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Failure to prevent cerebral palsy (CP) is the most common cause of lawsuits filed against obstetricians and results in the largest jury awards. Many an obstetrical care provider has felt the wrath of a jury for not "divining" some subtle feature on a fetal heart rate (FHR) tracing as ominous and immediately performing a cesarean delivery. The truth is that despite the "miracles" of modern medicine, including antepartum and intrapartum FHR testing, we have little or no ability to prevent most cases of CP.
First, only 4% of all cases of neonatal encephalopathy, an obligatory precursor to CP due to intrapartum asphyxia, are solely caused by intrapartum events, with another 25% attributable to both antepartum and intrapartum events.1 More frustrating is the observation that by the time antepartum testing reveals a clearly abnormal pattern, it is often too late to prevent an adverse outcome. In one study, perinatal mortality and neurological handicap rates were 28% and 27%, respectively, for fetuses displaying nonreactive positive contraction stress tests.2 Conversely, 99% of nonreassuring FHR patterns are not associated with CP.3 Most telling, randomized trials of intrapartum fetal monitoring have failed to show a decrease in abnormal neurological outcomes.4
The truth is that CP defies Occam's Razor, given its multiple, synergistic, and often unpreventable etiologies. Cognizant of the dilemma faced by obstetrical care providers, Dr. Frank Miller, then president of the American College of Obstetricians and Gynecologists appointed a Task Force on Neonatal Encephalopathy and Cerebral Palsy that was charged with collating and reviewing the best scientific data available on the topic and publishing its findings.5 The task force's final report was co-authored with the American Academy of Pediatrics, and endorsed by the National Institute of Child Health and Human Development, the Centers for Disease Control and Prevention, the Society for Maternal-Fetal Medicine, the Society of Obstetricians and Gynaecologists of Canada, and the Royal Australian and New Zealand College of Obstetricians and Gynecologists, among others.
The report provides a backdrop for considering CP, noting that while CP has many causes it cannot be attributed to intrapartum "asphyxia" in the absence of newborn encephalopathy. On the other hand, newborn encephalopathy, rather loosely defined as a combination of abnormal consciousness, tone and reflexes, feeding, respiration, or seizures, can be due to myriad causes other than intrapartum asphyxia and does not invariably result in CP. The report also notes that hypoxic-ischemic encephalopathy (HIE) is a better term than intrapartum asphyxia, and that the incidence of neonatal encephalopathy due to HIE is very low: 1.6 per 10,000 births.5 Moreover, while 70% of infants with rigorously defined HIE may develop CP, only 10% of CP cases follow intrapartum HIE.
The report points out that CP is a collection of disorders characterized by "a chronic disability of central nervous system origin characterized by aberrant control of movement and posture, appearing early in life and not as a result of progressive neurologic disease." Of the various forms of CP, only spastic quadriplegia, especially when associated with a movement disorder, can be due to neonatal encephalopathy. In contrast, spastic diplegia usually results from prematurity-related periventricular leukomalacia (PVL) while spastic hemiplegia usually results from a stroke due to venous thromboembolism. The report notes that absent the presence of CP, neither epilepsy, mental retardation, nor attention-deficit hyperactivity disorder are caused by HIE.
What are the causes of the 96% of cases of newborn encephalopathy that are not solely due to intrapartum HIE? The most important antepartum risk factors cited include: maternal age over 30 years, maternal thyroid disease, preeclampsia, gestational age greater than 41 weeks and birthweight lower than the 3rd percentile, each of which has an adjusted odds ratio greater than 6.0. Recent attention has focused on inflammation and thrombophilia-induced thrombosis as causes of CP. While inflammation and thrombosis are now appreciated as major causes of prematurity (see the March and April 2003 editorials) which is itself a major risk factor for CP, inflammation and thrombosis also appear to be independent risk factors for CP in both preterm and term infants. Additional risk factors include multifetal pregnancies with rates of CP of 7 per 1,000 in twins, 80 per 1,000 in triplets, and nearly 50% in quadruplets! Here again, prematurity is the major contributor to CP but monozygozity, monochorionic disorders of shared circulation, impairment in growth, and aberrant placentation (e.g., vasa-previa) also play independent roles. Finally, a host of fetal genetic disorders can present as neonatal encephalopathy and mimic HIE. These include metabolic, neurodegenerative, and chromosomal disorders.
The task force's report attempts to define the duration of the hypoxic/acidotic insult required to induce intrapartum HIE. Based on catastrophic events, such as umbilical cord prolapse, uterine rupture, and shoulder dystocia, it appears that HIE develops 17 minutes after a catastrophic event in a previously normal fetus, but in as little as 10 minutes if such an event follows a period of severe late decelerations. Both time intervals suggest that in many cases, it will be impossible to prevent HIE caused by acute catastrophic intrapartum events, particularly in a low-volume, rural, obstetrical setting.
What, then, are the essential criteria for defining CP due to intrapartum HIE? Historical risk factors such as meconium-stained amniotic fluid, low Apgar scores, and as noted above, nonreassuring FHR tracings are not at all specific for the diagnosis. Indeed, since 70% of neonatal encephalopathy is not at all attributable to intrapartum HIE, the task of defining criteria is formidable. First, antepartum ischemia, thrombosis, and infection, as well as trauma, cerebral malformation, and genetic conditions must be excluded by detailed placental histologic and microbial examinations, neonatal CNS imaging studies, a thrombophilia work-up on the child, an exhaustive maternal history, and an evaluation by a geneticist with karyotype and metabolic studies as indicated. Here, then, are the criteria defined by the task force as evidence that an acute intrapartum HIE was sufficient to have caused CP:
Essential criteria (must meet all four):
1. evidence of a metabolic acidosis in fetal, umbilical cord arterial blood obtained at delivery (pH <7.00 and base deficit >12 mmol/L);
2. early onset of severe or moderate neonatal encephalopathy in infants born at 34 or more weeks' gestation;
3. CP of the spastic quadriplegic or dyskinetic type*;
4. exclusion of other identifiable etiologies such as trauma, coagulation disorders, infectious conditions, or genetic disorders.
Criteria that collectively suggest intrapartum timing with close proximity to labor and delivery, that is, 0 to 48 hours but are nonspecific to asphyxial insult include:
A. a sentinel (signal) hypoxic event occurring immediately before or during labor;
B. a sudden and sustained fetal bradycardia or the absence of FHR variability in the presence of persistent, late, or variable decelerations, usually after an hypoxic sentinel event when the pattern was previously normal;
C. Apgar scores of 0 to 3 after 5 minutes;
D. onset of multisystem involvement within 72 hours of birth; and
E. early imaging study showing evidence of acute nonfocal cerebral abnormality.
While the task force report has a number of limitations, including a somewhat unclear discussion of the association between thrombophilia and protein C levels (page 18), it does recognize the need for more research and for constantly updating the scientific database of HIE, neonatal encephalopathy, and CP.
All in all, Dr. Gary Hankins, the task force's chair, and its other members are to be congratulated on producing a clear, concise, and precise assessment of the causes of CP. The task force's findings are lucid, provocative, and "must" reading for all obstetrical care providers. The report points out the grave limitation in our current ability to prevent the vast majority of cases, underscores our collective frustration in not being able to better prevent this dreaded outcome, and reinforces the anger of many obstetrical care providers at being held accountable for not performing miracles.
1. Badawi N, Kurinczuk JJ, Keogh JM, et al. Intrapartum risk factors for newborn encephalopathy: The Western Australian case-control study. BMJ. 1998;317:1554-1558.
2. Beischer NA, Drew JH, Ashton PW, et al. Quality of survival of infants with critical fetal reserve detected by antenatal cardiotocography. Am J Obstet Gynecol. 1983;146:662-670.
3. Nelson KB, Grether JK. Potentially asphyxiating conditions and spastic cerebral palsy in infants of normal birth weight. Am J Obstet Gynecol. 1998;179:507-513.
4. Grant A. Epidemiological principles for the evaluation of monitoring programsthe Dublin experience. Clin Invest Med. 1993;16:149-158.
5. Neonatal encephalopathy and cerebral palsy: defining the pathogenesis and pathophysiology. The American College of Obstetricians and Gynecologists, January 2003.
*Spastic quadriplegia and, less commonly, dyskinetic CP are the only forms associated with acute, intrapartum HIE; however, spastic quadriplegia can also be caused by other conditions. Hemiparetic CP, hemiplegic CP, spastic diplegia, and ataxia are unlikely results from acute, intrapartum HIE.
Charles J. Lockwood, MD
Charles Lockwood. Editorial: Educating ourselves and the public about cerebral palsy. Contemporary Ob/Gyn May 1, 2003;48:12, 15.