Hypocapnia and Other Ventilation-Related Risk Factors for Cerebral Palsy in Low Birth Weight Infants

Abstract

Ventilatory management patterns in very low birth weight newborns, particularly iatrogenic hypocapnia, have occasionally been implicated in perinatal brain damage. However, such relationships have not been explored in large representative populations. To examine the risk of disabling cerebral palsy in mechanically ventilated very low birth weight infants in relation to hypocapnia and other ventilation-related variables, we conducted a population-based prospective cohort study of 1105 newborns with birth weights of 500 -2000 g born in New Jersey from mid-1984 through 1987, among whom 777 of 902 survivors (86%) had at least one neurodevelopmental assessment at age 2 y or older. Six hundred fifty-seven of 777 assessed survivors (85%), of whom 400 had been mechanically ventilated, had blood gases obtained during the neonatal period. Hypocapnia was defined as the highest quintile of cumulative exposure to arterial PCO 2 levels Ͻ35 mm Hg during the neonatal period. Disabling cerebral palsy was diagnosed in six of 257 unventilated newborns (2.3%), 30 of 320 ventilated newborns without hypocapnia (9.4%), and 22 of 80 ventilated newborns with hypocapnia (27.5%). Two additional ventilatory risk factors for disabling cerebral palsy were found-hyperoxia and prolonged duration of ventilation. In a multivariate analysis, each of the three ventilatory variables independently contributed a 2-to 3-fold increase in risk of disabling cerebral palsy. These risks were additive. Although duration of mechanical ventilation in very low birth weight newborns likely represents severity of illness, both hypocapnia and hyperoxia are largely controlled by ventilatory practice. Avoidance of arterial PCO 2 levels Ͻ35 mm Hg and arterial PO 2 levels Ͼ60 mm Hg in mechanically ventilated very low birth weight infants would seem prudent. The successes of neonatal intensive care during the past two decades in reducing neonatal mortality have not been matched by success in reducing the risk of CP and other neurodevelopmental disorders. The population prevalence of CP has changed little in developed countries during the past three decades (1-7).CP has generally been thought to be caused by antepartum or intrapartum factors. But some recent studies in low birth weight infants have focused on the relationship of components of neonatal intensive care, particularly the management of mechanical ventilation, as risk factors for brain damage. Several studies have pointed to the possibility that the iatrogenic induction of hypocapnia (low PaCO 2 ) might cause brain damage, mediated via the well-established effects of hypocapnia in decreasing CBF. Under normal circumstances, a direct monotonic relationship between CBF and PaCO 2 and an inverse relationship of CBF to PaO 2 provide a compensatory mechanism through which hypoxemia or hypercapnia can provoke cerebral vasodilation. However, under circumstances of artificial hypocapnia or hyperoxemia the same mechanism could result in an inappropriate reduction in CBF.Although some neonatologists try to avoid hypoc...

Visual and fine-motor outcomes in adolescent survivors of high-risk congenital diaphragmatic hernia who did not receive extracorporeal membrane oxygenation

“…[30][31][32][33] It must be recollected that, as a group, our CDH participants had abnormally high pH and abnormally low CO 2 , both pre-and post-operatively (see Table 2). The CDH survivors who showed the best intellectual and motor outcomes were those whose pH and CO 2 levels were closest to the normal range.…”

Hyperoxia Causes Maturation-Dependent Cell Death in the Developing White Matter

“…Recent studies have demonstrated that a change in clinical practice to avoid hyperoxia is associated with significant decrease in neonatal morbidity but does not have a detrimental effect on developmental outcome at 18 months (Deulofeut et al, 2006). Moreover, another study identified hyperoxia as one clinical risk factor for abnormal neurologic outcome of preterm infants (Collins et al, 2001). This finding is consistent with the observation that the duration of oxygen therapy in premature infants was predictive of the cognitive outcome at 8 years (Short et al, 2003).…”

“…Hyperoxia has been implicated in the pathogenesis of bronchopulmonary dysplasia and retinopathy of prematurity (Saugstad, 2001;Chow et al, 2003). There is increasing evidence that hyperoxia may negatively influence brain maturation and development (Collins et al, 2001;Felderhoff-Mueser et al, 2004;Klinger et al, 2005;Gerstner et al, 2006). However, the mechanism of hyperoxia-induced injury and the identification of vulnerable cells in the human brain are still unknown.…”

Clinical practices in neonatal oxygenation: where have we failed? What can we do?

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