McGillick EV, Davies IM, Hooper SB, Kerr LT, Thio M, DeKoninck P, Yamaoka S, Hodges R, Rodgers KA, Zahra VA, Moxham AM, Kashyap AJ, Crossley KJ. Effect of lung hypoplasia on the cardiorespiratory transition in newborn lambs. J Appl Physiol 127: 568 -578, 2019. First published June 13, 2019; doi:10.1152/ japplphysiol.00760.2018.-Newborns with lung hypoplasia (LH) commonly have limited respiratory function and often require ventilatory assistance after birth. We aimed to characterize the cardiorespiratory transition and respiratory function in newborn lambs with LH. LH was induced by draining fetal lung liquid in utero [110 -133 days (d), term 147d, n 6]. At ~133d gestation, LH and Control lambs (n 6) were instrumented and ventilated for 3 h to monitor blood-gas status, oxygenation, ventilator requirements, and hemodynamics during the transition from fetal to newborn life. Lambs with LH had significantly reduced relative wet and dry lung weights indicating hypoplastic lungs compared with Control lambs. LH lambs experienced persistent hypercapnia and acidosis during the ventilation period, had lower lung compliance, and had higher alveolar-arterial differences in oxygen and oxygenation index compared with Control lambs. As a result, LH lambs required greater respiratory support and more supplemental oxygen. Following delivery, LH lambs experienced periods of significantly lower pulmonary artery blood flow and higher carotid artery blood flow in association with the lower oxygenation levels. The detrimental effects of LH can be attributed to a reduction in lung size and poorer gas exchange capabilities. This study has provided greater understanding of the effect of LH itself on the physiology underpinning the transition from fetal to newborn life. Advances in this area is the key to identifying improved or novel management strategies for babies with LH starting in the delivery room, to favorably alter the fetal-to-newborn transition toward improved outcomes and reduced lifelong morbidity. NEW & NOTEWORTHY Current clinical management of newborns with lung hypoplasia (LH) is largely based on expert opinion rather than scientific evidence. We have generated physiological evidence for detrimental effects of LH on hemodynamics and respiratory function in newborn lambs, which mimics the morbidity observed in LH newborns clinically. The unfavorable consequences of LH can be attributed to a reduction in lung size and poorer gas exchange capabilities. cardiorespiratory transition; lung hypoplasia; newborn respiratory function; ventilation.