Opioids accelerate fetal rat lung maturation in vitro

Infants born to heroin- and cocaine-addicted mothers have been reported to have a lower incidence of respiratory distress syndrome (RDS) compared with nonaddicted infants. However, it is not known whether these are direct dru g-mediated effects or secondary phenomena. We therefore investigated the ef fect of opioids and cocaine on fetal rat lung maturation in vitro. Using 18 - to 20-d fetal rat lung explants and 20-d fetal type II cells, we measured the effect of varying concentrations (1 x 10(-8) to 1 x 10(-3) M) of heroi n, morphine, methadone, and the nonopioid cocaine on the rate of choline in corporation into phosphatidylcholine (PC) and disaturated PC. We also analy zed the morphology of 19-d explants after exposure to opioids. Significant increases in rate of choline incorporation were noted in 19- and 20-d expla nts using 1 x 10(-3) M heroin, 1 x 10(-3) M morphine, and 1 x 10(-4) M meth adone (P < 0.005). No acceleratory effect was seen with cocaine. Morphologi c analysis of the three opioid-treated groups revealed a significant (192 t o 251%) increase in type IT pneumocytes and lamellar bodies per alveolar li ning cell (P < 0.01). Choline incorporation into PC by type II cells was al so significantly increased by opioids (P < 0.01); lactate dehydrogenase rel ease and cell viability were not affected by opioid treatment. These data i ndicate that high-dose opioids have an acceleratory effect on biochemical a nd morphologic parameters of fetal lung maturation in vitro. The lack of in vitro acceleration with cocaine suggests that any cocaine-related reductio n in the incidence of RDS is a secondary effect.