COMMENTARY Apgar Scores As Predictors of Chronic Neurologic

cases, major outbreaks of influenza in 1983, 1984, and 2. Centers for Disease Control and Prevention. Outbreaks of Reye syn- 1985, and no change in reported varicella cases dur- drome—Utah, Arizona, Colorado. MMWR. 1979;28:39 20,21 3. Starko KM, Ray CG, Dominguez LB, et al. Reye’s syndrome and salic- ing the 6-year period. ylate use. Pediatrics. 1980;66:859–864 Starko’s paper, and those that followed, dramati- 4. Arrowsmith JB, Kennedy DL, Kuritsky JN, Faich GA. National patterns cally and permanently changed the choice of antipy- of aspirin use and Reye syndrome reporting, United States, 1980 to 1985. retics for children in North America. Every study Pediatrics. 1987;79:858–863 5. Linnemann CC, Shea L, Partin C. Reye’s syndrome: epidemiologic and supported the relationship between aspirin use and viral studies, 1963–1974. Am J Epidemiol. 1975;101:517–526 risk of Reye’s syndrome. Furthermore, the ORs in- 6. Waldman RJ, Hall WN, McGee H, et al. Aspirin as a risk factor in Reye’s creased rather than decreased in the more rigorously syndrome. JAMA. 1982;247:3089–3094 designed studies. A formal meta-analysis was not 7. Halpin TJ, Holtzhauer FJ, Campbell RJ, et al. Reye’s syndrome and necessary to conclude that this was a real and prob- medication use. JAMA. 1982;248:687–691 8. Kauffman RE. The Reye syndrome/aspirin controversy 1986. Contemp ably causal association. Fortunately, an acceptable Pediatr. 1986;Nov/Dec:16–24 alternative to aspirin that was not associated with 9. American Academy of Pediatrics, Committee on Infectious Diseases. increased risk of Reye’s syndrome was readily avail- Aspirin and Reye syndrome. Pediatrics. 1982;69:810–812 able. Both the case–control studies and marketing 10. Surgeon General’s advisory on the use of salicylates and Reye’s syn- drome. MMWR. 1982;81:289–290 data document the replacement of aspirin with acet- 11. Wall Street Journal, July 28, 1982;23 aminophen for childhood antipyretic treatment after 12. US Food and Drug Administration. Reye syndrome awareness pro- 1980. Today, acetaminophen products dominate the gram. FDA Drug Bull. 1982;12:24 pediatric antipyretic market, largely because of the 13. Glezen WP. Aspirin and Reye’s syndrome. Am J Dis Child. 1982;136: documented association of aspirin with increased 971–972 14. Aspirin Foundation of America, Inc, RS Working Group. Reye syn- risk of Reye’s syndrome. The shift from aspirin to drome and salicylates: a spurious association. Pediatrics. 1982;70: acetaminophen in the early 1980s represents a dra- 158–160 matic and rapid change in consumer and physician 15. Hurwitz ES, Barrett MJ, Bregman D, et al. Public Health Service study behavior with respect to antipyretic use in response on Reye’s syndrome and medications, report of the pilot phase. N Engl J Med. 1985;313:849–857 to public dissemination of information through a 16. Hurwitz ES, Barrett MJ, Bregman D, et al. Public Health Service study variety of media sources. It is worth noting that of Reye’s syndrome and medications, report of main study. N Engl implementation of public policy on this issue lagged J Med. 1987;257:1905–1911 far behind consumer and physician behavior. Nev- 17. Forsyth BW, Horwitz RI, Acampora D, et al. New epidemiologic evi- ertheless, careful and rigorous clinical research led to dence confirming that bias does not explain the aspirin/Reye’s syn- drome association. JAMA. 1989;261:2517–2524 changes in antipyretic use, in spite of economic and 18. Rahwan GL, Rahwan RG. Aspirin and Reye’s syndrome: the change in political pressures, that reduced dramatically the in- prescribing habits of health professionals. Drug Intell Clin Pharm. 1986; cidence of a devastating illness for which a specific 20:143–145 cause or treatment has not and may never be found. 19. Remington PL, Rowley D, McGee H, et al. Decreasing trends in Reye syn- drome and aspirin use in Michigan, 1979 to 1984. Pediatrics. 1986;77:93–98 REFERENCES 20. Centers for Disease Control and Prevention. Influenza—United States, 1985. MMWR. 1986;35:66–74 1. Reye RDK, Morgan G, Baral J. Encephalopathy and fatty degeneration 21. Barrett MJ, Hurwitz ES, Schonberger LB, et al. Changing epidemiology of the viscera: a disease entity in childhood. Lancet. 1963;2:749–752 of Reye syndrome in the United States. Pediatrics. 1986;77:598–602

COMMENTARY

Apgar Scores as Predictors of Chronic Neurologic Disability, by Karin B. Nelson, MD, and Jonas H. Ellenberg, PhD, Pediatrics, 1981;68:36–44

Comments by Gerald S. Golden, MD

ABSTRACT OF ORIGINAL ARTICLE. Apgar scores of 0 to 3 at 10, 15, or 20 minutes and survived, 12 (12%) were recorded at one and five minutes for ϳ49 000 had later cerebral palsy; 11 of the 12 also were mentally infants, and at 10, 15, and 20 minutes for babies who retarded (in 10, IQ <50) and half had seizure disorders. did not achieve a score of 8 or higher at five minutes. Eight children who survived after having very low late These children were followed to 7 years of age. Low Apgar scores and who did not have cerebral palsy had Apgar scores were risk factors for cerebral palsy, but lesser but significant disabilities. Of the children who 55% of children with later cerebral palsy had Apgar had Apgar scores of 0 to 3 at 10 minutes or later and scores of 7 to 10 at one minute, and 73% scored 7 to 10 survived, 80% were free of major handicap at early at five minutes. Of 99 children who had Apgar scores school age. COMMENTARY Received for publication Mar 19, 1998; accepted Mar 19, 1998. he relationship between perinatal asphyxia Address correspondence to: Gerald S. Golden, MD, National Board of Medical Examiners, 3750 Market St, Philadelphia, PA 19104. and prematurity, the condition of the infant at PEDIATRICS (ISSN 0031 4005). Copyright © 1998 by the American Acad- Tbirth, and motor and mental disability has emy of Pediatrics. been of interest since 1861 when William John Little,

262 SUPPLEMENT Downloaded from www.aappublications.org/news by guest on September 23, 2021 an orthopedic surgeon, first described cerebral pal- analyzers and interpreters of the NCPP data. Their sy.1,2 His hypothesis was that asphyxia neonatorum paper, Apgar Scores as Predictors of Chronic Neurologic was frequently the cause of the subsequent disabil- Disability, is one of the most important. The study ity. group was a cohort of ϳ49 000 singleton liveborn Sigmund Freud, who was trained in neurology children who had Apgar scores recorded at 1 minute and neuropathology, made extensive contributions and 5 minutes. Major analyses focused on the initial to the understanding of cerebral palsy, culminat- Apgar scores in children with and without cerebral ing with the publication of his important mono- palsy at 7 years of age, the predictive value of Apgar graph Die Infantile Cerebralla¨hmung (Infantile Cere- scores for death or cerebral palsy, the duration of bral Paralysis) in 1897.3 He basically supported very low Apgar scores, and the outcomes for infants Little’s concepts, but pointed out that in approxi- with very low late Apgar scores who survived. They mately one third of cases of cerebral palsy, no also analyzed the differential outcomes for groups of adverse perinatal events could be documented. children with birth weights Ͻ2500 g and Ն2501 g. Freud also hypothesized that in some cases, the There were 37 000 children whose status was known abnormalities found in the neonate might not be at 7 years of age. attributable to obstetric factors, but rather were the The authors confirmed the general concept that result of prenatal problems. low Apgar scores at 1 and 5 minutes were associated The relationship between the infant’s condition at with an increased risk of death or cerebral palsy, and birth and subsequent neurologic status could not be that persistently low Apgar scores at 10, 15, and 20 explored rigorously until the development of a sim- minutes also were predictive of these adverse out- ply administered, well standardized, reproducible comes. There was, however, no one-to-one correla- method of assessment of the neonate. Apgar first tion. In the group of children without cerebral palsy, published her approach in 1953, and the Apgar score 5% had 1-minute Apgar scores of 0 to 3 and 14% had became the standard for assessment of the condition Apgar scores of 4 to 6. At 5 minutes, 1% had Apgar of the newborn infant.4 Additional studies demon- scores of 0 to 3 and 3% had Apgar scores of 4 to 6. strated that this score was most valuable in defining The conclusion drawn is that a very low Apgar score, the subgroup of infants requiring active resuscita- even at 5 minutes, is not an absolute predictor of tion. Although a correlation was demonstrated be- cerebral palsy. tween a low Apgar score and subsequent neonatal Investigating the 120 children with cerebral palsy mortality,5 very little information on late adverse at 7 years of age, they found that 55% had Apgar outcomes was available. scores of 7 to 10 at 1 minute and 73% had Apgar The National Collaborative Perinatal Project scores of 7 to 10 at 5 minutes. One-minute scores of 0 (NCPP) began in 1959 and was designed to follow to 3 were present in 26% of these children, and 19% ϳ54 000 pregnant woman throughout their pregnan- had scores of 4 to 6 at 1 minute. At 5 minutes, 15% of cies and to study the children until 7 years of age.6 the group with cerebral palsy had scores of 0 to 3 at The data acquisition was carried out at 12 teaching 1 minute, and 19% had scores of 4 to 6 at 5 minutes. hospitals and completed in 1966. The Apgar score Here again, there was no absolute link between low was an important assessment tool and was obtained Apgar scores and cerebral palsy. In fact, most chil- at 1 and 5 minutes for virtually all infants. Children dren with cerebral palsy had high early Apgar whose Apgar scores were Ͻ8 at 5 minutes also were scores. evaluated at 10, 15, and 20 minutes. Analyses of those children who had very low (0 to The NCPP had three features that were impor- 3) Apgar scores at 10, 15, and 20 minutes also were tant for subsequent data analyses. The first was the carried out. There were 390 children with very low large sample size. This permitted the determina- scores at 20 minutes, and only 31% survived until 7 tion of statistically significant findings, not only years of age. The mortality rate was extraordinarily for the entire group, but also for subgroups that high (95.7%) in low birth weight infants in this group would have been too small to be meaningful if the and substantial (59%) in full-term infants. An impor- original study population had not been as large. tant and surprising finding, however, was that 87 of The second feature was the highly standardized the 99 children in the very low Apgar score group protocols for data capture and recording. The did not have disabling cerebral palsy. In fact, only 8 nurses and physicians who gathered the data were of these children had any handicaps (vision, hearing, articulation), and an additional 2 had minor prob- trained, and a number of quality-control measures lems with coordination. The authors noted that were built into the study protocol. The third im- many of these survivors without disabilities had bra- portant feature of the NCPP was the long fol- dycardia during the second stage of labor, although low-up period for the children. By the time a child none had complete loss of fetal heart tones. reached 7 years of age, most subtle or not so subtle The children with very low late Apgar scores and neurologic and behavioral abnormalities, except cerebral palsy were severely disabled. Eleven of the some learning disabilities, should be evident, and 12 had birth weights Ͼ2500 g, and all had spastic many reliable assessment tools, such as the Wech- quadriparesis, 6 with athetosis. All of the children in sler Intelligence Scale for Children, are available. this group also had mental retardation. Six of these The Study children had seizures that occurred beyond the neo- Nelson, a pediatric neurologist, and Ellenberg, an natal period. The remaining child in this group had a epidemiologist and biometrician, are the preeminent birth weight of 1673 g. She had spastic diplegia with

Downloaded from www.aappublications.org/news by guest on September 23, 2021 SUPPLEMENT 263 normal intelligence, the most common type of cere- and misuse of this construct. In fact, the reader bral palsy found in premature infants with periven- should note the entire body of research derived tricular leucomalacia. from the NCPP, much of it done by Nelson and Ellenberg as exemplified by some of their other Significance publications in these areas.7–9 Analysis of a large, carefully acquired dataset is of A second area of significance of this study is in fundamental importance in testing our previous hy- setting a baseline for expected outcomes in the care potheses and assumptions. During the 120 years be- of the sick neonate. Although the study now is 17 tween Little’s publication and that of Nelson and years old, there is no other data source this large and Ellenberg, a correlation between asphyxia neonatorum well studied. In addition, the 7-year follow-up of the and cerebral palsy was taken as a matter of faith. subjects was an important feature for minimizing There were some hints that this link was not as firm both false-negative and false-positive findings. Mild as thought previously, but an accurate definition of neurologic, language, and sensory problems may be the specific risk factors and determination of the difficult to detect before school age. The authors also level of risk could not be quantitated until a study of have found, in subsequent analyses, that cerebral the magnitude of the NCPP was implemented. palsy diagnosed in 1-year-old children may have This study did confirm that the Apgar score was a disappeared by age 7 years.10 New interventions useful tool for defining those children at risk of death need to be put to the test of carefully controlled or significant disability, but it also demonstrated that studies, but also need to pass the test of improving the correlation was far from absolute. The most sur- on outcomes documented in the past. This paper will prising finding, and perhaps the most significant, remain a landmark that can be used to measure our was that 80% of children who had very low Apgar progress in neonatal care for a long time. scores at 20 minutes and survived did not have sig- nificant disabilities. Those who were disabled, how- ever, had severe multiple handicaps. There were no REFERENCES children in this group who had an isolated motor 1. Little WJ. On the influence of abnormal parturition, difficult labor, defect or only seizures or mental retardation without premature birth, and asphyxia neonatorum on the mental and physical cerebral palsy. Children with very low late Apgar condition of the child, especially in relation to deformities. Trans Obstet scores, if they survive, are either quite functional or Soc Lond. 1861;3:293–344 2. Little WJ. On the influence of abnormal parturition, difficult labor, are severely disabled. premature birth, and asphyxia neonatorum on the mental and physical It is nearly impossible to read a medical journal condition of the child, especially in relation to deformities. Lancet. without coming across the phrase “evidence-based 1861;2:378–380 medicine.” Although the concept is certainly not as 3. Freud S. Die Infantile Cerebra¨llahmung. Wien, Germany: Holder; 1897 4. Apgar V. A proposal for a new method of evaluation of the newborn new as its prevalence in the literature would sug- infant. Curr Res Anesth Analg. 1953;32:260–267 gest, results of studies such as that of Nelson and 5. Drage JS, Kennedy C, Schwarz BK. The Apgar score as an index of Ellenberg are often ignored in another profession; neonatal mortality. A report from the collaborative study of cerebral one rarely sees the phrase “evidence-based law” in palsy. Obstet Gynecol. 1964;24:222–230 the context of malpractice or product liability suits. 6. Niswander K, Gordon M. The Women and Their Pregnancies. National Institutes of Health Publication 73-379. Washington, DC: US Dept of “Bad baby” lawsuits still are a real threat for the Health, Education and Welfare; 1972 practicing obstetrician and pediatrician who at- 7. Nelson KB, Ellenberg JH. Obstetric complications as risk factors for tend neonates. In many of these lawsuits, expert cerebral palsy or seizure disorders. JAMA. 1984;251:1843–1848 witnesses can be found who are willing to ascribe 8. Nelson KB, Ellenberg JH. Antecedents of cerebral palsy. I. Univariate all neurologic problems, such as isolated mental analysis of risks. Am J Dis Child. 1985;139:1031–1038 9. Nelson K, Ellenberg JH. Antecedents of cerebral palsy. Multivariate retardation or epilepsy, to asphyxia neonatorum in analysis of risk. N Engl J Med. 1986;315:81–86 any child with a low Apgar score. A careful read- 10. Nelson K, Ellenberg JH. Children who “outgrew” cerebral palsy. Pedi- ing of this paper should demonstrate the overuse atrics. 1982;69:529–536

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