AbstractFetal intervention has progressed in the past two decades from experimental proof-of-concept to practice-adopted, life saving interventions in human fetuses with congenital anomalies. This ...progress is informed by advances in innovative research, prenatal diagnosis, and fetal surgical techniques. Invasive open hysterotomy, associated with notable maternal-fetal risks, is steadily replaced by less invasive fetoscopic alternatives. A better understanding of the natural history and pathophysiology of congenital diseases has advanced the prenatal regenerative paradigm. By altering the natural course of disease through regrowth or redevelopment of malformed fetal organs, prenatal regenerative medicine has transformed maternal-fetal care. This review discusses the uses of regenerative medicine in the prenatal diagnosis and management of three congenital diseases: congenital diaphragmatic hernia, lower urinary tract obstruction, and spina bifida.
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BFBNIB, CMK, NMLJ, NUK, PNG, SAZU, UL, UM, UPUK
OBJECTIVE:To evaluate feasibility and initial outcomes of fetoscopic tracheal occlusion for severe diaphragmatic hernia compared with a historical cohort who had not received fetal tracheal ...occlusion.
METHODS:Outcomes in a prospective observational cohort who underwent fetoscopic tracheal occlusion for severe fetal left diaphragmatic hernia without associated anomalies were compared with our historical nontreated cohort of matched fetuses of similar severity. Fetuses were classified using the same ultrasonography and magnetic resonance imaging methodology—prospectively in the fetoscopic tracheal occlusion group and retrospectively in the historical nontreated cohort. Obstetric and postnatal outcomes were evaluated and compared.
RESULTS:Between January 2004 and June 2015, 218 fetuses with diaphragmatic hernia were evaluated. Twenty (9%) fetuses had severe left diaphragmatic hernia (lung–head ratio 1.0 or less and liver herniation), of which 9 of 20 were managed without tracheal occlusion. Eleven were offered the procedure and in 10, it was successful. Mean (±standard deviation) gestational age was 27.9±1.1 weeks at attempted balloon placement, 34.1±1.1 weeks at removal, and 35.3±2.2 weeks at delivery. One patient required an ex utero intrapartum treatment procedure at delivery to remove the balloon. There were no maternal complications or fetal deaths. All neonates underwent postnatal repair with a patch. The 6-month, 1-year, and 2-year survival rates were significantly higher in our treated cohort than in our nontreated historical cohort (80% compared with 11%, risk difference 69%, 95% confidence interval CI 38–100%, P=.01; 70% compared with 11%, risk difference 59%, 95% CI 24–94%, P=.02; and 67% compared with 11%, risk difference 56%, 95% CI 19–93%, P=.04, respectively) with reduced need for extracorporeal membrane oxygenation (30% compared with 70%, risk difference 40%, 95% CI 10–79%, P=.05).
CONCLUSION:Fetoscopic tracheal occlusion is feasible and is associated with improved postnatal outcomes in severe left diaphragmatic hernia.
CLINICAL TRIAL REGISTRATION:ClinicalTrials.gov, https://clinicaltrials.gov, NCT00881660.
Melatonin has been proposed as a possible treatment for the deleterious effects of hypoxia/reoxygenation (H/R), such as autophagy, inflammation, and apoptosis. Pathological pregnancies, such as ...preeclampsia, are associated with placental H/R, and decreased placental melatonin synthesis as well as lower melatonin levels in the placenta and maternal plasma. However, the effects of exogenous melatonin on inflammation and autophagy induced by pregnancy complications associated with H/R await investigation. This study aimed to determine as to whether melatonin protects human primary villous trophoblasts against H/R‐induced autophagy, inflammation, and apoptosis. Human primary villous cytotrophoblasts were isolated and immunopurified from normal term placentas. These cells were then exposed or not to 1 mmol/L melatonin for 72 hour in normoxia (8% O2), thereby inducing differentiation into syncytiotrophoblast that was then exposed to H/R (0.5% O2, for 4 hour) or normoxia. H/R decreased endogenous melatonin synthesis (by 68%) and interleukin (IL)‐10 levels (by 72%), coupled to increased tumor necrosis factor (TNF) (by 114%), IL‐6 (by 55%), and NFκB (by 399%), compared to normoxia. Melatonin treatment reversed the H/R effect, restoring IL‐10, TNF, and IL‐6 levels to those of the normoxia condition. Melatonin, as well as NFκB inhibition, enhanced autophagy activation, consequently increasing syncytiotrophoblast survival in H/R conditions. This study suggests that H/R, which is present in pregnancy complications, inhibits endogenous melatonin production, thereby contributing to reduced syncytiotrophoblast viability. Results indicate that exogenous melatonin treatment may afford protection against H/R‐induced damage, thereby enhancing placental cell survival, and contributing to improved fetal outcomes.
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DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UILJ, UKNU, UL, UM, UPUK
Problem
Pregnancy requires balance between tolerance to the haploidentical fetus and the mother's ability to mount immune responses. There are parallels to this phenomenon that occur in metastatic ...cancer. We assessed soluble program death ligand‐1 soluble PD‐L1 (sPD‐L1) and galectin‐9 in the blood of pregnant women during gestation as these molecules are highly involved in immune suppression during cancer.
Method of study
Maternal blood was collected from 30 primigravida women at monthly intervals during pregnancy, delivery and 6‐week post‐partum. Blood was analyzed for sPD‐L1 and galectin‐9 concentrations by ELISA. Term placentas were collected in formalin and IHC was completed for PD‐L1 and galectin‐9 expression.
Results
Maternal blood levels of sPD‐L1 (0.438 ng/mL) and galectin‐9 (1976 pg/mL) were elevated early in normal pregnancies compared to non‐pregnant controls (0.242 ng/mL and 773 pg/mL, respectively). sPD‐L1 increased throughout gestation, whereas galectin‐9 remained elevated until parturition; both proteins returned to control levels post‐partum. Women carrying male fetuses had significantly higher galectin‐9 levels, but not sPD‐L1, than those carrying females (2263 pg/mL vs 1874 pg/mL; P = .0005). Trophoblast cells of the term placenta coexpress galectin‐9 and PD‐L1.
Conclusion
Immune‐regulatory molecules galectin‐9 and sPD‐L1 increased during pregnancy and may play a role in immune tolerance that is critical for the fetus.
Normal human pregnancy is associated with increased levels of immunosuppressive soluble program death ligand‐1 (sPD‐L1) and galectin‐9.
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DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK
Background: Isolation measures used to contain epidemics generate social interaction restrictions and impose changes in routines of the public that increase negative psychological outcomes. Anxiety ...and depression are the most common symptoms. Objective: To evaluate the mental health of the Brazilian population during the SARs-CoV-2 pandemic and its relationship with demographic and health characteristics. Methods: Adults from all Brazilian States participated (n = 12,196; women: 69.8%, mean age = 35.2 years). The Depression, Anxiety and Stress Scale, and the Impact of Event Scale–revised were used (online survey). Data validity and reliability were verified by confirmatory factor analysis and ordinal alpha coefficient. The probability of presenting psychological symptoms was calculated by multiple logistic regression and odds ratio (OR) (0 = without symptoms, 1 = with mild, moderate, and severe levels of symptoms). Results: High prevalence of depression (61.3%), anxiety (44.2%), stress (50.8%), and psychological impact (54.9%) due to the isolation experienced from the pandemic was found. Younger individuals (OR = 1.58–3.58), those that felt unsafe (OR = 1.75–2.92), with a previous diagnosis of mental health (OR = 1.72–2.64) and/or had general health problems before the pandemic (OR = 1.17–1.51), who noticed changes in their mental state due to the pandemic context (OR = 2.53–9.07), and excessively exposed to the news (OR = 1.19–2.18) were at increased risk of developing symptoms. Women (OR = 1.35–1.65) and those with lower economic status (OR = 1.38–2.69) were more likely to develop psychological symptoms. Lower educational levels increased the likelihood of depressive (OR = 1.03–1.34) and intrusive symptoms (OR = 1.09–1.51). Conclusions: The pandemic and related factors can have a high impact on the mental health of the population. Demographic characteristics can influence the occurrence of psychological symptoms.
Introduction
Prenatal 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.
Methods
A survey regarding prenatal CDH work‐up was sent to each member center of the North American Fetal Therapy Network (NAFTNet) (n = 36).
Results
All 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.
Conclusion
Prenatal CDH work‐up and management differs considerably among North American fetal diagnostic centers, highlighting a need for its standardization.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
This study aims to evaluate the outcomes of fetal sacrococcygeal teratoma (SCT) submitted to prenatal interventions.
We performed a systematic literature review of fetal SCT patients and compared the ...outcomes between open fetal surgery and percutaneous intervention. In addition, we also compared the results of SCT fetuses who did not undergo any surgical intervention (NI).
We identified 16 cases of open fetal surgery (OS), 48 cases of percutaneous fetal intervention (PI), and 93 NI patients. The survival rate was 56.2% in OS, 45.8% in PI (
= 0.568), and 71.0% in NI patients. The gestational age at delivery was earlier in cases where there was no survival compared to cases where the fetuses did survive across all evaluated cohorts (OS:
= 0.033, PI:
< 0.001, NI:
< 0.001). The gestational weeks at delivery in OS and PI fetuses were more similar; however, OS tended to be performed later on in pregnancy, and the affected fetuses had more severe presented findings. In our evaluation, we determined that the presence of fetal hydrops and cardiac failure had no significant impact on survival in SCT cases. In NI patients, polyhydramnios was much higher in fetuses who did not survive compared to their surviving cohorts (
< 0.001).
In conclusion, gestational age at delivery can affect the short-term prognosis of fetuses affected with sacrococcygeal teratomas. Regardless of the mode of delivery or the necessity for intervention during the fetal period, monitoring for complications, including polyhydramnios, can prevent premature delivery.
Since the declaration of the global pandemic of COVID-19 by the World Health Organization on 11 March 2020, we have continued to see a steady rise in the number of patients infected by SARS-CoV-2. ...However, there is still very limited data on the course and outcomes of this serious infection in a vulnerable population of pregnant patients and their fetuses. International perinatal societies and institutions including SMFM, ACOG, RCOG, ISUOG, CDC, CNGOF, ISS/SIEOG, and CatSalut have released guidelines for the care of these patients. We aim to summarize these current guidelines in a comprehensive review for patients, healthcare workers, and healthcare institutions. We included 15 papers from 10 societies through a literature search of direct review of society's websites and their journal publications up till 20 April 2020. Recommendations specific to antepartum, intrapartum, and postpartum were abstracted from the publications and summarized into Tables. The summary of guidelines for the management of COVID-19 in pregnancy across different perinatal societies is fairly consistent, with some variation in the strength of recommendations. It is important to recognize that these guidelines are frequently updated, as we continue to learn more about the course and impact of COVID-19 in pregnancy.
Fetoscopic Release of Amniotic Band Syndrome Minella, Chris; Costantino, Benedicte; Ruano, Rodrigo ...
Journal of ultrasound in medicine,
05/2021, Volume:
40, Issue:
5
Journal Article
Peer reviewed
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.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK