To analyze reasons for low enrollment in a randomized controlled trial (RCT) of the effect of hydrocortisone for cardiovascular insufficiency on survival without neurodevelopmental impairment (NDI) in term/late preterm newborns. The original study was a multicenter RCT. Eligibility: ⩾34 weeks’ gestation, <72 h old, mechanically ventilated, receiving inotrope. Primary outcome was NDI at 2 years; infants with diagnoses at high risk for NDI were excluded. This paper presents an analysis of reasons for low patient enrollment. Two hundred and fifty-seven of the 932 otherwise eligible infants received inotropes; however, 207 (81%) had exclusionary diagnoses. Only 12 infants were randomized over 10 months; therefore, the study was terminated. Contributing factors included few eligible infants after exclusions, open-label steroid therapy and a narrow enrollment window. Despite an observational study to estimate the population, very few infants were enrolled. Successful RCTs of emergent therapy may require fewer exclusions, a short-term primary outcome, waiver of consent and/or other alternatives.

The extracellular matrix is important in the cellular differentiation and morphogenesis of the lung. The basement membrane (BM), an integral part of the extracellular matrix, is composed primarily of type IV collagen. The metabolism of type IV collagenase is important in remodeling of BM that occurs during growth. We examined the ontogeny of rat lung type IV collagenase mRNA expression, type IV collagenolytic activity and type IV collagen content during the perinatal period. In addition, the effect of prenatal glucocorticoid (GC) treatment on fetal lung type IV collagenase mRNA expression and type IV collagenolytic activity was studied. Lung polyadenylated RNA was extracted and subjected to Northern blot analysis and laser densitometry after hybridization with human type IV collagenase (∼72 kD) and rat actin cDNA probe. Type IV collagenolytic activity and type IV collagen concentration were quantitated by an enzymatic and a radioimmunoassay, respectively. While lung type IV collagenase mRNA to α-actin ratio and type IV collagenolytic activity were highest prior to birth (21-day fetus), the lung type IV collagen concentration was lowest at this time. Prenatal GC treatment did not influence type IV collagenase mRNA expression or the collagenolytic activity. A role for fetal lung type IV collagenase in preparation for the neonatal pulmonary vascular and/or alveolar adaption is proposed.

We observed approximately 45-50 kD GLUT 1 protein in mouse lung homogenates and demonstrated a greater abundance in fetus compared to adult. In situ immunohistochemical analysis demonstrated GLUT 1 expression only in the perineural sheath of nerves. While the trapped fetal red blood cells expressed GLUT 1 abundantly, adult red blood cells were devoid of GLUT 1. No GLUT 1 was evident in fetal and adult lung alveolar and bronchiolar epithelial cells, vascular endothelial cells and the lung mesenchymal elements. Thus, GLUT 1 is not the major lung glucose transporter.

We investigated the effect of maternally administered thyrotropin-releasing hormone on functional and morphologic fetal lung maturation. Thyrotropin-releasing hormone (40 micrograms/kg/day) or the vehicle was injected intravenously into the New Zealand White rabbit does on days 25, 26, and 27 of gestation. On day 27 of pregnancy, the does were killed and the fetuses were delivered. The functional pulmonary maturity was assessed by pressure-volume hysteresis while morphologic maturity was assessed by histologic techniques. Enhanced functional and morphologic fetal lung maturation was noted in animals treated with thyrotropin-releasing hormone when compared with controls. An important role of thyrotropin-releasing hormone in fetal lung maturation is proposed.

Recent experimental evidence suggests that a combination of glucocorticoid and thyroid hormone may be more effective than either hormone alone in accelerating morphologic as well as biochemical mammalian fetal lung maturation. We have demonstrated that IM administration of T3 to the rabbit doe is associated with enhanced functional fetal lung maturation. We investigated the effect of simultaneous administration of T3 and betamethasone on the development of functional fetal lung maturation and the duration of survival after premature delivery. On day 25 and 26 of pregnancy, T3 (175 μg/kg/dose) betamethasone (85 μg/kg/dose), T3 plus betamethasone or the appropriate amount of the vehicles were injected. The functional fetal pulmonary maturity and the duration of survival after premature delivery were assessed on day 27 of gestation. Although enhanced functional fetal lung maturation was observed after T3 or betamethasone administration, there was no additive effect after simultaneous administration of both. The duration of survival on premature delivery was enhanced in betamethasone but not T3 or T3 plus betamethasone group when compared to control. Further animal experimentation seems necessary before a clinical trial of T3 plus betamethasone therapy is considered.

We have recently demonstrated that intramuscular administration of triiodothyronine (T3) or thyroxine (T4) to the rabbit doe results in its transfer across the placenta. In this study we investigated the effect of maternally administered T3 upon the functional and morphologic fetal lung maturation. T3 (175 micrograms/kg) or the vehicle was injected intramuscularly into the New Zealand White rabbit does on days 25 and 26 of gestation. On day 27 of pregnancy, the does were killed and the fetuses were delivered. Maternal and fetal plasma T3, glucose and insulin and fetal plasma corticosteroid concentrations were determined. The functional pulmonary maturity was assessed by performing the pressure-volume hysteresis while morphologic maturity was established by histologic techniques. Enhanced functional as well as morphologic fetal lung maturation was observed in female as well as male fetuses in T3-treated animals. However, there was a significant increase in the fetal mortality after T3 treatment, and the duration of survival in the extrauterine environment on premature delivery was not prolonged.