Management advances for congenital diaphragmatic hernia: integrating prenatal and postnatal perspectives.

In congenital diaphragmatic hernia (CDH), abdominal organs are displaced into the chest, compress the lungs, and cause mediastinal shift. This contributes to development of pulmonary hypoplasia and hypertension, which is the primary determinant of morbidity and mortality for affected newborns. The severity is determined using prenatal imaging as early as the first trimester and is related to the laterality of the defect, extent of lung compression, and degree of liver herniation. Comprehensive evaluation of fetal CDH includes imaging-based severity assessment, severity assessment, and evaluation for structural or genetic abnormalities to differentiate isolated from complex cases. Prenatal management involves multispecialty counseling, consideration for fetal therapy with fetoscopic endoluminal tracheal occlusion (FETO) for severe cases, monitoring and intervention for associated polyhydramnios or signs of preterm labor if indicated, administration of antenatal corticosteroids in the appropriate setting, and planned delivery to optimize the fetal condition at birth. Integrated programs that provide a smooth transition from prenatal to postnatal care produce better outcomes. Neonatal care involves gentle ventilation to avoid hyperinflation and must account for transitional physiology to avoid exacerbating cardiac dysfunction and decompensation. Infants who have undergone and responded to FETO have greater pulmonary capacity than expected, but cardiac dysfunction seems unaffected. In about 25-30% of CDH neonates extracorporeal life support is utilized, and this provides a survival benefit for patients with the highest predicted mortality, including those who underwent FETO. Surgical repair after initial medical management for the first 24-48 hours of life is preferred since later repair is associated with delayed oral feeding, increased need for tube feeds, and increased post-repair ventilation requirement and supplemental oxygen at discharge. With overall survival rates >70%, contemporary care involves management of chronic morbidities in the context of a multidisciplinary clinic setting.

Neurodevelopmental Outcomes in Children After Fetoscopic Endoluminal Tracheal Occlusion for Severe Congenital Diaphragmatic Hernia: Results From a Multidisciplinary Clinic.

BACKGROUND: We compared early neurodevelopmental morbidity in young children with severe CDH who underwent FETO to those without fetal therapy. METHODS: We conducted a prospective study of severe CDH patients undergoing FETO (n = 18) at a single North American center from 2015 to 2021 (NCT02710968). Outpatient survivors (n = 12) were evaluated by a multidisciplinary team and compared to expectantly managed CDH patients. Neurodevelopmental outcomes were assessed using the Capute Scales [Clinical Linguistic and Auditory Milestone Scales (CLAMS) and Cognitive Adaptive Test (CAT)], with a developmental quotient (DQ) < 85 indicative of at-risk for delay. RESULTS: At one year, 58% (n = 7) of FETO patients underwent evaluation, with notable concern for language delay (CLAMS median DQ, 80.1 [interquartile range, 67.6-86.7]). FETO scores improved by 24-months, whereas high severity/non-FETO scores declined [CLAMS median DQ (Difference in DQ), 92.3 (+12.2) vs. 77.1 (-13.4), respectively; p = 0.049]. On the initial CAT, FETO patients had concern for visual motor and problem-solving delays, with a median DQ of 81.3 (62.1-89.4). At 24-months, FETO patients had improving scores [Median CAT DQ, 90.8 (+9.5)], whereas high severity/non-FETO [87.5 (-3.0), p = 0.28] had declining scores. CONCLUSION: These initial data suggest that FETO is associated with favorable neurodevelopmental outcomes at 24-months compared to severe CDH under expectant management. LEVEL OF EVIDENCE: III.

The role of fetal therapy in the management of mirror syndrome: a narrative review.

OBJECTIVES: Mirror syndrome (MS) is a condition characterized by the presence of maternal, fetal, and placental edema and is reversible through delivery or pregnancy termination. As fetal hydrops itself may be amenable to treatment, we sought to determine outcomes for MS primarily managed by fetal therapy through a narrative review of the literature and cases managed at our fetal center. STUDY DESIGN: PubMed, Embase, Web of Science, Scopus, and Google Scholar databases were searched through January 2024 using key words: mirror syndrome, Ballantyne's syndrome, fetal hydrops, maternal hydrops, pseudotoxemia, triple edema, maternal recovery, fetal therapy, and resolution. Manuscripts describing primary management by fetal therapy that included maternal and fetal outcomes were identified. Clinical details of MS patients managed with fetal therapy at our center were also included for descriptive analysis. RESULTS: 16 of 517 manuscripts (3.1%) described fetal therapy as the primary intended treatment in 17 patients. 3 patients managed at our center were included in the analysis. Among 20 patients undergoing primary fetal therapy for management of mirror syndrome, median gestational age of presentation was 24 weeks and 5 days gestation; predominant clinical findings were maternal edema (15/20), proteinuria (10/20), pulmonary edema (8/20), and hypertension (8/20); the primary laboratory abnormalities were anemia (8/20) and elevated creatinine or transaminases (5/20). Condition-specific fetal therapies led to resolution of hydrops in 17 (85%) cases and MS in 19 (95%) cases. The median time to hydrops resolution was 7.5 days and to resolution of mirror syndrome was 10 days. Fetal therapy prolonged pregnancy by a median of 10 weeks with a median gestational age of 35 weeks and 5 days at delivery. All women delivered for indications other than mirror syndrome and 19/20 fetuses survived. CONCLUSION: In appropriately selected cases, MS often resolves after fetal therapy of hydrops allowing for safe pregnancy prolongation with good maternal and infant outcomes.

Maternal exposure to polyethylene micro- and nanoplastics impairs umbilical blood flow but not fetal growth in pregnant mice.

While microplastics have been recently detected in human blood and the placenta, their impact on human health is not well understood. Using a mouse model of environmental exposure during pregnancy, our group has previously reported that exposure to polystyrene micro- and nanoplastics throughout gestation results in fetal growth restriction. While polystyrene is environmentally relevant, polyethylene is the most widely produced plastic and amongst the most commonly detected microplastic in drinking water and human blood. In this study, we investigated the effect of maternal exposure to polyethylene micro- and nanoplastics on fetal growth and placental function. Healthy, pregnant CD-1 dams were divided into three groups: 106 ng/L of 740-4990 nm polyethylene with surfactant in drinking water (n = 12), surfactant alone in drinking water (n = 12) or regular filtered drinking water (n = 11). At embryonic day 17.5, high-frequency ultrasound was used to investigate the placental and fetal hemodynamic responses following exposure. While maternal exposure to polyethylene did not impact fetal growth, there was a significant effect on placental function with a 43% increase in umbilical artery blood flow in the polyethylene group compared to controls (p < 0.01). These results suggest polyethylene has the potential to cause adverse pregnancy outcomes through abnormal placental function.

Precarious hope: Ethical considerations for offering experimental fetal therapies outside of research after initial studies in humans.

OBJECTIVE: Risks and benefits of experimental fetal therapies can remain uncertain after initial clinical studies, especially long-term effects. Nevertheless, pregnant individuals may request them, hoping to benefit their future child. Guidance about offering experimental fetal therapies outside research (as "innovative therapy") is limited, despite their ethical complexity. We propose points for clinicians and reviewers to consider when deciding whether and how to offer experimental fetal therapies as innovative therapies after initial clinical studies. METHOD: We used conceptual analysis and a current case to develop points for consideration, grounded in broader debates on innovative therapy and the unique challenges associated with experimental fetal therapies. RESULTS: Clinicians should evaluate whether offering experimental fetal therapies as innovative therapy is appropriate for a pregnant individual and their fetus. The anticipated risk-benefit ratio for the fetus should be favorable. For the pregnant individual, risks may outweigh benefits, within reasonable limits. Medical resources should be sufficient to ensure appropriate care. Clinicians should support pregnant individuals in making informed choices. Clinicians offering innovative therapies with more than minimal risk should collect and report data on outcomes. Independent review should take place. CONCLUSION: Considering these points may advance the interests of fetuses, future children, and their families.

Polystyrene micro- and nanoplastics cause placental dysfunction in mice†.

Maternal exposure to microplastics and nanoplastics has been shown to result in fetal growth restriction in mice. In this study, we investigated the placental and fetal hemodynamic responses to plastics exposure in mice using high-frequency ultrasound. Healthy, pregnant CD-1 dams were given either 106 ng/L of 5 µm polystyrene microplastics or 106 ng/L of 50 nm polystyrene nanoplastics in drinking water throughout gestation and were compared with controls. Maternal exposure to both microplastics and nanoplastics resulted in evidence of placental dysfunction that was highly dependent on the particle size. The umbilical artery blood flow increased by 48% in the microplastic-exposed group and decreased by 25% in the nanoplastic-exposed group compared to controls (p < 0.05). The microplastic- and nanoplastic-exposed fetuses showed a significant decrease in the middle cerebral artery pulsatility index of 10% and 13%, respectively, compared to controls (p < 0.05), indicating vasodilation of the cerebral circulation, a fetal adaptation that is part of the brain sparing response to preserve oxygen delivery. Hemodynamic markers of placental dysfunction and fetal hypoxia were more pronounced in the group exposed to polystyrene nanoplastics, suggesting nanoplastic exposure during human pregnancy has the potential to disrupt fetal brain development, which in turn may cause suboptimal neurodevelopmental outcomes.

Cervical pessary to prevent preterm birth and poor neonatal outcome: An integrity meta-analysis of randomized controlled trials focusing on adherence to the European Medical Device Regulation.

BACKGROUND: Findings from randomized trials (RCTs) on cervical pessary treatment to prevent spontaneous preterm birth are inconsistent. OBJECTIVES: Our hypothesis suggests that adhering to the European Medical Device Regulation (MDR) and following the instructions for use are essential prerequisites for successful therapy. Conversely, the non-adherence to these guidelines will probably contribute to its failure. SEARCH STRATEGY AND SELECTION CRITERIA: Based on validated criteria from integrity assessments we performed a systematic review identifying 14 RCTs evaluating the effect of cervical pessaries. DATA COLLECTION AND ANALYSIS: We analyzed the implications of 14 criteria each accounting for 0-2 points of a score reflecting the clinical evaluation plan (CEP) as proposed by the MDR to evaluate the risk-benefit ratio of medical devices. MAIN RESULTS: Seven RCTs in each singleton and twin pregnancies (5193 "cases") were included, detecting a high heterogeneity within control groups (I2 = 85% and 87%, respectively, P < 0.01). The CEP score varied from 11 to 26 points for all studies. The most common reasons for low scores and potential data compromise were poor recruitment rates, no (completed) power analysis, and no pre-registration, but mainly non-adherence to technical, biological, and clinical equivalence to the instructions for use as required by the MDR. All trials with score values greater than 20 had applied audit procedures. Within this group we found significantly reduced rates of spontaneous preterm birth at less than 34 weeks within the pessary group in singleton (odds ratio 0.28; 95% confidence interval 0.12-0.65) and twin pregnancies (odds ratio 0.30; 95% confidence interval 0.13-0.67). Similarly, there was a significant reduction in the composite poor neonatal outcome in singleton (odds ratio 0.25; 95% confidence interval 0.10-0.61) and twin pregnancies (odds ratio 0.54; 95% confidence interval 0.35-0.82) after a pessary as compared with controls. CONCLUSION: Non-audited RCTs and meta-analyses mixing studies of different clinical quality as pre-defined by a CEP and the MDR pose the risk for erroneous conclusions.

Fetoscopic Endoluminal Tracheal Occlusion for Severe, Left-Sided Congenital Diaphragmatic Hernia: The North American Fetal Therapy Network Fetoscopic Endoluminal Tracheal Occlusion Consortium Experience.

OBJECTIVE: To report the outcomes of fetoscopic endoluminal tracheal occlusion in a multicenter North American cohort of patients with isolated, left-sided congenital diaphragmatic hernia (CDH) and to compare neonatal mortality and morbidity in patients with severe left-sided congenital diaphragmatic hernia who underwent fetoscopic endoluminal tracheal occlusion with those expectantly managed. METHODS: We analyzed data from 10 centers in the NAFTNet (North American Fetal Therapy Network) FETO (Fetoscopic Endoluminal Tracheal Occlusion) Consortium registry, collected between November 1, 2008, and December 31, 2020. In addition to reporting procedure-related surgical outcomes of fetoscopic endoluminal tracheal occlusion, we performed a comparative analysis of fetoscopic endoluminal tracheal occlusion compared with contemporaneous expectantly managed patients. RESULTS: Fetoscopic endoluminal tracheal occlusion was successfully performed in 87 of 89 patients (97.8%). Six-month survival in patients with severe left-sided congenital diaphragmatic hernia did not differ significantly between patients who underwent fetoscopic endoluminal tracheal occlusion and those managed expectantly (69.8% vs 58.1%, P =.30). Patients who underwent fetoscopic endoluminal tracheal occlusion had higher rates of preterm prelabor rupture of membranes (54.0% vs 14.3%, P <.001), earlier gestational age at delivery (median 35.0 weeks vs 38.3 weeks, P <.001), and lower birth weights (mean 2,487 g vs 2,857 g, P =.001). On subanalysis, in patients for whom all recorded observed-to-expected lung/head ratio measurements were below 25%, patients with fetoscopic endoluminal tracheal occlusion required fewer days of extracorporeal membrane oxygenation (ECMO) (median 9.0 days vs 17.0 days, P =.014). CONCLUSION: In this cohort, fetoscopic endoluminal tracheal occlusion was successfully implemented across several North American fetal therapy centers. Although survival was similar among patients undergoing fetoscopic endoluminal tracheal occlusion and those expectantly managed, fetoscopic endoluminal tracheal occlusion in North American centers may reduce morbidity, as suggested by fewer days of ECMO in those patients with persistently reduced lung volumes (observed-to-expected lung/head ratio below 25%).

Neonatal Survival After Serial Amnioinfusions for Bilateral Renal Agenesis: The Renal Anhydramnios Fetal Therapy Trial.

Importance: Early anhydramnios during pregnancy, resulting from fetal bilateral renal agenesis, causes lethal pulmonary hypoplasia in neonates. Restoring amniotic fluid via serial amnioinfusions may promote lung development, enabling survival. Objective: To assess neonatal outcomes of serial amnioinfusions initiated before 26 weeks' gestation to mitigate lethal pulmonary hypoplasia. Design, Setting, and Participants: Prospective, nonrandomized clinical trial conducted at 9 US fetal therapy centers between December 2018 and July 2022. Outcomes are reported for 21 maternal-fetal pairs with confirmed anhydramnios due to isolated fetal bilateral renal agenesis without other identified congenital anomalies. Exposure: Enrolled participants initiated ultrasound-guided percutaneous amnioinfusions of isotonic fluid before 26 weeks' gestation, with frequency of infusions individualized to maintain normal amniotic fluid levels for gestational age. Main Outcomes and Measures: The primary end point was postnatal infant survival to 14 days of life or longer with dialysis access placement. Results: The trial was stopped early based on an interim analysis of 18 maternal-fetal pairs given concern about neonatal morbidity and mortality beyond the primary end point despite demonstration of the efficacy of the intervention. There were 17 live births (94%), with a median gestational age at delivery of 32 weeks, 4 days (IQR, 32-34 weeks). All participants delivered prior to 37 weeks' gestation. The primary outcome was achieved in 14 (82%) of 17 live-born infants (95% CI, 44%-99%). Factors associated with survival to the primary outcome included a higher number of amnioinfusions (P = .01), gestational age greater than 32 weeks (P = .005), and higher birth weight (P = .03). Only 6 (35%) of the 17 neonates born alive survived to hospital discharge while receiving peritoneal dialysis at a median age of 24 weeks of life (range, 12-32 weeks). Conclusions and Relevance: Serial amnioinfusions mitigated lethal pulmonary hypoplasia but were associated with preterm delivery. The lower rate of survival to discharge highlights the additional mortality burden independent of lung function. Additional long-term data are needed to fully characterize the outcomes in surviving neonates and assess the morbidity and mortality burden. Trial Registration: ClinicalTrials.gov Identifier: NCT03101891.

Maternal exposure to polystyrene nanoplastics alters fetal brain metabolism in mice.

INTRODUCTION: Plastics used in everyday materials accumulate as waste in the environment and degrade over time. The impacts of the resulting particulate micro- and nanoplastics on human health remain largely unknown. In pregnant mice, we recently demonstrated that exposure to nanoplastics throughout gestation and during lactation resulted in changes in brain structure detected on MRI. One possible explanation for this abnormal postnatal brain development is altered fetal brain metabolism. OBJECTIVES: To determine the effect of maternal exposure to nanoplastics on fetal brain metabolism. METHODS: Healthy pregnant CD-1 mice were exposed to 50 nm polystyrene nanoplastics at a concentration of 106 ng/L through drinking water during gestation. Fetal brain samples were collected at embryonic day 17.5 (n = 18-21 per group per sex) and snap-frozen in liquid nitrogen. Magic angle spinning nuclear magnetic resonance was used to determine metabolite profiles and their relative concentrations in the fetal brain. RESULTS: The relative concentrations of gamma-aminobutyric acid (GABA), creatine and glucose were found to decrease by 40%, 21% and 30% respectively following maternal nanoplastic exposure when compared to the controls (p < 0.05). The change in relative concentration of asparagine with nanoplastic exposure was dependent on fetal sex (p < 0.005). CONCLUSION: Maternal exposure to polystyrene nanoplastics caused abnormal fetal brain metabolism in mice. The present study demonstrates the potential impacts of nanoplastic exposure during fetal development and motivates further studies to evaluate the risk to human pregnancies.

Serial lung mass volume ratios as prognostic indicators of neonatal respiratory morbidity in fetal pulmonary malformations.

BACKGROUND: Several studies have shown that the congenital pulmonary airway malformation volume ratio is a useful prognosticator of neonatal outcome in prenatally diagnosed lung lesions. However, there remains a lack of consensus on which congenital pulmonary airway malformation volume ratio values have the best predictive value because of operator dependence, inherent changes in lung lesion size throughout gestation, and the widespread use of maternal steroids. OBJECTIVE: This study sought to determine the association between serial congenital pulmonary airway malformation volume ratio measurements and neonatal outcomes among fetuses with lung malformations. STUDY DESIGN: This was a retrospective cohort study of fetuses with a prenatally diagnosed lung malformation managed at 2 major fetal centers from January 2010 to December 2021. Prenatal variables, including prospectively measured congenital pulmonary airway malformation volume ratio measurements (initial, maximum, and final), were analyzed. The results were correlated with 3 outcome measures, namely surgical resection before 30 days of life, a need for supplemental O2 at birth, and endotracheal intubation at birth. Statistical analyses were performed using receiver operating characteristic curve analyses, Welch 2 sample t tests, and multivariable logistic regressions (P<.05). RESULTS: There were 123 fetuses with isolated lung lesions identified. Eight (6.5%) had hydrops. The mean initial congenital pulmonary airway malformation volume ratio was 0.67±0.61 cm2 at 22.9±3.9 weeks' gestation. The mean maximum congenital pulmonary airway malformation volume ratio was 1.08 ± 0.94 cm2 at 27.0 ± 4.0 weeks' gestation. The mean final congenital pulmonary airway malformation volume ratio was 0.58±0.60 cm2 at 33.2±4.1 weeks' gestation. At a mean gestational age at delivery of 38.3±2.6 weeks, 15 (12.2%) underwent neonatal lung resection for symptomatic disease. In a multivariable regression, all 3 congenital pulmonary airway malformation volume ratio measurements showed a significant correlation with neonatal lung resection (P<.001). Optimal congenital pulmonary airway malformation volume ratio cutoffs were established based on an initial congenital pulmonary airway malformation volume ratio of ≥0.8 cm2, maximum congenital pulmonary airway malformation volume ratio of ≥1.5 cm2, and a final congenital pulmonary airway malformation volume ratio of ≥1.3 cm2 with associated areas under the curve of 0.89, 0.97, and 0.93, respectively. The final congenital pulmonary airway malformation volume ratio had the highest specificity for predicting surgical lung resection in the early postnatal period. CONCLUSION: Measuring congenital pulmonary airway malformation volume ratios throughout pregnancy in fetuses with pulmonary malformations has clinical value for prenatal counseling and planning care transition after delivery. Fetuses with a final congenital pulmonary airway malformation volume ratio of more than 1.3 cm2 are likely to require neonatal surgery and therefore should be delivered at tertiary care centers with a neonatal intensive care unit and pediatric surgical expertise.

Potential higher risk of tethered spinal cord in children after prenatal surgery for myelomeningocele: A systematic review and meta-analysis.

INTRODUCTION: We performed a systematic review and meta-analysis on the incidence of secondary tethered spinal cord (TSC) between prenatal and postnatal closure in patients with MMC. The objectives was to understand the incidence of secondary TSC after prenatal surgery for MMC compared to postnatal surgery for MMC. MATERIAL AND METHODS: On May 4, 2023, a systematic search was conducted in Medline, Embase, and the Cochrane Library to gather relevant data. Primary studies focusing on repair type, lesion level, and TSC were included, while non-English or non-Dutch reports, case reports, conference abstracts, editorials, letters, comments, and animal studies were excluded. Two reviewers assessed the included studies for bias risk, following PRISMA guidelines. TSC frequency in MMC closure types was determined, and the relationship between TSC occurrence and closure technique was analyzed using relative risk and Fisher's exact test. Subgroup analysis revealed relative risk differences based on study designs and follow-up periods. A total of ten studies, involving 2,724 patients, were assessed. Among them, 2,293 patients underwent postnatal closure, while 431 received prenatal closure for the MMC defect. In the prenatal closure group, TSC occurred in 21.6% (n = 93), compared to 18.8% (n = 432) in the postnatal closure group. The relative risk (RR) of TSC in patients with prenatal MMC closure versus postnatal MMC closure was 1.145 (95%CI 0.939 to 1.398). Fisher's exact test indicated a statistically non-significant association (p = 0.106) between TSC and closure technique. When considering only RCT and controlled cohort studies, the overall RR for TSC was 1.308 (95%CI 1.007 to 1.698) with a non-significant association (p = .053). For studies focusing on children up until early puberty (maximum 12 years follow-up), the RR for tethering was 1.104 (95%CI 0.876 to 1.391), with a non-significant association (p = 0.409). CONCLUSION AND DISCUSSION: This review found no significant increase in relative risk of TSC between prenatal and postnatal closure in MMC patients, but a trend of increased TSC in the prenatal group. More long-term data on TSC after fetal closure is needed for better counseling and outcomes in MMC.

Hypertensive Disorders of Pregnancy and the Cardiovascular System: Causes, Consequences, Therapy, and Prevention.

Hypertensive disorders of pregnancy continue to be significant contributors to adverse perinatal outcome and maternal mortality, as well as inducing life-long cardiovascular health impacts that are proportional to the severity and frequency of pregnancy complications. The placenta is the interface between the mother and fetus and its failure to undergo vascular maturation in tandem with maternal cardiovascular adaptation by the end of the first trimester predisposes to hypertensive disorders and fetal growth restriction. While primary failure of trophoblastic invasion with incomplete maternal spiral artery remodeling has been considered central to the pathogenesis of preeclampsia, cardiovascular risk factors associated with abnormal first trimester maternal blood pressure and cardiovascular adaptation produce identical placental pathology leading to hypertensive pregnancy disorders. Outside pregnancy blood pressure treatment thresholds are identified with the goal to prevent immediate risks from severe hypertension >160/100 mm Hg and long-term health impacts that arise from elevated blood pressures as low as 120/80 mm Hg. Until recently, the trend for less aggressive blood pressure management during pregnancy was driven by fear of inducing placental malperfusion without a clear clinical benefit. However, placental perfusion is not dependent on maternal perfusion pressure during the first trimester and risk-appropriate blood pressure normalization may provide the opportunity to protect from the placental maldevelopment that predisposes to hypertensive disorders of pregnancy. Recent randomized trials set the stage for more aggressive risk-appropriate blood pressure management that may offer a greater potential for prevention for hypertensive disorders of pregnancy. KEY POINTS: · Optimal management of maternal blood pressure to prevent preeclampsia and its risks is undefined.. · Early gestational rheological damage to the intervillous space predisposes to preeclampsia and FGR.. · First trimester blood pressure management may need to aim for normotension to prevent preeclampsia..

Development of a simulator for training of fetoscopic myelomeningocele surgery.

OBJECTIVE: To develop a realistic simulation model for laparotomy-assisted fetoscopic spina bifida aperta (SBa) surgery, to be used for training purposes and preoperative planning. METHODS: The predefined general requirement was a realistic model of an exteriorized uterus, allowing all neurosurgical steps of the intervention. The uterus was modelled using ultrasound and MRI images of a 25 weeks' gravid uterus, consisting of flexible polyurethane foam coated with pigmented silicone. The fetal model, contained an opening on the dorsal side for a customizable spinal insert with all the aspects of a SBa, including a cele, placode, and myofascial and skin layer. The model was assessed in a series of validation experiments. RESULTS: Production costs are low, uterus and fetus are reusable. Placental localization and the level and size of the spinal defect are adjustable, enabling case-specific adaptations. All aspects of the simulator were scored close to realistic or higher for both appearance and functional capacities. CONCLUSIONS: This innovative model provides an excellent training opportunity for centers that are starting a fetoscopic SBa repair program. It is the first simulation model with adjustable spinal defect and placental localisation. Further objective validation is required, but the potential for using this model in preoperative planning is promising.

Morbidity in children after fetoscopic endoluminal tracheal occlusion for severe congenital diaphragmatic hernia: Results from a multidisciplinary clinic.

BACKGROUND: Although fetoscopic endoluminal tracheal occlusion (FETO) was recently shown to improve survival in a multicenter, randomized trial of severe congenital diaphragmatic hernia (CDH), morbidity outcomes remain essentially unknown. The purpose of this study was to assess long-term outcomes in children with severe CDH who underwent FETO. METHODS: We conducted a prospective study of severe CDH patients undergoing FETO at an experienced North American center from 2015-2021 (NCT02710968). This group was compared to a cohort of non-FETO CDH patients with severe disease as defined by liver herniation, large defect size, and/or ECMO use. Clinical data were collected through a multidisciplinary CDH clinic. Statistics were performed with t-tests and Chi-squared analyses (p≤0.05). RESULTS: There were 18 FETO and 17 non-FETO patients. ECMO utilization was 56% in the FETO cohort. Despite significantly lower median observed/expected lung-to-head ratio (O/E LHR) in the FETO group, [FETO: 23% (IQR:18-25) vs. non-FETO: 36% (IQR: 28-41), p<0.001], there were comparable survival rates at discharge (FETO: 78% vs. non-FETO: 59%, p = 0.23) and at 5-years (FETO: 67% vs. non-FETO: 59%, p = 0.53) between the two cohorts. At a median follow up of 5.8 years, metrics of pulmonary hypertension, pulmonary morbidity, and gastroesophageal reflux disease improved among patients after FETO. However, most FETO patients remained on bronchodilators/inhaled corticosteroids (58%) and were feeding tube dependent (67%). CONCLUSIONS: These North American data show that prenatal tracheal occlusion, in conjunction with a long-term multidisciplinary CDH clinic, is associated with acceptable long-term survival and morbidity in children after FETO. LEVEL OF EVIDENCE: Level III.

Maternal exposure to polystyrene microplastics alters placental metabolism in mice.

INTRODUCTION: The rapid growth in the worldwide use of plastics has resulted in a vast accumulation of microplastics in the air, soil and water. The impact of these microplastics on pregnancy and fetal development remains largely unknown. In pregnant mice, we recently demonstrated that exposure to micro- and nanoplastics throughout gestation resulted in significant fetal growth restriction. One possible explanation for reduced fetal growth is abnormal placental metabolism. OBJECTIVES: To evaluate the effect of maternal exposure to microplastics on placental metabolism. METHODS: In the present study, CD-1 pregnant mice were exposed to 5 µm polystyrene microplastics in filtered drinking water at one of four concentrations (0 ng/L (controls), 102 ng/L, 104 ng/L, 106 ng/L) throughout gestation (n = 7-11/group). At embryonic day 17.5, placental tissue samples were collected (n = 28-44/group). Metabolite profiles were determined using 1 H high-resolution magic angle spinning magnetic resonance spectroscopy. RESULTS: The relative concentration of lysine (p = 0.003) and glucose (p < 0.0001) in the placenta were found to decrease with increasing microplastic concentrations, with a significant reduction at the highest exposure concentration. Multivariate analysis identified shifts in the metabolic profile with MP exposure and pathway analysis identified perturbations in the biotin metabolism, lysine degradation, and glycolysis/gluconeogenesis pathways. CONCLUSION: Maternal exposure to microplastics resulted in significant alterations in placental metabolism. This study highlights the potential impact of microplastic exposure on pregnancy outcomes and that efforts should be made to minimize exposure to plastics, particularly during pregnancy.

Fetal Therapy for Renal Anhydramnios.

The most severe forms of congenital anomalies of the kidney and urinary tract present in fetal life with early pregnancy renal anhydramnios and are considered lethal due to pulmonary hypoplasia without fetal therapy. Due to the high rate of additional structural anomalies, genetic abnormalities, and associated syndromes, detailed anatomic survey and genetic testing are imperative when stratifying which pregnancies are appropriate for fetal intervention. Restoring amniotic fluid around the fetus is the principal goal of prenatal treatment. The ongoing multi-center Renal Anhydramnios Fetal Therapy (RAFT) trial is assessing the safety and efficacy of serial amnioinfusions to prevent pulmonary hypoplasia so that the underlying renal disease can be addressed.

Current Status of the Workforce and Training at Fetal Therapy Centers in North America.

INTRODUCTION: We sought to characterize the current workforce and training for fetal intervention procedures at fetal centers in North America. METHODS: An anonymous electronic survey was developed to query the 34 centers in the North American Fetal Treatment Network regarding the demographics and training of their faculty. Telephone surveys were conducted with directors of known fetal intervention fellowships. RESULTS: More than 50% of maternal-fetal medicine (MFM) faculty at fetal centers were female; more than two-thirds of pediatric surgical faculty were male. Most of the training of faculty was undertaken by visiting more experienced centers or having new faculty work with more experienced ones at the same center. Current fetal intervention fellowships appear to achieve levels of competency for intrauterine transfusions and laser therapy for twin-twin transfusion syndrome. Two-thirds of centers stated that they would be able to offer a position to an MFM who completed a formal fellowship in fetal intervention. CONCLUSION: A collaborative effort should be undertaken to establish formal fellowships in fetal medicine and intervention.

Postnatal care setting and survival after fetoscopic tracheal occlusion for severe congenital diaphragmatic hernia: A systematic review and meta-analysis.

BACKGROUND: Fetoscopic endoluminal tracheal occlusion (FETO) was recently shown to improve postnatal survival in a multicenter, randomized controlled trial of infants with severe congenital diaphragmatic hernia (CDH). However, the external validity of this study remains unclear given a lack of standardization in postnatal management approaches. The purpose of this study was to evaluate the impact of an integrated prenatal and postnatal care setting on survival outcomes in severe CDH after FETO. STUDY DESIGN: A systematic review, meta-analysis, and individual participant analysis of FETO outcomes in severe CDH were conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. The primary outcome was survival to discharge. Subgroup analyses of patients managed in integrated versus nonintegrated settings were performed to identify predictors of outcome. RESULTS: The review generated five studies (n = 192) for the meta-analysis of FETO versus expectant prenatal management. These data revealed a significant survival benefit after FETO that was restricted to an integrated setting (OR 2.97, 95% Confidence Interval 1.69-4.26). There were nine studies (n = 150) for the individual participant analysis, which showed that FETO managed in an integrated setting had significantly increased survival rates when compared to FETO treated in a nonintegrated setting (70.7% vs. 45.7%, p = 0.003). Multi-level logistic regression identified increased availability of extracorporeal membrane oxygenation (ECMO) as the strongest determinant of postnatal survival (OR=18.8, p = 0.049). CONCLUSION: This systematic review shows that institutional integration of prenatal and postnatal care is associated with the highest overall survival in children with severe CDH. These data highlight the importance of a standardized, multidisciplinary approach, including access to ECMO, as a critical postnatal component in optimizing FETO outcomes in CDH.

Care Levels for Fetal Therapy Centers.

Fetal therapies undertaken to improve fetal outcome or to optimize transition to neonate life often entail some level of maternal, fetal, or neonatal risk. A fetal therapy center needs access to resources to carry out such therapies and to manage maternal, fetal, and neonatal complications that might arise, either related to the therapy per se or as part of the underlying fetal or maternal condition. Accordingly, a fetal therapy center requires a dedicated operational infrastructure and necessary resources to allow for appropriate oversight and monitoring of clinical performance and to facilitate multidisciplinary collaboration between the relevant specialties. Three care levels for fetal therapy centers are proposed to match the anticipated care complexity, with appropriate resources to achieve an optimal outcome at an institutional and regional level. A level I fetal therapy center should be capable of offering fetal interventions that may be associated with obstetric risks of preterm birth or membrane rupture but that would be very unlikely to require maternal medical subspecialty or intensive care, with neonatal risks not exceeding those of moderate prematurity. A level II center should have the incremental capacity to provide maternal intensive care and to manage extreme neonatal prematurity. A level III therapy center should offer the full range of fetal interventions (including open fetal surgery) and be able manage any of the associated maternal complications and comorbidities, as well as have access to neonatal and pediatric surgical intervention including indicated surgery for neonates with congenital anomalies.