Surviving preterm infants of less than 34 weeks' gestation who were selected on the basis of serial cranial ultrasonographic findings during their nursery course had repeated neurologic and developmental examinations during late infancy and early childhood that established the presence (n = 46) or absence (n = 205) of spastic forms of cerebral palsy. Of the 205 infants without cerebral palsy, 22 scored abnormally low on standardized developmental testing during early childhood. The need for mechanical ventilation beginning on the first day of life (n = 92) was significantly related to gestational age, birth weight, Apgar scores, patent ductus arteriosus, grade III/IV intracranial hemorrhage, large periventricular cysts, and the development of cerebral palsy. In the 192 mechanically ventilated infants, vaginal bleeding during the third trimester, low Apgar scores, and maximally low PCO2 values during the first 3 days of life were significantly related to large periventricular cysts (n = 41) and cerebral palsy (n = 43), but not to developmental delay in the absence of cerebral palsy (n = 18). The severity of intracranial hemorrhage in mechanically ventilated infants was significantly associated with gestational age and maximally low measurements of PCO2 and pH, but not with Apgar scores or maximally low measurements Of PO2. Logistic regression analyses controlling for possible confounding variables disclosed that PCO2 values of less than 17 mm Hg during the first 3 days of life in mechanically ventilated infants were associated with a significantly increased risk of moderate to severe periventricular echodensity, large periventricular cysts, grade III/IV intracranial hemorrhage, and cerebral palsy. Neurosonographic abnormalities were highly predictive of cerebral palsy independent of PCO2 measurements. However, neither hypocarbia nor neurosonographic abnormalities were associated with a significantly increased risk of developmental delay in the absence of cerebral palsy. In this preterm infant population, therefore, the risk factors for developmental delay differed from those predictive of spastic forms of cerebral palsy. Of the 57 ventilated preterm infants who were exposed to a maximally low PCO2 Of less than 20 mm Hg at least once during the first 3 days of life, 21 developed large periventricular cysts or cerebral palsy or both. Those results suggest that prenatal and neonatal factors including the need for mechanical ventilation beginning on the first day of life and marked hypocarbia during the first 3 postnatal days are associated with an increased risk of damage to the periventricular white matter of some preterm infants. However, a causal relationship between hypocarbia and brain damage in preterm infants remains unproven.
