timing was informed by cerebral blood flow redistribution in 72% (176/244), used from ≥32 weeks of gestation. Maternal biomarkers and hemodynamics, as additional tools in the context of early-onset fetal growth restriction (≤32 weeks of gestation), were used by 22% (51/232) and 46% (106/230), respectively. CONCLUSIONS: The diagnosis and management of fetal growth restriction are fairly homogeneous among different countries and levels of practice, particularly for early fetal growth restriction. Indices of cerebral flow distribution are widely used in the diagnosis and management of late fetal growth restriction, whereas maternal biomarkers and hemodynamics are less frequently assessed but more so in early rather than late fetal growth restriction. Further standardization is needed for the definition of cerebral blood flow redistribution.

The role of melatonin in pregnancies complicated by placental insufficiency: A systematic review.

Placental insufficiency affects about 10% of pregnancies and can lead to pre-eclampsia, fetal growth restriction, and preterm birth. Despite significant advances in early prediction and prevention of preterm pre-eclampsia with aspirin, the effects of prophylaxis on fetal growth restriction are less certain, and the rates of late-onset pre-eclampsia are not influenced by aspirin treatment. Pregnancies complicated by placental insufficiency are characterized by increased oxidative stress, and recent studies suggest that melatonin has antioxidant properties and contributes to maintaining placental homeostasis. We aimed to systematically review the available literature about melatonin in pregnancies complicated by placental insufficiency, specifically preeclampsia and fetal growth restriction, exploring three different aspects: 1) maternal melatonin levels; 2) expression and activity of melatonin placental receptors; 3) effects of maternal melatonin administration. PubMed (Medline) and Scopus were searched until December 2020. Identified studies were screened and assessed independently by two authors. Data were extracted and compiled in qualitative evidence synthesis. The circadian pattern of melatonin secretion seems to be altered in pregnancies complicated by placental insufficiency reflected by lower production of melatonin, with consequent lower systemic and placental concentrations and lower expression of melatonin receptors, thus reducing the local release of the indole and its autocrine function. Small intervention studies also suggest that treatment is safe and may lead to prolongation of pregnancy and better outcomes, but double-blind, randomized placebo-controlled trials are lacking.

Accuracy and clinical utility of standard postmortem radiological imaging after early second trimester termination of pregnancy.

OBJECTIVE: This study aims to assess accuracy and clinical utility of postmortem radiological exams [Magnetic Resonance Imaging (MRI), Computed Tomography (CT) and Radiography (XR)] after termination of pregnancy at <23 weeks' gestation for congenital fetal malformations in comparison to autopsy. STUDY DESIGN: This a prospective single-center study on fetuses underwent termination of pregnancy for fetal defects. Overall concordance between any radiological exam and autopsy was evaluated. For postmortem MRI only, the following subgroups were analyzed: 1) total agreement; 2) agreement for main findings; 3) agreement for main findings but major relevant additional findings at autopsy; 4) total disagreement. RESULTS: 174 cases were collected. The overall concordance with autopsy for main findings was 71% (115/163) for postmortem MRI and 99% (173/174) for prenatal ultrasound (US). Postmortem MRI detection rate was high for central nervous system (CNS) defects (98%), gastrointestinal, genitourinary and respiratory defects (100%), while it was poor for cardiovascular and musculoskeletal defects (25% and 42%, respectively). For musculoskeletal abnormalities, the performance of postmortem XR and postmortem CT exams improved the detection rate from 42% for postmortem MRI alone to 92%. CONCLUSIONS: Postmortem MRI has a good overall concordance for fetal defects after termination of pregnancy performed at <23 weeks. Along with autopsy, postmortem MRI may be offered for all cases of CNS defects in order to prevent inconclusive exams due to autolysis of the brain tissue, while postmortem CT and postmortem XR are indicated for musculoskeletal defects. In the presence of multiple abnormalities or cardiac defects the couple should be counseled on the poor performance of radiological investigations.

Perinatal and 2-year neurodevelopmental outcome in late preterm fetal compromise: the TRUFFLE 2 randomised trial protocol.

INTRODUCTION: Following the detection of fetal growth restriction, there is no consensus about the criteria that should trigger delivery in the late preterm period. The consequences of inappropriate early or late delivery are potentially important yet practice varies widely around the world, with abnormal findings from fetal heart rate monitoring invariably leading to delivery. Indices derived from fetal cerebral Doppler examination may guide such decisions although there are few studies in this area. We propose a randomised, controlled trial to establish the optimum method of timing delivery between 32 weeks and 36 weeks 6 days of gestation. We hypothesise that delivery on evidence of cerebral blood flow redistribution reduces a composite of perinatal poor outcome, death and short-term hypoxia-related morbidity, with no worsening of neurodevelopmental outcome at 2 years. METHODS AND ANALYSIS: Women with non-anomalous singleton pregnancies 32+0 to 36+6 weeks of gestation in whom the estimated fetal weight or abdominal circumference is <10th percentile or has decreased by 50 percentiles since 18-32 weeks will be included for observational data collection. Participants will be randomised if cerebral blood flow redistribution is identified, based on umbilical to middle cerebral artery pulsatility index ratio values. Computerised cardiotocography (cCTG) must show normal fetal heart rate short term variation (≥4.5 msec) and absence of decelerations at randomisation. Randomisation will be 1:1 to immediate delivery or delayed delivery (based on cCTG abnormalities or other worsening fetal condition). The primary outcome is poor condition at birth and/or fetal or neonatal death and/or major neonatal morbidity, the secondary non-inferiority outcome is 2-year infant general health and neurodevelopmental outcome based on the Parent Report of Children's Abilities-Revised questionnaire. ETHICS AND DISSEMINATION: The Study Coordination Centre has obtained approval from London-Riverside Research Ethics Committee (REC) and Health Regulatory Authority (HRA). Publication will be in line with NIHR Open Access policy. TRIAL REGISTRATION NUMBER: Main sponsor: Imperial College London, Reference: 19QC5491. Funders: NIHR HTA, Reference: 127 976. Study coordination centre: Imperial College Healthcare NHS Trust, Du Cane Road, London, W12 0HS with Centre for Trials Research, College of Biomedical & Life Sciences, Cardiff University. IRAS Project ID: 266 400. REC reference: 20/LO/0031. ISRCTN registry: 76 016 200.

Late-term fetuses with reduced umbilical vein blood flow volume: An under-recognized population at increased risk of growth restriction.

OBJECTIVES: To investigate the umbilical vein and uterine arteries blood flow volume (UV-Q, UtA-Q) in late-term pregnancies. STUDY DESIGN: This was a prospective observational cohort study of singleton pregnancies ≥40 + 0 weeks in which UV-Q and UtA-Q, both absolute and normalized for estimated fetal weight (EFW) values, were evaluated in relation to AC drop of ≥20 percentiles from 20 weeks to term, Doppler signs of fetal cerebral blood flow redistribution and composite adverse perinatal outcome. The presence of neonatal hypoglycaemia and the need of formula milk supplementation were also examined. RESULTS: The study population comprised 200 women. Fetuses with AC drop (n = 34) had a significantly lower UV-Q and UV-Q/EFW than fetuses without AC drop (n = 166): median UV-Q 184 ml/min (IQR 143-225) vs 233 ml/min (IQR 181-277), p = 0.0006; median UV-Q/EFW 55 ml/min/kg (IQR 42-66) vs 63 ml/min/kg (IQR 48-74), p = 0.03. Fetuses with cerebral blood flow redistribution (n = 48) had a significantly lower UV-Q and UV-Q/EFW than those without (n = 134): median UV-Q 210 ml/min (IQR 155-263) vs 236 ml/min (IQR 184-278), p = 0.04; median UV-Q/EFV 58 ml/min/kg (IQR 45-70) vs 65 ml/min/kg (IQR 50-76), p = 0.04. There was a significant moderate correlation between middle cerebral artery pulsatility index (MCA-PI) and UV-Q and UV-Q/EFW (Spearman Rho -0.20 and -0.20; p = 0.008 and p = 0.006). CONCLUSIONS: The umbilical vein blood flow volume might have a potential role to identify fetuses with stunted growth in late-term pregnancies.

Role of prenatal magnetic resonance imaging in fetuses with isolated severe ventriculomegaly at neurosonography: A multicenter study.

OBJECTIVE: The aim of this study was to report the rate of additional anomalies detected exclusively at prenatal magnetic resonance imaging (MRI) in fetuses with isolated severe ventriculomegaly undergoing neurosonography. METHOD: Multicenter, retrospective, cohort study involving 20 referral fetal medicine centers in Italy, United Kingdom, Spain and Denmark. Inclusion criteria were fetuses affected by isolated severe ventriculomegaly (≥15 mm), defined as ventriculomegaly with normal karyotype and no other additional central nervous system (CNS) and extra-CNS anomalies on ultrasound. In all cases, a multiplanar assessment of fetal brain as suggested by ISUOG guidelines on fetal neurosonography had been performed. The primary outcome was the rate of additional CNS anomalies detected exclusively at fetal MRI within two weeks from neurosonography. Subgroup analyses according to gestational age at MRI (

The international Perinatal Outcomes in the Pandemic (iPOP) study: protocol.

Preterm birth is the leading cause of infant death worldwide, but the causes of preterm birth are largely unknown. During the early COVID-19 lockdowns, dramatic reductions in preterm birth were reported; however, these trends may be offset by increases in stillbirth rates. It is important to study these trends globally as the pandemic continues, and to understand the underlying cause(s). Lockdowns have dramatically impacted maternal workload, access to healthcare, hygiene practices, and air pollution - all of which could impact perinatal outcomes and might affect pregnant women differently in different regions of the world. In the international Perinatal Outcomes in the Pandemic (iPOP) Study, we will seize the unique opportunity offered by the COVID-19 pandemic to answer urgent questions about perinatal health. In the first two study phases, we will use population-based aggregate data and standardized outcome definitions to: 1) Determine rates of preterm birth, low birth weight, and stillbirth and describe changes during lockdowns; and assess if these changes are consistent globally, or differ by region and income setting, 2) Determine if the magnitude of changes in adverse perinatal outcomes during lockdown are modified by regional differences in COVID-19 infection rates, lockdown stringency, adherence to lockdown measures, air quality, or other social and economic markers, obtained from publicly available datasets. We will undertake an interrupted time series analysis covering births from January 2015 through July 2020. The iPOP Study will involve at least 121 researchers in 37 countries, including obstetricians, neonatologists, epidemiologists, public health researchers, environmental scientists, and policymakers. We will leverage the most disruptive and widespread "natural experiment" of our lifetime to make rapid discoveries about preterm birth. Whether the COVID-19 pandemic is worsening or unexpectedly improving perinatal outcomes, our research will provide critical new information to shape prenatal care strategies throughout (and well beyond) the pandemic.

Prenatal diagnosis of isolated clubfoot: Diagnostic accuracy and long-term postnatal outcomes.

OBJECTIVE: To evaluate concordance between prenatal and postnatal diagnosis of congenital talipes equinovarus (cTEV), rates of surgery and postnatal outcomes in relation to the prenatal classification of severity. STUDY DESIGN: This is a retrospective observational cohort study on fetuses with a prenatal diagnosis of cTEV between 2004 and 2018. All cases of isolated cTEV in singleton pregnancies were included. Postnatally, the Ponseti method was applied. Children were followed-up postnatally for at least two years, with a specific focus on neurodevelopmental outcome. RESULTS: The cohort included 81 fetuses with a prenatal diagnosis of cTEV confirmed postnatally in 86.4% of cases. Concordance between prenatal and postnatal assessment was good for both laterality and degree of severity (k = 0.61 and 0.66, respectively). The average Pirani score, number of casts and rates of Achilles tendon tenotomy were higher for III degree cTEV (p < 0.001). Within this group only, the rate of relapse was 11% and the rates of major surgery was 6%. The postnatal outcome was normal in 68.6% newborns, while 14% of cases had a diagnosis of minor additional findings and 17% had an impairment of neurological development. None of the outcome was statistically correlated to the prenatal assessment of laterality or degree. CONCLUSIONS: The accuracy of prenatal ultrasound for isolated cTEV is 86% with a false positive diagnosis of 14%. The grade of cTEV assigned prenatally correlates to postnatal severity and longer orthopedic rehabilitation in terms of number of casts and need of surgery. The assessment of the correlation between cTEV and neurological impairment requires further prospective studies on larger cohorts.