Effect of triamcinolone acetonide on the development of the pulmonary airways in the fetal rat

Abstract

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.

Intranasal triamcinolone use during pregnancy and the risk of adverse pregnancy outcomes

“…In addition, further studies are required to rule out chance findings. Nevertheless, intramuscular triamcinolone was shown to be teratogenic in animals and has been shown to affect lung development, [11][12][13] which is consistent with our findings. Although adjustment was made on maternal AR (indication) and other known risk factors for major congenital malformations (maternal asthma and severity of maternal respiratory diseases), residual confounding cannot be excluded completely.…”

“…Although we could not adjust for these variables, the fact that our findings are consistent with those of Kallen et al, 9 who adjusted for these variables, suggests that the level of confounding would not have changed our conclusions. In addition, defects identified in our study have been seen in animal studies, [11][12][13] suggesting a probable mechanism of action. Although confounding by indication was reduced by the fact that exposure to other intranasal corticosteroids was not associated with the outcomes studied, confounding can still occur because of different patterns of prescribing, and hence residual confounding cannot be completely ruled out.…”

“…11,12 Indeed, triamcinolone acetonide has the potential to have a potent teratogenic effect on various mammalian fetal tissues, as well as a steroid effect on the lung, fetal growth retardation, and cleft palate anomalies. 13 At present, no human pregnancy data are available for intranasal triamcinolone.…”

Maternally Administered Dexamethasone Transiently Increases Apoptosis in Lungs of Fetal Rats

“…Studies in experimental animals have shown that maternal administration of glucocorticoids in the latter part of gestation has complex effects on the developing fetal lung, effects that are incompletely understood. In addition to the well-described acceleration of formation [5] and release [6] of pulmonary surfactant, exogenous glucocorticoids also accelerate interstitial thinning and increase the size of distal airspaces [7][8][9][10]. Glucocorticoids also decrease the amount of interluminal tissue in cultured explants of fetal lungs [11].…”

Inhaled steroids in children: adrenal suppression and growth impairment

“…This is mostly due to the general fear of the side-effects of inhaled steroids, but also because of an awareness of the possible effects upon lung growth in young children, as has been reported by the use of systemic steroids in animal experiments [15].…”