Fetal ultrasound markers of severity predict resolution of pulmonary hypertension in congenital diaphragmatic hernia

Abstract

Objective Congenital diaphragmatic hernia (CDH) results in morbidity and mortality due to lung hypoplasia and persistent pulmonary hypertension (PH). We sought to define the relationship between fetal ultrasound markers of severity in CDH and the time to resolution of neonatal PH. Study design We conducted a retrospective study of fetuses with an antenatal ultrasound and left-sided CDH cared for at the University of California San Francisco (2002–12). Fetal liver position was classified on ultrasound as abdominal (entire liver within the abdomen) or thoracic (any portion of the liver within the thorax). Fetal stomach position was classified from least to most aberrant: abdominal, anterior left chest, mid-posterior left chest, or retrocardiac (right chest). Lung-to-head ratio (LHR) was determined from available scans at 20–29 weeks gestational age (GA). Routine neonatal echocardiograms were performed weekly for up to 6 weeks or until PH resolved, or until discharge. PH was assessed by echocardiogram using a hierarchy of ductus arteriosus level shunt, interventricular septal position, and tricuspid regurgitant jet velocity. Days to PH-free survival was defined as the age at which pulmonary artery pressure was estimated to be <2/3 systemic blood pressure. Cox proportional hazards models adjusted for GA at birth, era of birth, fetal surgery, and GA at ultrasound (LHR model only), with censoring at 100 days. Results Of 118 patients, fetal markers were available as follows: LHR (n=53), liver position (n=112), and stomach position (n=80). Fewer infants resolved PH if they had LHR<1 (p=0.006), thoracic liver position (p=0.001), or more aberrant stomach position (p<0.001). There was also a decreased rate of resolution of PH in infants with LHR <1 (hazard ratio 0.30, p=0.007), thoracic liver position (hazard ratio 0.38, p<0.001), and more aberrant stomach position (hazard ratios 0.28, p=0.002; 0.1, p<0.001; 0.07 p<0.001). Conclusion Fetal ultrasound markers of CDH severity are predictive not just of mortality but also of significant morbidity. LHR<1, thoracic liver, and aberrant stomach position are associated with delayed time to resolution of PH in infants with CDH and may be used to identify fetuses at high risk of persistent PH.

Congenital Diaphragmatic Hernia: 10-Year Evaluation of Survival, Extracorporeal Membrane Oxygenation, and Foetoscopic Endotracheal Occlusion in Four High-Volume Centres

“…Patient characteristics, such as foetal liver position (intra-abdominal or intrathoracic) [2], stomach position [3], lung-to-head ratio (LHR) [4], observed-to-expected LHR [5], and the diaphragmatic defect size [6] can influence outcome as well as treatment in a high- or low-volume centre. There are differences in opinion about whether extracorporeal membrane oxygenation (ECMO) improves survival as no specific trials have been conducted with the primary aim of evaluating the role of ECMO specifically for high-risk CDH patients [7,8].…”

Lung size and liver herniation predict need for extracorporeal membrane oxygenation but not pulmonary hypertension in isolated congenital diaphragmatic hernia: systematic review and meta‐analysis

“…postnatal series, n = 5), in addition to a number of other reasons ( n = 15). Of the selected papers, 15 reported on the occurrence of PPH, 19 on the need for ECMO and four reported on both outcomes (Figure ). The corresponding authors of seven studies provided relevant unpublished data.…”

“…The main cause of bias for PPH studies was the absence of specified timing for the reference test for the diagnosis of PPH. This was provided in the article for a single study and on request from the author of another study.…”

“…These were mainly related to measurement of lung size, using either US or MRI. The most commonly proposed tests were lung‐to‐head ratio (LHR), observed to expected LHR (o/e‐LHR) and o/e total lung volume (o/e‐TLV), reported in seven, five and four studies, respectively. Tests for direct assessment of the pulmonary vasculature, either anatomical or functional, have also been proposed.…”

Are Cytokines Useful Biomarkers to Determine Disease Severity in Neonates with Congenital Diaphragmatic Hernia?

“…hypertension in neonates with CDH. 3 CLD is defined as a need for supplemental oxygen at the 28th day of life and is divided by severity into mild, moderate, and severe CLD at day 56. 4,5 Moreover, there are some efforts to predict outcome in the early postnatal phase by scoring for low birth weight, low 5minute Apgar score presence of chromosomal or major cardiac anomaly, and suprasystemic pulmonary hypertension.…”