Cerebral palsy in term infants—birth or before birth?
2001; Elsevier BV; Volume: 138; Issue: 6 Linguagem: Inglês
10.1067/mpd.2001.116048
ISSN1097-6833
Autores Tópico(s)Infant Development and Preterm Care
ResumoSee related articles, p 798 and p 804.A pair of studies in this issue of The Journal of Pediatrics confirms two long-standing, but at first glance, disparate observations about the origins of cerebral palsy in term infants. Moster et al1Moster D Lie RT Irgens LM Bjerkedal T Markestad T. The association of Apgar score with subsequent death and cerebral palsy: a population-based study in term infants.J Pediatr. 2001; 138: 798-803Abstract Full Text Full Text PDF PubMed Scopus (215) Google Scholar show that low Apgar scores, particularly those recorded at age 5 minutes, greatly increase the risk for CP in infants weighing >2500 g. Compared with infants with normal Apgar scores (7-10 at 1 minute), Norwegian babies with 5-minute Apgar scores of ≤3 experienced 81 times the risk of CP. In California, Croen et al2Croen LA Grether JK Curry CJ Nelson KB. Congenital abnormalities among children with cerebral palsy: more evidence for prenatal antecedents.J Pediatr. 2001; 138: 804-810Abstract Full Text Full Text PDF PubMed Scopus (61) Google Scholar found that children with CP were 5 times as likely to have congenital malformations as were children without CP. Not surprisingly, the bulk of this excess was in malformations of the central nervous system. The first observation seems to support the long-standing belief that CP is due to birth asphyxia and obstetrical malfeasance. The other, however, appears to suggest just the opposite, that CP is determined prenatally.Neither observation is completely new. Both were major discoveries of the largest study to prospectively investigate risk factors for CP, the National Collaborative Perinatal Project, whose subjects were born 35 to 40 years ago.3Niswander KR Gordon M. The Women and Their Pregnancies: the Collaborative Perinatal Study of the National of Neurological Diseases and Stroke. : Saunders, Philadelphia1972Google Scholar In that study, an Apgar score of 0 to 3 at 5 minutes in infants of normal birth weight predicted a CP risk of 4.7%, which was about 25 times the risk for infants who had optimum Apgar scores of 7 to 10 at 1 minute.4Nelson KB Ellenberg JH. Apgar scores as predictors of chronic neurologic disability.Pediatrics. 1981; 68: 36-44PubMed Google Scholar In the new study by Moster et al,1Moster D Lie RT Irgens LM Bjerkedal T Markestad T. The association of Apgar score with subsequent death and cerebral palsy: a population-based study in term infants.J Pediatr. 2001; 138: 798-803Abstract Full Text Full Text PDF PubMed Scopus (215) Google Scholar the risk of CP with a low 5-minute score was slightly higher, 6.8%, but the relative risk was 81 times that of infants with the best Apgar scores. Thus the new study demonstrates much the same absolute risk of CP in infants with birth depression but a much lower rate of CP in healthy children. This difference is, in part, an artifact of the ways in which the studies were performed. In the NCPP, each child was examined at the age of 7 years, whereas in the Norwegian study, cases of CP were ascertained through disability claims data. The overall rate of CP in normal weight infants in the NCPP was 2.7/1000, whereas in the Norwegian study it was less than half that, 1.1/1000. Milder forms of motor impairment or dysfunction, presumably less closely related to birth depression, are likely to have been included under the term CP by the careful examinations of the NCPP. A very consistent finding in both the NCPP and the study by Moster et al1Moster D Lie RT Irgens LM Bjerkedal T Markestad T. The association of Apgar score with subsequent death and cerebral palsy: a population-based study in term infants.J Pediatr. 2001; 138: 798-803Abstract Full Text Full Text PDF PubMed Scopus (215) Google Scholar is the reassuring news that 93% to 95% of infants with 5-minute Apgar scores of 0 to 3 will not have CP.The NCPP also reported that congenital malformations, including those outside the nervous system, as well as other prenatal phenomena such as maternal IQ and thyroid status, were associated with CP.5Nelson KB Ellenberg JH. Antecedents of cerebral palsy. 2. Multivariate analysis of risks.N Engl J Med. 1986; 315: 81-86Crossref PubMed Scopus (733) Google Scholar These reports from the NCPP stimulated a change in thinking about CP. Long viewed as largely caused by birth asphyxia and other untoward labor events, CP came to be viewed more and more as a condition determined long before the obstetrician entered the delivery room. Advances in neuro-imaging have also contributed to this change in perspective. Magnetic resonance images obtained from children with CP born at term have commonly demonstrated brain malformations that must have originated during pregnancy.6Truwit CL Barkovich AJ Koch TK Ferriero DM. Cerebral palsy: MRI findings in 40 patients.Am J Neuroradiol. 1992; 13: 67-78PubMed Google Scholar It is for this reason that some pediatric neurologists recommend performing cranial magnetic resonance imaging scans in children with CP, particularly if legal action for alleged obstetrical malpractice is being considered. Some definitions of CP exclude children with recognized brain malformations,7Paneth N Kiely JL. the frequency of cerebral palsy: a review of population studies in industrialized nations since 1950.Clin Dev Med. 1984; 87: 46-56Google Scholar but unless brain imaging is undertaken, such exclusions cannot reliably be accomplished. The study by Croen et al2Croen LA Grether JK Curry CJ Nelson KB. Congenital abnormalities among children with cerebral palsy: more evidence for prenatal antecedents.J Pediatr. 2001; 138: 804-810Abstract Full Text Full Text PDF PubMed Scopus (61) Google Scholar reminds us that some of the children we refer to as having CP in fact have underlying brain malformations, and therefore the CP must have originated long before the onset of labor.It is common for clinicians to equate low Apgar scores with “birth asphyxia,” but this is a mistake, and the findings of Moster et al1Moster D Lie RT Irgens LM Bjerkedal T Markestad T. The association of Apgar score with subsequent death and cerebral palsy: a population-based study in term infants.J Pediatr. 2001; 138: 798-803Abstract Full Text Full Text PDF PubMed Scopus (215) Google Scholar should not automatically be interpreted as providing support for the idea that CP has its origin in labor difficulties.8American Academy of Pediatrics, Committee on Fetus and Newborn Use and abuse of the Apgar score.Pediatrics. 1986; 78: 1148-1149PubMed Google Scholar The Apgar score is a shorthand measurement of the functioning of the cardiopulmonary system (pulse), the central nervous system (grimace, tone), and a combination of the two (respiration, color). Many factors other than forces of labor can affect one or both of these systems, including infection, pharmacologic agents, and preexisting neurologic abnormalities. Apgar score correlates poorly with cord blood acidosis.9Hoffmann AL Hjortdal JO Secher NJ Weile B. The relationship between Apgar score, umbilical artery pH and operative delivery for fetal distress in 2778 infants born at term.Eur J Obstet Gynecol Reprod Biol. 1991; 38: 97-101Abstract Full Text PDF PubMed Scopus (17) Google ScholarBoth studies achieved their goals of associating CP with the risk factors of interest without the expensive and laborious task undertaken by the NCPP of examining every study child. The work was accomplished, instead, by data linkage. In Norway, the linkage was from birth certificates to disability claims; in California, birth certificates were linked to the regional CP registry and to the statewide birth defects registry. It is safe to assume that both studies were accomplished at a fraction of the cost of the NCPP. Unfortunately, such efficiencies in clinical investigation are endangered by the increasing sensitivity of the public and of government authorities to the privacy and confidentiality of medical data. New federal rules may make it impossible to perform such studies without first obtaining written permission from each child or family represented in the databases.10US Department of Health and Human Services Standards for privacy of individually identifiable health information, 65 Federal Register 82462.Dec 28, 2000Google Scholar, 11Hodge JG Goston LO Jacobson PD. Legal issues concerning electronic health information: privacy, quality, and liability.JAMA. 1999; 282: 1466-1471Crossref PubMed Scopus (152) Google Scholar, 12Carney PA Geller BM Moffett H Ganger M Sewell M Barlow WE et al.Current medicolegal and confidentiality issues in large, multicenter research programs.Am J Epidemiol. 2000; 152: 371-378Crossref PubMed Scopus (70) Google Scholar If exemptions from such rules permitting vital medical research are not created, the price of obtaining critical medical understanding will hugely escalate, and some kinds of research will simply not take place.13Association of American Medical Colleges Memorandum #01-11. The final HIPAA privacy regulation. AAMC, Washington (DC)2001Google Scholar, 14AAMC testimony on the final HHS privacy regulations. Available from: http://www.aamc.org/advocacy/ testimny/research/privacyreg0102.htm.Google Scholar Record linkage can often provide quick and reliable answers to questions about the prognosis of disease, outcomes after treatment, and risk factors for adverse outcomes. When the price of obtaining such information becomes too expensive, clinical decisions are, of necessity, made in an atmosphere of ignorance; and adverse outcomes for patients are an inevitable consequence. Academic medicine must work hard to convince the public and governmental authorities of the great value of record linkage to medical care.What should practicing clinicians take away from these two studies? First, we should not assume that just because the Apgar score is low, the child is doomed. Providing gloomy prognoses to parents on the basis of Apgar score alone is a mistake. The study by Moster et al,1Moster D Lie RT Irgens LM Bjerkedal T Markestad T. The association of Apgar score with subsequent death and cerebral palsy: a population-based study in term infants.J Pediatr. 2001; 138: 798-803Abstract Full Text Full Text PDF PubMed Scopus (215) Google Scholar the NCPP, and much additional research provide evidence that when CP develops, depressed babies virtually always have had major neurologic abnormalities in the neonatal period (eg, seizures, coma, need for ventilatory support). Even among such severely affected infants, CP is not the invariable outcome.15Collins MP Paneth N. The relationship of birth asphyxia to later motor disability.in: Current issues in fetal and neonatal asphyxial brain injury. : Futura Publishing, Armonk (NY)2001Google Scholar Second, we should search carefully for other anomalies, particularly central nervous system anomalies, in children given the diagnosis of CP. This search should probably include cranial magnetic resonance imaging. Third, in a world in which the causes of CP still remain very uncertain, we must avoid entering, in the medical charts of children with CP or with low Apgar scores, our speculative assumptions about the asphyxial origins of these conditions. Such misinformation only provides grist for the legal mill. See related articles, p 798 and p 804. A pair of studies in this issue of The Journal of Pediatrics confirms two long-standing, but at first glance, disparate observations about the origins of cerebral palsy in term infants. Moster et al1Moster D Lie RT Irgens LM Bjerkedal T Markestad T. The association of Apgar score with subsequent death and cerebral palsy: a population-based study in term infants.J Pediatr. 2001; 138: 798-803Abstract Full Text Full Text PDF PubMed Scopus (215) Google Scholar show that low Apgar scores, particularly those recorded at age 5 minutes, greatly increase the risk for CP in infants weighing >2500 g. Compared with infants with normal Apgar scores (7-10 at 1 minute), Norwegian babies with 5-minute Apgar scores of ≤3 experienced 81 times the risk of CP. In California, Croen et al2Croen LA Grether JK Curry CJ Nelson KB. Congenital abnormalities among children with cerebral palsy: more evidence for prenatal antecedents.J Pediatr. 2001; 138: 804-810Abstract Full Text Full Text PDF PubMed Scopus (61) Google Scholar found that children with CP were 5 times as likely to have congenital malformations as were children without CP. Not surprisingly, the bulk of this excess was in malformations of the central nervous system. The first observation seems to support the long-standing belief that CP is due to birth asphyxia and obstetrical malfeasance. The other, however, appears to suggest just the opposite, that CP is determined prenatally. Neither observation is completely new. Both were major discoveries of the largest study to prospectively investigate risk factors for CP, the National Collaborative Perinatal Project, whose subjects were born 35 to 40 years ago.3Niswander KR Gordon M. The Women and Their Pregnancies: the Collaborative Perinatal Study of the National of Neurological Diseases and Stroke. : Saunders, Philadelphia1972Google Scholar In that study, an Apgar score of 0 to 3 at 5 minutes in infants of normal birth weight predicted a CP risk of 4.7%, which was about 25 times the risk for infants who had optimum Apgar scores of 7 to 10 at 1 minute.4Nelson KB Ellenberg JH. Apgar scores as predictors of chronic neurologic disability.Pediatrics. 1981; 68: 36-44PubMed Google Scholar In the new study by Moster et al,1Moster D Lie RT Irgens LM Bjerkedal T Markestad T. The association of Apgar score with subsequent death and cerebral palsy: a population-based study in term infants.J Pediatr. 2001; 138: 798-803Abstract Full Text Full Text PDF PubMed Scopus (215) Google Scholar the risk of CP with a low 5-minute score was slightly higher, 6.8%, but the relative risk was 81 times that of infants with the best Apgar scores. Thus the new study demonstrates much the same absolute risk of CP in infants with birth depression but a much lower rate of CP in healthy children. This difference is, in part, an artifact of the ways in which the studies were performed. In the NCPP, each child was examined at the age of 7 years, whereas in the Norwegian study, cases of CP were ascertained through disability claims data. The overall rate of CP in normal weight infants in the NCPP was 2.7/1000, whereas in the Norwegian study it was less than half that, 1.1/1000. Milder forms of motor impairment or dysfunction, presumably less closely related to birth depression, are likely to have been included under the term CP by the careful examinations of the NCPP. A very consistent finding in both the NCPP and the study by Moster et al1Moster D Lie RT Irgens LM Bjerkedal T Markestad T. The association of Apgar score with subsequent death and cerebral palsy: a population-based study in term infants.J Pediatr. 2001; 138: 798-803Abstract Full Text Full Text PDF PubMed Scopus (215) Google Scholar is the reassuring news that 93% to 95% of infants with 5-minute Apgar scores of 0 to 3 will not have CP. The NCPP also reported that congenital malformations, including those outside the nervous system, as well as other prenatal phenomena such as maternal IQ and thyroid status, were associated with CP.5Nelson KB Ellenberg JH. Antecedents of cerebral palsy. 2. Multivariate analysis of risks.N Engl J Med. 1986; 315: 81-86Crossref PubMed Scopus (733) Google Scholar These reports from the NCPP stimulated a change in thinking about CP. Long viewed as largely caused by birth asphyxia and other untoward labor events, CP came to be viewed more and more as a condition determined long before the obstetrician entered the delivery room. Advances in neuro-imaging have also contributed to this change in perspective. Magnetic resonance images obtained from children with CP born at term have commonly demonstrated brain malformations that must have originated during pregnancy.6Truwit CL Barkovich AJ Koch TK Ferriero DM. Cerebral palsy: MRI findings in 40 patients.Am J Neuroradiol. 1992; 13: 67-78PubMed Google Scholar It is for this reason that some pediatric neurologists recommend performing cranial magnetic resonance imaging scans in children with CP, particularly if legal action for alleged obstetrical malpractice is being considered. Some definitions of CP exclude children with recognized brain malformations,7Paneth N Kiely JL. the frequency of cerebral palsy: a review of population studies in industrialized nations since 1950.Clin Dev Med. 1984; 87: 46-56Google Scholar but unless brain imaging is undertaken, such exclusions cannot reliably be accomplished. The study by Croen et al2Croen LA Grether JK Curry CJ Nelson KB. Congenital abnormalities among children with cerebral palsy: more evidence for prenatal antecedents.J Pediatr. 2001; 138: 804-810Abstract Full Text Full Text PDF PubMed Scopus (61) Google Scholar reminds us that some of the children we refer to as having CP in fact have underlying brain malformations, and therefore the CP must have originated long before the onset of labor. It is common for clinicians to equate low Apgar scores with “birth asphyxia,” but this is a mistake, and the findings of Moster et al1Moster D Lie RT Irgens LM Bjerkedal T Markestad T. The association of Apgar score with subsequent death and cerebral palsy: a population-based study in term infants.J Pediatr. 2001; 138: 798-803Abstract Full Text Full Text PDF PubMed Scopus (215) Google Scholar should not automatically be interpreted as providing support for the idea that CP has its origin in labor difficulties.8American Academy of Pediatrics, Committee on Fetus and Newborn Use and abuse of the Apgar score.Pediatrics. 1986; 78: 1148-1149PubMed Google Scholar The Apgar score is a shorthand measurement of the functioning of the cardiopulmonary system (pulse), the central nervous system (grimace, tone), and a combination of the two (respiration, color). Many factors other than forces of labor can affect one or both of these systems, including infection, pharmacologic agents, and preexisting neurologic abnormalities. Apgar score correlates poorly with cord blood acidosis.9Hoffmann AL Hjortdal JO Secher NJ Weile B. The relationship between Apgar score, umbilical artery pH and operative delivery for fetal distress in 2778 infants born at term.Eur J Obstet Gynecol Reprod Biol. 1991; 38: 97-101Abstract Full Text PDF PubMed Scopus (17) Google Scholar Both studies achieved their goals of associating CP with the risk factors of interest without the expensive and laborious task undertaken by the NCPP of examining every study child. The work was accomplished, instead, by data linkage. In Norway, the linkage was from birth certificates to disability claims; in California, birth certificates were linked to the regional CP registry and to the statewide birth defects registry. It is safe to assume that both studies were accomplished at a fraction of the cost of the NCPP. Unfortunately, such efficiencies in clinical investigation are endangered by the increasing sensitivity of the public and of government authorities to the privacy and confidentiality of medical data. New federal rules may make it impossible to perform such studies without first obtaining written permission from each child or family represented in the databases.10US Department of Health and Human Services Standards for privacy of individually identifiable health information, 65 Federal Register 82462.Dec 28, 2000Google Scholar, 11Hodge JG Goston LO Jacobson PD. Legal issues concerning electronic health information: privacy, quality, and liability.JAMA. 1999; 282: 1466-1471Crossref PubMed Scopus (152) Google Scholar, 12Carney PA Geller BM Moffett H Ganger M Sewell M Barlow WE et al.Current medicolegal and confidentiality issues in large, multicenter research programs.Am J Epidemiol. 2000; 152: 371-378Crossref PubMed Scopus (70) Google Scholar If exemptions from such rules permitting vital medical research are not created, the price of obtaining critical medical understanding will hugely escalate, and some kinds of research will simply not take place.13Association of American Medical Colleges Memorandum #01-11. The final HIPAA privacy regulation. AAMC, Washington (DC)2001Google Scholar, 14AAMC testimony on the final HHS privacy regulations. Available from: http://www.aamc.org/advocacy/ testimny/research/privacyreg0102.htm.Google Scholar Record linkage can often provide quick and reliable answers to questions about the prognosis of disease, outcomes after treatment, and risk factors for adverse outcomes. When the price of obtaining such information becomes too expensive, clinical decisions are, of necessity, made in an atmosphere of ignorance; and adverse outcomes for patients are an inevitable consequence. Academic medicine must work hard to convince the public and governmental authorities of the great value of record linkage to medical care. What should practicing clinicians take away from these two studies? First, we should not assume that just because the Apgar score is low, the child is doomed. Providing gloomy prognoses to parents on the basis of Apgar score alone is a mistake. The study by Moster et al,1Moster D Lie RT Irgens LM Bjerkedal T Markestad T. The association of Apgar score with subsequent death and cerebral palsy: a population-based study in term infants.J Pediatr. 2001; 138: 798-803Abstract Full Text Full Text PDF PubMed Scopus (215) Google Scholar the NCPP, and much additional research provide evidence that when CP develops, depressed babies virtually always have had major neurologic abnormalities in the neonatal period (eg, seizures, coma, need for ventilatory support). Even among such severely affected infants, CP is not the invariable outcome.15Collins MP Paneth N. The relationship of birth asphyxia to later motor disability.in: Current issues in fetal and neonatal asphyxial brain injury. : Futura Publishing, Armonk (NY)2001Google Scholar Second, we should search carefully for other anomalies, particularly central nervous system anomalies, in children given the diagnosis of CP. This search should probably include cranial magnetic resonance imaging. Third, in a world in which the causes of CP still remain very uncertain, we must avoid entering, in the medical charts of children with CP or with low Apgar scores, our speculative assumptions about the asphyxial origins of these conditions. Such misinformation only provides grist for the legal mill. The association of Apgar score with subsequent death and cerebral palsy: A population-based study in term infantsThe Journal of PediatricsVol. 138Issue 6PreviewObjective: To estimate the risk of adverse outcomes for newborns with a low Apgar score. Study design: Population-based cohort study. All 235,165 children born between 1983 and 1987 in Norway with a birth weight of at least 2500 g and no registered birth defects were followed up from birth to age 8 to 12 years by linkage of 3 national registries. Outcomes were death and cerebral palsy (CP). Results: Five-minute Apgar scores of 0 to 3 were recorded for 0.1%, and scores of 4 to 6 were recorded for 0.6% of the children. Full-Text PDF Congenital abnormalities among children with cerebral palsy: More evidence for prenatal antecedentsThe Journal of PediatricsVol. 138Issue 6PreviewObjectives: To investigate the association between cerebral palsy (CP) and congenital abnormalities among children with very low, low, and normal birth weight. Study design: A population-based, case-control study among the cohort of 155,636 live births delivered between 1983 and 1985 in 4 California counties. Children with moderate or severe congenital CP (n = 192) diagnosed by age 3 were identified from 2 California State service agencies, and 551 control children were randomly sampled from birth certificate files. Full-Text PDF
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