Prenatal Predictors of Survival in Isolated Congenital Diaphragmatic Hernia: A Systematic Review and Meta-analysis

Abstract

OBJECTIVE: To evaluate prenatal fetal imaging findings associated with survival to hospital discharge, persistent pulmonary hypertension (PH), and need for extracorporeal membrane oxygenation (ECMO) in fetuses with isolated congenital diaphragmatic hernia (CDH) that are undergoing prenatal expectant management.

DATA SOURCES: A systematic search was conducted in MEDLINE through PubMed, EMBASE, Web of Science, and The Cochrane Central, and ClinicalTrials.gov from 2000 up to July 2023.

METHODS OF STUDY SELECTION: Studies that reported on prenatal imaging in fetuses with isolated CDH that were undergoing expectant management were included. Primary outcomes were survival to hospital discharge, persistent PH within 28 days of age, and need for ECMO. The quality of studies was assessed using the Newcastle-Ottawa Scale. Meta-analysis was performed when at least two studies reported on the same prenatal imaging evaluation. Subgroup analyses were performed according to the side (left or right) of CDH.

TABULATION, INTEGRATION, AND RESULTS: A total of 161 full-text articles were assessed for eligibility, with 48 studies meeting the inclusion criteria: 45 (N=3,977) assessed survival, eight (N=994) assessed persistent PH, and 12 (N=2,085) assessed need for ECMO. The pooled proportion was 2,833 of 3,977 (71.2%, 95% CI, 69.8–72.6%) for survival, 565 of 2,085 (27.1%, 95% CI, 25.2–29.1%) for need for ECMO, and 531 of 994 (53.4%, 95% CI, 50.3–56.6%) for need for persistent PH. Prenatal imaging findings that were significantly associated with survival included: total fetal lung volume (mean difference [MD] 13.42, 95% CI, 11.22–15.62), observed-to-expected (O-E) total fetal lung volume less than 30% (odds ratio [OR] 0.09, 95% CI, 0.05–0.17), O-E total fetal lung volume (MD 14.73, 95% CI, 11.62–17.84, I2 46%), liver/intrathoracic ratio (MD −9.59, 95% CI, −15.73 to −3.46), O-E lung/head ratio (MD 14.03, 95% CI, 12.69–15.36), O-E lung/head ratio less than 25% (OR 0.07, 95% CI, 0.04–0.13), mediastinal shift angle (MD −6.17, 95% CI, −7.70 to −4.64), stomach position in mid-chest (OR 0.14, 95% CI, 0.06–0.36), and intrathoracic liver (OR 0.23, 95% CI, 0.15–0.35). In subgroup analyses, findings for left-sided CDH remained significant in all the aforementioned findings. The only prenatal imaging finding that was significantly associated with persistent PH was intrathoracic liver (OR 1.96, 95% CI, 1.14–3.37), but this association was no longer significant in subgroup analyses. Prenatal imaging findings that were significantly associated with need for ECMO included: O-E total fetal lung volume (MD −10.08, 95% CI, −13.54 to −6.62), O-E lung/head ratio (MD −9.88, 95% CI, 14.44 to −5.33, I2 30%), subgroup analysis to the left-sided CDH remained significant, percentage of predicted lung volume (MD −9.81, 95% CI, −13.56 to −6.06, I2 34%), and intrathoracic liver (OR 2.70, 95% CI, 1.60–4.57, I2 0%), but this association was no longer significant in left-sided CDH subgroup analysis.

CONCLUSION: Several prenatal imaging findings, including lung measurements, intrathoracic liver, and stomach position, were predictive of neonatal survival. Lung measurement was predictive of need for ECMO, and intrathoracic liver was significantly associated with persistent PH and need for ECMO.