Prenatal vitamin E treatment improves lung growth in fetal rats with congenital diaphragmatic hernia

Purpose: Congenital diaphragmatic hernia (CDH) is associated with pulmonary hypoplasia. To discover factors that would accelerate fetal lung growth, t he authors developed models of hypoplasia, found that antioxidants im prove d lung growth in vitro, and then proceeded to in vivo studies. Methods: Timed-pregnant rats were fed nitrofen (100 mg) on gestational day 9.5 (term, 22), and fetal lungs were harvested at day 13.5 and placed in or gan culture in serum-free media with (n = 10) or without (n = 9) additional vitamin E (0.134 IU/mL). Camera lucida tracings were made daily on live, u nstained lungs for 4 days, scanned, digitized, and analyzed for multiple gr owth parameters. Similar nitrofen-exposed rats were fed an optimized total dose of 150 IU vitamin E (n = 19) or olive oil (n = 13) from days 16.5 to 2 0.5, and fetal lungs were harvested at day 21.5, weighed and fixed for hist ology, or homogenized and biochemically analyzed. Results: Vitamin E accelerated hypoplastic fetal lung growth in vitro as me asured by area, perimeter, lung bud count, perimeter over square root area, and fractal dimension. In vivo Vitamin E significantly increased lung weig hts, total DNA, and protein contents. Conclusions: Vitamin E accelerates hypoplastic fetal rat lung growth and co mplexity in vitro, and prenatal vitamin E treatment in vivo improves pulmon ary hypoplasia in fetal rats with CDH. J Pediatr Surg 34:172-177. Copyright (C) 1999 by W.B. Saunders Company.