Periventricular nodular heterotopia in patients with a prenatal diagnosis of myelomeningocele/myeloschisis: associations with seizures and neurodevelopmental outcomes during early childhood.

PURPOSE: Historically, the presence of gray matter heterotopia was a concern for adverse postnatal neurocognitive status in patients undergoing fetal closure of open spinal dysraphism. The purpose of this study was to evaluate neurodevelopmental outcomes and the onset of seizures during early childhood in patients with a prenatal diagnosis of myelomeningocele/myeloschisis (MMC) and periventricular nodular heterotopia (PVNH). METHODS: All patients evaluated at the Center for Fetal Diagnosis and Treatment with a diagnosis of MMC between June 2016 to March 2023 were identified. PVNH was determined from prenatal and/or postnatal MRI. The Bayley Scales of Infant and Toddler Development (edition III or IV) were used for neurodevelopmental assessments. Patients were screened for seizures/epilepsy. RESULTS: Of 497 patients evaluated with a prenatal diagnosis of MMC, 99 were found to have PVNH on prenatal MRI, of which 35 had confirmed PVNH on postnatal imaging. From the 497 patients, 398 initially did not exhibit heterotopia on prenatal MRI, but 47 of these then had confirmed postnatal PVNH. The presence of PVNH was not a significant risk factor for postnatal seizures in early childhood. The average neurodevelopmental scores were not significantly different among heterotopia groups for cognitive, language, and motor domains. CONCLUSION: The presence of PVNH in patients with a prenatal diagnosis of MMC does not indicate an increased risk for neurodevelopmental delay at 1 year of age. We did not demonstrate an association with seizures/epilepsy. These findings can aid clinicians in prenatal consultation regarding fetal repair of open spinal dysraphism. Long-term follow-up is required to discern the true association between PVNH seen on prenatal imaging and postnatal seizures/epilepsy and neurodevelopmental outcomes.

A clinical outcomes data archive for a comprehensive fetal diagnosis and treatment center.

INTRODUCTION: Data on near and long-term outcomes are critical for the care of all maternal-fetal patients presenting to a fetal center. This is important since physiologic and neurodevelopmental attributes do not manifest until childhood when multi-level factors influence health outcomes. Electronic health records (EHR) 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. Moreover, the fetus lacks a digital identity and requires relinking attributes documented in the maternal chart to those in the pediatric EHR. This conundrum amplifies in the setting of multiple gestation, returning maternal patients, and pregnancies with fetal demise. Current data 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 multi-purpose use. METHODS: A unified platform for longitudinal follow-up of maternal-child dyads named the Clinical Outcomes Data Archive (CODA) was constructed. CODA was designed using a data dictionary based on multidisciplinary input, a relational identity for each patient, fetus, and pregnancy, and a process by which EHR-sourced and chart-abstracted data are validated. Descriptive analyses were performed for data acquired between July 2022 - 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. 85% of condition-specific variables required manual chart abstraction. The study conducted with CODA contributed to 18 studies. CODA successfully merges EHR-sourced and manually abstracted documentation for longitudinal study of the maternal-child dyad.

Treprostinil in Neonates with Congenital Diaphragmatic Hernia-Related Pulmonary Hypertension.

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.

The Impact of Comprehensive Fetal Care on Mortality of Children With Congenital Diaphragmatic Hernia when Delivery is Co-located in a Pediatric Hospital.

BACKGROUND: We evaluated the impact of delivery at a comprehensive fetal care center co-located in a pediatric hospital on extracorporeal membrane oxygenation (ECMO) exposure and survivorship of children with CDH. METHODS: This retrospective study includes maternal-fetal dyads with a prenatal diagnosis of isolated CDH who received any prenatal care at a single fetal center between February 2006 and March 2021. The principal variables included: (1) delivery setting (children born in the pediatric hospital ["inborn"] vs. children who were delivered elsewhere ["outborn"]), (2) exposure to ECMO (yes vs. no), and (3) survival-at-discharge from birth hospitalization (yes vs. no). Multivariable logistic regression was used to evaluate the association between delivery setting and ECMO cannulation, and whether delivery setting moderates the association between exposure to ECMO and survival-at-discharge. RESULTS: Among 418 maternal-fetal dyads, 77.0% of children were inborn and 32.0% of children were exposed to ECMO during their index hospitalization. Inborn children had more severe prenatal prognostic indicators but had a 57% lower odds of extracorporeal than outborn children. In multivariable logistic regression, delivery setting moderated the association between exposure to ECMO and survival-at-discharge. Although there was no statistically significant difference in mortality between inborn and outborn children who were not exposed to ECMO, inborn children exposed to ECMO had a 6.86 (1.98, 23.74) increased odds of death and outborn children exposed to ECMO had a 17.71 (4.69, 66.87) increased odds of death when both were compared to non-cannulated outborn children. CONCLUSIONS: Comprehensive fetal care with delivery co-located in a pediatric hospital was associated with decreased exposure to ECMO and a survivorship advantage among children with CDH who required extracorporeal support. LEVEL OF EVIDENCE: Level III.

Exploring Demographic Representation and Reporting in Lung Cancer Clinical Trials with Canadian Sites from 2013 to 2023.

This review evaluates the reporting of demographic characteristics and the diversity of participants of phase III lung cancer clinical trials with Canadian research sites. A literature search was conducted using the ClinicalTrials.gov registry to identify clinical trials conducted between 1 January 2013, and 31 December 2023. The demographic reporting practices and the representation of sex/gender, racial, and ethnic groups were assessed. The location of Canadian research sites was also examined for trends in reporting and representation. Associated publications were reviewed for demographic data collection methods. Of the 25 clinical trials, 24 reported race and 18 also reported ethnicity. All clinical trials reported sex/gender, and the city and province of the participating Canadian sites. Most participants were White (66.1%), identified as not Hispanic or Latino (81.4%), and were male (57.8%). The provinces with the most clinical trial sites were Ontario (43.6%) and Quebec (34.2%). Lung cancer clinical trials lack adequate demographic reporting and representation of females, diverse patient groups, and geographical locations in Canada with high lung cancer incidence rates. Specifically, the Indigenous Peoples of Canada and Nunavut require better representation in lung cancer clinical trials conducted in Canada. These findings highlight the need to improve diversity and demographic representation in clinical research.

Prevalence and patterns of executive function, adaptive function, and behavioral outcomes in preschool and school age children with congenital diaphragmatic hernia.

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.

Tuberculosis-Associated Respiratory Disability in Children, Adolescents, and Adults: Protocol for a Systematic Review and Individual Participant Data Meta-Analysis.

Background: Approximately 2% of the global population has survived tuberculosis (TB). Increasing evidence indicates that a significant proportion of pulmonary TB survivors develop TB-associated respiratory disability, commonly referred to as post-TB lung disease (PLTD) and marked by impaired respiratory function, persistent symptoms, and activity limitations. However, the prevalence, risk factors, and progression of TB-associated respiratory disability throughout the life course are not well understood. To address these gaps, we will undertake a systematic review and individual participant-level data meta-analysis (IPD-MA) focusing on TB-associated respiratory disability in children, adolescents, and adults successfully treated for pulmonary TB. Methods and analysis: We will systematically search MEDLINE, Embase, CENTRAL, Global Index Medicus, and medRxiv for original studies investigating TB-associated respiratory disability in people of all ages who have completed treatment for microbiologically confirmed or clinically diagnosed pulmonary TB. Authors of eligible studies will be invited to contribute de-identified data and form a collaborative group. Primary outcomes will be (1) abnormal lung function based on spirometry parameters and (2) chronic respiratory symptoms. We will estimate the overall and subgroup-specific prevalence of each outcome through IPD meta-analysis. Next, we will develop clinical prediction tools assessing the risk of future TB-associated respiratory disability at (i) the start of TB treatment and (ii) end of TB treatment for those without existing signs of disability. Finally, we will use stepwise hierarchical modelling to identify epidemiological determinants of respiratory disability. Ethics and dissemination: This study has been approved by the ethics review boards at the Rhode Island Hospital (2138217-2) and the Research Institute of the McGill University Health Centre (2024-10345). Individual study authors will be required to obtain institutional approval prior to sharing data. Results will be disseminated through open-access, peer-reviewed publications and conference presentations. Prospero registration number: CRD42024529906.

Birth Admission Length-of-Stay and Hospital Readmission in Children With Congenital Diaphragmatic Hernia.

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.