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Triamcinolone acetonide (TAC) has a potent teratogenic effect on various mammalian fetal tissues as well as a steroid effect on the lung. Less well documented is the fact that it produces profound oligohydramnios. We wished to determine what effect TAC would have on branching morphogenesis and other aspects of lung development, using an in vivo model described previously. Thirty rats were randomized to receive 0.6 mg/kg of TAC or saline on days 12, 13, and 14 of gestation. At gestational days 15, 17, 18, and 21, the left lungs of 365 fetuses were studied by dissecting microscopy, histology, and morphometry. TAC produced profound pulmonary hypoplasia (dry lung weight/body weight 0.025, compared with 0.06 in controls) on day 21. TAC decreased maternal weight gain, fetal weight, placental weight, amniotic fluid, and pole to pole length (PTP), while it increased the peripheral airway count (PAC). The number of central and intermediate airway branches was reduced, and they were dilated. Growth of peripheral airways was enhanced. In treated fetuses epithelial cells lining these airspaces were histologically more mature and the mesenchyme thinner than in controls. These findings were confirmed by the morphometric measurements. We conclude that when TAC is administered in the early phase of fetal rat lung development, the lungs become hypoplastic, with hypoplasia of the intermediate airways, an increase in the number of peripheral airways, and increased differentiation. We speculate that these effects are primarily due to the steroid action of TAC and that the mechanisms of monopodial branching are different from those of dichotomous branching. Pediatr Pulmonol. 1997; 23:76–86. © 1997 Wiley-Liss, Inc.

We studied the left lung using multi-focus microphotography in 378 rat fetuses, assessing airway branching from day 13 to day 19 of gestation, and lung growth variables from day 13 to day 21. Longitudinal growth, and monopodial and dichotomous branching brought about a consistent airway pattern with variations within each day of gestation and a small overlap between adjacent days. Amniotic fluid weight and pole to pole (PTP) distance of the lung increased quadratically with age, while fetal weight and the peripheral airway count (PAC) increased exponentially. The location of the fetus within the uterus had no effect on fetal variables, but correlations were found between maternal weight gain and both fetal weight and PTP. Fetal weight was the best predictor of PAC from gestational ages 15 to 19 days (P < 0.008). The method described allows for observations that are reproducible within the environmental variations present in normal gestation and can be used to study the effect of external factors on lung development.

The objective of this study was to compare the incidence of chronic lung disease following neonatal ventilation in two geographically defined populations. Prospective data collection was carried out over a 1 year period from March 11, 1990 to February 28, 1991 in the Trent Health Region (England) and in British Columbia, Canada. All infants < or = 32 weeks gestation and/or < or = 1500 g birthweight born to mothers normally resident in either the Trent Health Region or British Columbia were included. The main outcome measures were mortality rate, presence of chronic lung disease, days of ventilation, and oxygen used by each infant. The proportion of shortened gestation, low birthweight babies was 1.5% in Trent and 1.2% in British Columbia (957 of 63,350 births in Trent and 526 of 45,333 births in British Columbia). There were no significant differences in mean birthweight or gestation between the two cohorts, but there was a trend towards lower mortality for infants 750-1500 g birthweight in British Columbia. The incidence of chronic lung disease (using either of two definitions) was significantly higher in British Columbia, with a corresponding greater amount of respiratory care required. This occurred despite higher use of antenatal steroids and surfactant therapy in the British Columbia group. We conclude that there are important clinical and resource implications resulting from the number of ventilator and oxygen days used by the preterm population in terms of planning of neonatal services. The role of individual treatment modalities in producing differences in the incidence of chronic lung disease warrants further study in the setting of a geographically defined population.

Triamcinolone acetonide (TAC) has a potent teratogenic effect on various mammalian fetal tissues as well as a steroid effect on the lung. Less well documented is the fact that it produces profound oligohydramnios. We wished to determine what effect TAC would have on branching morphogenesis and other aspects of lung development, using an in vivo model described previously. Thirty rats were randomized to receive 0.6 mg/kg of TAC or saline on days 12, 13, and 14 of gestation. At gestational days 15, 17, 18, and 21, the left lungs of 365 fetuses were studied by dissecting microscopy, histology, and morphometry. TAC produced profound pulmonary hypoplasia (dry Jung weight/body weight 0.025, compared with 0.06 in controls) on day 21. TAC decreased maternal weight gain, fetal weight, placental weight, aminiotic fluid, and pole to pole length (PTP), while it increased the peripheral airway count (PAC). The number of central and intermediate airway branches was reduced, and they were dilated. Growth of peripheral airways was enhanced. In treated fetuses epithelial cells lining these airspaces were histologically more mature and the mesenchyme thinner than in controls. These findings were confirmed by the morphometric measurements. We conclude that when TAC is administered in the early phase of fetal rat lung development, the lungs become hypoplastic, with hypoplasia of the intermediate airways, an increase in the number of peripheral airways, and increased differentiation. We speculate that these effects are primarily due to the steroid action of TAC and that the mechanisms of monopodial branching are different from those of dichotomous branching.

We studied the left lung using multi-focus microphotography in 378 rat fetuses, assessing airway branching from day 13 to day 19 of gestation, and lung growth variables from day 13 to day 21. Longitudinal growth, and monopodial and dichotomous branching brought about a consistent airway pattern with variations within each day of gestation and a small overlap between adjacent days. Amniotic fluid weight and pole to pole (PTP) distance of the lung increased quadratically with age, while fetal weight and the peripheral airway count (PAC) increased exponentially. The location of the fetus within the uterus had no effect on fetal variables, but correlations were found between maternal weight gain and both fetal weight and PTP. Fetal weight was the best predictor of PAC from gestational ages 15 to 19 days (P0.008). The method described allows for observations that are reproducible within the environmental variations present in normal gestation and can be used to study the effect of external factors on lung development.

The objective of this study was to compare the incidence of chronic lung disease following neonatal ventilation in two geographically defined populations. Prospective data collection was carried out over a 1 year period from March 11, 1990 to February 28, 1991 in the Trent Health Region (England) and in British Columbia, Canada. All infantsor = 32 weeks gestation and/oror = 1500 g birthweight born to mothers normally resident in either the Trent Health Region or British Columbia were included. The main outcome measures were mortality rate, presence of chronic lung disease, days of ventilation, and oxygen used by each infant. The proportion of shortened gestation, low birthweight babies was 1.5% in Trent and 1.2% in British Columbia (957 of 63,350 births in Trent and 526 of 45,333 births in British Columbia). There were no significant differences in mean birthweight or gestation between the two cohorts, but there was a trend towards lower mortality for infants 750-1500 g birthweight in British Columbia. The incidence of chronic lung disease (using either of two definitions) was significantly higher in British Columbia, with a corresponding greater amount of respiratory care required. This occurred despite higher use of antenatal steroids and surfactant therapy in the British Columbia group. We conclude that there are important clinical and resource implications resulting from the number of ventilator and oxygen days used by the preterm population in terms of planning of neonatal services. The role of individual treatment modalities in producing differences in the incidence of chronic lung disease warrants further study in the setting of a geographically defined population.