Background Congenital diaphragmatic hernia (CDH) is a life-threatening birth defect. Most of the genetic factors that contribute to the development of CDH remain unidentified. Objective Identify genomic alterations that contribute to the development of diaphragmatic defects. Methods A cohort of 45 unrelated patients with CDH or diaphragmatic eventrations were screened for genomic alterations by array comparative genomic hybridization (aCGH) or SNP-based copy number analysis. Results Genomic alterations that were likely to have contributed to the development of CDH were identified in eight patients. Inherited deletions of ZFPM2 were identified in two patients with isolated diaphragmatic defects and a large de novo 8q deletion overlapping the same gene was found in a patient with non-isolated CDH. A de novo microdeletion of chromosome 1q41q42 and two de novo microdeletions on chromosome 16p11.2 were identified in patients with non-isolated CDH. Duplications of distal 11q and proximal 13q were found in a patient with non-isolated CDH and a de novo single gene deletion of FZD2 was also identified in a patient with a partial pentalogy of Cantrell phenotype. Conclusions Haploinsufficiency of ZFPM2 can cause dominantly inherited isolated diaphragmatic defects with incomplete penetrance. Our data define a new minimal deleted region for CDH on 1q41q42, provide evidence for the existence of CDH-related genes on chromosomes 16p11.2, 11q23-24 and 13q12 and suggest a possible role for FZD2 and Wnt signaling in pentalogy of Cantrell phenotypes. These results demonstrate the clinical utility of screening for genomic alterations in individuals with both isolated and non-isolated diaphragmatic defects.

Objective To determine associations between fetal lung and liver herniation volumes measured by magnetic resonance imaging (MRI) and mortality/need for extracorporeal membrane oxygenation (ECMO) in cases of isolated congenital diaphragmatic hernia (CDH

Non-isolated congenital diaphragmatic hernia (CDH+) is a severe birth defect that is often caused by de novo chromosomal anomalies. In this report, we use genome-wide oligonucleotide-based array comparative genome hybridization (aCGH) followed by rapid real-time quantitative PCR analysis to identify, confirm and map chromosomal anomalies in a cohort of 26 CDH+ patients. One hundred and five putative copy number changes were identified by aCGH in our cohort of CDH+ patients. Sixty-one of these changes (58%) had been previously described in normal controls. Twenty of the remaining 44 changes (45%) were confirmed by quantitative real-time PCR or standard cytogenetic techniques. These changes included de novo chromosomal abnormalities in five of the 26 patients (19%), two of whom had previously normal G-banded chromosome analyses. Data from these patients provide evidence for the existence of CDH-related genes on chromosomes 2q37, 6p22-25 and 14q, and refine the CDH minimal deleted region on 15q26 to an interval that contains COUP-TFII and only eight other known genes. Although COUP-TFII is likely to play a role in the development of CDH in patients with 15q26 deletions, we did not find COUP-TFII mutations in 73 CDH samples. We conclude that the combination of oligonucleotide-based aCGH and quantitative real-time PCR is an effective method of identifying, confirming and mapping clinically relevant copy number changes in patients with CDH+. This method is more sensitive than G-banded chromosome analysis and may find wide application in screening patients with congenital anomalies.

Free radicals have been implicated in the pathogenesis of a wide spectrum of human diseases. Premature infants are probably developmentally unprepared for extrauterine life in an oxygen-rich environment and exhibit a unique sensitivity to oxidant injury. Diseases associated with premature infants, including bronchopulmonary dysplasia, periventricular leukomalacia, intraventricular hemorrhage, retinopathy of prematurity, and necrotizing enterocolitis, have been linked to free radical-mediated cell and tissue injury. With the advent of therapies designed to combat the injurious effects of free radicals, the role of these highly reactive chemical molecules in the pathogenesis of neonatal diseases needs to be fully determined.

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BACKGROUND AND OBJECTIVES: Echocardiogram is the gold standard for the diagnosis of hemodynamically significant patent ductus arteriosus (hsPDA) in preterm neonates. A simple blood assay for brain natriuretic peptide (BNP) or amino-terminal pro-B-type natriuretic peptide (NT-proBNP) may be useful in the diagnosis and management of hsPDA. Our objectives were to determine the diagnostic accuracy of BNP and NT-proBNP for hsPDA in preterm neonates and to explore heterogeneity by analyzing subgroups. METHODS:The systematic review was performed as recommended by the Cochrane Diagnostic Test Accuracy Working Group. Electronic databases, conference abstracts, and cross-references were searched. We included studies that evaluated BNP or NT-proBNP (index test) in preterm neonates with suspected hsPDA (participants) in comparison with echocardiogram (reference standard). A bivariate random effects model was used for meta-analysis, and summary receiver operating characteristic curves were generated.RESULTS: Ten BNP and 11 NT-proBNP studies were included. Studies varied by methodological quality, type of commercial assay, thresholds, age at testing, gestational age, and whether the assay was used to initiate medical or surgical therapy. Sensitivity and specificity for BNP at summary point were 88% and 92%, respectively, and for NT-proBNP they were 90% and 84%, respectively. CONCLUSIONS:The studies evaluating the diagnostic accuracy of BNP and NT-proBNP for hsPDA varied widely by assay characteristics (assay kit and threshold) and patient characteristics (gestational and chronological age); therefore, generalizability between centers is not possible. We recommend that BNP or NT-proBNP assays be locally validated for specific patient population and outcomes, to initiate therapy or follow response to therapy.

ClinicalTrials.gov, https://clinicaltrials.gov, NCT00881660.

This retrospective analysis suggests that greater number and volume of platelet transfusions in infants with necrotizing enterocolitis are associated with greater morbidity in the form of short bowel syndrome and/or cholestasis without the benefit of lower mortality.