When the fetus is exposed to insufficient oxygen to allow the complete metabolism of glucose, lactic acid accumulates and results in metabolic acidosis. Acute impairment of the umbilical circulation will result in hypercarbia and respiratory acidosis due to decreased exchange of CO₂, but uteroplacental insufficiency may or may not be associated with hypercarbia because exchange of CO₂ at the placenta is more efficient than is exchange of oxygen. The term fetal asphyxia is overused and should be limited to fetal hypoxia accompanied by metabolic acidosis. Although it has become a popular legal theory, there remains no scientific basis for the notion that cerebral ischemia caused by the pressures of labor and in the absence of fetal hypoxia with metabolic acidosis is a cause of CP.

Fetal circulatory responses to hypoxia include redistribution of blood flow to the more vital organs resulting in preservation of circulation to the brain, myocardium, and adrenal glands. There is a resulting decrease in blood flow to the kidney, intestine, and muscle. Another consequence of hypoxia is a loss of cerebral vascular autoregulation resulting in a pressure-passive circulation. When the level of hypoxemia is near lethal, there is a decrease in fetal cardiac output resulting in hypotension and decreased cerebral blood flow (2,3 and 4). It appears that when fetal cardiac output declines, resulting in a decrease in cerebral blood flow below a critical level, neuronal necrosis results. Subsequent development of cerebral edema in the neonate further compromises cerebral blood flow, aggravating the degree of neuronal necrosis.

When fetal hypoxia occurs at sublethal levels, permanent damage to the fetus may result; however, the frequency with which this occurs in the intrapartum period and the ability of the clinician using fetal monitoring to prevent it are a subject of intense debate. References to perinatal brain damage can be found earlier, but the English orthopedic surgeon, Little (5), is credited with the first specific hypothesis suggesting adverse perinatal events as the main etiologic factors in infantile spastic palsies. He reviewed the histories of more than 200 cases of spasticity of congenital origin and presented his paper entitled “On the influence of abnormal parturition, difficult labours, premature birth and asphyxia neonatorum, on the mental and physical condition of the child, especially in relation to deformities” to the Obstetrical
Society of London. He concluded that these 200 cases had one thing in common, that is, some abnormal characteristic of parturition. The form of CP that he described has often been called “Little’s disease.” Little later went so far as to conclude that virtually nothing other than abnormalities of birth could cause the clinical picture he described (5). Subsequently, other neurologic problems including mental retardation, epilepsy, and behavioral and learning disorders have been attributed to various intrapartum problems.

Animal data corroborating the concept that perinatal asphyxia may cause profound sublethal neurologic damage can be found in the classic papers of Windle and Becker (6). Between 1943 and 1963, Windle (7) performed experimental asphyxiation of rhesus monkeys and evaluated the immediate, long-term, and neuropathologic effects. The monkeys were asphyxiated in one of two ways, both involving hysterotomy. Either the placenta and membranes were delivered with the fetus within the intact amniotic sac or the fetal head was covered by a fluid-filled sac and the umbilical cord was completely occluded. The fetal oxygen supply was completely interrupted for 5 to 20 minutes. Monkeys allowed to breathe in 6 minutes or less showed no neurologic deficits and no pathologic brain changes. Asphyxiation for more than 7 minutes produced at least transient motor and behavioral changes and relatively consistent brain pathology, along with necrosis of brain-stem cells in the inferior colliculi and ventrolateral thalamic nuclei with secondary glial proliferative scarring. The most profound changes were found in monkeys left anoxic for 12 to 17 minutes. Resuscitation was invariably necessary. More severe brain-stem lesions were created. Initially, the monkeys were hypoactive and hypotonic. Seizures, ataxia, and athetosis were often seen. The monkeys were observed for 8 years and, as they matured, most deficits gradually improved, leaving residual hypoactivity and clumsiness. Although this model indeed supported the hypothesis that perinatal asphyxia is associated with permanent neurologic damage, the pattern of damage did not seem to correspond with the mental retardation and spasticity seen most commonly in humans. In later experiments, Windle (7) subjected monkeys to prolonged labor with oxytocin, and the asphyxiated neonates did not show the midbrain and brain-stem lesions of acute total asphyxia but rather primarily cortical damage.

Myers (8) suggested that total asphyxia may not be the usual case in humans and that prolonged partial asphyxia is more likely. Myers was able to produce partial asphyxia in the rhesus monkey by various techniques including oxytocininduced tachysystole, compression of the maternal abdominal aorta, maternal infusion of catecholamines, and inspiration by the pregnant monkey of reduced oxygen concentrations. These were controlled by maintaining fetal pO₂ at 5 to 9 mm Hg. Myers et al. (9) later demonstrated that late decelerations of the FHR were caused by this fetal hypoxemia. Fetuses were maintained in such partially asphyctic states for at least 1 hour, then delivered and resuscitated. The immediate effect on the newborn was flaccidity, which evolved after several hours into generalized hypertonus and decerebrate posturing, at which time the newborns began to have periodic generalized seizures. Many fetuses developed ileus and cardiogenic shock, and then died. A minority of fetuses survived. Extensive histopathologic examination of the brain led Myers to conclude that such prolonged partial hypoxia led to a vicious cycle of brain swelling, which caused decreased cerebral blood flow that further aggravated the brain swelling. In extreme degrees, such diminished blood flow led to total hemispheric cortical necrosis. In lesser degrees, cortical damage was seen in the middle third of the paracentral cerebral cortex and in the basal ganglia. Such lesions correspond closely with the intellectual deficits and spastic motor defects seen in humans in whom prolonged intermittent asphyxia is more common than acute total asphyxia as described by Windle.

Many authors have reviewed obstetric histories of children with congenital neurologic damage. Early in his career, Freud became interested in the etiology of CP. In his 1897 monograph, Die Infantile Cerebrallahmung (10), Freud concluded that one-third of the cases were the result of traumatic birth, one-sixth consequent to prematurity, one-sixth were of prenatal or postnatal cause, and one-third unknown. Interestingly, Freud questioned whether the real etiology of the damage was the birth process or if abnormalities seen at birth were a reflection of a previously existing abnormality. For example, Nelson and Ellenberg (11) found that a third of breech deliveries had major malformations, hence a conclusion that abnormal development was caused by breech delivery rather than the reality that existing fetal abnormalities contribute to the incidence of breech presentation. Torfs et al. (12) found a 3.8-fold increase in CP for breech-delivered children over those presenting as a vertex. Lilienfeld and Pasamanick (13) reviewed birth certificates of 561 congenitally spastic children and found a very high incidence of abruptio placentae and placenta previa. Eastman and DeLeon (14) reported an analysis of 96 obstetric records of infants in whom CP developed. Only 18 of these births were uncomplicated; 34 babies were premature. Of the 96 infants, 30% had apnea of more than 30 seconds at birth. Compared with controls, there was a doubling of third-trimester hemorrhage, a threefold increase in breech delivery, a fourfold increase in both anesthetic complications and fetal distress by auscultation, and a tenfold increase in shoulder dystocia among affected infants. Eastman’s findings in a subsequent, more extensive review (15) of 753 cases are summarized in Table 3.1.

Finally, Steer and Bonney (16) in 1962 reviewed 317 patients with CP and concluded that 5% were a result of kernicterus, 8% were caused by congenital defects and neurologic infections, and 87% were cases “with possible obstetric causes.”

Thus, for many years, it has been the impression that CP was primarily caused by perinatal events. Fetal monitoring was developed with the hope that, by identifying fetal
hypoxia early enough and with prompt and appropriate intervention, death and damage could be prevented (17).

Contrary to the classic theory of intrapartum hypoxia as the major cause of CP, epidemiologic studies have shown that only a small percentage of CP is attributable solely to intrapartum events and that most cases of CP with intrapartum factors also have antepartum risk factors. In a 1998 case-controlled review by Badawi et al., involving 164 term infants with moderate or severe neonatal encephalopathy compared with 400 term control infants without neonatal encephalopathy, antepartum and intrapartum risk factors for the development of CP were categorized. When adjusting for antepartum risk factors, they concluded that only maternal pyrexia during labor, occipital posterior presentation, an acute intrapartum event, instrumental vaginal delivery, emergency cesarean section, and general anesthesia were significant intrapartum risk factors for neonatal encephalopathy (Table 3.2). Such things as general anesthesia and emergency cesarean section are not believed to be causative in themselves but by association with the reasons for these interventions. They concluded that 70% of term or near-term neonates with neonatal encephalopathy had only antepartum risk factors with no evidence of adverse intrapartum events, 25% had evidence of antepartum risk factors and intrapartum hypoxia, and only 4% had only intrapartum hypoxia as a risk factor (18). A problem with this analysis assumes that if any antepartum risk factor is present, the cause cannot be only intrapartum. For example, if a patient has antepartum pre-eclampsia and enters labor with normal electronic fetal monitoring (EFM) and subsequently has a prolapsed cord with prolonged deceleration or bradycardia and profound metabolic acidemia at birth, this would not be an isolated intrapartum event. The small contribution of intrapartum asphyxia as a cause of CP probably accounts largely for the fact that intrapartum FHR monitoring has
been disappointing as a strategy to prevent CP (19,20), but the epidemiologic analysis of Badawi probably underestimates the actual intrapartum contribution. A recent population-based study of children with CP in California revealed that about one-third of 7,242 children with CP had an adverse intrapartum identifiable event compared to 12.9% in controls without CP. The effect was more pronounced in children born prematurely (36.8%) than children born at term (28.3%). Maternal and neonatal infections were also significantly more common in birth records of children with CP (21). While the various estimates of the contribution of acute intrapartum events to the development of CP continue to vary between 5% and 35%, it is clear that adverse intrapartum events are a definite contributor to later CP.

Asphyxia is one cause of prenatal and perinatal neurologic damage. Other factors may be causative or contributive, or indeed, as pointed out by Freud (10), in babies apparently distressed and hypoxic at birth, there may have been precedent damage or anomaly unrelated to hypoxia.

Redistribution of blood flow in response to fetal hypoxia affects non-CNS organs acutely. Neurologic damage is not the only sublethal result of intrauterine fetal hypoxemia. It is well known that the lungs, kidney, and gastrointestinal tract are also sensitive to hypoxic ischemia and that newborn sequelae may result; however, nonneurologic damage usually repairs itself (62).