Ruano, Rodrigo

AbstractProblemCell‐free fetal DNA (cffDNA) shed from the placenta can be detected in maternal blood and increases incrementally during gestation. Concentrations are further elevated with pregnancy complications. Specific activators of cffDNA release in such complications have not been identified. Here, we use trophoblast cells from early and term placenta to examine cffDNA release following apoptosis, infection, and sterile inflammatory stress.Method of StudyHTR8/SVneo cells were used to model first‐trimester trophoblasts, and term cytotrophoblasts (CTBs) were isolated from placentae collected after uncomplicated deliveries. Trophoblasts were treated with varying concentrations of doxorubicin (DOX), lipopolysaccharide (LPS), or high‐mobility group box protein 1 (HMGB1) for 18 h. Cells or supernatants were quantified for caspase‐3/7 cleavage, pro‐inflammatory cytokine secretion, and cffDNA release.ResultsBoth HTR8/SVneo and CTBs underwent caspase‐3/7 cleavage following DOX treatment, with HTR8/SVneo cells more sensitive to apoptosis than term CTBs. Apoptotic cells released more cffDNA in a dose‐dependent manner. Treatment with LPS resulted in an increase in pro‐inflammatory IL‐6 release, particularly in term CTBs compared to early trophoblasts; however, LPS did not affect cffDNA release. Lastly, while neither cell released more TNF‐α following stimulation with HMGB1, both HTR8/SVneo and CTBs released significantly more cffDNA in the presence of HMGB1.ConclusionsThese data show that apoptosis and sterile inflammation induced by DOX and HMGB1, respectively, cause an increase in cffDNA concentrations in both first‐trimester and term trophoblasts. Understanding physiologic release of cffDNA during healthy and complicated pregnancy can identify new targets for the diagnosis and treatment of gestational complications.

AbstractObjectiveTo evaluate inter‐rater agreement for sonographic classification of stomach position (as a surrogate for liver herniation) in fetal left congenital diaphragmatic hernia (LCDH) among: (i) fetal medicine specialists from the North American Fetal Therapy Network (NAFTNet) centers within and without the fetal endoscopic tracheal occlusion (FETO) consortium and in comparison to an expert external reviewer (ER1); and (iii) among two expert ERs (ER1 and ER2).MethodsForty‐eight physicians from 26 NAFTNet centers and 2 ERs were asked to assess 13 sonographic clips of isolated LCDH and classify stomach position as “intra‐abdominal,” “anterior left chest,” “mid to posterior left chest,” or “retro‐cardiac" based on the classification published by Basta et al.8 Interrater agreement was assessed by determining proportion of stomach position ratings concordant amongst NAFTNet participants and ER1. Agreement for stomach position between ERs was calculated using kappa statistics.ResultsAgreement for stomach position was 69% (39%–85%; n = 19) and 54% (23%–92%; n = 29) among FETO and non‐FETO NAFTNet participants, respectively, when compared to ER1. Most disagreement in stomach position was related to a discrepancy of one position. ERs were in agreement for stomach position in 5 of 13 cases (38.5%) and inter‐rater agreement was highest for “anterior” stomach position.ConclusionInterrater agreement for stomach position assessment in CDH was poor across NAFTNet and indeed amongst expert reviewers.

Background: The coronavirus disease 2019 (COVID-19) pandemic may have an effect on maternal anxiety and influence postpartum experience. Objective: To study the prevalence of maternal anxiety in late pregnancy in the context of the COVID-19 outbreak in Brazil and to analyze its association with maternal knowledge and concerns about the pandemic. Methods: This was a national multicenter cross-sectional study performed in 10 different public university hospitals, between 1 June and 31 August 2020, in Brazil. The inclusion criteria were: maternal age more than 18 years; gestational age more than 36 weeks at childbirth; single alive newborn without malformations; and absence of mental disorders. We applied a structured questionnaire to explore the knowledge and concerns about COVID-19. Maternal anxiety was assessed using the Beck Anxiety Inventory (BAI). Results: Of the 1662 women interviewed, the BAI score in late pregnancy indicated that 13.9% presented moderate and 9.6% severe maternal anxiety. Moderate or severe maternal anxiety was independently associated with the fear of being unaccompanied at childbirth (aOR1.12, 95% CI 1.10–1.35), and independent protective factors were confidence in knowing how to protect oneself from COVID-19 (aOR0.89, 95% CI 0.82–0.97) and how to safely breastfeed (aOR0.89, 95% CI 0.83–0.95). Conclusion: The COVID-19 pandemic has a significant impact on maternal anxiety.

Gestational diabetes mellitus (GDM) is a frequently observed complication of pregnancy and is associated with an elevated risk of adverse maternal and neonatal outcomes. Many women with GDM will go on to have future pregnancies, and these pregnancies may or may not be affected by GDM. We conducted a literature search, and based on data from key studies retrieved during the search, we describe the epidemiology of GDM recurrence. This includes a summary of the observed clinical risk factors of increasing maternal age, weight, ethnicity, and requirement for insulin in the index pregnancy. We then present our data from Mayo Clinic (January 2013–December 2017) which identifies a GDM recurrence rate of 47.6%, and illustrates the relevance of population-based studies to clinical practice. Lastly, we examine the available evidence on strategies to prevent GDM recurrence, and note that more research is needed to evaluate the effect of interventions before, during and after pregnancy.

AbstractIntroductionPrenatal work‐up for congenital diaphragmatic hernia (CDH) is important for risk stratification, standardization, counseling, and optimal therapeutic choice. To determine current practice patterns regarding prenatal CDH work‐up, including prenatal ultrasound and magnetic resonance imaging (MRI) use, and to identify areas for standardization of such evaluation between fetal centers.MethodsA survey regarding prenatal CDH work‐up was sent to each member center of the North American Fetal Therapy Network (NAFTNet) (n = 36).ResultsAll responded. Sonographic measurement of lung‐to‐head ratio (LHR) was determined by all, 89% (32/36) of which routinely calculate observed‐to‐expected LHR. The method for measuring LHR varied: 58% (21/36) used a “trace” method, 25% (9/36) used “longest axis,” and 17% (6/36) used an “antero‐posterior” method. Fetal MRI was routinely used in 78% (28/36) of centers, but there was significant variability in fetal lung volume measurement. Whereas all generated a total fetal lung volume, the planes, methodology and references values varied significantly. All evaluated liver position, 71% (20/28) evaluated stomach position and 54% (15/28) quantified the degree of liver herniation. More consistency in workup was seen between centers offering fetal intervention.ConclusionPrenatal CDH work‐up and management differs considerably among North American fetal diagnostic centers, highlighting a need for its standardization.

Abstract Objective The present comprehensive review aims to show the full extent of what is known to date and provide a more thorough view on the effects of SARS-CoV2 in pregnancy. Methods Between March 29 and May, 2020, the words COVID-19, SARS-CoV2, COVID-19 and pregnancy, SARS-CoV2 and pregnancy, and SARS and pregnancy were searched in the PubMed and Google Scholar databases; the guidelines from well-known societies and institutions (Royal College of Obstetricians and Gynaecologists [RCOG], American College of Obstetricians and Gynecologists [ACOG], International Society of Ultrasound in Obstetrics & Gynecology [ISUOG], Centers for Disease Control and Prevention [CDC], International Federation of Gynecology and Obstetrics [FIGO]) were also included. Conclusion The COVID-19 outbreak resulted in a pandemic with > 3.3 million cases and 230 thousand deaths until May 2nd. It is caused by the SARS-CoV2 virus and may lead to severe pulmonary infection and multi-organ failure. Past experiences show that unique characteristics in pregnancy make pregnant women more susceptible to complications from viral infections. Yet, this has not been reported with this new virus. There are risk factors that seem to increase morbidity in pregnancy, such as obesity (body mass index [BMI] > 35), asthma and cardiovascular disease. Current reports describe an increased rate of preterm birth and C-section. Vertical transmission is still a possibility, due to a few reported cases of neonatal positive real-time polymerase chain reaction (RT-PCR) in nasal swab, amniotic fluid, and positive immunoglobulin M (IgM) in neonatal blood. Treatments must be weighed in with caution due to the lack of quality trials that prove their effectiveness and safety during pregnancy. Medical staff must use personal protective equipment in handling SARS-CoV2 suspected or positive patients and be alert for respiratory decompensations.

Amniotic band syndrome is a rare condition. There have been few cases reported of fetoscopic band dissection. The aim of this case series is to report 3 cases of fetoscopic treatment for amniotic band syndrome, including indication for surgery, technical aspects, complications and outcomes.Fetoscopic treatment was performed respectively at 23 5/7, 26 5/7 and 18 3/7 weeks' gestation. Two procedures were performed with a laser fiber through a single trocar whereas one surgery was performed with scissors.In conclusion, fetoscopic release of the amniotic bands in case of amniotic band syndrome is feasible with encouraging results in order to prevent amputation and dysfunction of the extremities.