Original article
Fetal tracheal occlusion for severe congenital diaphragmatic hernia in humans: a morphometric study of lung parenchyma and muscularization of pulmonary arterioles

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Abstract

Objective

The aim of this study is to examine structure of lung parenchyma (Pp) and muscularization of pulmonary arterioles (PAs) in human fetuses that underwent tracheal occlusion (TO) therapy for severe congenital diaphragmatic hernia (CDH).

Material

Fifteen fetuses underwent TO, with 5 survivors (Am J Obstet Gynecol. 2000:183;1059-1066). Paraffin-embedded lung specimens from 7 of 10 nonsurvivors (CDH-TO) and 6 age-matched fetuses (CDH) were available for morphometric analysis, which included measurements of point fraction of lung Pp and surface density. The PAs were categorized according to external diameter (<70 μm and 70 ≤ 140 μm). Percent medial wall thickness (%MWT) was calculated by dividing raw measurements of MWT by external diameter.

Results

Gestational age at TO was 27.6 ± 0.9 weeks with a mean duration of TO of 32.6 ± 6.8 days. Gestational age at delivery (CDH-TO 31.9 ± 0.9 vs CDH 35.4 ± 1.8 weeks; P = .18) and postnatal survival time (CDH-TO 20.5 ± 6.0 vs CDH 18.6 ± 7.8 days; P = .85) were not significantly different between groups. Tracheal occlusion significantly increased the lung–to–body weight ratio (CDH-TO 13.0 ± 2.2 vs CDH 6.6 ± 0.9; P = .02). Tracheal occlusion tended to decrease right-lung Pp (CDH-TO 54.6% ± 2.6% vs CDH 65.7% ± 5.9%; P = .05), whereas left-lung Pp was not different between groups (CDH-TO 63.0% ± 3.5% vs CDH 66.7% ± 4.1%; P = .51). Surface density of airspaces was not different between groups in either left (CDH-TO 171.3 ± 16.1 cm−1 vs CDH 151.1 ± 8.1 cm−1; P = .34) or right (CDH-TO 172.0 ± 10.6 cm−1 vs CDH 160.8 ± 3.6 cm−1; P = .33) lungs. The %MWT in small and large PA was similar between groups.

Conclusions

Open prenatal TO in human fetuses increased lung growth, as evidenced by an increase in lung weight, but did not improve parenchymal structure or muscularization of PAs.

Section snippets

Methods

This study was approved by the Committee for Protection of Human Subjects Institutional Review Board at The Children's Hospital of Philadelphia (IRB# 2004-7-3848).

Clinical background

For the TO group, mean gestational age (GA) at evaluation at our institution and mean GA at fetal TO were 23.7 ± 0.7 and 27.6 ± 0.9 weeks gestation, respectively. Mean duration of TO was 32.6 ± 6.8 days. All fetuses demonstrated herniation of liver into the fetal chest on prenatal ultrasound. The lung area–to–head circumference ratio (LHR) ranged from 0.41 to 1.04 (mean, 0.79 ± 0.1). A total of 3 patients with TO were eligible for and required extracorporeal membrane oxygenation (ECMO), and 4

Discussion

The limited success of open fetal TO therapy for severe CDH [7], [8], with respect to poor neonatal outcome, can be attributed to persistent abnormalities in pulmonary function (ie, reduced gas exchange and persistent pulmonary hypertension) and prematurity of birth caused by open fetal surgery techniques. The current morphological study was undertaken to compare key aspects of lung structure that impact neonatal lung function. We found that fetal TO accelerated prenatal lung growth, as

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    Presented in part at the 37th Annual Meeting of the American Pediatric Surgery Association in Hilton Head in 2006.

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