Long term consequences of oxygen therapy in the neonatal period

Abstract

Preterm and term infants are frequently exposed to high concentrations of oxygen for prolonged periods. In experimental models, high and prolonged oxygen exposures cause delayed alveolar septation and a bronchopulmonary dysplasia phenotype. Often, however, the oxygen exposure is tolerated in that the infants recover without severe lung or systemic injury. Multiple exposures change oxygen sensitivity in adult and newborn animals. Examples are antenatal corticosteroids, inflammatory mediators or preconditioning with oxygen, which will increase tolerance to oxygen injury. Intrauterine growth restriction or postnatal nutritional deficits will increase oxygen injury. Different infants probably have quite variable sensitivities to oxygen injury, but there are no biomarkers available to predict the risk of oxygen injury.

Figure 1

Effect of careful O₂ saturation monitoring on the incidence of retinopathy of prematurity (ROP) and need for laser therapy at Cedars Sinai Medical Center (CSMC, closed bars) relative to the Vermont–Oxford Neonatal database (VON, open bars). Data are for infants 500–1500 g for 1997 and 2001. A clinical emphasis on keeping O₂ saturations >93–95% correlated with a large decrease in ROP at CSMC. Data from Chow et al.

Figure 2

Intraperitoneal endotoxin protects adult rats from death caused by >95% oxygen for 72 h. Rats received doses of 0.1–0.5 mg endotoxin/day or control injections. Endotoxin protected the animals from oxygen. Data from Frank and Roberts.

Figure 3

Dose response of antioxidant enzymes to intra-amniotic endotoxin in the lungs of fetal sheep. The fetuses were exposed to different doses of endotoxin by intra-amniotic injection administered 7 days before preterm delivery at 125 days of gestation. The endotoxin exposure increased antioxidant enzymes. Data from Sosenko and Jobe. Artwork: Fig. 3. In key, black circles should be labelled ‘Glutathione’ (t for l)