Correction of congenital diaphragmatic hernia in utero IX: Fetuses with poor prognosis (Liver herniation and low lung-to-head ratio) can be saved by fetoscopic temporary tracheal occlusion

Infants with congenital diaphragmatic hernia (CDH) are at high risk of postnatal mortality due to lung hypoplasia and arterial pulmonary hypertension. In severe cases, prenatal intervention by fetal endoscopic tracheal occlusion (FETO) can improve survival by accelerating lung growth. However, postnatal mortality remains in the range of about 50% despite fetal treatment, and there is currently no clear explanation for this different clinical response to FETO. We evaluated the concentration of extracellular vesicles (EVs) and associated microRNA expression in amniotic and tracheal fluids of fetuses with CDH undergoing FETO, and we examined the association between molecular findings and postnatal survival. We observed a higher count of EVs in the amniotic fluid of non-survivors and in the tracheal fluid sampled in utero at the time of reversal of tracheal occlusion, suggesting a pro-inflammatory lung reactivity that is already established in utero and that could be associated with a worse postnatal clinical course. In addition, we observed differential regulation of four EV-enclosed miRNAs (miR-379-5p, miR-889-3p; miR-223-3p; miR-503-5p) in relation to postnatal survival, with target genes possibly involved in altered lung development. Future research should investigate molecular therapeutic agents targeting differentially regulated miRNAs to normalize their expression and potentially improve clinical outcomes.

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Prenatal Diagnosis of Congenital Diaphragmatic Hernia: Does Laterality Predict Perinatal Outcomes?

American Journal of Perinatology ◽

10.1055/s-0037-1617754 ◽

2018 ◽

Vol 35 (10) ◽

pp. 919-924 ◽

Cited By ~ 5

Author(s):

Teresa Sparks ◽

Victoria Berger ◽

Jody Farrell ◽

Kristen Gosnell ◽

Roberta Keller ◽

...

Keyword(s):

Congenital Diaphragmatic Hernia ◽

Diaphragmatic Hernia ◽

Poor Prognosis ◽

Primary Outcome ◽

Mode Of Delivery ◽

Perinatal Outcomes ◽

Lung Area ◽

Liver Herniation ◽

Secondary Outcomes ◽

Univariate Analyses

Objective The objective of this study was to examine laterality as a predictor of outcomes among fetuses with prenatally diagnosed congenital diaphragmatic hernia (CDH). Methods This is a retrospective cohort study of pregnancies with CDH evaluated at our center from 2008 to 2016 compared cases with right-sided CDH (RCDH) versus left-sided CDH (LCDH). The primary outcome was survival to discharge. Secondary outcomes included ultrasound predictors of poor prognosis (liver herniation, stomach herniation, lung area-to-head circumference ratio [LHR]), concurrent anomalies, hydrops, stillbirth, preterm birth, mode of delivery, small for gestational age, use of extracorporeal membrane oxygenation, and length of stay. Terminations and stillbirths were excluded from analyses of neonatal outcomes. Results In this study, 157 (83%) LCDH and 32 (17%) RCDH cases were identified. Survival to discharge was similar (64 vs. 66.4%, p = 0.49) with regard to laterality. RCDH had higher rates of liver herniation (90.6 vs. 72%, p = 0.03), hydrops fetalis (15.6 vs. 1.3%, p < 0.01), and lower LHR (0.87 vs. 0.99, p = 0.04). LCDH had higher rates of stomach herniation (69.4 vs. 12.5%, p < 0.01). Rates of other outcomes were similar in univariate analyses. Adjusting for microarray abnormalities, the odds for survival to discharge for RCDH compared with LCDH was 0.93 (0.38–2.30, p = 0.88). Conclusion Compared with LCDH, fetuses with RCDH had higher rates of adverse ultrasound predictors, but equivalent survival.

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