Antenatal factors, such as chorioamnionitis(CA) and preeclampsia(PE), and postnatal injury are associated with an increased risk for BPD and PH after preterm birth. IGF-1 is markedly decreased in normal preterm infants, but whether IGF-1 treatment can prevent BPD or PH is unknown.
To evaluate whether postnatal treatment with rhIGF-1/BP3 improves lung growth and prevents PH in 2 antenatal models of BPD induced by intra-amniotic exposure to ETX or sFlt-1 and in a postnatal model due to prolonged hyperoxia.
ETX or sFlt-1 were administered into the amniotic sac of pregnant rats at E20 to simulate antenatal models of CA and PE, respectively. Pups were delivered by c-section at E22 and treated with rhIGF-1/BP-3 (0.02-20 mg/kg/day, intraperitoneal) or buffer for 2 weeks. Study endpoints included radial alveolar counts(RAC), vessel density, and right ventricular hypertrophy(RVH). Direct effects of rhIGF-1/BP-3 (250 ng/ml) on fetal lung endothelial cell(LEC) proliferation and tube formation and alveolar type 2 cell(AT2C) proliferation were studied by standard methods in vitro.
Antenatal ETX and antenatal sFlt-1 reduced RAC and decreased RVH in infant rats. In both models, postnatal rhIGF-1/BP-3 treatment restored RAC and RVH to normal values when compared with placebo injections. rhIGF-1/BP3 treatment also preserved lung structure and prevented RVH after postnatal hyperoxia. In vitro studies showed that rhIGF-1/BP3 treatment increased LEC and AT2 cell proliferation.
Postnatal rhIGF-1/IGFBP-3 treatment preserved lung structure and prevented RVH in antenatal and postnatal BPD models. rhIGF-1/BP-3 treatment may provide a novel strategy for the prevention of BPD in preterms.