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Rationale: Density-based morphometric studies have demonstrated decreased capillary density in infants with bronchopulmonary dysplasia (BPD) and in BPD-like animal models, leading to the prevailing view that microvascular development is disrupted in BPD. Objective: To perform a comprehensive analysis of the early and late effects of ventilation on pulmonary microvascular growth in preterm infants. Methods: Postmortem lung samples were collected from ventilated preterm infants who died between 23 and 29 wk ("short-term ventilated") or between 36 and 39 wk ("long-term ventilated") corrected postmenstrual age. Results were compared with age-matched infants or stillborn infants ("early" and "late" control subjects). Microvascular growth was studied by anti-platelet endothelial cell adhesion molecule (PECAM)-1 immunohistochemistry, quantitative stereology, analysis of endothelial cell proliferation, and Western blot analysis of pulmonary PECAM-1 protein levels. Measurements: Measurements were made of capillary density, volume of air-exchanging parenchyma, volume of microvascular endothelial cells, Ki67 labeling index of endothelial cells, and PECAM-1/actin protein levels. Main Results: Lungs of long-term ventilated infants showed a significant (more than twofold) increase in volume of air-exchanging parenchyma and a 60% increase in total pulmonary microvascular endothelial volume compared with late control subjects, associated with 60% higher pulmonary PECAM-1 protein levels. The marked expansion of the pulmonary microvasculature in ventilated lungs was, at least partly, attributable to brisk endothelial cell proliferation. The microvasculature of ventilated lungs appeared immature, retaining a saccular architectural pattern. Conclusions:The pulmonary microvasculature of ventilated preterm infants displayed marked angiogenesis, nearly proportionate to the growth of the air-exchanging lung parenchyma. These results challenge the paradigm of microvascular growth arrest as a major pathogenic factor in BPD.Keywords: bronchopulmonary dysplasia; chronic lung disease of prematurity; neonatal lung disease Despite major advances in perinatal medicine, including the introduction of surfactant therapy, antenatal glucocorticoids, and new ventilator strategies, preterm newborns treated with ventilation and supplemental oxygen frequently develop bronchopulmonary dysplasia (BPD), a chronic lung disease of newborn infants associated with significant mortality and morbidity (1). BPD in the postsurfactant era is seen primarily in very low birth weight infants and affects 30% of infants born at 24 to 28 wk, many of whom will require long-term ventilation and/or supplemental oxygen (2, 3).The dominant pathologic finding at autopsy in postsurfactant BPD is an arrest in alveolar development, resulting in lungs with large and simplified airspaces showing varying degrees of interstitial fibrosis (2, 4-8). Impairment of alveolar formation in BPD leads to long-term global reduction in alveolar number and gas-exchange surface area (6, 7). The ...

Background Fetoscopic endoluminal tracheal occlusion (FETO) has been associated with increased postnatal survival among infants with severe pulmonary hypoplasia due to isolated congenital diaphragmatic hernia on the left side, but data are lacking to inform its effects in infants with moderate disease. Methods In this open-label trial conducted at many centers with experience in FETO and other types of prenatal surgery, we randomly assigned, in a 1:1 ratio, women carrying singleton fetuses with a moderate isolated congenital diaphragmatic hernia on the left side to FETO at 30 to 32 weeks of gestation or expectant care. Both treatments were followed by standardized postnatal care. The primary outcomes were infant survival to discharge from a neonatal intensive care unit (NICU) and survival without oxygen supplementation at 6 months of age. Results In an intention-to-treat analysis involving 196 women, 62 of 98 infants in the FETO group (63%) and 49 of 98 infants in the expectant care group (50%) survived to discharge (relative risk, 1.27; 95% confidence interval [CI], 0.99 to 1.63; twosided P = 0.06). At 6 months of age, 53 of 98 infants (54%) in the FETO group and 43 of 98 infants (44%) in the expectant care group were alive without oxygen supplementation (relative risk, 1.23; 95% CI, 0.93 to 1.65). The incidence of pre-term, prelabor rupture of membranes was higher among women in the FETO group than among those in the expectant care group (44% vs. 12%; relative risk, 3.79; 95% CI, 2.13 to 6.91), as was the incidence of preterm birth (64% vs. 22%, respectively; relative risk, 2.86; 95% CI, 1.94 to 4.34), but FETO was not associated with any other serious maternal complications. There were two spontaneous fetal deaths (one in each group) without obvious cause and one neonatal death that was associated with balloon removal. Conclusions This trial involving fetuses with moderate congenital diaphragmatic hernia on the left side did not show a significant benefit of FETO performed at 30 to 32 weeks of gestation over expectant care with respect to survival to discharge or the need for oxygen supplementation at 6 months. FETO increased the risks of preterm, prelabor rupture of membranes and preterm birth. (Funded by the European Commission and others; TOTAL ClinicalTrials.gov number, NCT00763737.)

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In the rabbit model for DH, antenatal sildenafil rescues vascular branching and architecture, reduces pulmonary vascular resistances and also improves airway morphometry and respiratory mechanics.

Objective To report a recent update on fetuses with right-sided congenital diaphragmatic hernia (RCDH) in the era of fetal surgery.Design Retrospective review of prospectively collected data.Setting Fetal treatment centres in Leuven and Barcelona.Population Consecutive cases of RCDH between 2002 and 2012.Methods Data on prenatal imaging, genetic testing, pregnancy and neonatal outcomes were extracted from our databases, including structural and genetic anomalies, candidate outcome predictors such as lung size, liver herniation ratio, polyhydramnios, cervical length, preterm prelabour rupture of membranes and gestational age at birth.Main outcome measures Survival and oxygen dependency at discharge.Results Ten out of 86 fetuses with RCDH had associated abnormalities. Of 76 isolated pregnancies, eight women opted for termination of pregnancy, most with severe hypoplasia and one was lost to follow up. Nineteen pregnancies were expectantly managed and delivered at a mean gestational age of 36.0 AE 3.0 weeks. Survival at discharge was 53% (10/19), one being oxygen dependent. In the fetal surgery group (n = 48), mean gestational age at delivery was 34.5 AE 3.0 weeks. In our recent experience not previously published (n = 23) survival rate was 52 and 39% were oxygen dependent at discharge. Pooling these data with earlier reported observations by our group we observed a 42% survival rate in 57 fetuses. Lung size on magnetic resonance imaging and an interval of >24 hours between reversal of tracheal occlusion and delivery were predictors of outcome.Conclusions Right-sided CDH seems to have a poorer outcome than that reported for fetuses with left-sided CDH with similar lung size before birth. Survival rates after expectant management with observed/expected lung-to-head ratio values ≤45 and ≤30% were 17 and 0%, respectively. In those undergoing fetal surgery (observed/expected lung-to-head ratio ≤45%) there was an apparent increase (42%).Keywords Congenital diaphragmatic hernia, fetal therapy, magnetic resonance imaging, tracheal occlusion, ultrasound.Linked article This article is commented on by J Balayla, p. 947 in this issue. To view this mini commentary visit http:// dx.doi.org/10.1111/1471-0528.13077.Please cite this paper as: DeKoninck P, Gomez O, Sandaite I, Richter J, Nawapun K, Eerdekens A, Ramirez JC, Claus F, Gratacos E, Deprest J. Right-sided congenital diaphragmatic hernia in a decade of fetal surgery. BJOG 2015;122:940-946.