Novel variant in ACTA1 identified in a fetus with akinesia deformation sequence and cortical development delay.

We present a case of fetal akinesia deformation sequence due to nemaline myopathy (NM). In addition to the muscle manifestations, prenatal observations included an enlarged subarachnoid space and delayed cortical development. Trio whole-exome sequencing revealed a de novo novel pathogenic variant in the ACTA1 gene, which encodes skeletal muscle alpha-actin. Our findings suggest that brain abnormalities can occur prenatally in NM and support the potential role of skeletal muscle alpha-actin in the central nervous system.

The Arabin cervical pessary for the prevention of preterm birth in twin-to-twin transfusion syndrome treated by fetoscopic laser coagulation: a multicenter randomized controlled trial.

BACKGROUND: Miscarriage and preterm birth are leading causes of loss and disability in monochorionic twins after laser treatment of twin-twin transfusion syndrome. OBJECTIVE: This study aimed to investigate the use of cervical pessary to reduce preterm birth before 32 weeks of gestation in monochorionic diamniotic twin pregnancies after fetal surgery for twin-twin transfusion syndrome. STUDY DESIGN: In this open-label multicenter randomized trial, pregnant women carrying monochorionic diamniotic twins requiring fetoscopic laser coagulation for twin-twin transfusion syndrome were randomly assigned in a 1:1 ratio to pessary placement or conservative management. The primary outcome was birth before 32 weeks of gestation. The secondary outcomes were birth before 28, 30, 34, or 37 weeks of gestation; preterm premature rupture of membranes; fetal and neonatal survival; and a composite of maternal and neonatal complications. The estimated sample size was 364 patients, with 182 cases in each arm of the study. The analysis was performed according to the intention-to-treat principle. Moreover, 2 interim analyses were planned. RESULTS: The trial was stopped prematurely after the first planned interim analysis for futility. Overall, 137 women were included in the analysis, 67 in the pessary group and 70 in the conservative management group. Preterm birth before 32 weeks of gestation occurred in 27 of 67 women (40.3%) in the pessary group and in 25 of 70 women (35.7%) in the conservative management group (adjusted odds ratio, 1.19; 95% confidence interval, 0.58-2.47; P=.63). No differences between groups was observed in the rate of deliveries before 28, 30, 34, and 37 weeks of gestation. Overall survival to delivery was 91.2% (125/137) for at least 1 twin, and 70.8% (97/137) for both twins, with no difference between groups. Neonatal survival at 30 days was 76.5% (208/272). There was no difference between the groups in maternal or neonatal morbidity. CONCLUSION: In monochorionic diamniotic twin pregnancies requiring fetal therapy for twin-twin transfusion syndrome, routine use of cervical pessary did not reduce the rate of preterm birth before 32 weeks of gestation.

Fetal abdominal cysts: Predicting adverse outcomes.

INTRODUCTION: The primary aim of the study was to identify risk factors associated with fetal or neonatal loss, neonatal morbidity, and the need for surgery in fetuses diagnosed with an abdominal cyst. The secondary aim was to compare the characteristics of the cyst according to trimester at diagnosis. MATERIAL AND METHODS: This was an observational retrospective study performed at Vall d'Hebron University Hospital. The study included pregnant women aged 18 years or older with diagnosis of a fetal abdominal cyst from 2008 to 2021. RESULTS: A total of 82 women with a median gestational age of 31+1 weeks (12+0-39+4) were included in the analysis. Seven (8.5%) cases were diagnosed in the first trimester, 28 (34.1%) in the second trimester, and 47 (57.3%) in the third trimester. Fetal or neonatal loss occurred in 10 (12.2%) cases; significant predictors were diagnosis in the first trimester (OR 36.67, 95% CI: 4.89-274.79), male gender (OR 4.75, 95% CI: 1.13-19.9), and associated abnormalities (OR 15.2, 95% CI: 2.92-79.19). A total of 10 of 75 (13.3%) neonates showed at least one neonatal complication, and the only predictor was occurrence of associated abnormalities (OR 7.36, 95% CI: 1.78-30.51). A total of 16 of 75 (21.3%) neonates required postnatal surgery, and the predictors were second-trimester diagnosis (OR 3.92, 95% CI: 1.23-12.51), associated abnormalities (OR 3.81, 95% CI: 1.15-12.64), and bowel location (OR 10.0, 95% CI: 1.48-67.55). CONCLUSIONS: Factors associated with adverse outcomes in fetuses diagnosed with abdominal cysts are first-trimester diagnosis and associated abnormalities. Cysts detected in the second trimester and those of intestinal origin are more likely to require surgery.

Reference values for interleukin-6 in the amniotic fluid of asymptomatic pregnant women.

INTRODUCTION: Nowadays, proinflammatory factors are considered to play an important role in the pathophysiology of threatened preterm labor or chorioamnionitis. The aim of this study was to establish the normal reference range for interleukin-6 (IL-6) levels in the amniotic fluid and to identify factors which may alter this value. MATERIAL AND METHODS: Prospective study in a tertiary-level center including asymptomatic pregnant women undergoing amniocentesis for genetic studies from October 2016 to September 2019. IL-6 measurements in amniotic fluid were performed using a fluorescence immunoassay with microfluidic technology (ELLA Proteinsimple, Bio Techne). Maternal history and pregnancy data were also recorded. RESULTS: This study included 140 pregnant women. Of those, women who underwent termination of pregnancy were excluded. Therefore, a total of 98 pregnancies were included in the final statistical analysis. The mean gestational age was 21.86 weeks (range: 15-38.7) at the time of amniocentesis, and 38.6 weeks (range: 30.9-41.4) at delivery. No cases of chorioamnionitis were reported. The log10 IL-6 values follow a normal distribution (W = 0.990, p = 0.692). The median, and the 5th, 10th, 90th, and 95th percentiles for IL-6 levels were 573, 105, 130, 1645, and 2260 pg/mL, respectively. The log10 IL-6 values were not affected by gestational age (p = 0.395), maternal age (p = 0.376), body mass index (p = 0.551), ethnicity (p = 0.467), smoking status (p = 0.933), parity (p = 0.557), method of conception (p = 0.322), or diabetes mellitus (p = 0.381). CONCLUSIONS: The log10 IL-6 values follow a normal distribution. IL-6 values are independent of gestational age, maternal age, body mass index, ethnicity, smoking status, parity and method of conception. Our study provides a normal reference range for IL-6 levels in the amniotic fluid that can be used in future studies. We also observed that normal IL-6 values were higher in the amniotic fluid than in serum.

Array study in fetuses with nuchal translucency above the 95th percentile: a 4-year observational single-centre study.

PURPOSE: To evaluate the performance of chromosomal microarray analysis (CMA) in fetuses with nuchal translucency (NT) > 95th percentile. Secondary objectives were to analyze these results according to NT thickness, below or above 3.5 mm, and those without associated anomalies. METHODS: This observational single-cohort study was conducted between 2015 and 2018 in fetuses with NT > 95th percentile. Following an invasive test, quantitative fluorescence-polymerase chain reaction (QF-PCR) was performed, and if normal, CMA was performed. Pathogenic copy number variants (CNVs), non-reported pathogenic CNV, pathogenic autosomal recessive variants and variants of unknown significance (VUS) were analysed. RESULTS: One-hundred and sixty-two fetuses with NT > 95th percentile, normal QF-PCR and CMA were included. Amongst 128 fetuses with NT between the 95th percentile and 3.5 mm, one (0.8%) had a pathogenic CNV, four (3.1%) had non-reported pathogenic CNV, one (0.8%) had pathogenic autosomal recessive variant and 13 (10.2%) had VUS. Amongst 34 fetuses with NT ≥ 3.5 mm, four (11.8%) had pathogenic CNV, one (2.9%) had non-reported pathogenic CNV, one (2.9%) had pathogenic autosomal recessive variant and four (11.8%) had VUS. Four in 162 (2.5%) fetuses had CNVs at the chromosome 16p13.11 region. Amongst 154 fetuses without structural abnormalities and normal QF-PCR, three (1.9%) had a pathogenic CNV, 5 (3.2%) had non-reported pathogenic CNV, one (0.6%) autosomal recessive pathogenic CNV and 16 (10.4%) had VUS. CONCLUSION: Pathogenic CNVs were found in 1% of fetuses with an NT thickness between the 95th percentile and 3.5 mm and in 12% of fetuses with NT ≥ 3.5 mm. CNVs were found at the 16p13.11 region in 2.5% of cases.

First-trimester screening for pre-eclampsia and small for gestational age: A comparison of the gaussian and Fetal Medicine Foundation algorithms.

OBJECTIVE: Pre-eclampsia (PE) and small for gestational age (SGA) can be predicted from the first trimester. The most widely used algorithm worldwide is the Fetal Medicine Foundation (FMF) algorithm. The recently described Gaussian algorithm has reported excellent results although it is unlikely to be externally validated. Therefore, as an alternative approach, we compared the predictive accuracy for PE and SGA of the Gaussian and FMF algorithms. METHODS: Secondary analysis of a prospective cohort study was conducted at Vall d'Hebron University Hospital (Barcelona) with 2641 singleton pregnancies. The areas under the curve for the predictive performance for early-onset and preterm PE and early-onset and preterm SGA were calculated with the Gaussian and FMF algorithms and subsequently compared. RESULTS: The FMF and Gaussian algorithms showed a similar predictive performance for most outcomes and marker combinations. Nevertheless, significant differences for early-onset PE prediction favored the Gaussian algorithm in the following combinations: mean arterial blood pressure (MAP) with pregnancy-associated plasma protein A, MAP with placental growth factor, and MAP alone. CONCLUSIONS: The first-trimester Gaussian and FMF algorithms have similar performances for PE and SGA prediction when applied with all markers within a routine care setting in a Spanish population, adding evidence to the external validity of the FMF algorithm.

Transplantation of Human-Fetal-Spinal-Cord-Derived NPCs Primed with a Polyglutamate-Conjugated Rho/Rock Inhibitor in Acute Spinal Cord Injury.

Neural precursor cell (NPC) transplantation represents a promising therapy for treating spinal cord injuries (SCIs); however, despite successful results obtained in preclinical models, the clinical translation of this approach remains challenging due, in part, to the lack of consensus on an optimal cell source for human neuronal cells. Depending on the cell source, additional limitations to NPC-based therapies include high tumorigenic potential, alongside poor graft survival and engraftment into host spinal tissue. We previously demonstrated that NPCs derived from rat fetal spinal cords primed with a polyglutamate (PGA)-conjugated form of the Rho/Rock inhibitor fasudil (PGA-SS-FAS) displayed enhanced neuronal differentiation and graft survival when compared to non-primed NPCs. We now conducted a similar study of human-fetal-spinal-cord-derived NPCs (hfNPCs) from legal gestational interruptions at the late gestational stage, at 19-21.6 weeks. In vitro, expanded hfNPCs retained neural features, multipotency, and self-renewal, which supported the development of a cell banking strategy. Before transplantation, we established a simple procedure to prime hfNPCs by overnight incubation with PGA-SS-FAS (at 50 µM FAS equiv.), which improved neuronal differentiation and overcame neurite-like retraction after lysophosphatidic-acid-induced Rho/Rock activation. The transplantation of primed hfNPCs into immune-deficient mice (NU(NCr)-Foxn1nu) immediately after the eighth thoracic segment compression prompted enhanced migration of grafted cells from the dorsal to the ventral spinal cord, increased preservation of GABAergic inhibitory Lbx1-expressing and glutamatergic excitatory Tlx3-expressing somatosensory interneurons, and elevated the numbers of preserved, c-Fos-expressing, activated neurons surrounding the injury epicenter, all in a low percentage. Overall, the priming procedure using PGA-SS-FAS could represent an alternative methodology to improve the capabilities of the hfNPC lines for a translational approach for acute SCI treatment.

Neurological Short-Term Outcomes of a Cohort of Children Born to Zika Virus-Infected Mothers in Barcelona.

Zika virus (ZIKV) is a vector-borne flavivirus with a known teratogenic effect, yet the full spectrum has not been delineated. Studies on endemic areas tried to characterize the clinical outcomes of ZIKV intrauterine exposure. We aimed to describe early neurodevelopmental outcomes on prenatally ZIKV-exposed children in a non-endemic ZIKV area. This is a prospective observational cohort study conducted from May 2016 to December 2021 at Hospital Universitari Vall d'Hebron in Barcelona, Catalonia, Spain. We monitored for up to 24 months 152 children extracted from a pregnant women cohort with suspected ZIKV infection; eleven women (11/150; 7.3%) fulfilled the criteria for a confirmed ZIKV infection. Among the 152 children included, we describe two cases of congenital ZIKV syndrome (CZS) born from women with a confirmed ZIKV infection. Additionally, we describe five cases of other potentially ZIKV-related outcomes (OPZROs), all with normal birth cranial circumference and born to women with probable ZIKV infection. The low exposed prevalence of adverse outcomes in asymptomatic children at birth in a non-endemic area suggests that close follow-up should be addressed by primary care pediatricians instead of pediatric specialists. Further studies are needed to assess the effects of ZIKV intrauterine exposure beyond two years of life.

Gestational age-based reference ranges for cervical length and preterm birth prediction in triplet pregnancies: an observational retrospective study.

OBJECTIVES: To develop gestational age-based reference ranges for cervical length in triplet pregnancies. The secondary objective was to assess the performance of cervical length measured between 18 and 20 + 6 days for the prediction of preterm delivery before 28 and 32 weeks, respectively. METHODS: Observational retrospective study of triplet pregnancies in three Spanish tertiary-care hospitals between 2001 and 2019. Cervical length measurements were consecutively obtained between 15 and 34 weeks of gestation. Pregnancies undergoing multifetal reduction or fetal surgery were excluded. RESULTS: Two hundred and six triplet pregnancies were included in the final analysis. There was a quadratic decrease in cervical length with gestational age. The median and fifth centiles for cervical length at 20 weeks were 35 and 13 mm. In the prediction of preterm birth < 28 weeks, for a false positive rate of 5%, and 10%, the detection rates were 40.9%, and 40.9%, respectively, and the prediction of preterm birth < 32 weeks, 22.0% and 26.0%, respectively. CONCLUSIONS: In triplet pregnancies, cervical length decreases with gestational age. The performance of cervical length at 18-20 + 6 in screening for preterm birth before 28 and 32 weeks is poor.

Prenatal phenotyping: A community effort to enhance the Human Phenotype Ontology.

Technological advances in both genome sequencing and prenatal imaging are increasing our ability to accurately recognize and diagnose Mendelian conditions prenatally. Phenotype-driven early genetic diagnosis of fetal genetic disease can help to strategize treatment options and clinical preventive measures during the perinatal period, to plan in utero therapies, and to inform parental decision-making. Fetal phenotypes of genetic diseases are often unique and at present are not well understood; more comprehensive knowledge about prenatal phenotypes and computational resources have an enormous potential to improve diagnostics and translational research. The Human Phenotype Ontology (HPO) has been widely used to support diagnostics and translational research in human genetics. To better support prenatal usage, the HPO consortium conducted a series of workshops with a group of domain experts in a variety of medical specialties, diagnostic techniques, as well as diseases and phenotypes related to prenatal medicine, including perinatal pathology, musculoskeletal anomalies, neurology, medical genetics, hydrops fetalis, craniofacial malformations, cardiology, neonatal-perinatal medicine, fetal medicine, placental pathology, prenatal imaging, and bioinformatics. We expanded the representation of prenatal phenotypes in HPO by adding 95 new phenotype terms under the Abnormality of prenatal development or birth (HP:0001197) grouping term, and revised definitions, synonyms, and disease annotations for most of the 152 terms that existed before the beginning of this effort. The expansion of prenatal phenotypes in HPO will support phenotype-driven prenatal exome and genome sequencing for precision genetic diagnostics of rare diseases to support prenatal care.

Maternal Infection and Adverse Pregnancy Outcomes among Pregnant Travellers: Results of the International Zika Virus in Pregnancy Registry.

In this multicentre cohort study, we evaluated the risks of maternal ZIKV infections and adverse pregnancy outcomes among exposed travellers compared to women living in areas with ZIKV circulation (residents). The risk of maternal infection was lower among travellers compared to residents: 25.0% (n = 36/144) versus 42.9% (n = 309/721); aRR 0.6; 95% CI 0.5-0.8. Risk factors associated with maternal infection among travellers were travelling during the epidemic period (i.e., June 2015 to December 2016) (aOR 29.4; 95% CI 3.7-228.1), travelling to the Caribbean Islands (aOR 3.2; 95% CI 1.2-8.7) and stay duration >2 weeks (aOR 8.7; 95% CI 1.1-71.5). Adverse pregnancy outcomes were observed in 8.3% (n = 3/36) of infected travellers and 12.7% (n = 39/309) of infected residents. Overall, the risk of maternal infections is lower among travellers compared to residents and related to the presence of ongoing outbreaks and stay duration, with stays <2 weeks associated with minimal risk in the absence of ongoing outbreaks.

Gestation and COVID-19: clinical and microbiological observational study (Gesta-COVID19).

BACKGROUND: The Coronavirus Disease 2019 (COVID-19) is a novel disease which has been having a worldwide affect since December 2019. Evidence regarding the effects of SARS-CoV-2 during pregnancy is conflicting. The presence of SARS-CoV-2 has been demonstrated in biological samples during pregnancy (placenta, umbilical cord or amniotic fluid); however, maternal and fetal effects of the virus are not well known. METHODS: Descriptive, multicentre, longitudinal, observational study in eight tertiary care hospitals throughout Spain, that are referral centres for pregnant women with COVID-19. All pregnant women with positive SARS-CoV-2 real-time reverse transcriptase polymerase chain reaction during their pregnancy or 14 days preconception and newborns born to mothers infected with SARS-CoV-2 will be included. They will continue to be followed up until 4 weeks after delivery. The aim of the study is to investigate both the effect of COVID-19 on the pregnancy, and the effect of the pregnancy status with the evolution of the SARS-CoV-2 disease. Other samples (faeces, urine, serum, amniotic fluid, cord and peripheral blood, placenta and breastmilk) will be collected in order to analyse whether or not there is a risk of vertical transmission and to describe the behaviour of the virus in other fluids. Neonates will be followed until 6 months after delivery to establish the rate of neonatal transmission. We aim to include 150 pregnant women and their babies. Ethics approval will be obtained from all the participating centres. DISCUSSION: There is little information known about COVID-19 and its unknown effects on pregnancy. This study will collect a large number of samples in pregnant women which will allow us to demonstrate the behaviour of the virus in pregnancy and postpartum in a representative cohort of the Spanish population.

Three-dimensional ultrasonography for advanced neurosonography (neurosofe-3D): Validation of a brain volume acquisition guideline.

INTRODUCTION: This study aimed to evaluate the quality of the brain volumes acquired following an evidence-based guideline for the acquisition of brain volumes. MATERIAL AND METHODS: This was a prospective multicenter study. Five centers recruited five cases each, acquiring two volumes per case, at different gestational age ranges. From the collected volumes, 10 operators performed an advanced neurosonography of each case. The evaluable anatomic structures were counted in each volume and expressed as a percentage. The results were compared with those obtained in a previous study where no recommendations had been made for the acquisition of the volumes. RESULTS: Five hundred evaluations were included in the study. In the axial plane, 91.5% of the structures were satisfactorily evaluated, 81.8% in the coronal plane and 89.9% in the sagittal plane. These results were significantly better than those obtained in a previous study where the volumes had been acquired without any guidelines and the percentage of evaluable structures were 80% (P < .001), 67.1% (P < .001) and 55.1% (P < .001) in the axial, coronal and sagittal planes, respectively. CONCLUSIONS: The application of an evidence-based guideline for the acquisition of brain volumes improves the quality of these by increasing the number of evaluable structures in the volume.

Prediction of preterm birth and adverse perinatal outcomes after cervical pessary placement in singleton pregnancies with short cervical length.

OBJECTIVES: To identify ultrasound-assessed cervical characteristics, modified after pessary placement, which could be predictive of spontaneous preterm birth (sPTB) at < 34 weeks of gestation (WG) or severe adverse perinatal outcomes (APO). STUDY DESIGN: This prospective observational study conducted at Vall d'Hebron Universitary Hospital assessed multiple cervical characteristics in women with short cervical length (CL). All participants were examined by transvaginal ultrasound before and immediately after a cervical pessary was placed. Cervical assessment included CL, uterocervical angles (UCA), and cervical consistency indexes (cervical consistency index (CCI) and cervical length consistency index (CLCI)). Pregnancy outcomes were recorded to determine the capacity of these variables for predicting sPTB at < 34 WG and severe APO. RESULTS: Thirty-one women with short CL, 17 (54.8%) with asymptomatic midtrimester short CL, and 14 (45.2%) after arrested threatened preterm labor were enrolled. After pessary placement, transvaginal ultrasound detected four participants in whom the pessary was not correctly placed around the cervix (12.9%); additionally, significant changes were observed in most cervical baseline characteristics, with CL, anterior UCA (A-UCA), CLCI, and intersegmentary angle (ISA) being predictive of sPTB at <34 WG and severe APO. Receiver operator curves were calculated to compare the predictive capacity of these variables, with CL and A-UCA after pessary placement being the best predictive parameters with an area under the curve of 0.88 and 0.87, respectively. CONCLUSIONS: Transvaginal ultrasound after pessary placement detects incorrect pessary placement after pessary insertion and during follow-up. APO and sPTB can be predicted by measuring CL, A-UCA, CLCI, and ISA immediately after pessary placement, being CL and A-UCA more accurate and easier to be measured. Our results help to better identify women in whom the pessary is more likely to fail. Further research is required to assess the effectiveness of applying alternative, sequential or additional treatments to reduce prematurity and our results could be considered when designing such studies.

Accuracy of prenatal ultrasound in the diagnosis of corpus callosum anomalies.

Objectives: The main objective of this study was to evaluate the accuracy of prenatal ultrasound to diagnose corpus callosum alterations, compared to prenatal magnetic resonance imaging (MRI), postnatal image techniques (ultrasound and/or MRI), and post-mortem examination in terminated pregnancies.Methods: Retrospective review of 86 cases of prenatal ultrasound diagnosis of corpus callosum anomalies between January 2007 and December 2015 at a third level Maternal Fetal Medicine center. The study reviewed the findings of prenatal ultrasound and MRI, post-mortem examination in cases of termination of pregnancy (TOP) or stillbirths and postnatal ultrasound, and MRI in neonates. The anomalies of corpus callosum (CC) were classified as complete agenesis of the corpus callosum (ACC), partial ACC, or dysgenesis of CC.Results: Fifty-eight (67.4%) cases resulted in TOP, 26 (30.2%) cases opted to continue with the pregnancy and two (2.3%) cases were lost to follow up. Among the 26 cases that continued with the pregnancy, 24 (92.3%) were live births and two (7.7%) were stillborn. All cases in which a third trimester MRI was performed (n = 46) confirmed the prenatal ultrasound diagnosis of CC anomaly. In seven (15.2%) of them, the MRI found additional intracranial findings and in three cases (6.5%) the type of CC anomaly (complete, partial, or dysgenesis) was reclassified (Kappa index: 0.86, 95% CI: 0.71-1.00). CC anomalies were confirmed in 46 (95.8%) of the 48 cases in which a post-mortem examination was available, the type of anomaly being reclassified in three cases (6.3%) (Kappa index: 0.88, 95% CI: 0.75-1.00). Among the 10 cases in which a postnatal ultrasound was performed, the CC anomaly was confirmed in all and the type of anomaly was reclassified in 1 (10%) of them (Kappa index: 0.75, 95% CI: 0.32-1.00).Conclusion: Corpus callosum agenesis can be detected on the routine mid-trimester ultrasound scan. Prenatal ultrasound and MRI can accurately classify the type of CC abnormality. Moreover, third trimester MRI can detect additional intracranial anomalies in 15% of cases.

Individual risk assessment for prenatal counseling in early-onset growth-restricted and small-for-gestational-age fetuses.

INTRODUCTION: Early-onset fetal growth restriction and small-for-gestational age of fetuses lead to an increased risk of adverse pregnancy outcomes. Doppler abnormalities can predict the occurrence of complications in the short term, but normal fetal Doppler values at the time of diagnosis do not exclude their occurrence in the long term. The objective of this study was to investigate the capacity of a predictive model to assess individual risks for prenatal counseling at the time of diagnosis. MATERIAL AND METHODS: This was a prospective observational study of singleton pregnancies with estimated fetal weight below the 10th centile between 20+0 and 31+6  weeks of gestational age. Placental growth factor (PlGF) and soluble fms-like tyrosine kinase-1 (sFlt-1) levels, estimated fetal weight centile, uterine artery pulsatility index, fetal Doppler and maternal risk factors for placental disease were assessed at the time of enrollment. The occurrence of adverse perinatal outcomes or the need for elective delivery at <30, <34 or <37 weeks was considered an adverse pregnancy outcomes. Univariable logistic regression analysis was used to examine the association between each predictive variable and the adverse outcomes. A multivariable logistic regression-based model was constructed with the combination of all variables. An additional model without sFlt-1/PlGF was also created. Both models, and the sFlt-1/PlGF alone, were used to develop the different formulas to assess individual risks. Receiver operating characteristic curves were constructed to assess and compare their performance of screening. RESULTS: Forty-nine small-for-gestational-age fetuses and 124 with fetal growth restriction were enrolled at a median gestational age of 23.6 weeks. Elective delivery was needed in 77 (44.5%) women at <37 weeks, 53 (30.6%) women at <34 weeks and 30 (17.3%) at <30 weeks. Adverse perinatal outcomes occurred in 81 (55.9%) pregnancies. When areas under the curve were compared among models, no statistically significant differences were observed between the model with sFlt-1/PlGF and sFlt-1/PlGF alone; however, the model without sFlt-1/PlGF yielded an overall poorer performance. CONCLUSIONS: Individual risk assessment can be made at the time of early-onset fetal growth restriction/small-for-gestational-age diagnosis, which permits accurate counseling of parents with an affected fetus. Two formulas could be used: one combining maternal characteristics and ultrasound findings and the other with a single sFlt-1/PlGF measurement.

Chromosomal microarray analysis in fetuses with central nervous system anomalies: An 8-year long observational study from a tertiary care university hospital.

OBJECTIVES: To evaluate the prevalence of DNA copy number variants (CNVs) detected with array comparative genomic hybridization (CGH) in fetuses with central nervous system (CNS) anomalies. Secondary objectives were to describe the prevalence of CNV in specific CNS abnormalities, in isolated defects or associated with other malformations or fetal growth restriction (FGR). METHODS: Observational cohort study in 238 fetuses with CNS anomalies in which an array-CGH had been performed between January 2009 and December 2017. Pathogenic CNV and variants of unknown significance (VUS) were reported. RESULTS: Pathogenic CNVs were found in 16/238 cases (6.7%), VUS in 18/238 (7.6%), and normal result in 204/238 (85.7%) cases. Pathogenic CNVs were more frequent in posterior fossa anomalies (cerebellar hypoplasia 33%, megacisterna magna 20%), moderate ventriculomegaly (11%) and spina bifida (3.7%). Pathogenic CNVs and VUS were found in 7/182 (3.8%) and 14/182 (7.7%) cases of isolated anomalies, in 9/49 (18.4%) and 4/49 (8.2%) presenting another malformation, and in 0/7 and 0/7 cases with associated FGR (P = .001, P = .741, respectively). CONCLUSION: These results provide strong evidence toward performing array in fetuses with CNS anomalies, particular in cases of posterior fossa anomalies. The prevalence of pathogenic CNVs is higher in association with other malformations.

Evaluating the Effect of Pravastatin in Early-Onset Fetal Growth Restriction: A Nonrandomized and Historically Controlled Pilot Study.

OBJECTIVE: This study aimed to analyze the effect of pravastatin on angiogenic factors, feto-maternal Doppler findings and pregnancy outcomes in women with early-onset fetal growth restriction (FGR) treated with pravastatin compared with nontreated controls. STUDY DESIGN: This was a pilot study conducted between March 2016 and September 2017. Women with single pregnancies and FGR diagnosed at ≤ 28 weeks of gestation were offered 40 mg of pravastatin daily. Doppler progression, soluble fms-like tyrosine kinase 1 (sFlt-1)/placental growth factor (PlGF) values, and pregnancy outcomes were assessed and compared with consecutive historical controls. Controls were matched to treated women for gestational age, maternal characteristics, maternal and obstetric history, Doppler severity classification, and angiogenic factors at diagnosis. The sFlt-1/PlGF was measured in maternal serum at two different times: before pravastatin was started (ratio M0) and during pravastatin treatment (ratio M1). Doppler severity was classified into four categories: normal, mild, moderate, and severe. RESULTS: A total of 38 women were enrolled in this study. No differences were observed in baseline characteristics between groups. However, when compared with the ratio M0, M1 was increased by a median (interquartile range) of 67.0 (-34.8 to 197.3) in the control group but decreased by a median (interquartile range) of -10.1 (-53.1 to -0.07) in the pravastatin treated group (p < 0.001). No significant differences were observed in Doppler progression throughout pregnancy. Median interval from diagnosis to delivery was extended by 16.5 days, the median newborn birthweight was increased from 1,040 to 1,300 g, and the number of women with preeclampsia decreased from 9 (47.4%) to 6 (31.6%) in treated women; however, these trends were not statistically significant. CONCLUSION: In women with early-onset FGR, treatment with pravastatin 40 mg daily was associated with significant improvement in the angiogenic profile. Additionally, median pregnancy duration and median birthweight increased and the incidence of PE was reduced in treated women. Nevertheless, since this pilot study was underpowered, none of these differences were statistically significant. KEY POINTS: · Pravastatin improves sFlt-1/PlGF in FGR.. · Pregnancy duration tended to be greater in treated women.. · Birthweight tended to be greater in treated women..

Zika Virus Infection in Tourists Travelling to Thailand: Case Series Report.

Thailand is a popular tourist destination where Zika virus (ZIKV) transmission is currently active. To our knowledge, there are no reports of ZIKV infection imported from Thailand and affecting children. Here, we describe the clinical and microbiological findings in three cases of vector-borne ZIKV infection: An 11-year-old boy, a 2-year-old girl, and her pregnant mother, this last case leading to the prenatal exposure of her second baby to ZIKV in the second trimester of pregnancy. All patients were diagnosed after traveling to Thailand between September 2019 and January 2020. No complications were detected in any patient at follow-up, and the prenatally exposed fetus showed no abnormalities during intensive antenatal health care monitoring. On postnatal study, there were no clinical signs or microbiological findings of mother-to-child ZIKV transmission. ZIKV IgG was initially positive, but seroreversion occurred at 4 months of life. This report describes the clinical and serological evolution of vector-borne ZIKV infection occurring in dengue-naïve tourists returning from Thailand. The World Health Organization currently recommends that pre-travel advice to prevent arbovirus infection should be maintained in travelers to Southeast Asia.

Fetal Transient Skin Edema in Two Pregnant Women With Coronavirus Disease 2019 (COVID-19).

BACKGROUND: The risk of vertical transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection remains unknown. Positive reverse-transcription polymerase chain reaction (RT-PCR) test results for SARS-CoV-2 infection in neonates and placental tissue have been reported, and immunoglobulin M antibodies have been detected in neonates born to mothers with infection. CASES: The first case is a woman at 22 3/7 weeks of gestation with coronavirus disease 2019 (COVID-19) who was admitted to the intensive care unit. In the second case, the patient remained at home with mild symptoms, starting at 20 weeks of gestation. In both cases, fetal skin edema was observed on ultrasound examination while maternal SARS-COV-2 RT-PCR test results were positive and resolved when maternal SARS-COV-2 RT-PCR test results became negative. The RT-PCR test result for SARS-CoV-2 in amniotic fluid was negative in both cases. The two pregnancies are ongoing and uneventful. CONCLUSION: Transient fetal skin edema noted in these two patients with COVID-19 in the second trimester may represent results of fetal infection or altered fetal physiology due to maternal disease or may be unrelated to the maternal illness.