Early Adjuvant Medication With the mTOR Inhibitor Sirolimus in a Preterm Neonate With Compressive Cystic Lymphatic Malformation.

Cystic lymphatic malformations result from an abnormal embryological development of the lymphatic structures. Here we report on a case of a preterm female baby, born at 34 weeks of gestation, with a voluminous cervicofacial cystic lymphatic malformation responsible for an airway obstruction. An mTOR inhibitor, sirolimus, was started from the first day of life, and was combined with iterative sclerotherapy procedures. This case illustrates a safe and successful early administration of sirolimus in a preterm neonate.

Retinoic acid and tracheal occlusion for diaphragmatic hernia treatment in rabbit fetuses.

INTRODUCTION: Lung hypoplasia and pulmonary arterial hypertension in congenital diaphragmatic hernia lead to a high perinatal mortality. Although sustained fetoscopic tracheal occlusion (TO) improves lung development, a major side effect is abnormal pneumocyte differentiation. This study evaluated the potential ability of intratracheal retinoic acid (RA) administration to reduce adverse effects of sustained TO in a rabbit model of diaphragmatic hernia. METHODS: A left diaphragmatic defect was created on day 23 in time-dated pregnant rabbits. On day 28, the same rabbits underwent sham surgery or TO, with an injection of empty or RA-loaded liposomes. On day 30, the fetuses were harvested, and the lungs were processed for histology, immunohistochemistry, and gene expression quantification. RESULTS: A tracheal RA injection at the time of TO had no effect on the lung-to-body-weight ratio, radial alveolar count or lung connective tissue composition. Retinoic acid plus TO had synergic effects on vascular measurements, proportional medial thickness, and endothelin-1 receptor type-A gene expression. The most noticeable effect was recovery of normal pneumocyte differentiation. CONCLUSION: Retinoic acid plus TO prevented abnormal pneumocyte differentiation and seemed to have a beneficial effect on pulmonary vascularization.

Hyperechoic congenital lung lesions in a non-selected population: from prenatal detection till perinatal management.

OBJECTIVE: To present longitudinal observations of hyperechoic lung lesions (HLL) in a non-selected population from the time of prenatal diagnosis by ultrasound (US) until postnatal surgery. METHODS: We conducted a retrospective study of all fetuses diagnosed with an HLL between 1990 and 2005 in our Fetal Medicine Unit. RESULTS: We observed 21 cases of HLL. Among the 17 fetuses with unilateral lesion, two cyst punctures were attempted on fetuses with signs of fetal compromise. Termination of pregnancy (TOP) was performed on seven fetuses. Fourteen fetuses were followed till birth. First Chest X-ray was abnormal in ten cases, while delayed CT scans revealed a lung lesion in 12 cases. Two neonates required emergency surgery and died post operatively. Surgery was successfully performed in all other cases (n = 10). Pathological examination revealed congenital high airway obstruction syndrome, CHAOS (n = 4), lower airway stenosis (n = 2), bronchogenic cyst (n = 1), congenital lobar emphysema (n = 1), and congenital cystic adenomatoid malformation, CCAM (n = 11) including two cases associated with a sequestration. CONCLUSION: HLL cover a wide spectrum of lung abnormalities of various severities. Post natal management should always include an early chest X-ray and CT scan to allow appropriate selection for surgery.

Effects of maternal retinoic acid administration in a congenital diaphragmatic hernia rabbit model.

Maternal retinoid administration has beneficial effects on lung development in the nitrofen rodent toxic model of congenital diaphragmatic hernia (DH). We wanted to investigate the effects in a surgical model, where the retinoid signaling pathway is not primarily disrupted by the toxic agent. We created DH in fetal rabbits at day 23 of gestation, administrated to the does all trans-retinoic acid (ATRA) or vehicle (VHC) intramuscularly for 8 consecutive days and harvested normal and operated (DH) fetuses at 31 d (n = 7 in each group). Normal lungs exposed to ATRA had increased surfactant protein mRNA levels without change in type II pneumocyte density. There was no measurable effect on lung-to-body weight ratio and airway morphometry by ATRA. In DH lungs (DH/VHC) surfactant protein mRNA levels were increased, as well as the density of type II pneumocytes. When supplemented with ATRA (DH/ATRA) these parameters returned to normal (VHC). Cell proliferation or apoptosis were not influenced by ATRA supplementation. In conclusion, maternal ATRA supplementation does not affect gross anatomic, morphologic or proliferation indices in hypoplastic lungs related to surgically induced DH in rabbit. However, ATRA lowers surfactant protein expression and normalizes type I/II pneumocyte ratio to what is observed in normal lungs.