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Temporal and demographic trends in cerebral palsy—Fact and fiction
Temporal and demographic trends in cerebral palsy—Fact and fiction Steven L. Clark, MD,a and Gary D. V. Hankins, MDb Salt Lake City, Utah, and Galveston, Tex The rate of cerebral palsy has not decreased in developed countries over the past 30 years, despite the widespread use of electronic fetal heart rate monitoring and a 5-fold increase in the cesarean delivery rate over the same period of time. However, neonatal survival has improved during these decades. These observations have lead to the hypothesis that increased survival of premature, neurologically impaired infants may have masked an actual reduction in cerebral palsy among term infants as a result of the use of electronic monitoring and the avoidance of intrapartum asphyxia. A review of the medical literature, as well as a demographic analysis of term and preterm birth rates in the United States, refutes this hypothesis on four grounds. First, cerebral palsy prevalence has been separately analyzed in term infants and shows no change over 30 years. Second, the prevalence of cerebral palsy is the same or lower in underdeveloped countries than in developed nations; in the former, the availability of emergency cesarean delivery based on electronic monitor data is limited or absent. Third, the increase in prevalence of cerebral palsy among lowbirth-weight infants and the increase in cesarean sections based on presumed fetal distress were not simultaneous events—the former preceded the latter by a decade. Improved neonatal survival since the 1980s has been associated with a stable or decreasing rate of neurologic impairment and thus could not have obscured improvement from reduced term asphyxia. Finally, compared with the number of infants born by cesarean section for fetal distress, there are simply not enough infants born in the most vulnerable weight groups to make any impact on even a minimal improvement of outcome in the group delivered by cesarean section for presumed fetal distress. Except in rare instances, cerebral palsy is a developmental event that is unpreventable given our current state of technology. (Am J Obstet Gynecol 2003;188:628-33.)
Key words: Electronic fetal heart rate monitoring, cerebral palsy, premature birth
Since the development of the electronic fetal heart rate monitor in the late 1960s, this device has gained widespread popularity for use during labor and delivery both in the United States and in most developed counties. Although it is clear that the use of this device has virtually eliminated unexpected intrapartum fetal death, the original hope of clinicians and researchers that the use of this device would have a positive impact on the rate of cerebral palsy has been unrealized.1-5 Indeed, the only clinical trial demonstrating any difference in long-term outcome among fetuses monitored electronically, compared with traditional auscultation techniques, showed a significant increase in cerebral palsy among preterm infants followed during labor with electronic monitoring.1,6 A reasonable question is whether these already-injured preterm infants would have simply died in utero but for the fetal monitoring.
From the University of Utah School of Medicine, LDS Hospital,a and the University of Texas Medical Branch.b Received for publication July 11, 2002; revised November 4, 2002; accepted December 5, 2002. Reprints not available from the authors. © 2003, Mosby, Inc. All rights reserved. 0002-9378/2003 $30.00 + 0 doi:10.1067/mob.2003.204
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On a broader scale, longitudinal evaluation of rates of cerebral palsy in both developed and underdeveloped countries has failed to demonstrate any significant reduction in net population prevalence of cerebral palsy over the past three decades, this despite a 5-fold increase in the rate of cesarean section based, in part, on the electronically derived diagnosis of “fetal distress.”1-5,7-19 In contrast, global cerebral palsy prevalence has remained stable at about 2 to 3 per 1000 for several decades7-19 (Figure). Such data has lead the international scientific community to conclude that intrapartum hypoxia leading to cerebral palsy is a distinctly rare occurrence and to establish strict and scientifically based guidelines for the evaluation of labor and delivery as a potential cause of a child’s later diagnosis of cerebral palsy.1,5,20 Faced with such data, one might ask whether an actual reduction in the rate of cerebral palsy among term infants, based on “timely” intervention for an abnormal electronic signal, has been masked by a simultaneous and coincidental rise in the survival of premature infants who once would have died, but now live and in whom cerebral palsy develops as a result of complications of prematurity. A critical evaluation of this hypothesis reveals it to be without scientific foundation.
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Lack of supportive data There is no question that prematurity is a significant risk factor for the later development of cerebral palsy.1,8,10,21-27 This is especially true in infants of extremely low birth weight, generally defined as <1000 g, in whom the rate of subsequent cerebral palsy is in the range of 8% to 10%.23,27 Further, advances in neonatal care have, in recent decades, allowed survival of such infants who would previously have died. Thus, there can be little question that some babies today who would previously have died are living only to develop cerebral palsy. In addition, both electronic monitoring and intermittent auscultation are effective for the detection of rare, sudden intrapartum catastrophes manifested by deep variable decelerations or bradycardia that may lead to cerebral palsy.1,20 In such cases, emergency intervention undoubtedly has the potential to avoid hypoxic injury and subsequent cerebral palsy. Although few would question the validity of the above two observations, additional conclusions regarding the relative demographic effects of such events require much more than an assumption that, with respect to cerebral palsy prevalence, one group effectively cancels out the effects of the other. To date, data supporting this assumption have not been presented. Thus, statements to this effect are, by definition, not scientifically founded. Indeed, overwhelming scientific evidence documents (vide infra) that such conclusions are invalid. Cerebral palsy and birth weight Several population analyses of cerebral palsy prevalence have distinguished term from preterm infants.7,11-13,16,28 Although rates of cerebral palsy have, in some studies, showed an increase among infants with birth weights <2500 g, each of the above studies also clearly demonstrated no change in the prevalence of cerebral palsy among infants with birth weights >2500 g. Thus, the issue of cerebral palsy prevalence in term infants has been specifically addressed in the literature and a lack of improvement since the advent of widespread electronic fetal heart rate monitoring confirmed. Underdeveloped countries If the ability for emergency cesarean delivery on the basis of an abnormal fetal heart rate tracing resulted in a significant improvement in the prevalence of cerebral palsy, one would logically expect a significant difference in the rates of cerebral palsy in developed compared with underdeveloped countries, where the electronic and surgical technology available in the developed world is lacking. On the other hand, if cerebral palsy is largely a developmental event and is not significantly influenced by perinatal care, one would expect global rates of this condition to be similar, as is seen with other developmental conditions such as monozygotic twins.
Fortunately, such data are available. Studies of cerebral palsy prevalence in China, Malta, Slovenia, and India all demonstrate cerebral palsy rates between 1.2 and 2.3 per 1000, identical to, or in some cases lower than, that seen in developed countries.11,29-31 In the latter nations, the availability of either electronic fetal monitoring or the capability of emergency cesarean delivery within 30 minutes, is, for the most part, lacking. Such data confirm cerebral palsy as primarily a developmental event, not influenced by current obstetric technologies available in developed countries. A fair question is to what extent data published from underdeveloped countries is valid or can be extrapolated to reach conclusions about care in developed nations. Certainly, cerebral palsy could be underreported as a result of primitive data collection systems. On the other hand, cerebral palsy could be overreported because of to primitive diagnostic systems that fail to differentiate this condition from other forms of neurologic impairment. In any event, reported similarities in cerebral palsy rates between underdeveloped and developed countries on several continents remain striking, especially because data concerning the spectrum of treatable or preventable disease entities, collected with these same data systems, consistently show dramatic differences in disease prevalence and outcome between developed and underdeveloped nations.32 Too little, too late The argument that lower rates of term cerebral palsy attributable to intervention on the basis of electronic monitoring has been masked by an increase in neurologically impaired preterm survivors rests on an assumption that the two events have been simultaneous. A careful review of the medical literature refutes this notion. Some studies comparing outcomes of preterm infants delivered in the mid-1960s with those delivered in later decades demonstrated an increase in the rate of cerebral palsy over time, attributable to improved survival of impaired infants.15,18 Such a finding is not, however, universal.33,34 More recent studies comparing the rates of cerebral palsy in low-birth-weight infants over the decades of the 1980s through 1990s have not shown such trends. Of six such later studies, four demonstrated an unchanged rate of cerebral palsy among premature infants and two described a decreasing cerebral palsy prevalence among premature infants over these decades.35-40 In a longitudinal study from Denmark, Topp et al12,13 demonstrated an increase in cerebral palsy among lowbirth-weight infants in the period from 1979 to 1986, followed by a decrease in the years beyond 1986. As in other studies, these investigators found no change in the rate of cerebral palsy in term infants during either period. In a similar manner, Parkes et al14 in Ireland demonstrated that perinatal mortality rates for preterm infants were unchanged after 1989, yet the rate of cerebral palsy re-
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Table. Reported rates of cerebral palsy, 1966-1996* Years 1966-1977 1975-1980 1980-1985
1985-1990
1990-1995 1996
Country England Norway Sweden Australia United States Slovenia England Norway Japan Denmark Ireland Sweden Australia Canada Slovenia Scotland Denmark England United States India Denmark Ireland Sweden England China Malta
Cerebral palsy prevalence(per 1000) 1.5, 1.7, 2.2 2.6 2.5 1.6 2.0 2.3 2.3 2.1 1.4 3.0 2.2 2.4 1.6 2.6 2.3 2.1 3.0 2.3 2.3 1.2 2.4 2.2 2.1 2.5 1.5, 2.3, 2.1 2.0
*In some instances, the same data collection spans more than a single 5-year interval. Data from references 6-17, 27, 29-34, 37, and 51.
mained stable or increased. As summarized by Hagberg38 after a landmark longitudinal study involving patients over three decades, “the prevalence of [cerebral palsy] in preterms is no longer increasing, in spite of additional improvements in survival.” In a similar manner, Farnoff et al,41 reporting on prospective observations from 12 US centers, in 1995 concluded that the increase in survival of very-low-birth-weight infants seen after the introduction of surfactant therapy in the 1980s “was not accompanied by an increase in medical morbidity.” On the other hand, widespread electronic fetal monitoring, and the resultant increase in cesarean section rate, are largely products of the 1970s and beyond; no further increase in the cesarean section rate has been seen since the mid-1980s (Figure). Thus, the initial increase in the rate of preterm cerebral palsy seen in some, but not all, studies preceded, by a decade or more in most studies, the halcyon days of electronic monitoring. For the past two decades, cerebral palsy rates have been stable or decreasing among preterm infants, whereas cesarean section rates have been stable or increasing. Thus, any putative widespread neurologic benefit to monitored fetuses saved from cerebral palsy by timely cesarean delivery has now had almost two decades to manifest itself, unfettered by confounding increases in the rate of neurologically impaired preterm infants. Yet the rate remains unchanged, demonstrating the error of such assumptions.
Figure. Cerebral palsy prevalence (black bars) in developed countries and the United States. Dark gray bars, Cesarean section rate. (Based on pooled data from Sweden, Australia, Canada, Scotland, Denmark, England, United States, Norway, and Ireland.6-9,11-14,16,17,25,27,32,37,51)
Orders of magnitude Perhaps the most compelling demonstration of the inability of electronic fetal monitoring to affect the prevalence of cerebral palsy is a simple statistical comparison of the relative numbers of a preterm births resulting in cerebral palsy versus infants delivered by cesarean section for “fetal distress.” In this analysis, several facts are relevant. For infants of birth weights <1000 g, mortality in the years 1977 to 1981 was 68%.42 Data spanning the decade of the 1990s demonstrates an improvement in survival of these infants to the range of 65% to 70%, primarily attributable to the introduction of surfactant in the 1980s.41,43 Thus, there has been a rough doubling of survival among those infants at greatest risk for prematurityrelated cerebral palsy. Infants with birth weights <1000 g represent 0.43% of 4 million births in the United States annually.44 Between 3% and 8% of all births in the United State are performed by cesarean section for abnormalities detected with electronic fetal heart rate monitoring.45 Finally, 8% to 10% of infants with birth weights <1000 g will have cerebral palsy.8,23,24 If one uses a 5% rate of cesarean section for “fetal distress” and posits that 50% of such deliveries are actually of benefit to the infant in preventing cerebral palsy, 100,000 cases of cerebral palsy would be prevented annually in the United States. With a doubling of survival in infants weighing <1000 g, since the mid-1970s one finds that of approximately 17,000 babies born annually in this weight range, a change from 35% to 70% survival, means that an additional 6000 babies are now added to the <1000-g survival pool each year. If 10% of such infants have cerebral palsy, 600 new cases of cerebral palsy are now added to the population annually as a result of improved neonatal survival. If these assumptions regarding the efficacy of electronic fetal heart rate monitoring were valid, such changes would
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have resulted in a more than 160-fold net decrease in the overall prevalence of cerebral palsy over the past two to three decades. Even if only 5% of cesarean deliveries performed for fetal distress were actually effective in preventing cerebral palsy, a 16-fold reduction in cerebral palsy prevalence would have been demonstrated relative to the number of surviving but impaired premature infants. It is clear that the putative beneficial effects of cesarean section for “fetal distress” cannot have been “canceled out” by the survival of impaired premature infants. Additional demographic considerations further demonstrate the inefficacy of cesarean section based on an electronic diagnosis of “fetal distress,” without respect to considerations of prematurity. Because the overall rate of cerebral palsy is approximately 2 per 1000, in a birth population of 4 million there are only 8000 babies born with cerebral palsy each year from all etiologies combined. Thus, the theoretic 5% efficacy of cesarean section for fetal heart rate abnormalities discussed above would have long since eliminated this condition from the US population. Even one half of 1% efficacy of cesarean section in preventing cerebral palsy in term infants based on a diagnosis of “fetal distress” would result annually in the birth of 1000 fewer infants with cerebral palsy and would have reduced the incidence of cerebral palsy in term infants by more than 10%. Such figures stand in stark contrast to the manifest lack of any reduction in cerebral palsy prevalence documented in the literature (Table). A test leading to an unnecessary major abdominal operation in more than 99.5% of cases should be regarded by the medical community as absurd at best. Given such considerations, one must conclude that operative intervention based on electronic fetal heart rate monitoring has probably done more harm than good and has probably cost more in terms of maternal morbidity and mortality over the past 30 years than it has benefitted babies. We suggest that cesarean section for “fetal distress” be strictly limited to those conditions described in the International Consensus statement.20 Of course, the above conclusions regarding the inefficacy of electronic fetal monitoring in the prevention of cerebral palsy are predicated on the assumption that most obstetricians are well trained and competent and that cesarean sections based on abnormal fetal heart rate tracings are, for the most part, performed in a timely manner in accordance with traditional teachings regarding monitor interpretation. We feel an assumption of general competence among board-certified obstetriciangynecologists is justified. As outlined above, if obstetricians act competently in this respect even 5% of the time, cerebral palsy would have been statistically eliminated from the population, assuming that such monitoring is an effective technique for the prevention of cerebral palsy. On the other hand, even given an assumption of
general incompetence in monitor interpretation, our conclusions remain the same: if appropriate fetal monitor interpretation is such an arcane art that its true application is limited to a chosen few of superior intellect, this technique is still of no value in the US population in reducing the risk of cerebral palsy. This analysis confirms the conclusions of other investigators that electronic fetal monitoring is, except in very rare instances, of no benefit in preventing cerebral palsy, and that cerebral palsy is, for the most part, a developmental event related to unknown prelabor, or postdelivery events.1-5,20 Other recognized causes of cerebral palsy include fetal exposure to infection-related cytokines, twins, and consanguinity.46-53 Although a statistical association between preterm birth and cerebral palsy is well established, even in this situation, a causative link has been questioned. Stanley and English54 found that the majority of lowbirth-weight infants with cerebral palsy had perinatal courses no different from those who did not have this condition. These and other investigators have questioned whether the same factors giving rise to preterm birth may not also be responsible for the later development of cerebral palsy.54-56 Recent studies demonstrate a clear temporal relationship between the onset of fetal heart rate patterns of severe, repetitive variable decelerations or bradycardia associated with obstetric catastrophes such as maternal cardiac arrest and uterine rupture and newborn outcome based on time of delivery.57,58 Thus, expeditious delivery is clearly indicated in such instances.59 The International Consensus Statement20 also recommends expediting delivery in rare cases of absent variability and repetitive late decelerations; although these latter recommendations may also be reasonable as an investigative approach, it is important to clearly understand that with the exception of the obstetric catastrophes outlined above, no data exist in the entire medical literature to demonstrate that intervention based on any single or combination of fetal heart rate patterns reduces the risk of cerebral palsy in any population. When associated with newborn neurologic impairment, such abnormal patterns will, in most cases, reflect the presence of preexisting developmental abnormalities rather than the ongoing development of such impairment. REFERENCES
1. Freeman RK. Problems with intrapartum fetal heart rate monitoring interpretation and patient management. Obstet Gynecol 2002;100:813-25. 2. Freeman R. Intrapartum fetal monitoring: a disappointing story. N Engl J Med 1990;322:642-6. 3. American College of Obstetricians and Gynecologists. Fetal heart rate patterns Washington (DC): The College; 1995. Technical bulletin No.: 207. 4. Parer JT, King T. Fetal heart rate monitoring: is it salvageable? Am J Obstet Gynecol 2000;182:982-9.
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5. Nelson KB, Dambrosia JM, Ting TY, Grether JK. Uncertain value of electronic fetal monitoring in predicting cerebral palsy. N Engl J Med 1996;334:613-8. 6. Shy NE, Luthy DA, Bennett FC, Whitfield M, Larson EB, van Belle G, et al. Effects of electronic fetal heart rate monitoring as compared with periodic auscultation on the neurologic development of premature infants. N Engl J Med 1990;322:588-93. 7. Hagberg B, Hagber G. The changing panorama of cerebral palsy—bilateral spastic forms in particular. Acta Paediatr 1996;416(Suppl):48-52. 8. Hagberg B, Hagberg G, et al. The changing panorama of cerebral palsy in Sweden, VII: prevalence and origin in the birth year period 1987-90. Acta Paediatr 1996;85:954-60. 9. Hagberg B, Hagberg G, Olow I. The changing panorama of cerebral palsy in Sweden, VI: prevalence and origin during the birth year period 1983-1986. Acta Paediatr 1993;82: 387-93. 10. Robertson CMT, Svenson LW, Joffres MR. Prevalence of cerebral palsy in Alberta. Can J Neurol Sci 1998;25:117-22. 11. Kavcic A, Perat MV. Prevalence of cerebral palsy in Slovenia: birth years 1981 to 1990. Dev Med Child Neurol 1998;40:459-63. 12. Topp M, Uldall P, Greisen G. Cerebral palsy births in eastern Denmark, 1987 90: implications for neonatal care. Paediatr Perinat Epidemiol 2001;15:271-7. 13. Topp M, Uldall P, Langhoff-Roos J. Trend in cerebral palsy birth prevalence in eastern Denmark: birth year period 1979-86. Paediatr Perinat Epidemiol 1997;11:451-60. 14. Parkes J, Dolk H, Hill N, Pattenden J. Cerebral palsy in Northern Ireland; 1981-93. Paediatr Perinat Epidemiol 2001;15:278-86. 15. Colver AF, Gibson M, Hey EN, Jarvis SN, Mackie PC, Richmond S. Increasing rates of cerebral palsy across the severity spectrum in northeast England 1964-1993. Arch Dis Child Fetal Neonat Educ 2000;83:F7-12. 16. Pharoah POD. Cerebral palsy and perinatal care. Br J Obstet Gynaecol 1995;102:356-8. 17. Stanley FJ, Watson L. Trends in perinatal mortality and cerebral palsy in Western Australia, 1967 to 1985. BMJ 1992;304:1658-63. 18. Pharoah POD, Cooke T, Rosenbloom I, Cooke RWI. Trends in birth prevalence of cerebral palsy. Arch Dis Child 1987;62:37984. 19. American College of Obstetricians and Gynecologists. Fetal and neonatal neurologic injury. Washington (DC): The College; 1992. Technical bulletin No.: 163. 20. Maclennan A. A template for defining a causal relationship between acute intrapartum events and cerebral palsy: international consensus statement. BMJ 1999;319:1054-9. 21. Whyte HE, Fitzhardinge PM, Shennen AT, Lennox K, Smith L, Lacy J. Extreme immaturity: outcome of 568 pregnancy of 23-26 weeks’ gestation. Obstet Gynecol 1993;82:1-7. 22. Stevenson DK, Wright LL, Lemons JA, Oh W, Korones SB, Papile L, et al. Very-low-birth-weight outcomes of the National Institute of child health and human development neonatal research network, January 1993 through December 1994. Am J Obstet Gynecol 1998;179:1632-9. 23. Waugh J, O’Callaghan MJ, Tudehope PI, Mahay HA, Burns YR, Gray PH, et al. Prevalence and etiology of neurological impairment in extremely low birthweight infants. J Paediatr Child Health 1996;32:120-4. 24. Bowen JR, Starte DR, Simmons JL, Ma PJ, Leslie GI. Extremely low birthweight infants at 3 years; a developmental profile. J Paediatr Child Health 1993;29:276-81. 25. Pharoah P, Platt MJ, Cooke T. The changing epidemiology of cerebral palsy. Arch Dis Child 1996;75:F169-73. 26. Lorenz JM, Wooliever DE, Jetten JR, Pareth N. A quantitative review of mortality and developmental disability in extremely premature newborns. Arch Pediatr Adolesc Med 1998;152:425-35. 27. Cummins SK, Nelson KB, Grether JK, Velie EM. Cerebral palsy in four northern California counties, births 1983 through 1985. J Pediatr 1993;123:230-7. 28. Stanley FJ. Survival and cerebral palsy in low birthweight infants: implications for perinatal care. Paediatr Perinat Epidemiol 1992;6:298-310.
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29. Sciberras C, Spencer N. Cerebral palsy in Malta 1981 to 1990. Dev Med Child Neurol 1999;41:508-11. 30. Liu J, Li Z, Lin Q, Zhao P, Zhao F, Hong S, et al. Cerebral palsy and multiple births in China. Int J Epidemiol 2000;29:292-9. 31. Razdan S, Kaul RL, Motta A, Kaul S, Bhatt RK. Prevalence and pattern of major neurological disorders in rural Kashmir (India) in 1986. Neuroepidemiology 1994;13:113-9. 32. World Health Organization. World health report 2001, statistical annex, table 2. Available from: www.who.int/en/. Accessed 2001. 33. Kudrjavcev T, Schoenberg BS, Kurland LT, Groover RV. Cerebral palsy—trends in incidence and changes in concurrent neonatal mortality: Rochester, MN, 1950-1976. Neurology 1983;33:1433-8. 34. Stanley F. An epidemiological study of cerebral palsy in western Australia, 1986-1975, I: changes in total incidence of cerebral palsy and associated factors. Dev Med Child Neurol 1979; 21:701-13. 35. O’Shea TM, Preisser JS, Klinepeter KL, Dillard RG. Trends in mortality and cerebral palsy in a geographically based cohort of very low birth weight neonates born between 1982 to 1994. Pediatrics 1998;101:642-7. 36. Dunn-Wasowicz D, Rowecka-Trzebicka K, Milewska-Bobula B, Kasshr-Siemieska B, Idzik BA, Marciski P. Risk factors for cerebral palsy in very low birthweight infants in the 1980s and 1990s. J Child Neurol 2000;15:417-20. 37. Grogaard JB, Lindstrom DP, Parker RA, Culley B, Staklman MT. Increased survival rate in very low birth weight infants (1500 grams or less): no association with increased incidence of handicaps. J Pediatr 1990;117:139-46. 38. Hagberg B. Lessons and indications from three decades of WestSwedish cerebral palsy data. Neuropediatrics 2000;31:284-6. 39. Meberg A. Declining incidence of low birth weight—impact on perinatal mortality and incidence of cerebral palsy. J Perinat Med 1990;18:195-8. 40. Victorian Infant Collaborative Study Group. Improvement of outcome for infants of birth weight under 1000 g. Arch Dis Child 1991;66:765-9. 41. Fanaroff AA, Wright LL, Stevenson DK, Shankaran S, Donovan EF, Ehrenkranz RA, et al. Very low birth weight outcomes of the national institute of child health and human development neonatal research network, May 1991 through December 1992. Am J Obstet Gynecol 1995;173:1423-31. 42. Walker D-JB, Feldman A, Vohr BR, Oh W. Cost benefit analysis of neonatal intensive care for infants weighing less than 1,000 grams at birth. Pediatrics 1984;74:20-5. 43. Cunningham GF, Gant NF, Leveno KJ, Gilstrap LC, Hauth JC, Wenstrom KD, editors. Preterm birth. In: Williams’ obstetrics. 21st ed. New York: McGraw-Hill; 2001. 44. Avery GB. Neonatology pathophysiology and management of the newborn. 3rd ed. Philadelphia: JB Lippincott; 1981. 45. Thacker SB, Stroup DF, Peterson HB. Efficacy and safety of intrapartum electronic fetal monitoring: an update. Obstet Gynecol 1995;86:613-20. 46. Gaudet LM, Smith GN. Cerebral palsy and chorioamnionitis: the inflammatory cytokine link. Obstet Gynecol Surv 2001;56:433-7. 47. Grether JK, Nelson KB. Maternal infection and cerebral palsy in infants of normal birth weight. JAMA 1997;278:207-11. 48. Yoon BH, Jun JK, Romero R, Park KH, Gomez R, Choi JH, et al. Amniotic fluid inflammatory cytokines (interleukin-6, interleukin–1β and tumor necrosis factor-α), neonatal brain white matter lesions and cerebral palsy. Am J Obstet Gynecol 1997;177:19-26. 49. Al-Rajeh S, Bademosi O, Awada A, Ismail H, Al-Shammasi S, Dawodu A. Cerebral palsy in Saudi Arabia: a case control study of risk factors. Dev Med Child Neurol 1991;33:1048-52. 50. Yokoyama Y, Shimizu T, Hayakawa K. Prevalence of cerebral palsy in twins, triplets and quadruplets. Int J Epidemiol 1995;24:943-8. 51. Pharoah POD, Cooke RWI. A hypothesis for the aetiology of spastic cerebral palsy—the vanishing twin. Dev Med Child Neurol 1997;39:292-6.
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52. Sinha G, Corry P, Subesinghe D, Wilde J, Levene MI. Prevalence and type of cerebral palsy in a British ethnic community: the role of consanguinity. Dev Med Child Neurol 1997;39:259-62. 53. Wu YW, Colford JM. Chorioamnionitis as a risk factor for cerebral palsy, a meta-analysis. JAMA 2000;284:1417-24. 54. Stanley FJ, English DR. Prevalence of and risk factors for cerebral palsy in a total population cohort of low-birthweight (<2000G) infants. Dev Med Child Neurol 1986; 28:559-68. 55. Davis DW. Review of cerebral palsy, I: description, incidence, and etiology. Neonat Network 1997;16:7-11. 56. Stanley FJ. Survival and cerebral palsy in low birthweight infants:
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implications for perinatal care. Paediatr Perinat Epidemiol 1992;6:298-310. 57. Clark SL, Hankins GDV, Dudley DA, Dildy GA, Porter TF. Amniotic fluid embolism: analysis of a national registry. Am J Obstet Gynecol 1995;172:158-69. 58. Leung A, Leung EK, Paul RH. Uterine rupture after previous cesarean delivery: maternal and fetal consequences. Am J Obstet Gynecol 1993;169:945-50. 59. American College of Obstetricians and Gynecologists. Standards for Obstetric-Gynecologic Services, Seventh Edition, 1989. Washington, D.C.
Key words: Electronic fetal heart rate monitoring, cerebral palsy, premature birth
Since the development of the electronic fetal heart rate monitor in the late 1960s, this device has gained widespread popularity for use during labor and delivery both in the United States and in most developed counties. Although it is clear that the use of this device has virtually eliminated unexpected intrapartum fetal death, the original hope of clinicians and researchers that the use of this device would have a positive impact on the rate of cerebral palsy has been unrealized.1-5 Indeed, the only clinical trial demonstrating any difference in long-term outcome among fetuses monitored electronically, compared with traditional auscultation techniques, showed a significant increase in cerebral palsy among preterm infants followed during labor with electronic monitoring.1,6 A reasonable question is whether these already-injured preterm infants would have simply died in utero but for the fetal monitoring.
From the University of Utah School of Medicine, LDS Hospital,a and the University of Texas Medical Branch.b Received for publication July 11, 2002; revised November 4, 2002; accepted December 5, 2002. Reprints not available from the authors. © 2003, Mosby, Inc. All rights reserved. 0002-9378/2003 $30.00 + 0 doi:10.1067/mob.2003.204
628
On a broader scale, longitudinal evaluation of rates of cerebral palsy in both developed and underdeveloped countries has failed to demonstrate any significant reduction in net population prevalence of cerebral palsy over the past three decades, this despite a 5-fold increase in the rate of cesarean section based, in part, on the electronically derived diagnosis of “fetal distress.”1-5,7-19 In contrast, global cerebral palsy prevalence has remained stable at about 2 to 3 per 1000 for several decades7-19 (Figure). Such data has lead the international scientific community to conclude that intrapartum hypoxia leading to cerebral palsy is a distinctly rare occurrence and to establish strict and scientifically based guidelines for the evaluation of labor and delivery as a potential cause of a child’s later diagnosis of cerebral palsy.1,5,20 Faced with such data, one might ask whether an actual reduction in the rate of cerebral palsy among term infants, based on “timely” intervention for an abnormal electronic signal, has been masked by a simultaneous and coincidental rise in the survival of premature infants who once would have died, but now live and in whom cerebral palsy develops as a result of complications of prematurity. A critical evaluation of this hypothesis reveals it to be without scientific foundation.
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Lack of supportive data There is no question that prematurity is a significant risk factor for the later development of cerebral palsy.1,8,10,21-27 This is especially true in infants of extremely low birth weight, generally defined as <1000 g, in whom the rate of subsequent cerebral palsy is in the range of 8% to 10%.23,27 Further, advances in neonatal care have, in recent decades, allowed survival of such infants who would previously have died. Thus, there can be little question that some babies today who would previously have died are living only to develop cerebral palsy. In addition, both electronic monitoring and intermittent auscultation are effective for the detection of rare, sudden intrapartum catastrophes manifested by deep variable decelerations or bradycardia that may lead to cerebral palsy.1,20 In such cases, emergency intervention undoubtedly has the potential to avoid hypoxic injury and subsequent cerebral palsy. Although few would question the validity of the above two observations, additional conclusions regarding the relative demographic effects of such events require much more than an assumption that, with respect to cerebral palsy prevalence, one group effectively cancels out the effects of the other. To date, data supporting this assumption have not been presented. Thus, statements to this effect are, by definition, not scientifically founded. Indeed, overwhelming scientific evidence documents (vide infra) that such conclusions are invalid. Cerebral palsy and birth weight Several population analyses of cerebral palsy prevalence have distinguished term from preterm infants.7,11-13,16,28 Although rates of cerebral palsy have, in some studies, showed an increase among infants with birth weights <2500 g, each of the above studies also clearly demonstrated no change in the prevalence of cerebral palsy among infants with birth weights >2500 g. Thus, the issue of cerebral palsy prevalence in term infants has been specifically addressed in the literature and a lack of improvement since the advent of widespread electronic fetal heart rate monitoring confirmed. Underdeveloped countries If the ability for emergency cesarean delivery on the basis of an abnormal fetal heart rate tracing resulted in a significant improvement in the prevalence of cerebral palsy, one would logically expect a significant difference in the rates of cerebral palsy in developed compared with underdeveloped countries, where the electronic and surgical technology available in the developed world is lacking. On the other hand, if cerebral palsy is largely a developmental event and is not significantly influenced by perinatal care, one would expect global rates of this condition to be similar, as is seen with other developmental conditions such as monozygotic twins.
Fortunately, such data are available. Studies of cerebral palsy prevalence in China, Malta, Slovenia, and India all demonstrate cerebral palsy rates between 1.2 and 2.3 per 1000, identical to, or in some cases lower than, that seen in developed countries.11,29-31 In the latter nations, the availability of either electronic fetal monitoring or the capability of emergency cesarean delivery within 30 minutes, is, for the most part, lacking. Such data confirm cerebral palsy as primarily a developmental event, not influenced by current obstetric technologies available in developed countries. A fair question is to what extent data published from underdeveloped countries is valid or can be extrapolated to reach conclusions about care in developed nations. Certainly, cerebral palsy could be underreported as a result of primitive data collection systems. On the other hand, cerebral palsy could be overreported because of to primitive diagnostic systems that fail to differentiate this condition from other forms of neurologic impairment. In any event, reported similarities in cerebral palsy rates between underdeveloped and developed countries on several continents remain striking, especially because data concerning the spectrum of treatable or preventable disease entities, collected with these same data systems, consistently show dramatic differences in disease prevalence and outcome between developed and underdeveloped nations.32 Too little, too late The argument that lower rates of term cerebral palsy attributable to intervention on the basis of electronic monitoring has been masked by an increase in neurologically impaired preterm survivors rests on an assumption that the two events have been simultaneous. A careful review of the medical literature refutes this notion. Some studies comparing outcomes of preterm infants delivered in the mid-1960s with those delivered in later decades demonstrated an increase in the rate of cerebral palsy over time, attributable to improved survival of impaired infants.15,18 Such a finding is not, however, universal.33,34 More recent studies comparing the rates of cerebral palsy in low-birth-weight infants over the decades of the 1980s through 1990s have not shown such trends. Of six such later studies, four demonstrated an unchanged rate of cerebral palsy among premature infants and two described a decreasing cerebral palsy prevalence among premature infants over these decades.35-40 In a longitudinal study from Denmark, Topp et al12,13 demonstrated an increase in cerebral palsy among lowbirth-weight infants in the period from 1979 to 1986, followed by a decrease in the years beyond 1986. As in other studies, these investigators found no change in the rate of cerebral palsy in term infants during either period. In a similar manner, Parkes et al14 in Ireland demonstrated that perinatal mortality rates for preterm infants were unchanged after 1989, yet the rate of cerebral palsy re-
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Table. Reported rates of cerebral palsy, 1966-1996* Years 1966-1977 1975-1980 1980-1985
1985-1990
1990-1995 1996
Country England Norway Sweden Australia United States Slovenia England Norway Japan Denmark Ireland Sweden Australia Canada Slovenia Scotland Denmark England United States India Denmark Ireland Sweden England China Malta
Cerebral palsy prevalence(per 1000) 1.5, 1.7, 2.2 2.6 2.5 1.6 2.0 2.3 2.3 2.1 1.4 3.0 2.2 2.4 1.6 2.6 2.3 2.1 3.0 2.3 2.3 1.2 2.4 2.2 2.1 2.5 1.5, 2.3, 2.1 2.0
*In some instances, the same data collection spans more than a single 5-year interval. Data from references 6-17, 27, 29-34, 37, and 51.
mained stable or increased. As summarized by Hagberg38 after a landmark longitudinal study involving patients over three decades, “the prevalence of [cerebral palsy] in preterms is no longer increasing, in spite of additional improvements in survival.” In a similar manner, Farnoff et al,41 reporting on prospective observations from 12 US centers, in 1995 concluded that the increase in survival of very-low-birth-weight infants seen after the introduction of surfactant therapy in the 1980s “was not accompanied by an increase in medical morbidity.” On the other hand, widespread electronic fetal monitoring, and the resultant increase in cesarean section rate, are largely products of the 1970s and beyond; no further increase in the cesarean section rate has been seen since the mid-1980s (Figure). Thus, the initial increase in the rate of preterm cerebral palsy seen in some, but not all, studies preceded, by a decade or more in most studies, the halcyon days of electronic monitoring. For the past two decades, cerebral palsy rates have been stable or decreasing among preterm infants, whereas cesarean section rates have been stable or increasing. Thus, any putative widespread neurologic benefit to monitored fetuses saved from cerebral palsy by timely cesarean delivery has now had almost two decades to manifest itself, unfettered by confounding increases in the rate of neurologically impaired preterm infants. Yet the rate remains unchanged, demonstrating the error of such assumptions.
Figure. Cerebral palsy prevalence (black bars) in developed countries and the United States. Dark gray bars, Cesarean section rate. (Based on pooled data from Sweden, Australia, Canada, Scotland, Denmark, England, United States, Norway, and Ireland.6-9,11-14,16,17,25,27,32,37,51)
Orders of magnitude Perhaps the most compelling demonstration of the inability of electronic fetal monitoring to affect the prevalence of cerebral palsy is a simple statistical comparison of the relative numbers of a preterm births resulting in cerebral palsy versus infants delivered by cesarean section for “fetal distress.” In this analysis, several facts are relevant. For infants of birth weights <1000 g, mortality in the years 1977 to 1981 was 68%.42 Data spanning the decade of the 1990s demonstrates an improvement in survival of these infants to the range of 65% to 70%, primarily attributable to the introduction of surfactant in the 1980s.41,43 Thus, there has been a rough doubling of survival among those infants at greatest risk for prematurityrelated cerebral palsy. Infants with birth weights <1000 g represent 0.43% of 4 million births in the United States annually.44 Between 3% and 8% of all births in the United State are performed by cesarean section for abnormalities detected with electronic fetal heart rate monitoring.45 Finally, 8% to 10% of infants with birth weights <1000 g will have cerebral palsy.8,23,24 If one uses a 5% rate of cesarean section for “fetal distress” and posits that 50% of such deliveries are actually of benefit to the infant in preventing cerebral palsy, 100,000 cases of cerebral palsy would be prevented annually in the United States. With a doubling of survival in infants weighing <1000 g, since the mid-1970s one finds that of approximately 17,000 babies born annually in this weight range, a change from 35% to 70% survival, means that an additional 6000 babies are now added to the <1000-g survival pool each year. If 10% of such infants have cerebral palsy, 600 new cases of cerebral palsy are now added to the population annually as a result of improved neonatal survival. If these assumptions regarding the efficacy of electronic fetal heart rate monitoring were valid, such changes would
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have resulted in a more than 160-fold net decrease in the overall prevalence of cerebral palsy over the past two to three decades. Even if only 5% of cesarean deliveries performed for fetal distress were actually effective in preventing cerebral palsy, a 16-fold reduction in cerebral palsy prevalence would have been demonstrated relative to the number of surviving but impaired premature infants. It is clear that the putative beneficial effects of cesarean section for “fetal distress” cannot have been “canceled out” by the survival of impaired premature infants. Additional demographic considerations further demonstrate the inefficacy of cesarean section based on an electronic diagnosis of “fetal distress,” without respect to considerations of prematurity. Because the overall rate of cerebral palsy is approximately 2 per 1000, in a birth population of 4 million there are only 8000 babies born with cerebral palsy each year from all etiologies combined. Thus, the theoretic 5% efficacy of cesarean section for fetal heart rate abnormalities discussed above would have long since eliminated this condition from the US population. Even one half of 1% efficacy of cesarean section in preventing cerebral palsy in term infants based on a diagnosis of “fetal distress” would result annually in the birth of 1000 fewer infants with cerebral palsy and would have reduced the incidence of cerebral palsy in term infants by more than 10%. Such figures stand in stark contrast to the manifest lack of any reduction in cerebral palsy prevalence documented in the literature (Table). A test leading to an unnecessary major abdominal operation in more than 99.5% of cases should be regarded by the medical community as absurd at best. Given such considerations, one must conclude that operative intervention based on electronic fetal heart rate monitoring has probably done more harm than good and has probably cost more in terms of maternal morbidity and mortality over the past 30 years than it has benefitted babies. We suggest that cesarean section for “fetal distress” be strictly limited to those conditions described in the International Consensus statement.20 Of course, the above conclusions regarding the inefficacy of electronic fetal monitoring in the prevention of cerebral palsy are predicated on the assumption that most obstetricians are well trained and competent and that cesarean sections based on abnormal fetal heart rate tracings are, for the most part, performed in a timely manner in accordance with traditional teachings regarding monitor interpretation. We feel an assumption of general competence among board-certified obstetriciangynecologists is justified. As outlined above, if obstetricians act competently in this respect even 5% of the time, cerebral palsy would have been statistically eliminated from the population, assuming that such monitoring is an effective technique for the prevention of cerebral palsy. On the other hand, even given an assumption of
general incompetence in monitor interpretation, our conclusions remain the same: if appropriate fetal monitor interpretation is such an arcane art that its true application is limited to a chosen few of superior intellect, this technique is still of no value in the US population in reducing the risk of cerebral palsy. This analysis confirms the conclusions of other investigators that electronic fetal monitoring is, except in very rare instances, of no benefit in preventing cerebral palsy, and that cerebral palsy is, for the most part, a developmental event related to unknown prelabor, or postdelivery events.1-5,20 Other recognized causes of cerebral palsy include fetal exposure to infection-related cytokines, twins, and consanguinity.46-53 Although a statistical association between preterm birth and cerebral palsy is well established, even in this situation, a causative link has been questioned. Stanley and English54 found that the majority of lowbirth-weight infants with cerebral palsy had perinatal courses no different from those who did not have this condition. These and other investigators have questioned whether the same factors giving rise to preterm birth may not also be responsible for the later development of cerebral palsy.54-56 Recent studies demonstrate a clear temporal relationship between the onset of fetal heart rate patterns of severe, repetitive variable decelerations or bradycardia associated with obstetric catastrophes such as maternal cardiac arrest and uterine rupture and newborn outcome based on time of delivery.57,58 Thus, expeditious delivery is clearly indicated in such instances.59 The International Consensus Statement20 also recommends expediting delivery in rare cases of absent variability and repetitive late decelerations; although these latter recommendations may also be reasonable as an investigative approach, it is important to clearly understand that with the exception of the obstetric catastrophes outlined above, no data exist in the entire medical literature to demonstrate that intervention based on any single or combination of fetal heart rate patterns reduces the risk of cerebral palsy in any population. When associated with newborn neurologic impairment, such abnormal patterns will, in most cases, reflect the presence of preexisting developmental abnormalities rather than the ongoing development of such impairment. REFERENCES
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5. Nelson KB, Dambrosia JM, Ting TY, Grether JK. Uncertain value of electronic fetal monitoring in predicting cerebral palsy. N Engl J Med 1996;334:613-8. 6. Shy NE, Luthy DA, Bennett FC, Whitfield M, Larson EB, van Belle G, et al. Effects of electronic fetal heart rate monitoring as compared with periodic auscultation on the neurologic development of premature infants. N Engl J Med 1990;322:588-93. 7. Hagberg B, Hagber G. The changing panorama of cerebral palsy—bilateral spastic forms in particular. Acta Paediatr 1996;416(Suppl):48-52. 8. Hagberg B, Hagberg G, et al. The changing panorama of cerebral palsy in Sweden, VII: prevalence and origin in the birth year period 1987-90. Acta Paediatr 1996;85:954-60. 9. Hagberg B, Hagberg G, Olow I. The changing panorama of cerebral palsy in Sweden, VI: prevalence and origin during the birth year period 1983-1986. Acta Paediatr 1993;82: 387-93. 10. Robertson CMT, Svenson LW, Joffres MR. Prevalence of cerebral palsy in Alberta. Can J Neurol Sci 1998;25:117-22. 11. Kavcic A, Perat MV. Prevalence of cerebral palsy in Slovenia: birth years 1981 to 1990. Dev Med Child Neurol 1998;40:459-63. 12. Topp M, Uldall P, Greisen G. Cerebral palsy births in eastern Denmark, 1987 90: implications for neonatal care. Paediatr Perinat Epidemiol 2001;15:271-7. 13. Topp M, Uldall P, Langhoff-Roos J. Trend in cerebral palsy birth prevalence in eastern Denmark: birth year period 1979-86. Paediatr Perinat Epidemiol 1997;11:451-60. 14. Parkes J, Dolk H, Hill N, Pattenden J. Cerebral palsy in Northern Ireland; 1981-93. Paediatr Perinat Epidemiol 2001;15:278-86. 15. Colver AF, Gibson M, Hey EN, Jarvis SN, Mackie PC, Richmond S. Increasing rates of cerebral palsy across the severity spectrum in northeast England 1964-1993. Arch Dis Child Fetal Neonat Educ 2000;83:F7-12. 16. Pharoah POD. Cerebral palsy and perinatal care. Br J Obstet Gynaecol 1995;102:356-8. 17. Stanley FJ, Watson L. Trends in perinatal mortality and cerebral palsy in Western Australia, 1967 to 1985. BMJ 1992;304:1658-63. 18. Pharoah POD, Cooke T, Rosenbloom I, Cooke RWI. Trends in birth prevalence of cerebral palsy. Arch Dis Child 1987;62:37984. 19. American College of Obstetricians and Gynecologists. Fetal and neonatal neurologic injury. Washington (DC): The College; 1992. Technical bulletin No.: 163. 20. Maclennan A. A template for defining a causal relationship between acute intrapartum events and cerebral palsy: international consensus statement. BMJ 1999;319:1054-9. 21. Whyte HE, Fitzhardinge PM, Shennen AT, Lennox K, Smith L, Lacy J. Extreme immaturity: outcome of 568 pregnancy of 23-26 weeks’ gestation. Obstet Gynecol 1993;82:1-7. 22. Stevenson DK, Wright LL, Lemons JA, Oh W, Korones SB, Papile L, et al. Very-low-birth-weight outcomes of the National Institute of child health and human development neonatal research network, January 1993 through December 1994. Am J Obstet Gynecol 1998;179:1632-9. 23. Waugh J, O’Callaghan MJ, Tudehope PI, Mahay HA, Burns YR, Gray PH, et al. Prevalence and etiology of neurological impairment in extremely low birthweight infants. J Paediatr Child Health 1996;32:120-4. 24. Bowen JR, Starte DR, Simmons JL, Ma PJ, Leslie GI. Extremely low birthweight infants at 3 years; a developmental profile. J Paediatr Child Health 1993;29:276-81. 25. Pharoah P, Platt MJ, Cooke T. The changing epidemiology of cerebral palsy. Arch Dis Child 1996;75:F169-73. 26. Lorenz JM, Wooliever DE, Jetten JR, Pareth N. A quantitative review of mortality and developmental disability in extremely premature newborns. Arch Pediatr Adolesc Med 1998;152:425-35. 27. Cummins SK, Nelson KB, Grether JK, Velie EM. Cerebral palsy in four northern California counties, births 1983 through 1985. J Pediatr 1993;123:230-7. 28. Stanley FJ. Survival and cerebral palsy in low birthweight infants: implications for perinatal care. Paediatr Perinat Epidemiol 1992;6:298-310.
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52. Sinha G, Corry P, Subesinghe D, Wilde J, Levene MI. Prevalence and type of cerebral palsy in a British ethnic community: the role of consanguinity. Dev Med Child Neurol 1997;39:259-62. 53. Wu YW, Colford JM. Chorioamnionitis as a risk factor for cerebral palsy, a meta-analysis. JAMA 2000;284:1417-24. 54. Stanley FJ, English DR. Prevalence of and risk factors for cerebral palsy in a total population cohort of low-birthweight (<2000G) infants. Dev Med Child Neurol 1986; 28:559-68. 55. Davis DW. Review of cerebral palsy, I: description, incidence, and etiology. Neonat Network 1997;16:7-11. 56. Stanley FJ. Survival and cerebral palsy in low birthweight infants:
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implications for perinatal care. Paediatr Perinat Epidemiol 1992;6:298-310. 57. Clark SL, Hankins GDV, Dudley DA, Dildy GA, Porter TF. Amniotic fluid embolism: analysis of a national registry. Am J Obstet Gynecol 1995;172:158-69. 58. Leung A, Leung EK, Paul RH. Uterine rupture after previous cesarean delivery: maternal and fetal consequences. Am J Obstet Gynecol 1993;169:945-50. 59. American College of Obstetricians and Gynecologists. Standards for Obstetric-Gynecologic Services, Seventh Edition, 1989. Washington, D.C.