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OBJECTIVE: The reproductive and gynecologic outcomes for women after the pregnancy complicated by open maternal-fetal surgery (OMFS) were evaluated. STUDY DESIGN: The retrospective review identified 93 women with OMFS from a single institution (1996-2007). Consent and questionnaires were sent to women. Institutional review board approval was obtained from the Committee for Protection of Human Subjects. RESULTS: The total return rate was 57.3%. Total pregnancies reported were 47, with 36 delivering after 20 weeks' gestation. The uterine dehiscence and rupture rates were 14% and 14%, respectively. Fetal anomalies occurred in 4 subsequent pregnancies. Normal conception occurred in 98% of subsequent pregnancies. Gynecologic issues were reported by 8 women, with infertility, abdominal pain, and ovarian and uterine factors. CONCLUSION: The reproductive outcomes of uterine dehiscence (14%) and rupture (14%) in a subsequent pregnancy continue to be a major counseling issue for OMFS. Fertility and gynecologic factors do not appear to be increased for women undergoing OMFS. [ABSTRACT FROM AUTHOR]

Background: Quantitative echocardiographic (echo) measures of ventricular function predict mortality in pediatric pulmonary hypertension (PH), but studies in congenital diaphragmatic hernia (CDH)-related PH are limited. Few studies report quantitative echo data beyond the first week of life in CDH non-survivors., Methods: A single-center retrospective, cross-sectional, cohort study included CDH patients born between January 2013 and April 2022 who survived to surgical repair but died during the neonatal hospitalization. Quantitative measures of right (RV) and left ventricular (LV) size and function including tricuspid annular plane systolic excursion Z-score (TAPSEZ), RV fractional area change (FAC), RV/LV ratio, LV eccentricity index, LV M-mode dimensions, and RV/LV systolic strain were performed offline on the last echocardiogram before death. Data were compared between patients who died ≤30 days after repair ("early") vs. >30 days after repair ("late") using the Wilcoxon rank sum test., Results: Twenty-five (11 early, 14 late) deceased patients had echo images available for analysis. LV size by end-diastolic dimension Z-score was smaller in patients who died early vs. late after repair [-3.03 (-3.93, -2.51) vs. -0.24 (-2.11, 0.53), p = 0.021]. There were trends toward worse RV function (TAPSEZ, RVFAC, RV global and free wall strain) and LV function (apical 4 chamber strain) in patients who died early vs. late after repair., Conclusion: These preliminary findings support future study of the impact of ventricular hypoplasia and dysfunction on mortality and opportunities for risk stratification based on quantitative echo findings in CDH., Level of Evidence: Cohort study, 4., Competing Interests: Conflicts of interest None., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Introduction: Data on near- and long-term clinical outcomes are critical for the care of all maternal-fetal patients presenting to a fetal center. This is especially important since physiologic and neurodevelopmental attributes do not manifest until later childhood when multilevel (e.g., individual, family, policy) factors have a direct influence on health outcomes. Electronic health records (EHRs) create opportunity for efficient data collection. However, documentation structures are not designed for acquisition of key attributes, and changes over time and between-clinician differences can affect resultant output. Therefore, EHR derived datasets have limited ability to accurately characterize the clinical presentation and care trajectory of patients with congenital anomalies. In addition, in most systems, the fetus lacks a digital identity and requires relinking fetal attributes documented in the maternal chart to those from the pediatric EHR. This conundrum amplifies in the setting of multiple gestation, returning maternal patients, and pregnancies with fetal demise. Moreover, current data capture systems result in incomplete abstraction of variables that may confound, mediate, or moderate critical associations. Our objective was to develop and implement a prospective data capture platform to transform EHR data into an analytic-grade database for multipurpose use., Methods: A unified platform for longitudinal follow-up of maternal-child dyads cared for at our fetal center, named the Clinical Outcomes Data Archive (CODA), was constructed. CODA was designed using a data dictionary based on multidisciplinary and interprofessional expert input, a relational identity for each patient, fetus, and pregnancy, and a process by which EHR-sourced and chart-abstracted data are validated by a well-trained team. Descriptive analyses were performed for data acquired between July 2022 and July 2023, and a comparison of studies before and after implementation of CODA is presented., Conclusion: 5,394,106 data points were validated for 7,662 patients across 12 conditions. 2% of data points were found to be unreliable or undocumented. 91% of data points were sourced from the EHR. Eighty-five percent of condition-specific variables required manual chart abstraction. The study conducted with CODA was able to contribute to 18 other studies. CODA successfully merges EHR-sourced and manually abstracted documentation for longitudinal study of the maternal-child dyad., (© 2024 S. Karger AG, Basel.)

Delivery room resuscitation of infants with surgical conditions can be complex and depends on an experienced and cohesive multidisciplinary team whose performance is more important than that of any individual team member. Existing resuscitation algorithms were not developed for infants with congenital anomalies, and delivery room resuscitation is largely dictated by expert opinion extrapolating physiologic expectations from infants without anomalies. As prenatal diagnosis rates improve, there is an increased ability to plan for the unique delivery room needs of infants with surgical conditions. In this review, we share expert opinion, including our center's delivery room management for neonatal noncardiac surgical conditions, and highlight knowledge gaps and the need for further studies and evidence-based practice to be incorporated into the delivery room care of infants with surgical conditions. Future research in this area is essential to move from an expert-based approach to a data-driven approach to improve and individualize delivery room resuscitation of infants with surgical conditions., (Copyright © 2024 by the American Academy of Pediatrics.)

Introduction: Congenital pulmonary airway malformations (CPAM), intra- and extralobar bronchopulmonary sequestrations (iBPS/eBPS), CPAM-BPS hybrid lesions (HL), congenital lobar emphysema (CLE), bronchial atresia (BA), and foregut duplication cysts (FDC), collectively referred to as congenital thoracic lesions (CTL), are mostly solitary. Patients with multiple CTL are rare, and reports on such cases are scarce. To address this dearth, we analyzed a large multifocal CTL patient cohort., Methods: Retrospective chart review of patients born between September 1, 2013, and March 31, 2023, who underwent surgery for a CTL at our tertiary center. Patients with radiological and surgical diagnosis of multifocal CTL, defined as ≥2 CTL present in more than one lobe were included to record pre-, peri-, and postnatal patient characteristics., Results: Among 701 CTL patients, 74 (10.5%) had multiple CTL. CTL multifocality was prenatally recognized correctly in 8 (12.9%) patients. Most multiple CTL were right-sided, unilateral multilobar lesions (n = 33, 44%). Bilateral CTL were found in 9 (12.1%) patients. CPAM-CPAM lesions were the most prevalent CTL types (n = 36, 49%). Genetic syndromes were confirmed in 3 (4%) and additional congenital anomalies in 9 (12.9%) patients, 5 of those had multiple congenital anomalies. Of 49 (65%) patients with multilobar CTL, 25 (51%) underwent bilobectomy and 24 (49%) lung-sparing surgery. Length of stay was similar. Mortality was 5.4%., Conclusion: We report on the largest patient cohort with multiple CTL to date. Multiple CTL occurred in 1/10 patients with CTL, and only 12.9% were recognized prenatally. Lung-sparing surgery can be considered. Multiple additional congenital anomalies and genetic syndromes may be more common and genetic testing should be considered. Overall, outcomes in this patient population are favorable., (© 2024 S. Karger AG, Basel.)

Objective: To determine the association between initial delivery room (DR) ventilator (conventional mechanical ventilation [CMV] versus high frequency oscillatory ventilation [HFOV] and hospital outcomes for infants with severe congenital diaphragmatic hernia (CDH)., Study Design: Quasi-experimental design before/after introducing a clinical protocol promoting HFOV. The primary outcome was first blood gas parameters. Secondary outcomes included serial blood gas assessments, ECMO, survival, duration of ventilation, and length of hospitalization., Results: First pH and CO 2 were more favorable in the HFOV group (n = 75) than CMV group (n = 85), median (interquartile range (IQR)) pH 7.18 (7.03, 7.24) vs. 7.05 (6.93, 7.17), adjusted p-value < 0.001; median CO 2 62.0 (46.0, 82.0) vs 85.9 (59.0, 103.0), adjusted p-value < 0.001. ECMO, survival, duration of ventilation, and length of hospitalization did not differ between groups in adjusted analysis., Conclusion: Among infants with severe CDH, initial DR HFOV was associated with improved early gas exchange with no adverse differences in hospital outcomes., (© 2024. The Author(s).)

Infants with congenital diaphragmatic hernia (CDH) benefit from comprehensive multidisciplinary teams that have experience in caring for the unique and complex issues associated with CDH. Despite prenatal referral to specialized high-volume centers, advanced ventilation strategies and pulmonary hypertension management, and extracorporeal membrane oxygenation, mortality and morbidity remain high. These infants have unique and complex issues that begin in fetal and infant life, but persist through adulthood. Here we will review the literature and share our clinical care pathway for neonatal care and follow up. While many advances have occurred in the past few decades, our work is just beginning to continue to improve the mortality, but also importantly the morbidity of CDH., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Competing Interests: We declare no competing interests.

Objective: To evaluate genetic testing utilization and diagnostic yield in infants with esophageal atresia (EA)/tracheoesophageal fistula (TEF) over the past 12 years to inform future practices and individualize prognostication and management., Study Design: A retrospective cohort study was performed for all infants with EA or EA/TEF hospitalized between January 2011 and January 2023 at a quaternary children's hospital. For each infant, demographic information, prenatal and postnatal history, and genetic testing were reviewed., Results: There were 212 infants who were classified as follows: 1) complex/syndromic with EA/TEF plus an additional major anatomic anomaly (n = 114, of which 74 met VACTERL criteria); 2) isolated/nonsyndromic EA/TEF (n = 88) and 3) isolated/nonsyndromic EA (n = 10). A range of genetic tests were sent with varying diagnostic rates including karyotype analysis in 12 (all with complex/syndromic phenotypes and all positive), chromosomal microarray analysis in 189 (114 of whom were complex/syndromic with an overall diagnostic rate of 3/189), single gene testing for CHD7 in 18 (4 positive), and exome analysis in 37 complex/syndromic patients (8 positive)., Conclusions: EA/TEF with and without additional anomalies is genetically heterogeneous with a broad range of associated phenotypes. While the genetic etiology of EA/TEF with or without VACTERL remains largely unknown, genome wide testing (exome or genome) including copy number analysis is recommended over chromosomal microarray testing. We anticipate that expanded genetic/genomic testing modalities such as RNA sequencing and tissue specific molecular testing are needed in this cohort to improve our understanding of the genomic contributors to EA/TEF., Competing Interests: Declaration of Competing Interest Children's Hospital of Philadelphia Research Foundation (GRT-00003206). The authors have indicated they have no potential conflicts of interest to disclose., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objectives: To describe the scope of left ventricular (LV) dysfunction and left heart hypoplasia (LHH) in infants with congenital diaphragmatic hernia (CDH), to determine associations with CDH severity, and to evaluate the odds of extracorporeal membrane oxygenation (ECMO) and death with categories of left heart disease., Study Design: Demographic and clinical variables were collected from a single-center, retrospective cohort of patients with CDH from January 2017 through May 2022. Quantitative measures of LV function and LHH were prospectively performed on initial echocardiograms. LHH was defined as ≥2 of the following: z score ≤ -2 of any left heart structure or LV end-diastolic volume <3 mL. LV dysfunction was defined as shortening fraction <28%, ejection fraction <60%, or global longitudinal strain <20%. The exposure was operationalized as a 4-group categorical variable (LV dysfunction +/-, LHH +/-). Logistic regression models evaluated associations with ECMO and death, adjusting for CDH severity., Results: One hundred eight-two patients (80.8% left CDH, 63.2% liver herniation, 23.6% ECMO, 12.1% mortality) were included. Twenty percent demonstrated normal LV function and no LHH (LV dysfunction-/LHH-), 37% normal LV function with LHH (LV dysfunction-/LHH+), 14% LV dysfunction without LHH (LV dysfunction+/LHH-), and 28% both LV dysfunction and LHH (LV dysfunction+/LHH+). There was a dose-response effect between increasing severity of left heart disease, ECMO use, and mortality. LV dysfunction+/LHH + infants had the highest odds of ECMO use and death, after adjustment for CDH severity [OR (95% CI); 1.76 (1.20, 2.62) for ECMO, 2.76 (1.63, 5.17) for death]., Conclusions: In our large single-center cohort, patients with CDH with LV dysfunction+/LHH + had the highest risk of ECMO use and death., Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objective: To develop a consensus guideline to meet nutritional challenges faced by infants with congenital diaphragmatic hernia (CDH)., Study Design: The CDH Focus Group utilized a modified Delphi method to develop these clinical consensus guidelines (CCG). Topic leaders drafted recommendations after literature review and group discussion. Each recommendation was sent to focus group members via a REDCap survey tool, and members scored on a Likert scale of 0-100. A score of > 85 with no more than 25% outliers was designated a priori as demonstrating consensus among the group., Results: In the first survey 24/25 recommendations received a median score > 90 and after discussion and second round of surveys all 25 recommendations received a median score of 100., Conclusions: We present a consensus evidence-based framework for managing parenteral and enteral nutrition, somatic growth, gastroesophageal reflux disease, chylothorax, and long-term follow-up of infants with CDH., (© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Introduction: Neonates have a high incidence of respiratory and cardiac perioperative events. Disease severity and indications for surgical intervention often dovetail with an overall complex clinical course and predispose these infants to adverse long-term neurodevelopmental outcomes and increased length of stay. Our aims were to describe severe and nonsevere early postoperative complications to establish a baseline of care outcomes and to identify subgroups of surgical neonates and procedures for future prospective studies., Methods: Electronic health record data were examined retrospectively for a cohort of patients who had general anesthesia from January 26, 2015 to August 31, 2018. Inclusion criteria were full-term infants with postmenstrual age less than 44 weeks or premature infants less than 60 weeks postmenstrual age undergoing nonimaging, noncardiac surgery. Severe postoperative complications were defined as mortality, reintubation, positive blood culture, and surgical site infection. Nonsevere early postoperative outcomes were defined as hypoglycemia, hyperglycemia, hypothermia, hyperthermia, and readmission within 30 days., Results: About 2569 procedures were performed in 1842 neonates of which 10.9% were emergency surgeries. There were 120 postoperative severe complications and 965 nonsevere postoperative outcomes. Overall, 30-day mortality was 1.8% for the first procedure performed, with higher mortality seen on subgroup analysis for patients who underwent exploratory laparotomy (10.3%) and congenital lung lesion resection (4.9%). Postoperative areas for improvement included hyperglycemia (13.9%) and hypothermia (7.9%)., Discussion: The mortality rate in our study was comparable to other studies of neonatal surgery despite a high rate of emergency surgery and a high prevalence of prematurity in our cohort. The early outcomes data identified areas for improvement, including prevention of postoperative glucose and temperature derangements., Conclusions: Neonates in this cohort were at risk for severe and nonsevere adverse postoperative outcomes. Future studies are suggested to improve mortality and adverse event rates., (© 2023 John Wiley & Sons Ltd.)

Introduction: Delivery room (DR) interventions for infants with congenital diaphragmatic hernia (CDH) are not well described. This study sought to describe timing and order of DR interventions and identify system factors impacting CDH DR resuscitations using a human factors framework., Methods: Single center observational study of video recorded CDH DR resuscitations documenting timing and order of interventions. The team used the Systems Engineering Initiative for Patient Safety (SEIPS) model to identify system factors impacting DR resuscitations and time to invasive ventilation., Results: We analyzed 31 video recorded CDH resuscitations. We observed variability in timing and order of resuscitation tasks. The 'Internal Environment' and 'Tasks' components of the SEIPS model were prominent factors affecting resuscitation efficiency; significant room and bed spatial constraints exist, and nurses have a significant task burden. Additionally, endotracheal tube preparation was a prominent barrier to timely invasive ventilation., Conclusion: Video review revealed variation in event timing and order during CDH resuscitations. Standardization of room set-up, equipment, and event order and reallocation of tasks facilitate more efficient intubation and ventilation, representing targets for CDH DR improvement initiatives. This work emphasizes the utility of rigorous human factors review to identify areas for improvement during DR resuscitation., (S. Karger AG, Basel.)

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%)., Competing Interests: Financial Disclosure Eric Bergh disclosed that the NFocus Goldvalve balloon is no longer commercially available, and he receives royalties from UpToDate. Dr. Cromblehome disclosed that the Balt GOLDBAL2 balloon and catheter and Storz fetoscope are used under an investigational device exemption from the Food and Drug Administration, which are not otherwise available for use in the United States. Ahmet A. Baschat disclosed that the instrumentation was provided in-kind by Karl Storz, and he receives royalties from UpToDate. Holly Hedrick receives royalties from UpToDate. The other authors did not report any potential conflicts of interest., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

Introduction: Randomized controlled trials found that fetoscopic endoluminal tracheal occlusion (FETO) resulted in increased fetal lung volume and improved survival for infants with isolated, severe left-sided congenital diaphragmatic hernia (CDH). The delivery room resuscitation of these infants is particularly unique, and the specific delivery room events are largely unknown. The objective of this study was to compare the delivery room resuscitation of infants treated with FETO to standard of care (SOC) and describe lessons learned., Methods: Retrospective single-center cohort study of infants treated with FETO compared to infants who met FETO criteria during the same period but who received SOC., Results: FETO infants were more likely to be born prematurely with 8/12 infants born &lt;35 weeks gestational age compared to 3/35 SOC infants. There were 5 infants who required emergent balloon removal (2 ex utero intrapartum treatment and 3 tracheoscopic removal on placental bypass with delayed cord clamping) and 7 with prenatal balloon removal. Surfactant was administered in 6/12 FETO (50%) infants compared to 2/35 (6%) in the SOC group. Extracorporeal membrane oxygenation use was lower at 25% and survival was higher at 92% compared to 60% and 71% in the SOC infants, respectively., Conclusion: The delivery room resuscitation of infants treated with FETO requires thoughtful preparation with an experienced multidisciplinary team. Given increased survival, FETO should be offered to infants with severe isolated left-sided CDH, but only in high-volume centers with the experience and capability of removing the balloon, emergently if needed. The neonatal clinical team must be skilled in managing the unique postnatal physiology inherent to FETO where effective interdisciplinary teamwork is essential. Empiric and immediate surfactant administration should be considered in all FETO infants to lavage thick airway secretions, particularly those delivered &lt;48 h after balloon removal., (© 2024 S. Karger AG, Basel.)

Background: Executive function, adaptive function, and behavioral outcomes in congenital diaphragmatic hernia (CDH) survivors have not been well studied., Aim: To evaluate executive and neurobehavioral dysfunction in preschool and early school-aged children with CDH., Study Design: Retrospective cohort study., Subjects: All eligible CDH survivors ages 3 to 7 years enrolled in our follow-up program between February 2020 and February 2021., Outcome Measures: The Behavior Rating Inventory of Executive Function (BRIEF), the Adaptive Behavior Assessment System, 2nd Edition (ABAS-II), and the Child Behavior Checklist (CBCL) were used to assess functional and behavioral outcomes. Summary scores were compared to standard population norms., Results: A total of 100 patients were enrolled during the study period. Of those, 73 parents completed at least one of the questionnaires, resulting in completion of the BRIEF, ABAS-II, and CBCL for 63, 68, and 63 patients, respectively. Preschool children had normal executive function (BRIEF-P) while global executive composite (P = 0.012) and the emotional regulation index (P = 0.010) for school age patients (BRIEF-2) were worse. CDH survivors had favorable adaptive functioning (ABAS-II). Mean CBCL scores for preschool attention problems (P = 0.018), school age attention problems (P = 0.001), and attention deficits hyperactivity problems (P = 0.027) were significantly worse. Prematurity, surrogate markers of disease severity, non-white race, and public insurance status were associated with worse neurobehavioral dysfunction in bivariable analysis., Conclusions: The majority of preschool and school age CDH survivors have age-appropriate executive, adaptive and behavioral functioning. CDH survivors, however, have lower executive function and attention scores compared with the general population., Competing Interests: Declaration of competing interest None of the authors has any conflict of interest to disclose., (Copyright © 2023. Published by Elsevier B.V.)

Objective: To assess brain development in fetuses with congenital diaphragmatic hernia (CDH) using a fetal Total Maturation Score (fTMS)., Study Design: This is a retrospective cohort study using data from a single-center clinical registry. Neonates with an antenatal diagnosis of CDH between 2014 and 2020 and prenatal brain magnetic resonance imaging (MRI) (n = 48) were included. We compared our study sample with historical healthy controls (n = 48). The relationship between fTMS and gestational age (GA), as well as the association between fTMS and key prenatal variables and placental pathologic findings, were evaluated., Results: Compared with healthy controls, neonates with CDH had a significant delay in fTMS (P value <.001). Within the CDH cohort, there was no significant difference in fTMS based on CDH severity, intrathoracic liver position, right vs left CDH, sex, presence of abnormal echocardiogram findings, treatment with extracorporeal membrane oxygenation (ECMO), or in-hospital mortality. Placentas of neonates with CDH had a high proportion of fetal vascular malperfusion (56%) and chronic inflammation (67%), and relatively large placentas had a protective effect on prenatal brain maturation (P value = .025)., Conclusions: Prenatal brain maturation in neonates with CDH is delayed. Placental pathology may influence fetal brain development. The etiology and clinical impact of prenatal brain immaturity in neonates with CDH warrant further investigation., Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interest. No funding was received for this study., (Published by Elsevier Inc.)

Background: The objective of this study was to identify factors associated with prolonged birth admission length of stay (LOS) and to evaluate the association between these characteristics and readmission in the year following discharge for children with congenital diaphragmatic hernia (CDH)., Methods: This was a single-center retrospective cohort study of children with isolated CDH born in the Special Delivery Unit and admitted to the Newborn/Infant Intensive Care Unit at Children's Hospital of Philadelphia from April 2008 to August 2019. Birth admission hospitalization was categorized into 3 groups (≤35, 36-75, and >76 days) based on the data distribution. Participant factors included gestational age (days), side of CDH (right/left), liver position (up/down), CDH repair technique (open/minimally invasive), exposure to extracorporeal membrane oxygenation, lung-to-head circumference ratio, and feeding tube at discharge. Chi-squared, t-tests and analysis of variance were used to examine bivariable associations between participant characteristics, birth admission LOS and readmission in the year following initial hospital discharge. Multivariable logistic regression was used to evaluate factors associated with readmission., Results: Children hospitalized ≥76 days at birth had 4.33 (95% CI: 1.2, 15.2) higher odds of readmission than those admitted for ≤35 days. Children with a non-operative feeding tube at discharge had 4.12 (895% CI: 1.6, 10.5) higher odds of readmission when compared to those with no feeding tube at discharge., Conclusions: Longer birth hospitalization and non-operative feeding tube are associated with increased readmissions in the year after discharge., Level of Evidence: Level III., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Introduction: Fetuses with large lung lesions including congenital cystic adenomatoid malformations (CCAMs) are at risk for cardiopulmonary compromise. Prenatal maternal betamethasone and cyst drainage for micro- and macrocystic lesions respectively have improved outcomes yet some lesions remain large and require resection before birth (open fetal surgery, OFS), at delivery via an Ex Utero Intrapartum Treatment (EXIT), or immediately post cesarean section (section-to-resection, STR). We sought to compare prenatal characteristics and outcomes in fetuses undergoing OFS, EXIT, or STR to inform decision-making and prenatal counseling., Methods: A single institution retrospective review was conducted evaluating patients undergoing OFS, EXIT, or STR for prenatally diagnosed lung lesions from 2000 to 2021. Specimens were reviewed by an anatomic pathologist. Lesions were divided into "CCAMs" (the largest pathology group) and "all lung lesions" since pathologic diagnosis is not possible during prenatal evaluation when care decisions are made. Prenatal variables included initial, greatest, and final CCAM volume-ratio (CVR), betamethasone use/frequency, cyst drainage, and the presence of hydrops. Outcomes included survival, ECMO utilization, NICU length of stay (LOS), postnatal nitric oxide use, and ventilator days., Results: Sixty-nine percent (59 of 85 patients) of lung lesions undergoing resection were CCAMs. Among patients with pathologic diagnosis of CCAM, the initial, largest, and final CVRs were greatest in OFS followed by EXIT and STR patients. Similarly, the incidence of hydrops was significantly greater and the rate of hydrops resolution was lower in the OFS group. Although the rate of cyst drainage did not differ between groups, maternal betamethasone use varied significantly (OFS 60.0%, EXIT 100.0%, STR 74.3%; p = 0.0378). Notably, all OFS took place prior to 2014. There was no difference in survival, ventilator days, nitric oxide, NICU LOS, or ECMO between groups. In multiple variable logistic modeling, determinants of survival to NICU discharge among patients undergoing resection with a pathologic diagnosis of CCAM included initial CVR <3.5 and need for <3 maternal betamethasone doses., Conclusion: For CCAMs that remain large despite maternal betamethasone or cyst drainage, surgical resection via OFS, EXIT, or STR are viable options with favorable and comparable survival between groups. In the modern era there has been a shift from OFS and EXIT procedures to STR for fetuses with persistently large lung lesions. This shift has been fueled by the increased use of maternal betamethasone and introduction of a Special Delivery Unit during the study period and the appreciation of similar fetal and neonatal outcomes for STR vs. EXIT and OFS with reduced maternal morbidity associated with a STR. Accordingly, efforts to optimize multidisciplinary perinatal care for fetuses with large lung lesions are important to inform patient selection criteria and promote STR as the preferred surgical approach in the modern era., Level of Evidence: Level IV., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objective: To evaluate associations between cardiac catheterization (cath) hemodynamics, quantitative measures of right ventricular (RV) function by echocardiogram, and survival in patients with congenital diaphragmatic hernia (CDH)., Study Design: This single-center retrospective cohort study enrolled patients with CDH who underwent index cath from 2003 to 2022. Tricuspid annular plane systolic excursion z score, RV fractional area change, RV free wall and global longitudinal strain, left ventricular (LV) eccentricity index, RV/LV ratio, and pulmonary artery acceleration time were measured from preprocedure echocardiograms. Associations between hemodynamic values, echocardiographic measures, and survival were evaluated by Spearman correlation and Wilcoxon rank sum test, respectively., Results: Fifty-three patients (68% left-sided, 74% liver herniation, 57% extracorporeal membrane oxygenation, 93% survival) underwent cath (39 during index hospitalization, 14 later) including device closure of a patent ductus arteriosus in 5. Most patients (n = 31, 58%) were on pulmonary hypertension treatment at cath, most commonly sildenafil (n = 24, 45%) and/or intravenous treprostinil (n = 16, 30%). Overall, hemodynamics were consistent with precapillary pulmonary hypertension. Pulmonary capillary wedge pressure was >15 mm Hg in 2 patients (4%). Lower fractional area change and worse ventricular strain were associated with higher pulmonary artery pressure while higher LV eccentricity index and higher RV/LV ratio were associated with both higher pulmonary artery pressure and higher pulmonary vascular resistance. Hemodynamics did not differ based on survival status., Conclusions: Worse RV dilation and dysfunction by echocardiogram correlate with higher pulmonary artery pressure and pulmonary vascular resistance on cath in this CDH cohort. These measures may represent novel, noninvasive clinical trial targets in this population., Competing Interests: Declaration of Competing Interest Grant 2021262 from the Doris Duke Charitable Foundation through the COVID-19 Fund to Retain Clinical Scientists Collaborative Grant Program. C.M.V. is also supported by 1K23 HL150337-01. The authors declare no conflicts of interest., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objective: To develop a core set of prenatal and neonatal outcomes for clinical studies evaluating perinatal interventions for congenital diaphragmatic hernia, using a validated consensus-building method., Methods: An international steering group comprising 13 leading maternal-fetal medicine specialists, neonatologists, pediatric surgeons, patient representatives, researchers and methodologists guided the development of this core outcome set. Potential outcomes were collected through a systematic review of the literature and entered into a two-round online Delphi survey. A call was made for stakeholders with experience of congenital diaphragmatic hernia to review the list and score outcomes based on their perceived relevance. Outcomes that fulfilled the consensus criteria defined a priori were discussed subsequently in online breakout meetings. Results were reviewed in a consensus meeting, during which the core outcome set was defined. Finally, the definitions, measurement methods and aspirational outcomes were defined in online and in-person definition meetings by a selection of 45 stakeholders., Results: Overall, 221 stakeholders participated in the Delphi survey and 198 completed both rounds. Fifty outcomes met the consensus criteria and were discussed and rescored by 78 stakeholders in the breakout meetings. During the consensus meeting, 93 stakeholders agreed eventually on eight outcomes, which constituted the core outcome set. Maternal and obstetric outcomes included maternal morbidity related to the intervention and gestational age at delivery. Fetal outcomes included intrauterine demise, interval between intervention and delivery and change in lung size in utero around the time of the intervention. Neonatal outcomes included neonatal mortality, pulmonary hypertension and use of extracorporeal membrane oxygenation. Definitions and measurement methods were formulated by 45 stakeholders, who also added three aspirational outcomes: duration of invasive ventilation, duration of oxygen supplementation and use of pulmonary vasodilators at discharge., Conclusions: We developed with relevant stakeholders a core outcome set for studies evaluating perinatal interventions in congenital diaphragmatic hernia. Its implementation should facilitate the comparison and combination of trial results, enabling future research to better guide clinical practice. © 2023 International Society of Ultrasound in Obstetrics and Gynecology., (© 2023 International Society of Ultrasound in Obstetrics and Gynecology.)

Objective: To characterise the transitional pulmonary physiology of infants with congenital diaphragmatic hernia (CDH) using measures of expiratory tidal volume (TV) and end-tidal carbon dioxide (ETCO 2 )., Design: Prospective single-centre observational study., Setting: Quaternary neonatal intensive care unit., Patients: Infants with an antenatal diagnosis of CDH born at the Children's Hospital of Philadelphia., Interventions: TV and ETCO 2 were simultaneously recorded using a respiratory function monitor (RFM) during invasive positive pressure ventilation immediately after birth., Main Outcome Measures: TV per birth weight and ETCO 2 values were summarised for each minute after birth. Subgroups of interest were defined by liver position (thoracic vs abdominal) and extracorporeal membrane oxygenation (ECMO) treatment., Results: RFM data were available for 50 infants from intubation until a median (IQR) of 9 (7-14) min after birth. TV and ETCO 2 values increased for the first 10 min after birth, but intersubject values were heterogeneous. TVs were overall lower and ETCO 2 values higher in infants with an intrathoracic liver and infants who were ultimately treated with ECMO. On hospital discharge, survival was 88% (n=43) and 34% (n=17) of infants were treated with ECMO., Conclusion: Respiratory function immediately after birth is heterogeneous for infants with CDH. Lung aeration, as evidenced by expired TV and ETCO 2 , appears to be ongoing throughout the first 10 min after birth during invasive positive pressure ventilation. Close attention to expired TV and ETCO 2 levels by 10 min after birth may provide an opportunity to optimise and individualise ventilatory support for this high-risk population., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: To describe our experience with treprostinil, evaluate correlations with cardiac function, and assess for adverse effects in neonates with congenital diaphragmatic hernia-related pulmonary hypertension (CDH-PH)., Study Design: A retrospective review of a single-center prospective registry at a quaternary care children's hospital. Patients included in the study had CDH-PH treated with treprostinil between April 2013 and September 2021. Assessed outcomes were brain-type natriuretic peptide levels and quantitative echocardiographic parameters collected at baseline, 1 week, 2 weeks, and 1 month after treprostinil initiation. Right ventricular (RV) function was assessed by tricuspid annular plane systolic excursion Z-score and speckle tracking echocardiography (global longitudinal and free wall strain). Septal position and left ventricular (LV) compression were assessed by eccentricity index and M-mode Z-scores., Results: Fifty-one patients were included, with an average expected/observed lung-to-head ratio of 28.4 ± 9.0%. Most patients required extra-corporeal membrane oxygenation (n = 45, 88%). Survival to hospital discharge was 31/49 (63%). Treprostinil was initiated at a median age of 19 days with a median effective dose of 34 ng/kg/minute. Median baseline brain-type natriuretic peptide level decreased from 416.9 pg/mL to 120.5 pg/mL after 1 month. Treprostinil was associated with improved tricuspid annular plane systolic excursion Z-score, RV global longitudinal strain, RV free wall strain, LV eccentricity index, and LV diastolic and systolic dimensions, reflecting less compression by the RV, regardless of ultimate patient survival. No serious adverse effects were recorded., Conclusions: In neonates with CDH-PH, treprostinil administration is well tolerated and is associated with improved RV size and function., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: The utilization of 3-T magnetic field strength in obstetric imaging is increasingly common. It is important to ensure that magnetic resonance (MR) imaging with higher magnetic field strength is safe for the fetus. Comparison of neurodevelopmental outcome in neonates undergoing prenatal MR imaging with 1.5-T versus 3-T is of interest but has not yet been examined., Objective: We hypothesized no clinically meaningful difference in neurodevelopmental outcome between fetuses undergoing 1.5-T versus 3-T fetal MR imaging. As imaging a normal fetus for research purposes is illegal in Pennsylvania, this study was conducted in a population of fetuses with left congenital diaphragmatic hernia (left-CDH)., Materials and Methods: A retrospective review of neurodevelopmental outcome of fetuses with left-CDH scanned at 1.5-T (n=75) versus 3-T (n=25) magnetic field strength between July of 2012 and December of 2019 was performed. Neurodevelopmental outcomes were assessed using the Bayley Scales of Infant Development, 3rd Edition (BSID-III)., Results: There were no statistical differences in median age of assessment (1.5-T: 18 [12, 25] versus 3-T: 21 [11, 26], P=0.79), in mean BSID-III cognitive (1.5-T: 91 ± 14 versus 3-T: 90 ± 16, P=0.82), language (1.5-T: 92 ± 20 versus 3-T: 91 ± 20, P=0.91), and motor composite (1.5-T: 89 ± 15 versus 3-T: 87 ± 18, P=0.59) scores, subscales scores (for all, P>0.50), or in risk of abnormal neuromuscular exam (P=0.29) between neonates with left-CDH undergoing a 1.5-T versus 3-T MR imaging during fetal life. Additionally, the distribution of patients with average, mildly delayed, and severely delayed BSID-III scores was similar between the two groups (for all, P>0.50). The overall distribution of the composite scores in this CDH population was similar to the general population independent of exposure to 1.5-T or 3-T fetal MR imaging. Two 3-T patients (8%) and five 1.5-T patients (7%) scored within the significant delayed range for all BSID-III domains. Subjects with lower observed-to-expected fetal lung volume (O/E FLV) and postnatal need for ECMO had lower cognitive, language, motor, and subscales scores (for all, P<0.03) regardless of being imaged at 1.5-T versus 3-T., Conclusion: This preliminary study suggests that, compared to 1.5-T MR imaging, fetal exposure to 3-T MR imaging does not increase the risk of neurodevelopmental impairment in fetuses with left-CDH. Additional MR imaging studies in larger CDH cohorts and other fetal populations are needed to replicate and extend the present findings., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objectives: We aimed to determine the prevalence of electrographic seizures and associated odds of adverse outcomes of electrographic seizures in neonates with congenital diaphragmatic hernia (CDH) receiving extracorporeal membrane oxygenation (ECMO)., Design: Retrospective, descriptive case series., Setting: Neonatal ICU (NICU) in a quaternary care institution., Patients: All neonates with CDH receiving ECMO undergoing continuous electroencephalographic monitoring (CEEG) and follow-up between January 2012 and December 2019., Interventions: None., Measurements and Main Results: All eligible neonates with CDH receiving ECMO underwent CEEG (n = 75). Electrographic seizures occurred in 14 of 75 (19%): they were exclusively electrographic-only in nine of 14, both electrographic-only and electroclinical in three of 14, and electroclinical only in two of 14. Two neonates developed status epilepticus. We identified an association between presence of seizures, rather than not, and longer duration of initial session of CEEG monitoring (55.7 hr [48.2-87.3 hr] vs 48.0 hr [43.0-48.3 hr]; p = 0.001). We also found an association between presence of seizures, rather than not, and greater odds of use of a second CEEG monitoring (12/14 vs 21/61; odds ratio [OR], 11.43 [95% CI, 2.34-55.90; p = 0.0026). Most neonates with seizures (10/14), experienced their onset of seizures more than 96 hours after the start of ECMO. Overall, the presence of electrographic seizures, compared with not, was associated with lower odds of survival to NICU discharge (4/14 vs 49/61; OR 0.10 [95% CI 0.03 to 0.37], p = 0.0006). Also, the presence of seizures-rather than not-was associated with greater odds of a composite of death and all abnormal outcomes on follow-up (13/14 vs 26/61; OR, 17.5; 95% CI, 2.15-142.39; p = 0.0074)., Conclusions: Nearly one in five neonates with CDH receiving ECMO developed seizures during the ECMO course. Seizures were predominantly electrographic-only and when present were associated with great odds of adverse outcomes. The current study provides evidence to support standardized CEEG in this population., Competing Interests: Dr. Massey received support for article research from the National Institutes of Health. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2023 by the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies.)

Background: Mediastinal and pericardial teratomas have overlapping imaging features that may make accurate prenatal diagnosis challenging., Objective: To identify prenatal imaging features that may aid in distinguishing between mediastinal and pericardial teratomas., Materials and Methods: Prenatally diagnosed pericardial and mediastinal teratomas evaluated at our fetal center from 1995 to 2020 were included in this Institutional Review Board-approved study. Lesion volume was calculated using prospectively reported ultrasound (US) measurements and the formula of a prolate ellipsoid, which was then normalized to head circumference. Prenatal US and magnetic resonance imaging (MRI) studies were anonymized with two fetal imagers reviewing the US studies and two different fetal imagers reviewing the MRI studies. These experienced reviewers scored location of the mass in the craniocaudal axis and in the transverse axis. MRI reviewers also scored the presence of inferior cardiac compression by the lesion and whether there was identifiable thymic tissue. Reviewer disagreements were resolved by consensus review., Results: Eleven pericardial teratomas and 10 mediastinal teratomas were identified. All cases underwent detailed fetal anatomic US and fetal echocardiogram and 10/11 (91%) pericardial teratomas and 8/10 (80%) mediastinal teratomas underwent fetal MRI. Median volume was higher for mediastinal teratomas compared to pericardial teratomas (42.5 mL [interquartile range (IQR) 15.9 - 67.2 mL] vs. 8.1 mL [IQR 7.7 - 27.7 mL], P=0.01) and median volume/head circumference was also statistically higher in mediastinal teratomas (1.33 [IQR 0.78 - 2.61] vs. 0.43 [IQR 0.38 - 1.10], P=0.01). Logistic regression analysis demonstrated a statistical difference between teratoma types with respect to location in the craniocaudal axis by both modalities with mediastinal teratomas more commonly located in the upper and upper-middle thorax compared to pericardial teratomas, which were more commonly found in the middle thorax (US, P=0.03; MRI, P=0.04). Logistic regression analysis also demonstrated a statistical difference between teratoma types with respect to position along the transverse axis by both modalities with mediastinal teratomas more commonly located midline or left paramedian and pericardial teratomas more often right paramedian in location (US, P&lt;0.01; MRI, P=0.02). Inferior cardiac compression observed by MRI was associated more commonly with mediastinal teratomas compared to pericardial teratomas (87.5% [7/8] vs. 10% [1/10], P&lt;0.01). Identifiable thymus by MRI was more commonly observed in cases of pericardial teratomas, however, this difference was not statistically significant (P=0.32)., Conclusion: Mediastinal teratomas are associated with larger lesion size and inferior cardiac compression when compared to pericardial teratomas. These features combined with lesion location in the craniocaudal and transverse axes may allow for more accurate prenatal diagnosis and optimal perinatal and surgical management., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: To evaluate genetic testing use in infants with congenital diaphragmatic hernia (CDH) over the past decade to better inform future practices and individualize prognostication and management., Study Design: A retrospective cohort study was performed of all infants with CDH enrolled in the Pulmonary Hypoplasia Program at Children's Hospital of Philadelphia, born between January 2011 and February 2021. For each infant, demographic information, prenatal and postnatal history, and genetic testing were reviewed., Results: The charts of 411 infants were analyzed. Overall, 22% (n = 89) were complex/syndromic and 78% (n = 322) were isolated/nonsyndromic. Mortality was significantly higher in complex/syndromic infants (P < .001) and in infants with diagnostic genetic testing (P < .001). Microarray was diagnostic in 9% (n = 34/399) and exome sequencing was diagnostic in 38% (n = 15/39). Genetic testing was diagnostic in 57% (n = 51/89) of complex/syndromic infants, but in only 2% of isolated/nonsyndromic infants (n = 8/322). Overall, genetic testing was diagnostic in 14% (n = 56)., Conclusions: The high diagnostic rate in this cohort highlights the utility of comprehensive genetic testing in infants with CDH. However, 43% of complex/syndromic and 98% of isolated/nonsyndromic infants do not have a genetic etiology identified. This finding underscores the need for additional genetic and genomic studies (eg, whole genome, RNA sequencing) to identify novel genes and mutational mechanisms (single genes, regulatory elements, complex traits) that will allow for improved diagnostic rates and ultimately individualized management of infants with CDH., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Congenital diaphragmatic hernia (CDH) is a complex malformation characterised by a triad of pulmonary hypoplasia, pulmonary hypertension (PH) and cardiac ventricular dysfunction. Much of the mortality and morbidity in CDH is largely accounted for by PH, especially when persistent beyond the neonatal period and refractory to available treatment. Gentle ventilation, haemodynamic optimisation and pulmonary vasodilation constitute the foundations of neonatal treatment of CDH-related PH (CDH-PH). Moreover, early prenatal diagnosis, the ability to assess severity and the developmental nature of the condition generate the perfect rationale for fetal therapy. Shortcomings of currently available clinical therapies in combination with increased understanding of CDH pathophysiology have spurred experimental drug trials, exploring new therapeutic mechanisms to tackle CDH-PH. We herein discuss clinically available neonatal and fetal therapies specifically targeting CDH-PH and review the most promising experimental treatments and future research avenues., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Enteral nutrition is a critical intervention that supports the growth of children with pulmonary hypoplasia (PH). We explored the experiences of caregivers and providers caring for children with PH to better understand gaps in knowledge transfer and identify barriers and facilitators to caregiving to inform interventions that may improve support., Methods: This qualitative study included 10 interviews with caregivers and 10 clinical team members at a single integrated care program for children with PH. An inductive and iterative coding strategy was employed to produce a codebook. After cluster analysis, themes were generated to capture participant sentiments., Results: Themes were defined along a care continuum (1) initiation, (2) adaptation, and (3) maintenance that represented distinct phases of adjustment to enteral nutrition support (1) in the perinatal period and initial neonatal intensive care unit (NICU) admission, (2) from discharge planning through the family's first days at home and establishment of a stable feeding regime, and (3) through long-term follow-up and weaning. Notable subthemes included uncertainty, partnerships in training, and obstacles to adaptation., Conclusions: Among children with PH, the caregiver-provider relationship during the perinatal and NICU course is critical to promoting caregiver adaptation to the needs of the child. Ongoing considerations to support resource alignment and transition to a stable feeding regimen may facilitate caregiver adjustment to a "new normal," culminating in successful growth and/or weaning. These findings will inform interventions focused on training curricula, discharge planning, and the provision of follow-up in the context of an integrated care program for PH., (© 2022 American Society for Parenteral and Enteral Nutrition.)

Pediatric extreme thrombocytosis (EXT, platelet count > 1000 x 10 3 /µL) is rare. In a single center retrospective analysis of hospitalized children with EXT, infants with congenital diaphragmatic hernia (CDH) were overrepresented. In general pediatric patients, EXT is usually secondary to infection or inflammation, but most of the 14 CDH patients with EXT had no identifiable inciting factor. Instead, there was evidence that splenic dysfunction and bone marrow hyperactivity underlied EXT in CDH patients. None were associated with bleeding or thrombosis. Our findings identify mechanisms underlying EXT, and aid clinical interpretation and management of EXT in the pediatric population.

Background: Persistent pulmonary hypertension (PH) causes significant mortality and morbidity in infants with congenital diaphragmatic hernia (CDH). Since pulmonary vascular abnormalities in CDH develop early during foetal development, we hypothesized that prenatal maternal administration of treprostinil, through its anti-remodelling effect, would improve the PH-phenotype in the nitrofen rat model of CDH., Methods: In a dose-finding study in normal, healthy pregnant rats, we demonstrated target-range foetal plasma treprostinil concentrations without signs of toxicity. Next, an efficacy study was performed assessing the effects of treprostinil administration at 900 and 1500ng/kg/min from gestational day (GD) 16 until term (GD 21) in CDH and control pups. Pulmonary vascular and airway morphometry, lung mechanics, and expression patterns of genes implicated in the prostaglandin vasoactive pathway were studied., Findings: In rats maternal administration of 1500ng/kg/min treprostinil reached target foetal concentrations, with no detrimental maternal or foetal side-effects. Prenatal exposure to 900 and 1500 ng/kg/min treprostinil reduced the medial wall thickness (%MWT) (CDH·900, 38.5± 8·4%; CDH.1500, 40·2±9·7%; CDH, 46·6±8·2%; both p < 0·0001) in rat pups with CDH, however increased the %MWT in normal foetuses (C.T.900, 36·6±11·1%; C.T.1500, 36·9±9·3%; C.P., 26·9±6·2%; both p < 0·001). Pulmonary airway development, lung hypoplasia and pulmonary function were unaffected by drug exposure., Interpretation: In pregnant rats maternally administered treprostinil crosses the placenta, attains foetal target concentrations, and is well tolerated by both mother and foetuses. This report shows a significant reduction of pulmonary arteriole muscularization with prenatal treprostinil in a nitrofen rat model, supporting the promise of this treatment approach for PH of CDH., Funding: United Therapeutics Corporation provided treprostinil and financial support (ISS-2020-10879)., Competing Interests: Declaration of interests United Therapeutics Corporation provided treprostinil and financial support for this study (ISS-2020-10879). FRDB was supported by the Flanders Research Foundation (FWO-1S31720N) to conduct this work. The authors state that there are no other conflicts of interest., (Copyright © 2022. Published by Elsevier B.V.)

Objectives: To describe our experience treating prenatally diagnosed oropharyngeal masses in a novel, multidisciplinary collaboration. To identifying outcomes and risk factors associated with adverse postnatal outcomes., Methods: This is a sixty-two patient case series at an academic referral center. Patients with prenatally diagnosed oropharyngeal masses were identified through a programmatic database and confirmed in the electronic health record., Results: Sixty-two patient with prenatally diagnosed oropharyngeal mass were identified, with prenatal imaging at our institution confirming this diagnosis in fifty-seven patients, short term outcomes analysis conducted on forty-four patients, and long-term outcomes analysis conducted on seventeen patients. The most common pathology was lymphatic malformations (n = 27, 47.4%), followed by teratomas (n = 22, 38.6%). The median mass volume from all available patient imaging (n = 57) was 60.54 cm 3 (range 1.73-742.5 cm 3 ). Thirteen pregnancies were interrupted, six infants expired, and thirteen cases had an unknown fetal outcome. Confirmed mortality was 6/57 patients with imaging-confirmed oropharyngeal masses (10.5%). Fourteen (56%) of the surviving patients (n = 25) were delivered by Ex Utero Intrapartum Treatment (EXIT) procedure and the median NICU stay was thirty-six days (range: 3-215 days). There was no association between airway compression/deviation/displacement, stomach size, polyhydramnios, or mass size and mortality. Seventeen patients had more than one year of follow-up (mean 5.3 ± 2.4 years). These seventeen patients underwent general anesthesia a total of ninety-two times (mean 5.4 ± 4.3) and had a total of twenty-three mass-related surgeries. The great majority of patients required an artificial airway at birth, feeding support, and speech/swallow therapy., Conclusions: Oropharyngeal mass involvement of key anatomic structures-the neck, upper thorax, orbit, and ear, has a greater association with mortality than mass size. Regardless of the size and involved structures, oropharyngeal masses are associated with a high burden of intensive medical care and surgical care beginning at or before birth., (Copyright © 2021. Published by Elsevier B.V.)

Background/purpose: To evaluate the enteral feeding requirements, including caloric provisions, of infants with CDH in relation to growth patterns., Methods: A retrospective observational study was conducted on infants with CDH between August 2012 and March 2017. Electronic medical records were reviewed to extract detailed infant feeding data and anthropometric measurements at monthly intervals until discharge. Statistical methods of analysis included generalized linear models, Pearson correlation coefficient, Analysis of variance (ANOVA), Kruskal-Wallis, Wilcoxon rank sum, and Fisher's Exact tests., Results: Among 149 infants with CDH, 45% (n = 67) met criteria for malnutrition at discharge. Maternal human milk (HM) was initiated in 95% of infants (n = 142) and continued in 79% of infants (n = 118) at discharge. Overall, 50% received fortification of feeds, including 60% (n = 89) of formula fed infants compared to only 21% (n = 31) of HM fed infants (p<0.001). Infants fed formula had lower weight-for-length z-scores at discharge compared to those fed HM., Conclusions: Infants receiving HM demonstrated improved growth compared to formula fed infants. However, higher calorie feeding regimens need to be initiated earlier to improve growth velocity. Prompt recognition of malnutrition and growth failure with aggressive supplementation may improve the overall growth of infants with CDH and has the potential to improve long term neurodevelopmental outcomes., Competing Interests: Declaration of Competing Interest The authors have indicated they have no potential conflicts of interest to disclose., (Copyright © 2021. Published by Elsevier Inc.)

Objective: To evaluate the influence of stomach position on postnatal outcome in cases of left congenital diaphragmatic hernia (CDH) without liver herniation, diagnosed and characterized on prenatal ultrasound (US), by comparing those with ('stomach-up' CDH) to those without ('stomach-down' CDH) intrathoracic stomach herniation., Methods: Infants with left CDH who underwent prenatal US and postnatal repair at our institution between January 2008 and March 2017 were eligible for inclusion in this retrospective study. Detailed prenatal US examinations, fetal magnetic resonance imaging (MRI) studies, operative reports and medical records of infants enrolled in the pulmonary hypoplasia program at our institution were reviewed. Cases with liver herniation and those with an additional anomaly were excluded. Cases in which bowel loops were identified within the fetal chest on US while the stomach was intra-abdominal were categorized as having stomach-down CDH. Cases in which bowel loops and the stomach were visualized within the fetal chest on US were categorized as having stomach-up CDH. Prenatal imaging findings and postnatal outcomes were compared between the two groups., Results: In total, 152 patients with left CDH were initially eligible for inclusion. Seventy-eight patients had surgically confirmed liver herniation and were excluded. Of the 74 included CDH cases without liver herniation, 28 (37.8%) had stomach-down CDH and 46 (62.2%) had stomach-up CDH. Of the 28 stomach-down CDH cases, 10 (35.7%) were referred for a suspected lung lesion. Sixty-eight (91.9%) cases had postnatal outcome data available for analysis. There was no significant difference in median observed-to-expected (o/e) lung-area-to-head-circumference ratio (LHR) between cases with stomach-down CDH and those with stomach-up CDH (41.5% vs 38.4%; P = 0.41). Furthermore, there was no difference in median MRI o/e total lung volume (TLV) between the two groups (49.5% vs 44.0%; P = 0.22). Compared with stomach-up CDH patients, stomach-down CDH patients demonstrated lower median duration of intubation (18 days vs 9.5 days; P < 0.01), median duration of extracorporeal membrane oxygenation (495 h vs 223.5 h; P < 0.05), rate of supplemental oxygen requirement at 30 days of age (20/42 (47.6%) vs 3/26 (11.5%); P < 0.01) and rate of pulmonary hypertension at initial postnatal echocardiography (28/42 (66.7%) vs 9/26 (34.6%); P = 0.01). No neonatal death occurred in stomach-down CDH patients and one neonatal death was seen in a patient with intrathoracic stomach herniation., Conclusions: In infants with left CDH without liver herniation, despite similar o/e-LHR and o/e-TLV, those with stomach-down CDH have decreased neonatal morbidity compared to those with stomach herniation. Progressive or variable physiological distension of the stomach over the course of gestation may explain these findings. Stomach-down left CDH is mistaken for a lung mass in a substantial proportion of cases. Accurate prenatal US characterization of CDH is crucial for appropriate prenatal counseling and patient management. © 2021 International Society of Ultrasound in Obstetrics and Gynecology., (© 2021 International Society of Ultrasound in Obstetrics and Gynecology.)

Purpose: To investigate antenatally-determined imaging characteristics associated with invasive airway management at birth in patients with cervical masses, as well as to describe postnatal management and outcomes., Study Design: A retrospective analysis of 52 patients with antenatally diagnosed neck masses was performed using single-center data from January 2008 to January 2019. Antenatal imaging, method of delivery, management, and outcomes data were abstracted from the medical record and analyzed., Results: Antenatal diagnosis of neck masses in this cohort consisted of 41 lymphatic malformations (78.8%), 6 teratomas (11.5%), 3 hemangiomas (5.8%), 1 hemangioendothelioma (1.9%), and 1 giant foregut duplication cyst (1.9%). Mean gestational age at time of diagnostic imaging was 29 weeks 3 days (range: 19w4d - 37w). Overall, 22 patients (42.3%) required invasive airway management at birth, specifically 18 patients (34.6%) required endotracheal intubation and 4 (7.7%) required tracheostomy. 15 patients (28.8%) underwent ex-utero intrapartum treatment (EXIT) for the purposes of securing an airway. Polyhydramnios, tracheal deviation and compression, and anterior mass location on antenatal imaging were significantly associated with incidence of invasive airway intervention at birth, EXIT procedure, and tracheostomy during the neonatal hospitalization (p < 0.025; Fisher's exact test). Logistic regression analysis demonstrated statistically significant association between increasing antenatally-estimated mass volume and incidence of invasive airway management at birth (p = 0.02). Post-natal cervical mass management involved surgical excision (32.7%), sclerotherapy (50%), and adjuvant therapy with rapamycin (17.3%). Demise in the neonatal period occurred in 4 (7.7%) patients., Conclusion: This series documents the largest single-center experience of airway management in antenatally diagnosed cervical masses. Fetal imaging characteristics may help inform the appropriate method of delivery, airway management strategy at birth, and prenatal counseling., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Objective: To examine the association between prenatal magnetic resonance imaging (MRI) based observed/expected total lung volume (O/E TLV) and outcome in neonates with giant omphalocele (GO)., Methods: Between 06/2004 and 12/2019, 67 cases with isolated GO underwent prenatal and postnatal care at our institution. MRI-based O/E TLVs were calculated based on normative data from Meyers and from Rypens and correlated with postnatal survival and morbidities. O/E TLV scores were grouped based on severity into <25% (severe), between 25% and 50% (moderate), and >50% (mild) for risk stratification., Results: O/E TLV was calculated for all patients according to Meyers nomograms and for 49 patients according to Rypens nomograms. Survival for GO neonates with severe, moderate, and mild pulmonary hypoplasia based on Meyers O/E TLV categories was 60%, 92%, and 96%, respectively (p = 0.04). There was a significant inverse association between Meyers O/E TLV and risk of neonatal morbidities (p < 0.05). A similar trend was observed with Rypens O/E TLV, but associations were less often significant likely related to the smaller sample size., Conclusion: Neonatal outcomes are related to fetal lung size in isolated GO. Assessment of Meyers O/E TLV allows identification of GO fetuses at greatest risk for complications secondary to pulmonary hypoplasia., (© 2021 John Wiley & Sons Ltd.)

Objective: To assess the ability of point-of-care ultrasound (POCUS) to identify venous cannula position in neonates on extracorporeal membrane oxygenation (ECMO) and compare with conventional imaging., Study Design: Retrospective review of 37 infants on ECMO with 51 POCUS studies between January 2017 and October 2019. Studies were reviewed for identification of venous cannula location and compared with plain radiography and echocardiography. Kappa statistic and predictive values were calculated., Results: Venous cannula tip position was identified in 90% of POCUS studies. Fifty percent of the cannula tips were malpositioned. Plain radiography, the most commonly used method for evaluating tip position, showed poor agreement (57%) with POCUS (kappa 0.13). There was substantial agreement (89%) between echocardiography and POCUS (kappa 0.78)., Conclusion: This study provides preliminary evidence that POCUS is more accurate than plain radiography for the evaluation of ECMO venous cannula position. Adoption of this practice may prevent potentially catastrophic ECMO complications., (© 2021. The Author(s), under exclusive licence to Springer Nature America, Inc. part of Springer Nature.)

Objective: To evaluate the associations between the primary indication for extracorporeal membrane oxygenation (ECMO) in neonates and neurodevelopmental outcomes at 12 and 24 months of age., Study Design: This is a retrospective cohort study of neonates treated with ECMO between January 2006 and January 2016 in the Children's Hospital of Philadelphia newborn/infant intensive care unit. Primary indication for ECMO was classified as medical (eg, meconium aspiration syndrome) or surgical (eg, congenital diaphragmatic hernia). Primary study endpoints were assessed with the Bayley Scales of Infant and Toddler Development, Third Edition (Bayley-III). Groups were compared with standard bivariate testing and multivariable regression., Results: A total of 191 neonates met the study's inclusion criteria, including 96 with a medical indication and 95 with a surgical indication. Survival to discharge was 71%, with significantly higher survival in the medical group (82% vs 60%; P = .001). Survivors had high rates of developmental therapies and neurosensory abnormalities. Developmental outcomes were available for 66% at 12 months and 70% at 24 months. Average performance on the Bayley-III was significantly below expected population normative values. Surgical patients had modestly lower the Bayley-III scores over time; most notably, 15% of medical infants and 49% of surgical infants had motor delay at 24 months (P = .03)., Conclusions: In this single-center cohort, surgical patients had lower survival rates and higher incidence of motor delays. Strategies to reduce barriers to follow-up and improve rates of postdischarge developmental surveillance and intervention in this high-risk population are needed., (Published by Elsevier Inc.)

Aim: The optimal gestational age (GA) at delivery and mode of delivery (MoD) for pregnancies with fetal congenital diaphragmatic hernia (CDH) is undetermined. The impact of early term (37-38 weeks 6 days) versus full term (39-40 weeks 6 days) and MoD on immediate neonatal outcomes in prenatally diagnosed isolated CDH cases was evaluated., Material and Methods: A retrospective chart review of pregnancies evaluated and delivered with the prenatal diagnosis of CDH between July 1, 2008, and December 31, 2018. The primary outcome was survival to hospital discharge. Secondary outcomes included neonatal intensive care unit (NICU) length of stay (LOS), extracorporeal membrane oxygenation (ECMO) requirement and need for supplemental oxygen at day 30 of life., Results: A total of 296 patients were prenatally evaluated for CDH and delivered in a single center during the study period. After applying exclusion criteria, data were available on 113 women who delivered early term and 72 women who delivered full term. Survival to hospital discharge was comparable between the 2 groups - 83.2% in the early term versus 93.1% in the full term (p = 0.07; 95% CI of 0.13-1.04). No difference was observed in any other secondary outcomes. MoD was stratified into spontaneous vaginal, induced vaginal, unplanned cesarean and scheduled cesarean delivery with associated neonatal survival rates of 74.2, 90.6, 89.7 and 88.2%, respectively, p = 0.13. The 5-min Apgar score was higher in the elective cesarean group (7.94) followed by the induced vaginal delivery group (7.8) compared to 7.17 and 7.18 in the spontaneous vaginal and unplanned cesarean groups, respectively (p = 0.03). The GA and MoD did not influence survival to hospital discharge nor NICU LOS in multivariate analysis., Conclusions: Though there were no significant differences in neonatal outcomes for early term compared to full term deliveries of CDH neonates, a trend toward improved survival rates and lower ECMO requirements in the full term group may suggest an underlying importance GA at delivery. Further studies are warranted to validate these findings., (© 2021 S. Karger AG, Basel.)

Rationale: Brain-type natriuretic peptide (BNP) correlates with pulmonary hypertension as demonstrated by echocardiogram in congenital diaphragmatic hernia (CDH); however, its association with right ventricular (RV) function and mortality is unknown. Objectives: To characterize the relationships between echocardiogram-derived RV strain, BNP, and mortality in diaphragmatic hernia. Methods: We performed a single-center retrospective cohort study of infants with CDH and at least one BNP-echocardiogram pair within a 24-hour period. RV global longitudinal strain (GLS) and free-wall strain (FWS) were measured on existing echocardiograms. Associations among strain, BNP, and mortality were tested using mixed-effect linear and logistic regression models. Survival analysis was stratified by BNP and strain abnormalities. Results: There were 220 infants with 460 BNP-echocardiogram pairs obtained preoperatively ( n  = 237), ≤1 week postoperatively ( n  = 35), and >1 week postoperatively ("recovery"; n  = 188). Strain improved after repair ( P  < 0.0001 for all periods). Higher BNP level was associated with worse strain in recovery but not before or immediately after operation (estimate [95% confidence interval] for recovery: GLS, 1.03 [0.50-1.57]; P  = 0.0003; FWS, 0.62 [0.01-1.22]; P  = 0.047). BNP and strain abnormalities were associated with an extracorporeal-membrane oxygenation requirement. Higher BNP level in recovery was associated with greater mortality (odds ratio, 11.2 [1.2-571.3]; P  = 0.02). Abnormal strain in recovery had high sensitivity for detection of mortality (100% for GLS; 100% for FWS) but had low specificity for detection of mortality (28% for GLS; 48% for FWS). Conclusions: Persistent RV dysfunction after CDH repair may be detected by a high BNP level and abnormal RV strain.

Background: TREPROSTINIL IS A PROSTACYCLIN ANALOG USED FOR TREATMENT OF PULMONARY HYPERTENSION (PH) IN ADULTS AND CHILDREN, CURRENTLY AWAITING CLINICAL ASSESSMENT FOR USE IN NEONATES.: OBJECTIVES: WE AIMED TO INVESTIGATE THE USE OF TREPROSTINIL IN NEONATES WITH PH ON EXTRACORPOREAL MEMBRANE OXYGENATION (ECMO) SUPPORT AND MEASURE PLASMA CONCENTRATIONS OF THE DRUG.: METHODS: THIS IS A RETROSPECTIVE CASE-SERIES WITH PROSPECTIVELY COLLECTED BLOOD SAMPLES, CONDUCTED IN A QUATERNARY CARE NEONATAL INTENSIVE CARE UNIT. BRAIN NATRIURETIC PEPTIDE, CARDIAC FUNCTION ON DOPPLER ECHOCARDIOGRAPHY, AND THE OCCURRENCE OF ADVERSE EFFECTS WAS MONITORED. PLASMA CONCENTRATIONS WERE MEASURED USING HIGH-PERFORMANCE LIQUID CHROMATOGRAPHY AND MASS SPECTROMETRY.: RESULTS: FOUR PATIENTS WITH PH REQUIRING ECMO THERAPY WERE STUDIED. TREPROSTINIL DOSES OF 20-58 NG/KG/MIN REACHED CONCENTRATIONS OF 0.99-4.39 NG/ML AND INDUCED CLINICAL IMPROVEMENT. INFUSION OF TREPROSTINIL WAS ASSOCIATED WITH IMPROVED RIGHT VENTRICULAR FUNCTION, REVERSED RIGHT-TO-LEFT SHUNTING THROUGH THE DUCTUS ARTERIOSUS, AND STABLE OR DECREASING NEED FOR VASOPRESSOR SUPPORT., No Adverse Effects Were Observed: CONCLUSIONS: THIS IS THE FIRST STUDY TO REPORT CLINICALLY THERAPEUTIC TREPROSTINIL CONCENTRATIONS IN CIRCULATING PLASMA AFTER TREPROSTINIL ADMINISTRATION IN NEONATES ON ECMO, WITH ASSOCIATED CLINICAL IMPROVEMENT OF PH AND NO SIGNS OF HEMODYNAMIC INSTABILITY., (© 2020 Pharmacotherapy Publications, Inc.)

Introduction: Congenital diaphragmatic hernia (CDH) is associated with variable degrees of lung hypoplasia. Pulmonary support at 30 days postnatal age was found to be the strongest predictor of inpatient mortality and morbidity among CDH infants and was also associated with higher pulmonary morbidity at 1 and 5 years. It is not known, however, if there is a relationship between the need for medical therapy at 30 days of life and subsequent abnormalities in lung function as reflected in infant pulmonary function test (iPFT) measurements., Objective: We hypothesized that CDH infants who require more intensive therapy at 30 days would have more abnormal iPFT values at the time of their first infant pulmonary function study, reflecting the more severe spectrum of lung hypoplasia., Methods: A single-institution chart review of all CDH survivors who were enrolled in a Pulmonary Hypoplasia Program (PHP) through July 2019, and treated from 2002 to 2019 was performed. All infants were divided into groups based on their need for noninvasive (supplemental oxygen, high flow therapy, noninvasive mechanical ventilation) or invasive (mechanical ventilation, extracorporeal membrane oxygenation) respiratory assistance, bronchodilators, diuretic use, and pulmonary hypertension (PH) therapy (inhaled and/or systemic drugs) at 30 days. Descriptive and statistical analyses were performed between groups comparing subsequent lung function measurements., Results: A total of 382 infants (median gestational age [GA] 38.4 [interquartile range (IQR) = 37.1-39] weeks, 41.8% female, 70.9% Caucasian) with CDH were enrolled in the PHP through July 2019, and 118 infants underwent iPFT. The median age of the first iPFT was 6.6 (IQR = 5.3-11.7) months. Those requiring any pulmonary support at 30 days had a higher functional residual capacity (FRC) (z) (P = .03), residual volume (RV) (z) (P = .008), ratio of RV to total lung capacity (RV/TLC) (z) (P = .0001), and ratio of FRC to TLC (FRC/TLC) (z) (P = .001); a lower forced expiratory volume at 0.5 seconds (FEV0.5) (z) (P = .03) and a lower respiratory system compliance (Crs) (P = .01) than those who did not require any support. Similarly, those requiring diuretics and/or PH therapy at 30 days had higher fractional lung volumes, lower forced expiratory flows and Crs than infants who did not require such support (P < .05)., Conclusions: Infants requiring any pulmonary support, diuretics and/or PH therapy at 30 postnatal days have lower forced expiratory flows and higher fractional lung volumes, suggesting a greater degree of lung hypoplasia. Our study suggests that the continued need for PH, diuretic or pulmonary support therapy at 30 days can be used as additional risk-stratification measurements for evaluation of infants with CDH., (© 2020 Wiley Periodicals, Inc.)

Background: Infants with congenital diaphragmatic hernia (CDH) often experience hypoxaemia with acidosis immediately after birth. The traditional approach in the delivery room is immediate cord clamping followed by intubation. Initiating resuscitation prior to umbilical cord clamping (UCC) may support this transition., Objectives: To establish the safety and feasibility of intubation and ventilation prior to UCC for infants with CDH. To compare short-term outcomes between trial participants and matched controls treated with immediate cord clamping before intubation and ventilation., Design: Single-arm, single-site trial of infants with CDH and gestational age ≥36 weeks. Infants were placed on a trolley immediately after birth and underwent intubation and ventilation, with UCC performed after qualitative CO 2 detection. The primary feasibility endpoint was successful intubation prior to UCC. Prespecified safety and physiological outcomes were compared with historical controls matched for prognostic variables using standard bivariate tests., Results: Of 20 enrolled infants, all were placed on the trolley, and 17 (85%) infants were intubated before UCC. The first haemoglobin and mean blood pressure at 1 hour of life were significantly higher in trial participants than controls. There were no significant differences between groups for subsequent blood pressure values, vasoactive medications, inhaled nitric oxide or extracorporeal membrane oxygenation. Blood gas and oxygenation index values did not differ between groups at any point., Conclusions: Intubation and ventilation prior to UCC is safe and feasible among infants with CDH. The impact of this approach on clinically relevant outcomes deserves investigation in a randomised trial., Competing Interests: Competing interests: EEF is an unpaid member of the Scientific Advisory board for Concord Neonatal. NN receives research support from Draeger, Aerogen, Smiths Medical, Actuated Medical and Vero Biotech. No other competing interests are declared., (© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Neonatal sedation practices during extracorporeal membrane oxygenation (ECMO) are not well described and no universal guidelines exist. Current literature describes types of medications used in adult and pediatric ECMO patients, but to our knowledge no data is published on neonatal specific median daily dose requirements or descriptions of sedation practices. The objective of this study is to examine the types and median doses of sedation utilized and to describe sedation practices for neonatal patients requiring ECMO support. This study was a descriptive, retrospective analysis of sedation practices in a single center newborn/infant intensive care unit (N/IICU) from 2012 to 2016. Subjects included all neonates who required ECMO support in the N/IICU for >24 hours. Data were collected from 87 patients and showed the median daily dose of opioids converted to intravenous morphine equivalents was 1.2, 2.0, and 3.4 mg/kg on ECMO days 1, 7, and 14, respectively. The most commonly used continuous medication infusions included morphine, midazolam, and hydromorphone. Dexmedetomidine was used in eight patients and ketamine in two patients. Doses of opioids and sedatives typically escalated over time. Pain scores did not correlate with sedation or analgesic administrations.