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Does asphyxia cause cerebral palsy?
Does Asphyxia Cause Cerebral Palsy? E. Rebecca Pschirrer and Edward R. Yeomans
The incidence of cerebral palsy is 1 per 1,000, whereas the proportion caused by perinatal asphyxia is only 8% to 10%. The purpose of this article is to review the relationship between asphyxia and cerebral palsy. Only a minority of cases, those involving severe pathological fetal academia, are consistently associated with neonatal encephalopathy and an increased risk of cerebral palsy.
Copyright 9 2000 by W.B. Saunders Company xamination of the link between asphyxia
E and cerebral palsy (CP) would be facilitated
by a clear definition o f asphyxia as well as unequivocal ascertainment of a case of CP. Regrettably, review of the p e r t i n e n t literature permits neither to be achieved. This is further complicated by the fact that the surrogates for asphyxia used are, at best, p o o r stand-ins for a definitive diagnosis. The p u r p o s e of this review is to examine the evidence that asphyxia causes or is at least associated with CP in full-term infants. Surrogates for asphyxia can be a r r a n g e d along a time line f r o m conception to diagnosis of CP (Table 1). T h e closer o n e gets to the right e x t r e m e of the timeline, the stronger the association between the event and the diagnosis of CP appears. The a r g u m e n t has b e e n p r o m u l g a t e d that asphyxia results in CP only in cases where n e w b o r n e n c e p h a l o p a t h y is present. Certainly there is a relationship between CP and asphyxia, however, it is clear in reviewing the data that the relationship between the two is not so strong as the lay public, and even those in the medical profession believe. In m o r e than 75% of cases of CP a single identifiable cause c a n n o t be elucidated. It is a c o m m o n belief a m o n g patients, attorneys, a n d obstetricians that CP is caused by i n t r a p a r t u m asphyxia, despite data indicating that most children diagnosed with CP did not have asphyxia. Conversely, most asphyxiated babies do n o t develop CPA Only 8% to 10% o f cases of CP can be attributed to i n t r a p a r t u m asphyxiaY This does not imply that the obstetrician was negligent in the 8% to 10% of CP cases where asphyxia was possibly cause. A study published by Nelson and Ellenberg 3 e x a m i n e d the antecedents of CP in 189 children. Twenty-one p e r c e n t (40) of these children h a d at least 1 clinical m a r k e r suggestive of asphyxia, whereas 79% had no markers of as-
phyxia. O f the 40 with at least 1 marker, m o r e than half had a m a j o r congenital malformation.
Markers of Asphyxia An a b n o r m a l score on the biophysical profile may be a m a r k e r for antenatal fetal asphyxia. Surrogates for asphyxia during labor include various fetal heart rate (FHR) abnormalities and m e c o n i u m staining of the amniotic fluid. I m m e diate markers o f asphyxia that have b e e n used after birth include low Apgar scores and umbilical artery acidemia. Neonatal markers that have b e e n used include early onset seizures and newb o r n encephalopathy. O t h e r potential newborn markers being studied include nucleated red blood cells and urinary lactate:creatinine spect r o p h o t o m e t r i c ratio.
Antenatal Asphyxial Markers The fetal biophysical profile score (BPS) is a test designed to assess a n t e p a r t u m fetal well being, and is a reflection of antenatal acid-base status. 4 A retrospective study recently examined the incidence of CP in w o m e n with high-risk pregnancies, who received antenatal testing via the BPS, and women, b o t h low- and high-risk, who did not have antenatal testing. 5 T h e population included 26,290 live births who had received antenatal testing, of which 35 children were subsequently diagnosed with CP, for an incidence o f CP of 1.33 per 1,000 live births. In the untested From the Department of Obstetrics, Gynecology, and Repwductive Sciences, University of Texas-Houston Medical School, Houston, TX. Address reprint requests to Edward R. Yeomans, MD, Associate Professor, 5656 Kelley, LBJ Hospital, Department of OB-GYN, Houston, TX 77026. Copyright 9 2000 by W.B. Saunders Company O146-0005/00/2403-0005510. 00/0 doi: l O.1053/sper.2000. 7080
Seminars in Perinatology, Vol 24, No 3 (June), 2000: pp 215-220
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TaMe 1. Surrogates for Asphyxia Depicted Along the Timeline From Conception to the Diagnosis of Cerebral Palsy Conception
Antepartum
Intrapartum
Immediate Postpartum
Neonatal Period
Infancy and Childhood
Antenatal testing: Fetal heart rate Nuchal cord Newborn Cerebral biophysical profile encephalopathy palsy Meconium Apgar Umbilical cord blood gas Nucleated RBCs Lactate:Creatinine ratio
population, the incidence of CP was 4.74/1,000 live births, or 278 cases of CP f r o m 58,659 live births. T h e incidence of CP in the tested population was significantly less (P < .05) than that of the untested population. T h e r e were no significant differences in m e a n gestational age at delivery or birthweight in the tested and untested populations. T h e study also revealed a significant inverse correlation between last fetal BPS a n d subseq u e n t d e v e l o p m e n t of CP. If the last BPS perf o r m e d yielded a n o r m a l score (8/10, 8/8, or 10/10) the incidence of CP was 0.7/1,000; with an equivocal score (6/10) the incidence of CP was 13.1/1,000; with an a b n o r m a l score (4/10, 2 / 1 0 or 0 / 1 0 ) the incidences were 22.1/1,000, 146.3/1,000, and 333/1,000, respectively. It is i m p o r t a n t to note that the majority of newborns with a b n o r m a l scores did not have CP. T h e investigators postulate that the reduction in the incidence of CP a m o n g high-risk w o m e n referred for biophysical profile testing is attributable to altered m a n a g e m e n t on the basis of test score result. The investigators further acknowledge the limitations of this retrospective study, as well as the challenge of conducting the appropriate, and necessary, prospective studies. Asphyxial Markers During Labor FHR abnormalities have b e e n identified as a m a r k e r for asphyxia during labor. O n e of the most p r o f o u n d abnormalities is fetal bradycardia. T h e Collaborative Perinatal Project identified 1.3% of its population as having h a d a significant fetal bradycardia during monitoring, with a F H R -----60 beats p e r minute. 6 These infants h a d an increased risk of CP, with a relative risk of 2.9. Ninety percent of survivors who h a d p r o l o n g e d bradycardia however, did not develop CP.
Electronic F H R m o n i t o r i n g (EFM) has not led to a decrease in the n u m b e r of children with CpT; recently, a trend toward a rise in the frequency of CP has b e e n d o c u m e n t e d , s EFM during labor in low-risk pregnancies has led to an increase in the cesarean and operative vaginal delivery rates, but not to a d o c u m e n t e d improvem e n t in neonatal outcomes. If cesarean delivery decreased neurological morbidity t h e n such an increase would be warranted. However, a study p e r f o r m e d by Scheller and Nelson has shown that cesarean delivery does not decrease the risk of CP. ~ Nelson a n d colleagues identified a cohort of 95 children with m o d e r a t e to severe CP b o r n between 1983 and 1985, f r o m a population of 155,636 live births. 1~ T h e prevalence of CP a m o n g children who survived until 3 years of age was 1.1 per 1,000 live births. A case control study e x a m i n e d the EFM records of 78/95 children with CP and 300/378 r a n d o m l y chosen controls. Twenty-one of the children who later developed CP had late decelerations or decreased variability during labor. These 21 children with CP represent 0.19% of the total m o n i t o r e d population with a b n o r m a l fetal heart tracings (10,791). A m o n g children without CP, 9.3% (28/300) had late decelerations or diminished variability during labor. In a population of 100,000 liveborn children at term, one would expect 9,300 or 9.3% to have multiple late decelerations o r decreased beat-to-beat variability. A m o n g those with a b n o r m a l fetal heart rate tracings only 18 children would subsequently be diagnosed with CP. Therefore, this study reveals a 99.8% falsepositive rate in the ability of EFM to diagnose asphyxia of significant severity to cause CP. T h e Dublin r a n d o m i z e d trial of i n t r a p a r t u m m o n i t o r i n g c o m p a r e d EFM with intermittent auscultation (IA). 11 T h e initial study r e p o r t e d
Does Asphyxia Cause CerebralPalsy
that fetal blood acid-base assessment, cesarean delivery for low pH, a n d operative vaginal delivery were peIs m o r e frequently in the EFM group. T h e r e were no differences between groups with regard to neonatal mortality, however the EFM g r o u p was less likely to have neonatal seizures. A follow-up study to the Dublin EFM trial on the long-term neurological o u t c o m e of survivors o f neonatal seizures e x a m i n e d 9 children f r o m the EFM group a n d 21 in the IA group. 12 T h r e e children f r o m each g r o u p were diagnosed with CP by 4 years of age. O n e o t h e r child f r o m the EFM g r o u p who had neonatal neurological abnormalities o t h e r than seizure was also f o u n d to have a diagnosis of CP. T h e r e were 15 additional children without a history of neonatal neurological morbidity diagnosed with CP; all of these children had uneventful i n t r a p a r t u m and neonatal courses. O f these children without n e o n a tal morbidity, 8 children h a d b e e n in the EFM group, and 7 in the IA group. In total, 12 cases of CP were identified in the EFM group, and 10 in the IA group. T h e investigators conclude that although their study does n o t rule out a protective effect of EFM on the subsequent diagnosis of CP, any such effect must be modest. W h e n considering the impact of EFM on the incidence of CP, the question arises of w h e t h e r a change in m a n a g e m e n t during labor would affect neurological outcome. A study by Phelan et al reviewed the EFM strips of 209 neurologically i m p a i r e d full-term infants, is Seventy-five p e r c e n t (156) were classified as nonpreventable: persistent nonreassuring F H R tracing (90), reactive with a p r o l o n g e d deceleration (46), bradycardia on admission to labor and delivery (6), a n d reactive tracing (14). Twenty-five p e r c e n t (53) of the strips d o c u m e n t e d an abnormality arising d u r i n g the course o f labor. R i c h m o n d et al e x a m i n e d the relationship between obstetric m a n a g e m e n t of fetal distress a n d CP in a retrospective, case-control study, a4 T h e Dublin study criteria were used to define nonreassuring F H R for labors m o n i t o r e d with EFM and IA. Evaluation of appropriateness of response was p e r f o r m e d i n d e p e n d e n t l y by 2 observers, following prescribed criteria. W h e n different conclusions were reached, a j o i n t assessm e n t was p e r f o r m e d . Seventy children with CP were evaluated in the case group, of which 49 were full-term, and there were 532 controls, with
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502 full-term infants. Fetal distress at term was identified in 12/49 o f the children with CP (24%); 53/502 in the control g r o u p (11%). An inappropriate response to fetal distress was felt to have occurred in 6 / 7 0 infants with CP a n d 17/502 controls. Conversely, 91% of the infants with fetal distress in the case group received a p p r o p r i a t e obstetric m a n a g e m e n t . Examining only full-term pregnancies, there was an inappropriate response to fetal distress in 6 / 4 9 cases (12%), and 17/502 controls (3%). The investigators concluded that the complete elimination of fetal distress, (accepting for the m o m e n t the supposition that fetal distress "causes" CP), would reduce the overall prevalence of CP by only 15.6%. F u r t h e r m o r e , they argue that "perfect" obstetric m a n a g e m e n t would reduce the prevalence of CP by only 9% in term infants. Finally, they infer that fetal distress may in fact be a m a r k e r for prior fetal brain damage, not a h a r b i n g e r of brain d a m a g e to come. Nonreassuring F H R patterns are t h o u g h t to be reflective of fetal c o m p r o m i s e , possibly a surrogate for asphyxia. T h e majority of fetuses with nonreassuring tracings are neurologically intact, as evidenced by the high false-positive rate of EFM. Niswander, in a review of the literature, concluded that EFM plays a small role in preventing neurological deficits, but that it would be foolish to assume it c a n n o t prevent at least some cases of CP. 15 M e c o n i u m is frequently cited as a sign of fetal stress, whether intra- or peripartum. Studies have failed to identify a correlation between m e c o n i u m stained amniotic fluid and perman e n t neurological sequelae. O f newborns weighing greater than 2,500 grams with m e c o n i u m stained fluid, 99.6% did n o t develop CP. 16,17 F u r t h e r m o r e , there a p p e a r s to be little correlation between umbilical cord acid-base status and m e c o n i u m stained amniotic fluid, is Asphyxial Markers at Birth T h e Apgar score was originally used as a rapid m e t h o d of assessing the n e e d for newborn resuscitation, t9 Over time it has b e e n misused as a sole criterion to define n e w b o r n asphyxia. Indeed, the International Classification of Diseases (ICD)-9 coding system defines mild birth asphyxia as a 1-minute Apgar score of 4-6, a n d severe birth asphyxia as a 1-minute score of -<3.
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N u m e r o u s studies have b e e n published which indicate that the 1- a n d 5-minute Apgar scores are p o o r predictors of future neurological outcome. F r e e m a n and Nelson conclude that a low 1-minute Apgar score in and of itself does not indicate that significant hypoxia has occurred, a n d is of little "prognostic significance. "2~ A study by Nelson and Ellenberg revealed that 55% of children with CP h a d I-minute Apgar scores >--7. O f children with no CP at 7 years of age, 5% had Apgar scores <--3 and 14% had scores of 4 to 6. 21 All children e x a m i n e d with CP and Apgar scores -<3 at 1-minute had persistently low scores at later times. T h e 5-minute Apgar score also fails to predict long-term outcome. O f children e x a m i n e d with CP, 15% h a d a 5-minute Apgar -<3, whereas 73% of children with CP h a d 5-minute Apgar scores . -->7.21 Apgar scores evaluated at 10-minutes were m o r e predictive of outcomes: 17% of infants with scores --<3 h a d CP, but this n u m b e r decreased to 4.7% if the Apgar score increased at 15 to 20 minutes. Most newborns with scores -<3 who survived did well. Severely depressed scores (--<3) at 15 a n d 20 minutes were associated with a 53% and 59% mortality and 36% a n d 53% incidence of CP, respectively. Because Apgar scores are p o o r predictors of adverse neurological outcome, some investigators have suggested the use of fetal acid-base status as a m o r e objective predictor. Acidosis is defined by the umbilical cord b l o o d gas obtained immediately postnatally. Historically, acidosis was defined as an umbilical artery (Ua) p H < 7.20. This was obviously too high to serve as a cutoff. Gilstrap and colleagues f o u n d a good correlation between immediate neurological o u t c o m e a n d Apgar scores -<3 and U~ p H < 7.00 with a metabolic c o m p o n e n t . 22 In an a t t e m p t to define pathological fetal acidemia m o r e precisely, G o l d a b e r and colleagues evaluated 3,506 t e r m infants with U~ p H < 7.20. 23 Eighty-seven infants h a d U~ p H < 7.00. Two-thirds of the infants with Ua p H < 7.00 h a d a metabolic component. Significantly m o r e infants with low p H had c o n c u r r e n t low 1- and 5-minute Apgar scores (-<3), and significantly m o r e neonatal deaths o c c u r r e d in this group. Winkler and associates e x a m i n e d 358 term infants with U~ p H < 7.20. Neurological dysfunction a n d endo r g a n d a m a g e occurred only in infants with U~ p H < 7.00 a n d 1- and 5-minute Apgar scores
-<3. 24 In a review of 129 term births associated with U a p H < 7.00, the incidence of encephalopathy was 31%. Seizures o c c u r r e d in 9% of infants with Ua p H between 6.90 and 6.99, and 80% with U~ p H between 6.61 and 6.70. T h e r e were 3 stillbirths and 5 neonatal deaths in this populationY 5 T h e degree of metabolic acidosis is m e a s u r e d by the umbilical artery base deficit. Metabolic acidosis occurs as the tissue oxygen deficit increases in duration, reflecting hypoxia or impaired blood gas exchange of significant duration to allow the accumulation of fixed acids. In a study by Low and colleagues, the threshold of metabolic acidosis associated with n e w b o r n morbidity in the central nervous, respiratory, cardiovascular, and renal systems was examinedY 6 A significant increase in m o d e r a t e a n d severe enc e p h a l o p a t h y and respiratory complications was n o t e d with an umbilical artery base deficit > 1 6 mmol/L. Nagel and associates p e r f o r m e d a follow-up study of infants b o r n with significant acidosis. 27 O f 1,614 term deliveries, 30 (2%) h a d U~ p H < 7.00. O f these 30 infants, 77% were a d m i t t e d to the newborn intensive care unit (NICU), and 27% required v e n t i l a t o r / s u p p o r t . T h r e e infants had mild hypertonia on follow-up examination, 1 h a d mild m o t o r d e v e l o p m e n t delay, a n d there were 2 neonatal deaths. Van den Berg and colleagues evaluated 10,699 births and f o u n d an incidence of U a p H < 7.00 of 1.3%. 2s Twenty-seven p e r c e n t of infants with Ua p H between 6.80 a n d 7.00 had no identifiable morbidity. Fifteen of 16 infants with neurological dysfunction h a d a significant metabolic c o m p o n e n t to the acidemia, as evid e n c e d by a base deficit ->15 m m o l / L . All but 1 t e r m infant with neurological dysfunction had a U a p H < 6.90. Recently, Andres and colleagues f o u n d that neonatal morbidity was significantly greater in infants with U a p H < 6.90 c o m p a r e d with infants with Ua p H > 6.90, and that the extent of the metabolic c o m p o n e n t (bicarbonate and base deficit) was the most i m p o r t a n t variable in subsequent newborn morbidity. 29
Neonatal Asphyxial Markers I n t r a p a r t u m hypoxia causing brain i m p a i r m e n t is often associated with neonatal seizures. Sei-
Does Asphyxia Cause CerebralPalsy
zures attributable to hypoxia usually occur within the first 48 to 72 hours after birth. 3~ Infants with seizures have a 50- to 70-fold increased risk of CP, however 70% of infants with neonatal seizures do not subsequently develop CP. 31 In a study by Perlman and Risser, 96 high-risk t e r m infants admitted to the NICU were evaluated. 32 Five percent of these infants developed seizures. Factors associated with the highest risk of seizures included low 5-minute Apgar scores, respiratory depression requiring intubation, and severe fetal acidemia. In 1996, Korst a n d colleagues observed higher nucleated red blood cell (NRBC) counts in cord blood f r o m a g r o u p of neurologically i m p a i r e d infants c o m p a r e d with a control g r o u p of term nonasphyxiated newborns. -~ Recently, data obtained prospectively have b e e n published correlating the NRBC count in umbilical cord blood with n e u r o d e v e l o p m e n t a l status at age 3. 34 Infants with a b n o r m a l n e u r o d e v e l o p m e n t a l status had significantly higher NRBC counts at birth than did their normal counterparts. Further work on a data set confined to asphyxiainduced neurological i m p a i r m e n t is needed. In an attempt to identify infants at risk for encephalopathy, investigators have recently rep o r t e d their experience with the use of a ratio of lactate to creatinine in urine to differentiate n o r m a l infants f r o m infants with asphyxia, s5 T h e m e a s u r e m e n t s of urinary lactate a n d creatinine were obtained by magnetic resonance spectroscopy within 6 hours of birth. N o n e of 58 n o r m a l infants developed neonatal encephalopathy, whereas 16 of 40 infants with asphyxia went on to develop encephalopathy. The m e a n lactate: creatinine ratio in n o r m a l infants was 0.09. T h e ratio in infants who subsequently developed encephalopathy was 16.8. T h e hypothesis that intervention for infants at risk for n e w b o r n enc e p h a l o p a t h y may reduce the subsequent d e v e l o p m e n t of CP awaits further investigation.
Neonatal Encephalopathy Neonatal e n c e p h a l o p a t h y is characterized by abn o r m a l neonatal tone and reflexes , and central nervous system irritation manifested by seizure activity. The causes include asphyxia, trauma, infection, metabolic diseases of the newborn, and developmental abnormalities. ~6 Markers of acute hypoxic d a m a g e in the n e o n a t e have b e e n
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described primarily in term infants. Presentation in the infant is associated with the severity and duration of the insult, and the long-term prognosis is related to the severity of the signs in the infant. Mild e n c e p h a l o p a t h y is manifested by alterations in consciousness, hyperalertness, hyperreflexia, tachycardia, jitteriness, and dilated pupils. O n e - h u n d r e d p e r c e n t of these infants will be neurologically normal. 3<~7 Approximately 80% of infants with m o d e r a t e e n c e p h a l o p a t h y will be neurologically normal. Moderate encephalopathy is characterized by lethargy, miosis, bradycardia, hypotonia, weak suck, p o o r Moro reflex, and seizures. Finally, of those infants studied with severe n e w b o r n encephalopathy, all either died or had long-term neurological sequelae. These infants were initially stuporous, flaccid, had small, midposition pupils, either hypotonia or hyperreflexia, and absent suck, and Moro reflexes, a~
Conclusions Despite significant advances in b o t h perinatal and neonatal medicine, there has b e e n no change in the prevalence of CP over m a n y years. Moreover, the criteria to diagnose a n t e p a r t u m or i n t r a p a r t u m asphyxia are imprecise. T h e American College of Obstetricians and Gynecologists have concluded that hypoxia close to delivery severe e n o u g h to cause significant neonatal e n c e p h a l o p a t h y is associated with an umbilical artery p H < 7.00, a metabolic compon e n t to the acidosis, tow Apgar scores ( < 3 ) for m o r e than 5 minutes, multiorgan system dysfunction, and neurological sequelae. ~8 The cause of most cases of CP remains unknown, and the vast majority of cases cannot be predicted n o r prevented. Most cases of perinatal asphyxia are not followed by CP, and most CP is not associated with severe i n t r a p a r t u m asphyxia. A newborn infant who is crying at birth, who has normal Apgar scores and a n o r m a l U a pH, who feeds well and goes h o m e with m o t h e r on discharge, who ultimately has a diagnosis of CP, did not suffer i n t r a p a r t u m asphyxia or hypoxia as the cause. Conversely, infants with i n t r a p a r t u m brain d a m a g e will manifest signs and symptoms of such damage in the i m m e d i a t e newborn period.
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References 1. Niswander K: Does substandard care cause cerebral palsy? Contemp OB/GYN October 1987 2. Blair E, Stanley F: Intrapartum asphyxia: A rare cause of cerebral palsy. J Pediatr 112:515-519, 1988 3. Nelson KB, EllenbergJH: Antecedents of cerebral palsy: Multivariate analysis of risk. N EngJ Med 315-81-86, 1986 4. Vinzileos AM, Gafflaey SE, Salinger LM, et al: The relationships among the fetal biophysical profile, umbilical cord pH, and apgar scores. Am J Obstet Gynecol 157: 627-631, 1987 5. Manning FA, Bodanji N, Harman C, et ah Fetal assessment baged on fetal biophysical profile scoring: VIII. The incidence of cerebral palsy in tested and untested perinates~ Am J Obstet Gynecol 178:696-703, 1998 6. Nelson KB, EllenbergJH: Antecedents of cerebral palsy. I. Univariate analysis of risks. Am J Dis Child 139:10311038, 1985 7. Kiely J, Paneth N, Stein Z, et al: Cerebral palsy and newborn care. I. Secular trends in cerebral palsy. Dev Med Child Neurol 23:533-538, 1981 8. Jarvis SM, Holloway JS, Hey EN: Increase in cerebral palsy in normal birthweight babies. Arch Dis Childhood 60:1113-1121, 1985 9. Sheller JM, Nelson KB: Does cesarean delivery prevent cerebral palsy or other neurologic problems of childhood? Obstet Gynecol 83:624-630, 1994 10. Nelson KB, Dambrosia JM, Ting TY, et al: Uncertain value of electronic fetal monitoring in predicting CP. N EngJ Med 334:613-618, 1996 11. McDonald D, Grant A, Sheridan-Pereira M, et al: The Dublin randomized controlled trial of intraparmm fetal heart rate monitoring. Am J Obstet Gynecol 152:524539, 1985 12. Grant A, O'Brien N,Joy MT, et al: Cerebral palsy among children born during the Dublin randomized trial of intrapartum monitoring. Lancet 25:1233-1236, 1989 13. Phelan JP, Ahn MO, Korst L, et al: Is intraprtum fetal brain injury in the term fetus preventable? Am J Obstet Gynecol 174:318, 1996 14. Richmond S, Niswander K, Snodgrass CA, et al: The obstetric management of fetal distress and its association with cerebral palsy. Obstet Gynecol 83:643-646, 1994 15. Niswander K: Can electronic fetal monitoring predict neurologic damage? Ob/Gyn Report 1:128-139, 1989 16. Dijxhoorn MH, Visser GILA, Fidler VJ, et al: Apgar score, meconium, and acidemia at birth in relation to neonatal neurological morbidity in term infants. Br J Obstet Gynaecol 93:217-222, 1986 17. Nelson KB, EllenbergJH: Obstetric complications as risk factors for cerebral or seizure disorders. JAMA 251:18431848, 1984 18. Yeomans ER, Gilstrap LC, Leveno KJ, et al: Meconium in the anmiotic fluid and fetal acid-base status. Obst Gyn 73:175-178, 1989 19, Apgar V: A proposal for a new method of evaluation of the newborn infant. Curr Res Anesth Analg 32:260-267, 1953
20. Freeman JM, Nelson KB: Intrapartum asphyxia and cerebral palsy. Pediatrics 82:240-249, 1988 21. Nelson KB, EllenbergJH: Apgar scores as predictors of chronic neurologic disability. Pediatrics 68:36-44, 1981 22. Gilstrap LC, Leveno KJ, Burris J, et ah Diagnosis of birth asphyxia on tile basis of fetal pH, apgar score, and newborn cerebral dysfunction. Am J Obstet Gynecol 161:825-830, 1989 23. Goldaber KG, Gilstrap LC, Leveno KJ, et ah Pathologic fetal academia. Obstet Gynecol 78:1103-1107, 1991 24. Winkler CL, Hauth JC, Tucker JM, Owen J, Brumfield CG. Neonatal complications at term as related to the degree of umbilical artery acidemia. Am J Obstet Gynecol 164:637-641, 1991 25. Goodwin TM, Belai I, Hernandez P, et ah Asphyxial complications in the term newborn with severe umbilical acidemia, Am J Obstet Gynecol 162:1506-1512, 1992 26. LowJA, Lindsay BG, Derrick EJ: Threshold of metabolic acidosis associated with newborn complications. Am J Obstet Gynecol 177:1391-1394, 1997 27, Nagel HTC, Vandenbussche FPHA, Oepkes D, et al: Follow-up of children born with an umbilical areterial blood pH < 7. AmJ Obstet Gyneco1173:1758-1764, 1995 28. Van den Berg PP, Nelen WLDM, Jongsma HW, et al: Fetus-placenta-newborn: Neonatal complications in newborns with an umbilical artery pH < 7.00. Am J Obstet Gynecol 175:1152-1157, 1996 29. Andres RL, Saade G, Gilstrap LC, et ah Association between umbilical blood gas parameters and neonatal morbidity and death in neonates with pathologic fetal acidemia. Am J Obstet Gynecol 18!:867-871, 1999 30. Minchom P, Niswander K, Chalmers I, et ah Amecedents and outcome of very early neonatal seizures in infants born at or after term. BrJ Obstet Gynaecol 94:431-439, 1987 31. Holden KR, Mellits ED, FreemanJM: Neonatal seizures. I. Correlation of prenatal and perinatal events with outcomes. Pediatrics 70:165-176, 1982 32. PerlmanJM, Risser R: Can asphyxiated inI:ants at risk for neonatal seizures be rapidly identified by current highrisk markers? Pediatrics 97:456-462, 1996 33. Korst LM, Phelan JP, Ahn MO, et al: Nucleated red blood cells: An update on the marker for fetal asphyxia. A m J Obstet Gynecol 176:843-846, 1996 34. Buonocore G, Perrone S, Gioia D, et al: Nucleated red blood cell count at birth as an index of perinatal brain damage. A m J Obstet Gynecol 181:1500-1505, 1999 35. Huang CC, Wang ST, Chang YC, et al: Measurement of the urinary lactate: creatinine ratio for the early identification of newborn infants at risk for hypoxic-ischemic encephalopathy. N EnglJ Med 341:328-335, 1999 36. Freeman JM, Nelson KB: Intraparturn asphyxia and cerebral palsy. Pediatrics 82:240-249, 1988 37. Robertson CM, Finer NN: Terra infants with hypoxicischemic encephal0Pathy: Outcome at 3.5 years. Dev Med Child Neurol 27:473-484, 1985 38. American College of Obstetricians and Gynecologists Committee Opinion No. 138, April 1994, Utility of umbilical cord blood acid-base assessment. ACOG
The incidence of cerebral palsy is 1 per 1,000, whereas the proportion caused by perinatal asphyxia is only 8% to 10%. The purpose of this article is to review the relationship between asphyxia and cerebral palsy. Only a minority of cases, those involving severe pathological fetal academia, are consistently associated with neonatal encephalopathy and an increased risk of cerebral palsy.
Copyright 9 2000 by W.B. Saunders Company xamination of the link between asphyxia
E and cerebral palsy (CP) would be facilitated
by a clear definition o f asphyxia as well as unequivocal ascertainment of a case of CP. Regrettably, review of the p e r t i n e n t literature permits neither to be achieved. This is further complicated by the fact that the surrogates for asphyxia used are, at best, p o o r stand-ins for a definitive diagnosis. The p u r p o s e of this review is to examine the evidence that asphyxia causes or is at least associated with CP in full-term infants. Surrogates for asphyxia can be a r r a n g e d along a time line f r o m conception to diagnosis of CP (Table 1). T h e closer o n e gets to the right e x t r e m e of the timeline, the stronger the association between the event and the diagnosis of CP appears. The a r g u m e n t has b e e n p r o m u l g a t e d that asphyxia results in CP only in cases where n e w b o r n e n c e p h a l o p a t h y is present. Certainly there is a relationship between CP and asphyxia, however, it is clear in reviewing the data that the relationship between the two is not so strong as the lay public, and even those in the medical profession believe. In m o r e than 75% of cases of CP a single identifiable cause c a n n o t be elucidated. It is a c o m m o n belief a m o n g patients, attorneys, a n d obstetricians that CP is caused by i n t r a p a r t u m asphyxia, despite data indicating that most children diagnosed with CP did not have asphyxia. Conversely, most asphyxiated babies do n o t develop CPA Only 8% to 10% o f cases of CP can be attributed to i n t r a p a r t u m asphyxiaY This does not imply that the obstetrician was negligent in the 8% to 10% of CP cases where asphyxia was possibly cause. A study published by Nelson and Ellenberg 3 e x a m i n e d the antecedents of CP in 189 children. Twenty-one p e r c e n t (40) of these children h a d at least 1 clinical m a r k e r suggestive of asphyxia, whereas 79% had no markers of as-
phyxia. O f the 40 with at least 1 marker, m o r e than half had a m a j o r congenital malformation.
Markers of Asphyxia An a b n o r m a l score on the biophysical profile may be a m a r k e r for antenatal fetal asphyxia. Surrogates for asphyxia during labor include various fetal heart rate (FHR) abnormalities and m e c o n i u m staining of the amniotic fluid. I m m e diate markers o f asphyxia that have b e e n used after birth include low Apgar scores and umbilical artery acidemia. Neonatal markers that have b e e n used include early onset seizures and newb o r n encephalopathy. O t h e r potential newborn markers being studied include nucleated red blood cells and urinary lactate:creatinine spect r o p h o t o m e t r i c ratio.
Antenatal Asphyxial Markers The fetal biophysical profile score (BPS) is a test designed to assess a n t e p a r t u m fetal well being, and is a reflection of antenatal acid-base status. 4 A retrospective study recently examined the incidence of CP in w o m e n with high-risk pregnancies, who received antenatal testing via the BPS, and women, b o t h low- and high-risk, who did not have antenatal testing. 5 T h e population included 26,290 live births who had received antenatal testing, of which 35 children were subsequently diagnosed with CP, for an incidence o f CP of 1.33 per 1,000 live births. In the untested From the Department of Obstetrics, Gynecology, and Repwductive Sciences, University of Texas-Houston Medical School, Houston, TX. Address reprint requests to Edward R. Yeomans, MD, Associate Professor, 5656 Kelley, LBJ Hospital, Department of OB-GYN, Houston, TX 77026. Copyright 9 2000 by W.B. Saunders Company O146-0005/00/2403-0005510. 00/0 doi: l O.1053/sper.2000. 7080
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TaMe 1. Surrogates for Asphyxia Depicted Along the Timeline From Conception to the Diagnosis of Cerebral Palsy Conception
Antepartum
Intrapartum
Immediate Postpartum
Neonatal Period
Infancy and Childhood
Antenatal testing: Fetal heart rate Nuchal cord Newborn Cerebral biophysical profile encephalopathy palsy Meconium Apgar Umbilical cord blood gas Nucleated RBCs Lactate:Creatinine ratio
population, the incidence of CP was 4.74/1,000 live births, or 278 cases of CP f r o m 58,659 live births. T h e incidence of CP in the tested population was significantly less (P < .05) than that of the untested population. T h e r e were no significant differences in m e a n gestational age at delivery or birthweight in the tested and untested populations. T h e study also revealed a significant inverse correlation between last fetal BPS a n d subseq u e n t d e v e l o p m e n t of CP. If the last BPS perf o r m e d yielded a n o r m a l score (8/10, 8/8, or 10/10) the incidence of CP was 0.7/1,000; with an equivocal score (6/10) the incidence of CP was 13.1/1,000; with an a b n o r m a l score (4/10, 2 / 1 0 or 0 / 1 0 ) the incidences were 22.1/1,000, 146.3/1,000, and 333/1,000, respectively. It is i m p o r t a n t to note that the majority of newborns with a b n o r m a l scores did not have CP. T h e investigators postulate that the reduction in the incidence of CP a m o n g high-risk w o m e n referred for biophysical profile testing is attributable to altered m a n a g e m e n t on the basis of test score result. The investigators further acknowledge the limitations of this retrospective study, as well as the challenge of conducting the appropriate, and necessary, prospective studies. Asphyxial Markers During Labor FHR abnormalities have b e e n identified as a m a r k e r for asphyxia during labor. O n e of the most p r o f o u n d abnormalities is fetal bradycardia. T h e Collaborative Perinatal Project identified 1.3% of its population as having h a d a significant fetal bradycardia during monitoring, with a F H R -----60 beats p e r minute. 6 These infants h a d an increased risk of CP, with a relative risk of 2.9. Ninety percent of survivors who h a d p r o l o n g e d bradycardia however, did not develop CP.
Electronic F H R m o n i t o r i n g (EFM) has not led to a decrease in the n u m b e r of children with CpT; recently, a trend toward a rise in the frequency of CP has b e e n d o c u m e n t e d , s EFM during labor in low-risk pregnancies has led to an increase in the cesarean and operative vaginal delivery rates, but not to a d o c u m e n t e d improvem e n t in neonatal outcomes. If cesarean delivery decreased neurological morbidity t h e n such an increase would be warranted. However, a study p e r f o r m e d by Scheller and Nelson has shown that cesarean delivery does not decrease the risk of CP. ~ Nelson a n d colleagues identified a cohort of 95 children with m o d e r a t e to severe CP b o r n between 1983 and 1985, f r o m a population of 155,636 live births. 1~ T h e prevalence of CP a m o n g children who survived until 3 years of age was 1.1 per 1,000 live births. A case control study e x a m i n e d the EFM records of 78/95 children with CP and 300/378 r a n d o m l y chosen controls. Twenty-one of the children who later developed CP had late decelerations or decreased variability during labor. These 21 children with CP represent 0.19% of the total m o n i t o r e d population with a b n o r m a l fetal heart tracings (10,791). A m o n g children without CP, 9.3% (28/300) had late decelerations or diminished variability during labor. In a population of 100,000 liveborn children at term, one would expect 9,300 or 9.3% to have multiple late decelerations o r decreased beat-to-beat variability. A m o n g those with a b n o r m a l fetal heart rate tracings only 18 children would subsequently be diagnosed with CP. Therefore, this study reveals a 99.8% falsepositive rate in the ability of EFM to diagnose asphyxia of significant severity to cause CP. T h e Dublin r a n d o m i z e d trial of i n t r a p a r t u m m o n i t o r i n g c o m p a r e d EFM with intermittent auscultation (IA). 11 T h e initial study r e p o r t e d
Does Asphyxia Cause CerebralPalsy
that fetal blood acid-base assessment, cesarean delivery for low pH, a n d operative vaginal delivery were peIs m o r e frequently in the EFM group. T h e r e were no differences between groups with regard to neonatal mortality, however the EFM g r o u p was less likely to have neonatal seizures. A follow-up study to the Dublin EFM trial on the long-term neurological o u t c o m e of survivors o f neonatal seizures e x a m i n e d 9 children f r o m the EFM group a n d 21 in the IA group. 12 T h r e e children f r o m each g r o u p were diagnosed with CP by 4 years of age. O n e o t h e r child f r o m the EFM g r o u p who had neonatal neurological abnormalities o t h e r than seizure was also f o u n d to have a diagnosis of CP. T h e r e were 15 additional children without a history of neonatal neurological morbidity diagnosed with CP; all of these children had uneventful i n t r a p a r t u m and neonatal courses. O f these children without n e o n a tal morbidity, 8 children h a d b e e n in the EFM group, and 7 in the IA group. In total, 12 cases of CP were identified in the EFM group, and 10 in the IA group. T h e investigators conclude that although their study does n o t rule out a protective effect of EFM on the subsequent diagnosis of CP, any such effect must be modest. W h e n considering the impact of EFM on the incidence of CP, the question arises of w h e t h e r a change in m a n a g e m e n t during labor would affect neurological outcome. A study by Phelan et al reviewed the EFM strips of 209 neurologically i m p a i r e d full-term infants, is Seventy-five p e r c e n t (156) were classified as nonpreventable: persistent nonreassuring F H R tracing (90), reactive with a p r o l o n g e d deceleration (46), bradycardia on admission to labor and delivery (6), a n d reactive tracing (14). Twenty-five p e r c e n t (53) of the strips d o c u m e n t e d an abnormality arising d u r i n g the course o f labor. R i c h m o n d et al e x a m i n e d the relationship between obstetric m a n a g e m e n t of fetal distress a n d CP in a retrospective, case-control study, a4 T h e Dublin study criteria were used to define nonreassuring F H R for labors m o n i t o r e d with EFM and IA. Evaluation of appropriateness of response was p e r f o r m e d i n d e p e n d e n t l y by 2 observers, following prescribed criteria. W h e n different conclusions were reached, a j o i n t assessm e n t was p e r f o r m e d . Seventy children with CP were evaluated in the case group, of which 49 were full-term, and there were 532 controls, with
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502 full-term infants. Fetal distress at term was identified in 12/49 o f the children with CP (24%); 53/502 in the control g r o u p (11%). An inappropriate response to fetal distress was felt to have occurred in 6 / 7 0 infants with CP a n d 17/502 controls. Conversely, 91% of the infants with fetal distress in the case group received a p p r o p r i a t e obstetric m a n a g e m e n t . Examining only full-term pregnancies, there was an inappropriate response to fetal distress in 6 / 4 9 cases (12%), and 17/502 controls (3%). The investigators concluded that the complete elimination of fetal distress, (accepting for the m o m e n t the supposition that fetal distress "causes" CP), would reduce the overall prevalence of CP by only 15.6%. F u r t h e r m o r e , they argue that "perfect" obstetric m a n a g e m e n t would reduce the prevalence of CP by only 9% in term infants. Finally, they infer that fetal distress may in fact be a m a r k e r for prior fetal brain damage, not a h a r b i n g e r of brain d a m a g e to come. Nonreassuring F H R patterns are t h o u g h t to be reflective of fetal c o m p r o m i s e , possibly a surrogate for asphyxia. T h e majority of fetuses with nonreassuring tracings are neurologically intact, as evidenced by the high false-positive rate of EFM. Niswander, in a review of the literature, concluded that EFM plays a small role in preventing neurological deficits, but that it would be foolish to assume it c a n n o t prevent at least some cases of CP. 15 M e c o n i u m is frequently cited as a sign of fetal stress, whether intra- or peripartum. Studies have failed to identify a correlation between m e c o n i u m stained amniotic fluid and perman e n t neurological sequelae. O f newborns weighing greater than 2,500 grams with m e c o n i u m stained fluid, 99.6% did n o t develop CP. 16,17 F u r t h e r m o r e , there a p p e a r s to be little correlation between umbilical cord acid-base status and m e c o n i u m stained amniotic fluid, is Asphyxial Markers at Birth T h e Apgar score was originally used as a rapid m e t h o d of assessing the n e e d for newborn resuscitation, t9 Over time it has b e e n misused as a sole criterion to define n e w b o r n asphyxia. Indeed, the International Classification of Diseases (ICD)-9 coding system defines mild birth asphyxia as a 1-minute Apgar score of 4-6, a n d severe birth asphyxia as a 1-minute score of -<3.
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N u m e r o u s studies have b e e n published which indicate that the 1- a n d 5-minute Apgar scores are p o o r predictors of future neurological outcome. F r e e m a n and Nelson conclude that a low 1-minute Apgar score in and of itself does not indicate that significant hypoxia has occurred, a n d is of little "prognostic significance. "2~ A study by Nelson and Ellenberg revealed that 55% of children with CP h a d I-minute Apgar scores >--7. O f children with no CP at 7 years of age, 5% had Apgar scores <--3 and 14% had scores of 4 to 6. 21 All children e x a m i n e d with CP and Apgar scores -<3 at 1-minute had persistently low scores at later times. T h e 5-minute Apgar score also fails to predict long-term outcome. O f children e x a m i n e d with CP, 15% h a d a 5-minute Apgar -<3, whereas 73% of children with CP h a d 5-minute Apgar scores . -->7.21 Apgar scores evaluated at 10-minutes were m o r e predictive of outcomes: 17% of infants with scores --<3 h a d CP, but this n u m b e r decreased to 4.7% if the Apgar score increased at 15 to 20 minutes. Most newborns with scores -<3 who survived did well. Severely depressed scores (--<3) at 15 a n d 20 minutes were associated with a 53% and 59% mortality and 36% a n d 53% incidence of CP, respectively. Because Apgar scores are p o o r predictors of adverse neurological outcome, some investigators have suggested the use of fetal acid-base status as a m o r e objective predictor. Acidosis is defined by the umbilical cord b l o o d gas obtained immediately postnatally. Historically, acidosis was defined as an umbilical artery (Ua) p H < 7.20. This was obviously too high to serve as a cutoff. Gilstrap and colleagues f o u n d a good correlation between immediate neurological o u t c o m e a n d Apgar scores -<3 and U~ p H < 7.00 with a metabolic c o m p o n e n t . 22 In an a t t e m p t to define pathological fetal acidemia m o r e precisely, G o l d a b e r and colleagues evaluated 3,506 t e r m infants with U~ p H < 7.20. 23 Eighty-seven infants h a d U~ p H < 7.00. Two-thirds of the infants with Ua p H < 7.00 h a d a metabolic component. Significantly m o r e infants with low p H had c o n c u r r e n t low 1- and 5-minute Apgar scores (-<3), and significantly m o r e neonatal deaths o c c u r r e d in this group. Winkler and associates e x a m i n e d 358 term infants with U~ p H < 7.20. Neurological dysfunction a n d endo r g a n d a m a g e occurred only in infants with U~ p H < 7.00 a n d 1- and 5-minute Apgar scores
-<3. 24 In a review of 129 term births associated with U a p H < 7.00, the incidence of encephalopathy was 31%. Seizures o c c u r r e d in 9% of infants with Ua p H between 6.90 and 6.99, and 80% with U~ p H between 6.61 and 6.70. T h e r e were 3 stillbirths and 5 neonatal deaths in this populationY 5 T h e degree of metabolic acidosis is m e a s u r e d by the umbilical artery base deficit. Metabolic acidosis occurs as the tissue oxygen deficit increases in duration, reflecting hypoxia or impaired blood gas exchange of significant duration to allow the accumulation of fixed acids. In a study by Low and colleagues, the threshold of metabolic acidosis associated with n e w b o r n morbidity in the central nervous, respiratory, cardiovascular, and renal systems was examinedY 6 A significant increase in m o d e r a t e a n d severe enc e p h a l o p a t h y and respiratory complications was n o t e d with an umbilical artery base deficit > 1 6 mmol/L. Nagel and associates p e r f o r m e d a follow-up study of infants b o r n with significant acidosis. 27 O f 1,614 term deliveries, 30 (2%) h a d U~ p H < 7.00. O f these 30 infants, 77% were a d m i t t e d to the newborn intensive care unit (NICU), and 27% required v e n t i l a t o r / s u p p o r t . T h r e e infants had mild hypertonia on follow-up examination, 1 h a d mild m o t o r d e v e l o p m e n t delay, a n d there were 2 neonatal deaths. Van den Berg and colleagues evaluated 10,699 births and f o u n d an incidence of U a p H < 7.00 of 1.3%. 2s Twenty-seven p e r c e n t of infants with Ua p H between 6.80 a n d 7.00 had no identifiable morbidity. Fifteen of 16 infants with neurological dysfunction h a d a significant metabolic c o m p o n e n t to the acidemia, as evid e n c e d by a base deficit ->15 m m o l / L . All but 1 t e r m infant with neurological dysfunction had a U a p H < 6.90. Recently, Andres and colleagues f o u n d that neonatal morbidity was significantly greater in infants with U a p H < 6.90 c o m p a r e d with infants with Ua p H > 6.90, and that the extent of the metabolic c o m p o n e n t (bicarbonate and base deficit) was the most i m p o r t a n t variable in subsequent newborn morbidity. 29
Neonatal Asphyxial Markers I n t r a p a r t u m hypoxia causing brain i m p a i r m e n t is often associated with neonatal seizures. Sei-
Does Asphyxia Cause CerebralPalsy
zures attributable to hypoxia usually occur within the first 48 to 72 hours after birth. 3~ Infants with seizures have a 50- to 70-fold increased risk of CP, however 70% of infants with neonatal seizures do not subsequently develop CP. 31 In a study by Perlman and Risser, 96 high-risk t e r m infants admitted to the NICU were evaluated. 32 Five percent of these infants developed seizures. Factors associated with the highest risk of seizures included low 5-minute Apgar scores, respiratory depression requiring intubation, and severe fetal acidemia. In 1996, Korst a n d colleagues observed higher nucleated red blood cell (NRBC) counts in cord blood f r o m a g r o u p of neurologically i m p a i r e d infants c o m p a r e d with a control g r o u p of term nonasphyxiated newborns. -~ Recently, data obtained prospectively have b e e n published correlating the NRBC count in umbilical cord blood with n e u r o d e v e l o p m e n t a l status at age 3. 34 Infants with a b n o r m a l n e u r o d e v e l o p m e n t a l status had significantly higher NRBC counts at birth than did their normal counterparts. Further work on a data set confined to asphyxiainduced neurological i m p a i r m e n t is needed. In an attempt to identify infants at risk for encephalopathy, investigators have recently rep o r t e d their experience with the use of a ratio of lactate to creatinine in urine to differentiate n o r m a l infants f r o m infants with asphyxia, s5 T h e m e a s u r e m e n t s of urinary lactate a n d creatinine were obtained by magnetic resonance spectroscopy within 6 hours of birth. N o n e of 58 n o r m a l infants developed neonatal encephalopathy, whereas 16 of 40 infants with asphyxia went on to develop encephalopathy. The m e a n lactate: creatinine ratio in n o r m a l infants was 0.09. T h e ratio in infants who subsequently developed encephalopathy was 16.8. T h e hypothesis that intervention for infants at risk for n e w b o r n enc e p h a l o p a t h y may reduce the subsequent d e v e l o p m e n t of CP awaits further investigation.
Neonatal Encephalopathy Neonatal e n c e p h a l o p a t h y is characterized by abn o r m a l neonatal tone and reflexes , and central nervous system irritation manifested by seizure activity. The causes include asphyxia, trauma, infection, metabolic diseases of the newborn, and developmental abnormalities. ~6 Markers of acute hypoxic d a m a g e in the n e o n a t e have b e e n
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described primarily in term infants. Presentation in the infant is associated with the severity and duration of the insult, and the long-term prognosis is related to the severity of the signs in the infant. Mild e n c e p h a l o p a t h y is manifested by alterations in consciousness, hyperalertness, hyperreflexia, tachycardia, jitteriness, and dilated pupils. O n e - h u n d r e d p e r c e n t of these infants will be neurologically normal. 3<~7 Approximately 80% of infants with m o d e r a t e e n c e p h a l o p a t h y will be neurologically normal. Moderate encephalopathy is characterized by lethargy, miosis, bradycardia, hypotonia, weak suck, p o o r Moro reflex, and seizures. Finally, of those infants studied with severe n e w b o r n encephalopathy, all either died or had long-term neurological sequelae. These infants were initially stuporous, flaccid, had small, midposition pupils, either hypotonia or hyperreflexia, and absent suck, and Moro reflexes, a~
Conclusions Despite significant advances in b o t h perinatal and neonatal medicine, there has b e e n no change in the prevalence of CP over m a n y years. Moreover, the criteria to diagnose a n t e p a r t u m or i n t r a p a r t u m asphyxia are imprecise. T h e American College of Obstetricians and Gynecologists have concluded that hypoxia close to delivery severe e n o u g h to cause significant neonatal e n c e p h a l o p a t h y is associated with an umbilical artery p H < 7.00, a metabolic compon e n t to the acidosis, tow Apgar scores ( < 3 ) for m o r e than 5 minutes, multiorgan system dysfunction, and neurological sequelae. ~8 The cause of most cases of CP remains unknown, and the vast majority of cases cannot be predicted n o r prevented. Most cases of perinatal asphyxia are not followed by CP, and most CP is not associated with severe i n t r a p a r t u m asphyxia. A newborn infant who is crying at birth, who has normal Apgar scores and a n o r m a l U a pH, who feeds well and goes h o m e with m o t h e r on discharge, who ultimately has a diagnosis of CP, did not suffer i n t r a p a r t u m asphyxia or hypoxia as the cause. Conversely, infants with i n t r a p a r t u m brain d a m a g e will manifest signs and symptoms of such damage in the i m m e d i a t e newborn period.
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Pschir~r and Yeomans
References 1. Niswander K: Does substandard care cause cerebral palsy? Contemp OB/GYN October 1987 2. Blair E, Stanley F: Intrapartum asphyxia: A rare cause of cerebral palsy. J Pediatr 112:515-519, 1988 3. Nelson KB, EllenbergJH: Antecedents of cerebral palsy: Multivariate analysis of risk. N EngJ Med 315-81-86, 1986 4. Vinzileos AM, Gafflaey SE, Salinger LM, et al: The relationships among the fetal biophysical profile, umbilical cord pH, and apgar scores. Am J Obstet Gynecol 157: 627-631, 1987 5. Manning FA, Bodanji N, Harman C, et ah Fetal assessment baged on fetal biophysical profile scoring: VIII. The incidence of cerebral palsy in tested and untested perinates~ Am J Obstet Gynecol 178:696-703, 1998 6. Nelson KB, EllenbergJH: Antecedents of cerebral palsy. I. Univariate analysis of risks. Am J Dis Child 139:10311038, 1985 7. Kiely J, Paneth N, Stein Z, et al: Cerebral palsy and newborn care. I. Secular trends in cerebral palsy. Dev Med Child Neurol 23:533-538, 1981 8. Jarvis SM, Holloway JS, Hey EN: Increase in cerebral palsy in normal birthweight babies. Arch Dis Childhood 60:1113-1121, 1985 9. Sheller JM, Nelson KB: Does cesarean delivery prevent cerebral palsy or other neurologic problems of childhood? Obstet Gynecol 83:624-630, 1994 10. Nelson KB, Dambrosia JM, Ting TY, et al: Uncertain value of electronic fetal monitoring in predicting CP. N EngJ Med 334:613-618, 1996 11. McDonald D, Grant A, Sheridan-Pereira M, et al: The Dublin randomized controlled trial of intraparmm fetal heart rate monitoring. Am J Obstet Gynecol 152:524539, 1985 12. Grant A, O'Brien N,Joy MT, et al: Cerebral palsy among children born during the Dublin randomized trial of intrapartum monitoring. Lancet 25:1233-1236, 1989 13. Phelan JP, Ahn MO, Korst L, et al: Is intraprtum fetal brain injury in the term fetus preventable? Am J Obstet Gynecol 174:318, 1996 14. Richmond S, Niswander K, Snodgrass CA, et al: The obstetric management of fetal distress and its association with cerebral palsy. Obstet Gynecol 83:643-646, 1994 15. Niswander K: Can electronic fetal monitoring predict neurologic damage? Ob/Gyn Report 1:128-139, 1989 16. Dijxhoorn MH, Visser GILA, Fidler VJ, et al: Apgar score, meconium, and acidemia at birth in relation to neonatal neurological morbidity in term infants. Br J Obstet Gynaecol 93:217-222, 1986 17. Nelson KB, EllenbergJH: Obstetric complications as risk factors for cerebral or seizure disorders. JAMA 251:18431848, 1984 18. Yeomans ER, Gilstrap LC, Leveno KJ, et al: Meconium in the anmiotic fluid and fetal acid-base status. Obst Gyn 73:175-178, 1989 19, Apgar V: A proposal for a new method of evaluation of the newborn infant. Curr Res Anesth Analg 32:260-267, 1953
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