Considerable doubt has recently been cast on the assumption that perinatal hypoxia-ischemia is the primary cause of neonatal encephalopathy and cerebral palsy. Important epidemiological studies have suggested a wide range of alternative causal pathways, for example, stressing associations with maternal thyroid disease, or abnormalities of the hemostatic and immune systems (1, 2). A relation to inflammation has emerged: maternal fever in labor increases the offspring's risk of cerebral palsy even when there is no clinical evidence of impaired intrauterine gas exchange (3). The likelihood of specific genetic predispositions is often raised, with supporting evidence beginning to appear in some particular cases such as neonatal focal stroke.

The most consistent finding of the various epidemiological studies is that children with cerebral palsy only infrequently have evidence of perinatal hypoxia-ischemia. This should probably not surprise us. Not only can cerebral accidents presumably occur in unfortunate or predisposed individuals during the long period of intrauterine life, but the imprecise measures of fetal cerebral oxygenation and blood flow available to clinical researchers make it difficult to define perinatal hypoxia-ischemia with any certainty. Commonly quoted variables such as cardiotocography or meconium staining of the liquor are at best poor surrogate markers of brain metabolism which might be expected to predict neurologic outcome poorly (4).

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