Disease Model of GATA4 Mutation Reveals Transcription Factor Cooperativity in Human Cardiogenesis.

Mutation of highly conserved residues in transcription factors may affect protein-protein or protein-DNA interactions, leading to gene network dysregulation and human disease. Human mutations in GATA4, a cardiogenic transcription factor, cause cardiac septal defects and cardiomyopathy. Here, iPS-derived cardiomyocytes from subjects with a heterozygous GATA4-G296S missense mutation showed impaired contractility, calcium handling, and metabolic activity. In human cardiomyocytes, GATA4 broadly co-occupied cardiac enhancers with TBX5, another transcription factor that causes septal defects when mutated. The GATA4-G296S mutation disrupted TBX5 recruitment, particularly to cardiac super-enhancers, concomitant with dysregulation of genes related to the phenotypic abnormalities, including cardiac septation. Conversely, the GATA4-G296S mutation led to failure of GATA4 and TBX5-mediated repression at non-cardiac genes and enhanced open chromatin states at endothelial/endocardial promoters. These results reveal how disease-causing missense mutations can disrupt transcriptional cooperativity, leading to aberrant chromatin states and cellular dysfunction, including those related to morphogenetic defects.

Comparison of Adverse Clinical Outcomes in Children Hospitalized for Myocarditis with and Without COVID-19.

We used a nationally representative database of the US, which included 1995 myocarditis cases, among whom 620 children had COVID-19. While the risk of in-hospital mortality was not higher, illness severity and length of hospital stay were higher in patients with myocarditis and COVID-19 than those without COVID-19.

Fetal circulatory physiology and brain development in complex congenital heart disease: A multi-modal imaging study.

OBJECTIVE: Fetuses with complex congenital heart disease have altered physiology, contributing to abnormal neurodevelopment. The effects of altered physiology on brain development have not been well studied. We used multi-modal imaging to study fetal circulatory physiology and brain development in hypoplastic left heart syndrome (HLHS) and d-transposition of the great arteries (TGA). METHODS: This prospective, cross-sectional study investigated individuals with fetal congenital heart disease and controls undergoing fetal echocardiography and fetal brain MRI. MRI measured total brain volume and cerebral oxygenation by the MRI quantification method T2*. Indexed cardiac outputs (CCOi) and vascular impedances were calculated by fetal echocardiography. Descriptive statistics assessed MRI and echocardiogram measurement relationships by physiology. RESULTS: Sixty-six participants enrolled (control = 20; HLHS = 25; TGA = 21), mean gestational age 33.8 weeks (95% CI: 33.3-34.2). Total brain volume and T2* were significantly lower in fetuses with cardiac disease. CCOi was lower in HLHS, correlating with total brain volume - for every 10% CCOi increase, volume increased 8 mm3 (95% CI: 1.78-14.1; p = 0.012). Echocardiography parameters and cerebral oxygenation showed no correlation. TGA showed no CCOi or aortic output correlation with MRI measures. CONCLUSIONS: In HLHS, lower cardiac output is deleterious to brain development. Our findings provide insight into the role of fetal cardiovascular physiology in brain health.

Impact of congenital heart disease on outcomes among pediatric patients hospitalized for COVID-19 infection.

BACKGROUND: COVID-19 infection is generally regarded as an acute self-limiting illness in children, but it can cause significant morbidity and mortality in both healthy and high-risk children. There are limited data on the outcomes of children with congenital heart disease (CHD) and COVID-19. This study aimed to examine the risks of mortality, in-hospital cardiovascular and non-cardiovascular complications in this patient population. METHODS: We analyzed data from hospitalized pediatric patients from 2020 using the nationally representative National Inpatient Sample (NIS). Children hospitalized for COVID-19 were included, and weighted data were used to compare in-hospital mortality and morbidities between children with and without CHD. RESULTS: Out of 36,690 children admitted with a diagnosis of COVID-19 infection(ICD-10 code:U07.1 and B97.29) during calendar year 2020, 1240 (3.4%) had CHD. The risk of mortality in children with CHD was not significantly higher than those without CHD(1.2% vs. 0.8%, p = 0.50), with adjusted OR (aOR) of 1.7 (95% CI: 0.6-5.3). Tachyarrhythmias and heart block were more likely in CHD children with an aOR of 4.2 (95% CI: 1.8-9.9) and aOR of 5.0 (95% CI: 2.4-10.8), respectively. Similarly, respiratory failure [aOR = 2.0 (1.5-2.8)], respiratory failure requiring non-invasive mechanical ventilation [aOR = 2.7 (1.4-5.2)] and invasive mechanical ventilation [aOR = 2.6 (1.6-4.0)], and acute kidney injury [aOR = 3.4 (2.2-5.4)] were all significantly higher among patients with CHD. Median length of hospital stay in children with CHD was longer than those without CHD [5 days (IQR: 2-11) vs. 3 days (IQR: 2-5), p = < 0.001]. CONCLUSIONS: Children with CHD hospitalized with COVID-19 infection were at increased risk of serious cardiovascular and non-cardiovascular adverse clinical outcomes. They also had increased length of hospital stay and utilization of healthcare resources.

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.

The aorto-left ventricular tunnel from a fetal perspective: Original case series and literature review.

INTRODUCTION: Aorto-left ventricular tunnel (ALVT) accounts for <0.1% of congenital heart defects. Evidence on the prognosis from a fetal perspective is limited. With this retrospective international case series, we provide information on the outcome of fetuses with ALVT. METHODS: All members of the Association for European Pediatric and Congenital Cardiology's (AEPC) fetal working group and fetal medicine units worldwide were invited for participation. We observed antenatal parameters, neonatal outcome and postnatal follow-up. Additionally, a systematic search of the literature was performed. RESULTS: Twenty fetuses with ALVT were identified in 10 participating centers (2001-2019). Fetal echocardiographic characteristics of ALVT included an increased cardiac-thorax ratio (95%), left ventricular end-diastolic diameter (90%) and a dysplastic aortic valve (90%). Extracardiac malformations were rare (5%). Eight fetuses died at a median gestational age (GA) of 21 + 6 weeks (range, 19-24): all showed signs of hydrops prior to 24 weeks or at autopsy. All others (60%, 12/2) were live-born (median GA 38 + 4, range 37-40), underwent surgery and were alive at last follow up (median 3.2 years, range 0.1-17). The literature reported 22 ALVT fetuses with similar outcome. CONCLUSIONS: In the absence of fetal hydrops, ALVT carries a good prognosis. Fetuses who survive to 24 weeks without hydrops are likely to have a good outcome.

Pulmonary artery acceleration time in young children is determined by heart rate and transpulmonary gradient but not by pulmonary blood flow: A simultaneous echocardiography-cardiac catheterization study.

INTRODUCTION: Pulmonary artery acceleration time (PAAT) is considered useful for the non-invasive evaluation of pulmonary artery pressure (PAP) and pulmonary vascular resistance (PVR). PAAT is dependent on PAP, PVR, pulmonary artery compliance, stroke volume, and heart rate. Its relative dependency on these determinants may differ between young and older children, raising uncertainty regarding its utility in young children. We aim to identify the primary determinants of the PAAT in children less than 36 months undergoing cardiac catheterization and its utility for the diagnosis of elevated PVR. METHODS: We prospectively studied 42 children undergoing cardiac catheterization and simultaneous echocardiography. We determined the correlations of PAAT to the above-mentioned determinants and evaluated receiver operator characteristic (ROC) curves for diagnosis of PVR indexed to body surface area (PVRi) ≥3 Wu*m2 . RESULTS: Median age was 11.5 (IQR 5.2, 21.2) months. Moderate correlations were found between PAAT and mean PAP (R = -.66, p < .001), PVRi (R = -.54, p = .004), pulmonary artery compliance (R = .65, p < .001), transpulmonary gradient (R = -.67, p < .001), stroke volume (R = .61, p = .002), and heart rate (R = -.63, p < .001). In multivariate regression modeling, only transpulmonary gradient and heart rate were independent determinants of PAAT. PAAT ≤77 msec had acceptable utility for diagnosing PVRi ≥ 3 Wu*m2 (AUC .8 [.64, .95], n = 36), low sensitivity (59%), and excellent specificity (94%). CONCLUSION: Transpulmonary gradient and heart rate, but not pulmonary blood flow, are important determinants of PAAT in children <36 months undergoing cardiac catheterization. PAAT has low sensitivity for diagnosing elevated PVRi, therefore, should not be solely relied upon in screening for elevated PVRi in young children.

Congenital Aortic-Left Atrial Tunnel with Coarctation and Anomalous Left Coronary Artery from the Pulmonary Artery: A First-of-its-kind Case Report.

Aortic-left atrial (Ao-LA) tunnel is an extremely rare vascular anomaly that involves an abnormal channel originating from the sinuses of the Valsalva and terminating in the left atrium. We present an unusual case of prenatally diagnosed Ao-LA tunnel with postnatal diagnosis of coarctation of the aorta and anomalous origin of the left coronary artery from the pulmonary artery (ALCAPA).

Current State of Fetal Heart Disease Counseling and Training: Room for Improvement? : Endorsed by the Fetal Heart Society.

We sought to describe the fellowship experiences and current practice habits of pediatric cardiologists who counsel patients with fetal heart disease (FHD) and to identify fellowship experiences related to FHD counseling perceived as valuable by respondents as well as opportunities for improvement. A cross-sectional survey of attending pediatric cardiologists who care for patients with FHD was performed. The respondents' demographics, fellowship experiences related to FHD counseling, reflections on fellowship training, and current practice habits were collected. The Fetal Heart Society endorsed this survey. There were 164 survey responses. 56% of respondents did not have 4th-year subspecialty training in fetal cardiology. Observing and performing FHD counseling were the most commonly used methods of training, with the highest perceived effectiveness. The number of counseling sessions observed and performed correlated moderately with confidence in FHD counseling skills at fellowship graduation. Extracardiac pathology and neurodevelopment were the least frequently addressed topics in fellowship training and in current practice. Fewer than 50% of respondents received formal education and feedback in counseling techniques during fellowship training. A significant proportion of practicing pediatric cardiologists provide FHD counseling with only standard categorical training. This highlights the potential importance of expanding FHD counseling education into categorical fellowship curricula. We suggest increasing opportunities for fellows to perform FHD counseling and receive feedback as this is a valued and beneficial experience during training. A formalized curriculum including extracardiac pathology and neurodevelopment and the use of evidence-based workshops in counseling techniques may address identified gaps in fellowship education.

Placental Location in Maternal-Fetal Surgery for Myelomeningocele.

INTRODUCTION: Uterine incision based on the placental location in open maternal-fetal surgery (OMFS) has never been evaluated in regard to maternal or fetal outcomes. OBJECTIVE: The aim of this study was to investigate whether an anterior placenta was associated with increased rates of intraoperative, perioperative, antepartum, obstetric, or neonatal complications in mothers and babies who underwent OMFS for fetal myelomeningocele (fMMC) closure. METHODS: Data from the international multicenter prospective registry of patients who underwent OMFS for fMMC closure (fMMC Consortium Registry, December 15, 2010-June 31, 2019) was used to compare fetal and maternal outcomes between anterior and posterior placental locations. RESULTS: The placental location for 623 patients was evenly distributed between anterior (51%) and posterior (49%) locations. Intraoperative fetal bradycardia (8.3% vs. 3.0%, p = 0.005) and performance of fetal resuscitation (3.6% vs. 1.0%, p = 0.034) occurred more frequently in cases with an anterior placenta when compared to those with a posterior placenta. Obstetric outcomes including membrane separation, placental abruption, and spontaneous rupture of membranes were not different among the 2 groups. However, thinning of the hysterotomy site (27.7% vs. 17.7%, p = 0.008) occurred more frequently in cases of an anterior placenta. Gestational age (GA) at delivery (p = 0.583) and length of stay in the neonatal intensive care unit (p = 0.655) were similar between the 2 groups. Fetal incision dehiscence and wound revision were not significantly different between groups. Critical clinical outcomes including fetal demise, perinatal death, and neonatal death were all infrequent occurrences and not associated with the placental location. CONCLUSIONS: An anterior placental location is associated with increased risk of intraoperative fetal resuscitation and increased thinning at the hysterotomy closure site. Individual institutional experiences may have varied, but the aggregate data from the fMMC Consortium did not show a significant impact on the GA at delivery or maternal or fetal clinical outcomes.

Extracardiac Doppler indices predict perinatal mortality in fetuses with Ebstein anomaly and tricuspid valve dysplasia.

OBJECTIVES: Ebstein anomaly and tricuspid valve dysplasia (EA/TVD) carry high perinatal mortality. Past studies have focused on cardiac predictors of mortality; we sought to describe the fetal echo (FE) extracardiac Dopplers in this cohort and determine their association with perinatal mortality. METHOD: Fetuses with EA/TVD at 23 centers from 2005-2011 were included for retrospective study. Doppler pattern and velocity of the umbilical artery (UA), umbilical vein (UV), ductus venosus (DV), and middle cerebral artery (MCA) were collected. Bivariate and multivariate analyzes were performed. The primary outcome measure was perinatal mortality, defined as fetal demise or neonatal death. RESULTS: Of 190 cases that met eligibility criteria, alterations were seen in 50% of UA, 16% of UV, 48% of DV, and 8% of MCA Doppler indices on the last FE (median 27.4 weeks). Independent predictors of perinatal mortality included abnormal UA Doppler pattern of absence or reversed end diastolic flow (OR 9.7) and UV velocity z score <1 (OR 2.5), in addition to diagnosis <32 weeks (OR 4.2) and tricuspid valve (TV) annulus z score ≥6 (OR 5.3). CONCLUSION: Abnormal UA Doppler pattern and decreased UV velocity are independent predictors of perinatal mortality in EA/TVD fetuses and should be used to refine mortality risk and guide perinatal management.

Impact of congenital heart disease on outcomes among pediatric patients hospitalized for influenza infection.

BACKGROUND: Young children and those with chronic medical conditions are at risk for complications of influenza including cardiopulmonary compromise. Here we aim to examine risks of mortality, clinical complications in children with congenital heart disease (CHD) hospitalized for influenza. METHODS: We analyzed data from in-hospital pediatric patients from 2003, 2006, 2009, 2012 and 2016 using the nationally representative Kids Inpatient Database (KID). We included children 1 year and older and used weighted data to compare the incidence of in-hospital mortality and rates of complications such as respiratory failure, acute kidney injury, need for mechanical ventilation, arrhythmias and myocarditis. RESULTS: Data from the KID estimated 125,470 children who were admitted with a diagnosis of influenza infection. Out of those, 2174(1.73%) patients had discharge diagnosis of CHD. Children with CHD who required hospitalization for influenza had higher in-hospital mortality (2.0% vs 0.5%), with an adjusted OR (aOR) of 2.8 (95% CI: 1.7-4.5). Additionally, acute respiratory failure and acute kidney failure were more likely among patients with CHD, with aOR of 1.8 (95% CI: 1.5-2.2) and aOR of 2.2 (95% CI: 1.5-3.1), respectively. Similarly, the rate of mechanical ventilatory support was higher in patients with CHD compared to those without, 14.1% vs 5.6%, aOR of 1.9 (95% CI: 1.6-2.3). Median length of hospital stay in children with CHD was longer than those without CHD [4 (IQR: 2-8) days vs. 2 (IQR: 2-4) days]. Outcomes were similar between those with severe vs non-severe CHD. CONCLUSIONS: Children with CHD who require hospital admission for influenza are at significantly increased risk for in-hospital mortality, morbidities, emphasizing the need to reinforce preventative measures (e.g. vaccination, personal hygiene) in this particularly vulnerable population.

22q11.2 Deletion Status Influences Resource Utilization in Infants Requiring Repair of Tetralogy of Fallot and Common Arterial Trunk.

22q11.2 deletion syndrome leads to both cardiac and non-cardiac developmental defects. We aimed to study the impact of 22q11.2 deletion syndrome on in-hospital outcomes in children undergoing surgical repair for tetralogy of Fallot (TOF) and truncus arteriosus (TA). Using the nationally representative Kids Inpatient Database (KID), we analyzed data from in-hospital pediatric patients for the years 2003, 2006, 2009, and 2012. We compared the in-hospital outcomes between those with and those without 22q11.2 deletion syndrome. There were 6126 cases of TOF and 968 cases of TA. 22q11.2 deletion syndrome were documented in 7.2% (n = 441) of the TOF and 27.4% (n  =  265) of the TA group. 22q11.2 deletion did not significantly increase the risk of mortality in either group: [OR = 1.98 (95% CI 0.99-3.94), adjusted p  =  0.053] for TOF and OR = 1.07 (95% CI 0.57-1.99), adjusted p = 0.82 for TA. However, the length of hospitalization was longer in the 22q11.2 deletion group by 8.6 days (95% CI 5.2-12), adjusted p < 0.001 for TOF and by 8.15 days (95% CI 1.05-15.25), adjusted p = 0.025 for the TA group. Acute respiratory failure [10.6% vs 5.5%, p < 0.001] and acute renal failure [6.3% vs 2.6%, p < 0.001] were higher in 22q11.2 deletion cohort within the TOF group but not in the TA group. Though survival is not affected, children with 22q11.2 deletion syndrome who undergo surgical repair for TOF and TA use significantly more hospital resources-specifically longer hospital stay and higher hospitalization cost-than those without 22q11.2 deletion syndrome. Prenatal or preoperative testing for 22q11deletion is indicated to make appropriate adjustments in parental, caregiver, and administrative expectations.

Fetal Cardiac Intervention for Pulmonary Atresia with Intact Ventricular Septum: International Fetal Cardiac Intervention Registry.

INTRODUCTION: Invasive fetal cardiac intervention (FCI) for pulmonary atresia with intact ventricular septum (PAIVS) and critical pulmonary stenosis (PS) has been performed with small single-institution series reporting technical and physiological success. We present the first multicenter experience. OBJECTIVES: Describe fetal and maternal characteristics of those being evaluated for FCI, including pregnancy/neonatal outcome data using the International Fetal Cardiac Intervention Registry (IFCIR). METHODS: We queried the IFCIR for PAIVS/PS cases evaluated from January 2001 to April 2018 and reviewed maternal/fetal characteristics, procedural details, pregnancy and neonatal outcomes. Data were analyzed using standard descriptive statistics. RESULTS: Of the 84 maternal/fetal dyads in the registry, 58 underwent pulmonary valvuloplasty at a median gestational age of 26.1 (21.9-31.0) weeks. Characteristics of fetuses undergoing FCI varied in terms of tricuspid valve (TV) size, TV regurgitation, and pulmonary valve patency. There were fetal complications in 55% of cases, including 7 deaths and 2 delayed fetal losses. Among those who underwent successful FCI, the absolute measurement of the TV increased by 0.32 (±0.17) mm/week from intervention to birth. Among 60 liveborn with known outcome, there was a higher percentage having a biventricular circulation following successful FCI (87 vs. 43%). CONCLUSIONS: Our data suggest a possible benefit to fetal therapy for PAIVS/PS, though rates of technically unsuccessful procedures and procedure-related complications, including fetal loss were substantial. FCI criteria are extremely variable, making direct comparison to nonintervention patients challenging and potentially biased. More uniform FCI criteria for fetuses with PAIVS/PS are needed to avoid unnecessary procedures, expose only fetuses most likely to sustain a benefit, and to enable comparisons to be made with nonintervention patients.

Prenatal cardiac care: Goals, priorities & gaps in knowledge in fetal cardiovascular disease: Perspectives of the Fetal Heart Society.

Perinatal cardiovascular care has evolved considerably to become its own multidisciplinary field of care. Despite advancements, there remain significant gaps in providing optimal care for the fetus, child, mother, and family. Continued advancement in detection and diagnosis, perinatal care and delivery planning, and prediction and improvement of morbidity and mortality for fetuses affected by cardiac conditions such as heart defects or functional or rhythm disturbances requires collaboration between the multiple types of specialists and providers. The Fetal Heart Society was created to formalize and support collaboration between individuals, stakeholders, and institutions. This article summarizes the challenges faced to create the infrastructure for advancement of the field and the measures the FHS is undertaking to overcome the barriers to support progress in the field of perinatal cardiac care.

Novel and lethal case of cardiac involvement in DNM1L mitochondrial encephalopathy.

Pathogenic DNM1L mutations cause a mitochondrial disorder with a highly variable clinical phenotype characterized by developmental delay, hypotonia, seizures, microcephaly, poor feeding, ocular abnormalities, and dysarthria. We report the case of an 8-month-old female with autosomal dominant, de novo DNM1L c. 1228G>A (p. E410K) mutation and mitochondrial disorder, septo-optic dysplasia, hypotonia, developmental delay, elevated blood lactate, and severe mitochondrial cardiomyopathy leading to nonischemic congestive heart failure and cardiogenic shock resulting in death. This case suggests that cardiac involvement, previously undescribed, can be a clinically important feature of this syndrome and should be screened for at diagnosis.

Subsequent pregnancy outcomes after open maternal-fetal surgery for myelomeningocele.

BACKGROUND: Open maternal-fetal surgery for fetal myelomeningocele results in reduction in neonatal morbidity related to spina bifida but may be associated with fetal, neonatal, and maternal complications in subsequent pregnancies. OBJECTIVE: The objective of this study was to ascertain obstetric risk in subsequent pregnancies after open maternal-fetal surgery for fetal myelomeningocele closure. STUDY DESIGN: An international multicenter prospective observational registry created to track and report maternal, obstetric, fetal/neonatal, and subsequent pregnancy outcomes following open maternal-fetal surgery for fetal myelomeningocele was evaluated for subsequent pregnancy outcome variables. Institutional Review Board approval was obtained for the registry. RESULTS: From 693 cases of open maternal-fetal surgery for fetal myelomeningocele closure entered into the registry, 77 subsequent pregnancies in 60 women were identified. The overall live birth rate was 96.2%, with 52 pregnancies delivering beyond 20 weeks gestational age and median gestational age at delivery of 37 (36.3-37.1) weeks. The uterine rupture rate was 9.6% (n = 5), resulting in 2 fetal deaths. Maternal transfusion was required in 4 patients (7.7%). CONCLUSION: The risk of uterine rupture or dehiscence in subsequent pregnancies with associated fetal morbidity after open maternal-fetal surgery is significant, but is similar to that reported for subsequent pregnancies after classical cesarean deliveries. Future pregnancy considerations should be included in initial counseling for women contemplating open maternal-fetal surgery.

Incidence and Management of Umbilical Artery Flow Abnormalities during Open Fetal Surgery.

INTRODUCTION: Umbilical artery (UA) Doppler ultrasound is used to assess uteroplacental insufficiency. Absent or reversed end diastolic flow (AREDF) in the UA is associated with increased perinatal mortality in fetuses with intrauterine growth restriction. We describe the incidence of UA Doppler abnormalities during open fetal surgery. METHODS: We conducted a retrospective review of patients undergoing open in utero myelomeningocele (MMC) repair between 2008 and 2015. Intermittent UA Dopplers were performed during key portions of all cases. Our primary outcome was the rate of any AREDF. Secondary outcomes included analysis of absent versus reversed end diastolic flow (EDF), vasopressor use, and volatile anesthetic and clinical outcomes. RESULTS: Thirty-four of 47 fetuses developed UA Doppler abnormalities intraoperatively. Nineteen had absent EDF and 15 had reversed EDF. No AREDF was present before induction, and all AREDF resolved by postoperative day 1. Ten of 19 (52.6%) patients who received sevoflurane had reversed EDF, versus 5/28 (17.9%) for desflurane, odds ratio (95% CI) 5.11 (1.36-19.16), p = 0.02. One intraoperative fetal death occurred in the AREDF group. DISCUSSION: AREDF is a common phenomenon during open MMC repair. Anesthetic agent choice may influence this risk. Future studies of UA flow during fetal surgery are needed to further evaluate the impact of intraoperative AREDF on fetal well-being.

Epidemiology of Live Born Infants with Nonimmune Hydrops Fetalis-Insights from a Population-Based Dataset.

OBJECTIVE: To evaluate the incidence, etiology, and 1-year mortality of nonimmune hydrops fetalis (NIHF) and to identify risk factors for mortality in a contemporary population-based dataset. STUDY DESIGN: The California Office of Statewide Health Planning and Development maintains a database linking maternal and infant hospital discharge, readmissions, and birth and death certificate date from 1 year before to 1 year after birth. We searched the database (2005-2012) for infants with NIHF (identified by the International Classification of Diseases, 9th Revision, Clinical Modification code). Hazard models were used to identify risk factors for mortality in infants with NIHF; results are presented as hazard ratios (HRs, 95% CI). RESULTS: The incidence of NIHF was 2.5 out of 10 000 among live born infants. Neonatal mortality was 35.1% (364 out of 1037) and overall mortality was 43.2% (448 out of 1037) at 1 year of age. Gestational age (GA) was predictive of mortality with a HR of 2.4 (95% CI 1.9-3.2) for preterm compared with term infants. The GA-adjusted HR for mortality was 1.3 (95% CI 1.1-1.6) for polyhydramnios and 1.5 (95% CI 1.2-2.0) for large for gestational age infants compared with appropriate for GA infants. Aneuploid infants with critical congenital heart disease had an adjusted HR of 2.3 (95% CI 1.5-3.6) compared with euploid infants without a structural birth defect. CONCLUSIONS: In this large, population-based study, prematurity, polyhydramnios, and large for gestational age were predictors of increased mortality. Mortality is highly variable among euploid and aneuploid infants with and without structural birth defects and critical congenital heart disease.