RESUMEN

Twin infants born at 34 week gestation had frank blood in stools on day three of life on mixed feeds of formula and maternal breast milk. Sepsis work up was negative in these relatively well appearing infants with pneumatosis in the colon on abdominal x-ray. Blood in stools recurred on reintroduction of breast milk in Twin A. Both infants recovered from episodes of bloody stools on amino-acid based formula and were thriving at discharge. Early necrotizing enterocolitis in both twins is rare and has not been reported. Cow's milk protein sensitivity, possibly from in-utero sensitization, could explain non-infectious colitis in these twins, precipitated by formula or breast milk after birth.

Asunto(s)

Lactancia Materna , Enterocolitis Necrotizante/diagnóstico , Fórmulas Infantiles , Hipersensibilidad a la Leche/diagnóstico , Adulto , Edad de Inicio , Antibacterianos/uso terapéutico , Colon/diagnóstico por imagen , Enterocolitis Necrotizante/complicaciones , Enterocolitis Necrotizante/diagnóstico por imagen , Enterocolitis Necrotizante/terapia , Femenino , Hemorragia Gastrointestinal/etiología , Humanos , Recién Nacido , Hipersensibilidad a la Leche/complicaciones , Hipersensibilidad a la Leche/terapia , Nutrición Parenteral Total , Embarazo , Radiografía , Gemelos

RESUMEN

BACKGROUND: Premature birth disrupts hypoxia driven microvascular development that directs alveolar and lung growth. Changes in oxygen exposure after birth can perturb the regulation of angiogenesis leading to bronchopulmonary dysplasia (BPD). We studied the effects of intermittent hypoxia or hyperoxia on HIF and angiogenic gene expression and lung development in newborn mice. METHODS: Newborn litters were randomized within 12 h of birth to 12% O2 (4 h), 50% O2 (4 h) or 12% O2 (2 h)/50% O2 (2 h) followed by room air (RA) recovery for 20 h. Mice in RA were the control group. The mice were exposed to 6 such cycles (D1-D6) and sacrifice on D7. Whole lung mRNA was isolated and gene expression performed by qRT-PCR (HIF1α/2α/1ß; PHD2, Ang1, Tie2, Vegf, VegfR1 & VegfR2) and analyzed by PCR array data analysis web portal. HIF-1α, prolyl hydroxylase-2 and VEGF protein were analyzed in whole lung by ELISA. Lung morphology was assessed by H&E sections and radial alveolar counts; cell proliferation by Ki67 immunostaining. RESULTS: HIF-1α mRNA and VEGF protein were significantly downregulated in the 50% O2 group; VEGF mRNA and protein were significantly downregulated in the 12% O2-50% O2 group; Ang-1 and its receptor mRNA expression were downregulated in 12% O2 and 12% O2-50% O2 groups. 50% O2 (hyperoxia) and 12% O2-50% O2 (hypoxia-hyperoxia) groups demonstrated alveolar simplification by RAC and the same groups had decreased cell proliferation by Ki67 staining compared to RA and hypoxia (12% O2) groups. CONCLUSIONS: Downregulation of HIF and angiogenic gene expression with associated changes in lung histology following intermittent hypoxia-hyperoxia is likely an important contributing factor in the development of BPD.

Asunto(s)

Expresión Génica , Hiperoxia/fisiopatología , Hipoxia/fisiopatología , Pulmón/crecimiento & desarrollo , Neovascularización Fisiológica/genética , ARN Mensajero/análisis , Angiopoyetina 1/genética , Animales , Translocador Nuclear del Receptor de Aril Hidrocarburo/genética , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/genética , Proliferación Celular , Regulación hacia Abajo , Hiperoxia/complicaciones , Hipoxia/complicaciones , Subunidad alfa del Factor 1 Inducible por Hipoxia/análisis , Subunidad alfa del Factor 1 Inducible por Hipoxia/genética , Prolina Dioxigenasas del Factor Inducible por Hipoxia/análisis , Prolina Dioxigenasas del Factor Inducible por Hipoxia/genética , Antígeno Ki-67/análisis , Pulmón/química , Pulmón/patología , Ratones , Ratones Endogámicos C57BL , Distribución Aleatoria , Receptor TIE-2/genética , Factor A de Crecimiento Endotelial Vascular/análisis , Factor A de Crecimiento Endotelial Vascular/genética , Receptor 1 de Factores de Crecimiento Endotelial Vascular/genética , Receptor 2 de Factores de Crecimiento Endotelial Vascular/genética