Congenital heart disease associated with congenital diaphragmatic hernia: A systematic review on incidence, prenatal diagnosis, management, and outcome.

PURPOSE: The purpose of this study was to evaluate the impact of congenital heart disease (CHD) on infants with congenital diaphragmatic hernia (CDH). METHODS: Using a defined search strategy (PubMed, Cochrane, Embase, Web of Science MeSH headings), we searched studies reporting the incidence, management, and outcome of CDH infants born with associated CHD. RESULTS: Of 6410 abstracts, 117 met criteria. Overall, out of 28,974 babies with CDH, 4427 (15%) had CHD, of which 42% were critical. CDH repair was performed in a lower proportion of infants with CHD (72%) than in those without (85%; p < 0.0001). Compared to CDH babies without CHD, those born with a cardiac lesion were more likely to have a patch repair (45% vs. 30%; p < 0.01) and less likely to undergo minimally invasive surgery (5% vs. 17%; p < 0.0001). CDH babies with CHD had a lower survival rate than those without CHD (52 vs. 73%; p < 0.001). Survival was even lower (32%) in babies with critical CHD. CONCLUSION: CHD has a strong impact on the management and outcome of infants with CDH. The combination of CDH and CHD results in lower survival than those without CHD or an isolated cardiac defect. Further studies are needed to address some specific aspects of the management of this fragile CDH cohort. TYPE OF STUDY: Systematic review and meta-analysis. LEVEL OF EVIDENCE: Level III.

Assessment of the nitrofen model of congenital diaphragmatic hernia and of the dysregulated factors involved in pulmonary hypoplasia.

PURPOSE: To study pulmonary hypoplasia (PH) associated with congenital diaphragmatic hernia (CDH), investigators have been employing a fetal rat model based on nitrofen administration to dams. Herein, we aimed to: (1) investigate the validity of the model, and (2) synthesize the main biological pathways implicated in the development of PH associated with CDH. METHODS: Using a defined strategy, we conducted a systematic review of the literature searching for studies reporting the incidence of CDH or factors involved in PH development. We also searched for PH factor interactions, relevance to lung development and to human PH. RESULTS: Of 335 full-text articles, 116 reported the incidence of CDH after nitrofen exposure or dysregulated factors in the lungs of nitrofen-exposed rat fetuses. CDH incidence: 54% (27-85%) fetuses developed a diaphragmatic defect, whereas the whole litter had PH in varying degrees. Downregulated signaling pathways included FGF/FGFR, BMP/BMPR, Sonic Hedgehog and retinoid acid signaling pathway, resulting in a delay in early epithelial differentiation, immature distal epithelium and dysfunctional mesenchyme. CONCLUSIONS: The nitrofen model effectively reproduces PH as it disrupts pathways that are critical for lung branching morphogenesis and alveolar differentiation. The low CDH rate confirms that PH is an associated phenomenon rather than the result of mechanical compression alone.