The delivery of a clinically depressed or nonvigorous infant all too often results in a reflex diagnosis of acute birth asphyxia or acute intrapartum asphyxia. This is most unfortunate as these diagnoses carry an implication of mismanagement by the obstetric team during the intrapartum period by a failure to either make a timely diagnosis or to affect a timely delivery. One study1 shows that the potential for misclassification and misdiagnosis of birth asphyxia is enormous as the diagnosis relies on a combination of: 1) clinical markers for fetal distress, 2) laboratory markers, and 3) the newborn status. Although equivalence is often afforded to each of these areas, no data exist to support their equivalence or specificity as markers for intrapartum asphyxia. What is often referred to as acute birth asphyxia or acute intrapartum asphyxia should more accurately be termed neonatal encephalopathy—a clinically defined syndrome of disturbed neurologic function in the infant at or near term during the first week after birth, manifested by difficulty with initiating and maintaining respirations, depression of tone and reflexes, altered level of consciousness, and often seizures.2,3 It is well demonstrated that neonatal encephalopathies are seldom the result of intrapartum hypoxia or ischemia, but instead have their origins in either the antepartum period or postnatal period.2 For instance, Nelson et al4 have demonstrated the poor predictive value for neonatal encephalopathy with resultant cerebral palsy for one of the most commonly cited markers of “birth asphyxia”: significant abnormalities in the intrapartum fetal heart rate tracing. In this regard, the presence of multiple late decelerations and/or persistent decreased beat-to-beat variability had a false-positive predictive rate for subsequent development of cerebral palsy of 99.8%.4 Further, Blair and Stanley1 estimated that in only 8% of all the children with spastic cerebral palsy was intrapartum asphyxia even a possible cause of their brain damage. Similarly, the international consensus statement5 noted that epidemiologic studies suggest that in about 90% of cases of cerebral palsy, intrapartum hypoxia could not be the cause of cerebral palsy; and in the remaining 10%, intrapartum signs compatible with damaging hypoxia may have had either antenatal or intrapartum origins.
To await a definitive diagnosis of cerebral palsy to retrospectively determine what was a significant intrapartum event significantly time limits the use of the classification system proposed in the international consensus statement.5 Accordingly, the objective of this study was to identify the proportion of major organ system injuries in cases of acute intrapartum asphyxia sufficient to result in neonatal encephalopathy. It is recognized and appreciated that development of cerebral palsy of the spastic quadriplegic or dyskinetic type is a more stringent endpoint than that adapted for this analysis. Our hypothesis is that an intrapartum event sufficient to result in neonatal encephalopathy will result in multiple organ systems injury in the majority of cases.
MATERIALS AND METHODS
A prospectively maintained neonatal database was queried to identify all diagnoses of acute intrapartum asphyxia, acute birth asphyxia, or neonatal encephalopathy from January 1, 1994, to January 1, 2000, at the University of Texas Medical Branch at Galveston. The study was approved by the University of Texas Medical Branch institutional review board. This data set was cross-referenced using diagnostic coding in medical records. Maternal and neonatal records were then hand extracted for detailed information concerning the antepartum, intrapartum, postpartum, and neonatal course; and a computerized data set was established. Timing of occurrence of the acute event was emphasized.
Criteria used to define an acute intrapartum hypoxic event were as follows:
- a sentinel (signal) hypoxic event occurring during or immediately preceding labor, such as placental abruption or an umbilical cord prolapse,
- a sudden, rapid, and sustained deterioration of the fetal heart rate pattern, usually after the hypoxic sentinel event where the pattern was previously normal, or an obvious and acute catastrophic event evident immediately upon presentation,
- early onset of neonatal encephalopathy in infants ≥32 weeks' gestational age, and
- absence of a severe congenital abnormality that would impact transition from fetal to neonatal life.
All four criteria were required to make the diagnosis of an acute intrapartum event sufficient to result in neonatal encephalopathy. Neonatal encephalopathy was defined clinically as a syndrome of disturbed neurologic function in the infant at or near term during the first week after birth, manifested by difficulty with initiating and maintaining respirations, depression of time and reflexes, altered level of consciousness, and often seizures.2,3 This diagnosis was always made or confirmed by the attending neonatologist.
Because of the time course of this report (concentrating on defining a significant acute asphyxial event either intrapartum or immediately preceding delivery sufficient to result in neonatal encephalopathy), it was impractical to use spastic quadriplegia or dyskinetic cerebral palsy as criteria. Rather, the question that we sought to answer was: Given an acute intrapartum asphyxial event sufficient to result in neonatal encephalopathy of the term or near-term infant, how often will various organ systems reflect injury patterns using commonly available laboratory tests and/or imaging technologies?
The following definitions for organ system injury were used:
- Central nervous system (CNS) injury was diagnosed clinically as previously defined. Objective confirmatory evidence included electroencephalogram or neuroimaging abnormalities. Ultrasound, computed tomography, and magnetic resonance imaging studies were interpreted per the neuroradiologist and neonatologist. Among the factors evaluated on imaging studies were the presence or absence of cerebral edema, abnormalities of the basal ganglia, and/or intracranial bleeding.
- Hepatic injury was diagnosed based on elevation of aspartate transaminase, alanine transaminase, or lactic dehydrogenase to 1.5 × the upper control level with subsequent resolution of the abnormality.
- Cardiac injury was diagnosed on the need for pressor agents beyond 2 hours of life. Use of volume or pressors for acute resuscitation or within 2 hours of birth was not considered evidence of injury. Elevation of the creatinine kinase MB isoenzyme was also considered evidence of cardiac injury.
- Hematologic injury was defined as the development of early thrombocytopenia (≤100,000) in the absence of significant evidence for infection or the diagnosis of alloimmune or isoimmune thrombocytopenia or an increase in the nucleated red blood cell count to ≥26 per 100 white blood cells.6
- Renal injury was defined as an elevation in the serum creatinine to ≥1.0 mg% with subsequent return to normal. Oliguria, as defined by the neonatologist, that persisted for greater than 24 hours or persistent hematuria or proteinuria were also considered diagnostic for renal injury.
Statistical analysis of the results was reported via Epistat 5.0 (Epistat Services, Richardson, TX).
A total of 129 newborns were identified with the diagnosis of either acute intrapartum asphyxia, acute birth asphyxia, or neonatal encephalopathy. Five cases were excluded for insufficient data. Seventy cases were excluded as they failed to meet one of the four essential criteria. Of the remaining 54 cases that sustained an acute intrapartum asphyxial episode, eight were excluded because of gestational ages of less than 32 weeks. The remaining 46 patients are the subjects of this report.
Of the 46 patients included, the mean maternal age was 25.9 ± 5.86 years with a range of 16 to 39. Mean gravidity was 2.65 ± 1.72, and mean parity was 2.11 ± 1.34. The racial distribution was 16 white, 12 black, and 18 Hispanic women; this distribution mirrored our general population.
Table 1 demonstrates the percentage of neonates who developed laboratory or imaging evidence of organ system injury to the cardiac, central nervous, hematologic, hepatic, or renal system within the first 5 days of life. In every organ system, injury was more likely to occur than not to occur. In Table 2, the precise laboratory and/or imaging evidence of organ system injury in these 46 cases of acute intrapartum asphyxia that was sufficient to result in neonatal encephalopathy is listed. Table 3 shows umbilical cord arterial blood pH and base excess levels as well as Apgar scores of less than 6 at beyond 5 minutes.
Evidence of multiple organ system damage was the overwhelming rule, and not the exception, in this cohort of 46 cases of clearly demonstrated acute intrapartum asphyxia with resultant neonatal encephalopathy. Combinations of laboratory and imaging studies demonstrated involvement of the renal, hepatic, central nervous, and cardiac systems in over 70% of cases. The least likely organ system to show injury was the hematologic system, and even here, 54% of neonates showed evidence of injury.
We emphasize that the endpoint for this study was the development of neonatal encephalopathy with supporting evidence that the encephalopathy was secondary to an acute intrapartum event. This required presentation of a patient with an obvious acute obstetric catastrophe of recent onset, such as a placental abruption, umbilical cord prolapse, or the deterioration of a fetal heart rate pattern that previously had been normal. Important exclusion criteria were gestational age of less than 32 weeks or the presence of a significant congenital abnormality that would impact transition from fetal to neonatal life.
When umbilical arterial blood gases were analyzed, in 67% of patients the pH was less than 7.0, and in 75% the base excess was greater than −12 mEq/L. Although it varied, severe acidemia was the usual occurrence. Similarly, 83% of infants had Apgar scores of less than 6 beyond 5 minutes of age. In this regard, these three parameters would seem to carry approximately the same predictive value as the evidence of organ system injury to the neonate. These findings are entirely consistent with the fact that a significant intrapartum event can occur, followed by partial recovery of the acute metabolic condition as measured at the moment of birth, yet still result in significant organ system injury to the fetus while in utero. Accordingly, it would appear from these data that the parameters of Apgar score and acidemia should carry no more nor less weight than evidence of organ system damage in defining injurious asphyxia.
In conclusion, when an infant presumed to be normal upon entering the intrapartum period is subsequently born with or develops an encephalopathy in the early neonatal period, the term “birth asphyxia” should be reserved for those cases meeting the essential criteria that we and others have outlined.5 Acute intrapartum asphyxia sufficient to result in neonatal encephalopathy will most often result in multiple organ system injury. The absence of evidence of such injury is inconsistent with the diagnosis of significant intrapartum asphyxia.
1. Blair E, Stanley F. Intrapartum asphyxia: A rare cause of cerebral palsy. J Pediatr 1988;112:515–9.
2. Badawi N, Kurinczuk JJ, Keogh JM, Alessandri LM, O'sullivan F, Burton PF, et al. Antepartum risk factors for newborn encephalopathy: The Western Australian case-control study. BMJ 1998;317:1549–53.
3. Badawi N, Kurinczuk JJ, Keogh JM, Alessandri LM, O'sullivan F, Burton PF, et al. Intrapartum risk factors for newborn encephalopathy: The Western Australian case-control study. BMJ 1998;317:1554–8.
4. Nelson KB, Dambrosia JM, Ting TY, Grether JK. Uncertain value of electronic fetal monitoring in predicting cerebral palsy. N Eng J Med 1996;334:613–8.
5. MacLennan A. A template for defining a causal relation between acute intrapartum events and cerebral palsy: International consensus statement. BMJ 1999;319:1054–9.
6. Green DW, Mimouni F. Nucleated erythrocytes in healthy infants and in infants of diabetic mothers. J Pediatr 1990; 116:129–31.