A systematic review of the role of intrapartum hypoxia-ischemia in the causation of neonatal encephalopathy
2008; Elsevier BV; Volume: 199; Issue: 6 Linguagem: Inglês
10.1016/j.ajog.2008.06.094
ISSN1097-6868
AutoresErnest M. Graham, Kristy A. Ruis, Adam L. Hartman, Frances J. Northington, Harold E. Fox,
Tópico(s)Traumatic Brain Injury and Neurovascular Disturbances
ResumoThe object of this review was to determine the incidence, morbidity, and mortality of an umbilical arterial pH < 7.0; the incidence of hypoxic-ischemic encephalopathy; and the proportion of cerebral palsy associated with intrapartum hypoxia-ischemia in nonanomalous term infants. A systematic review of the English language literature on the association between intrapartum hypoxia-ischemia and neonatal encephalopathy was conducted by using Pubmed and Embase. For nonanomalous term infants, the incidence of an umbilical arterial pH < 7.0 at birth is 3.7 of 1000, of which 51 of 297 (17.2%) survived with neonatal neurologic morbidity, 45 of 276 (16.3%) had seizures, and 24 of 407 (5.9%) died during the neonatal period. The incidence of neonatal neurologic morbidity and mortality for term infants born with cord pH < 7.0 was 23.1%. The incidence of hypoxic-ischemic encephalopathy is 2.5 of 1000 live births. The proportion of cerebral palsy associated with intrapartum hypoxia-ischemia is 14.5%. The vast majority of cases of cerebral palsy in nonanomalous term infants are not associated with intrapartum hypoxia-ischemia. The object of this review was to determine the incidence, morbidity, and mortality of an umbilical arterial pH < 7.0; the incidence of hypoxic-ischemic encephalopathy; and the proportion of cerebral palsy associated with intrapartum hypoxia-ischemia in nonanomalous term infants. A systematic review of the English language literature on the association between intrapartum hypoxia-ischemia and neonatal encephalopathy was conducted by using Pubmed and Embase. For nonanomalous term infants, the incidence of an umbilical arterial pH < 7.0 at birth is 3.7 of 1000, of which 51 of 297 (17.2%) survived with neonatal neurologic morbidity, 45 of 276 (16.3%) had seizures, and 24 of 407 (5.9%) died during the neonatal period. The incidence of neonatal neurologic morbidity and mortality for term infants born with cord pH < 7.0 was 23.1%. The incidence of hypoxic-ischemic encephalopathy is 2.5 of 1000 live births. The proportion of cerebral palsy associated with intrapartum hypoxia-ischemia is 14.5%. The vast majority of cases of cerebral palsy in nonanomalous term infants are not associated with intrapartum hypoxia-ischemia. Intrapartum hypoxia-ischemia can lead to neurologic injuries, seizures, and death; however, this is only 1 of many pathologic processes in the differential diagnosis of neonatal encephalopathy. When electronic fetal monitoring was first introduced, it was assumed that intrapartum hypoxia-ischemia accounted for 50% of perinatal morbidity and mortality.1Quilligan E.J. Paul R.H. Fetal monitoring: is it worth it?.Obstet Gynecol. 1975; 45: 96-100PubMed Google Scholar Subsequent population-based studies have found intrapartum hypoxia-ischemia to be present in a smaller percentage of term children with cerebral palsy, ranging from 8% in Australia2Blair E. Stanley F.J. Intrapartum asphyxia: a rare cause of cerebral palsy.J Pediatr. 1988; 112: 515-519Abstract Full Text PDF PubMed Scopus (440) Google Scholar to 28% in western Sweden.3Hagberg B. Hagberg G. Beckung E. Uvebrant P. Changing panorama of cerebral palsy in Sweden: VIII, prevalence and origin in the birth year period 1991-94.Acta Paediatr. 2001; 90: 271-277Crossref PubMed Google Scholar As many as 65% of children with cerebral palsy are born at term,4Thorngren-Jerneck K. Herbst A. Perinatal factors associated with cerebral palsy in children born in Sweden.Obstet Gynecol. 2006; 108: 1499-1505Crossref PubMed Scopus (156) Google Scholar and 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.5Clark S.L. Hankins G.D. Temporal and demographic trends in cerebral palsy—fact and fiction.Am J Obstet Gynecol. 2003; 188: 628-633Abstract Full Text Full Text PDF PubMed Scopus (230) Google Scholar Although not population based, a study of 351 term infants who presented within 72 hours of birth with neonatal encephalopathy, seizures, or both at 2 tertiary referral intensive care units defined intrapartum asphyxia as the presence of at least 3 of the following: (1) late decelerations on fetal monitoring or meconium staining, (2) delayed onset of respiration, (3) arterial cord blood pH < 7.1, (4) Apgar score < 7 at 5 minutes, and (5) multiorgan damage.6Cowan F. Rutherford M. Groenendaal F. et al.Origin and timing of brain lesions in term infants with neonatal encephalopathy.Lancet. 2003; 361: 736-742Abstract Full Text Full Text PDF PubMed Scopus (502) Google Scholar On the basis of magnetic resonance imaging (MRI) within 2 weeks of birth or postmortem examination, 80% of the neonates with encephalopathy and asphyxia had lesions of the deep gray matter, cortex, or white matter consistent with an evolving hypoxic-ischemic insult, and 69% of neonates with only seizures (ie, no signs or symptoms of encephalopathy) within 3 days of birth had acute ischemic or hemorrhagic lesions. The authors concluded that events in the immediate perinatal period are most important in neonatal brain injury.6Cowan F. Rutherford M. Groenendaal F. et al.Origin and timing of brain lesions in term infants with neonatal encephalopathy.Lancet. 2003; 361: 736-742Abstract Full Text Full Text PDF PubMed Scopus (502) Google ScholarFor Editors' Commentary, see Table of ContentsSee related editorial, page 585 For Editors' Commentary, see Table of Contents See related editorial, page 585 Controversy exists concerning the definition of intrapartum hypoxia-ischemia. Electronic fetal heart rate (FHR) monitoring has been shown to be very imprecise in detecting fetuses with metabolic acidosis and hypoxic-ischemic encephalopathy (HIE),7Larma J.D. Silva A.M. Holcroft C.J. Thompson R.E. Donohue P.K. Graham E.M. Intrapartum electronic fetal heart rate monitoring and the identification of metabolic acidosis and hypoxic-ischemic encephalopathy.Am J Obstet Gynecol. 2007; 197: 301.e1-301.e8Abstract Full Text Full Text PDF PubMed Scopus (60) Google Scholar and newer technologies, such as fetal pulse oximetry and fetal electrocardiogram, are being studied to determine whether they can more accurately identify these fetuses. Early interventions for the neonate who has had an intrapartum hypoxic-ischemic insult, such as head cooling and total body cooling, are being studied, but the therapeutic window is short and may only be 2-6 hours after birth.8Perlman J.M. Summary proceedings from the neurology group on hypoxic-ischemic encephalopathy.Pediatrics. 2006; 117: S28-S33Crossref PubMed Scopus (1) Google Scholar The greater the prevalence of intrapartum hypoxia-ischemia, the larger the impact of these new technologies will be in decreasing neonatal neurologic morbidity and mortality. A confidential inquiry to assess the quality of care and the timing of possible intrapartum asphyxial events of all neonates in Trent, United Kingdom, presenting with grade 2 or 3 neonatal encephalopathy in 1997 concluded that nearly 90% of neonatal encephalopathy cases had evidence of a peripartum insult and that this insult alone was thought likely to account for the clinical condition of 45% of the cases, which implied that better care might reduce the incidence of neonatal encephalopathy by half.9Draper E.S. Kurinczuk J.J. Lamming C.R. Clarke M. James D. Field D. A confidential enquiry into cases of neonatal encephalopathy.Arch Dis Child Fetal Neonatal Ed. 2002; 87: F176-F180Crossref PubMed Google Scholar Our objective is to systematically review the medical literature to examine the role of intrapartum hypoxia-ischemia in causing neonatal encephalopathy in nonanomalous term infants in developed countries. We used published guidelines of the Metaanalysis of Observational Studies in Epidemiology Group (MOOSE) to perform this metaanalysis.10Stroup D.F. Berlin J.A. Morton S.C. et al.Meta-analysis of observational studies in epidemiology: a proposal for reporting. Meta-analysis Of Observational Studies in Epidemiology (MOOSE) group.JAMA. 2000; 283: 2008-2012Crossref PubMed Scopus (16529) Google Scholar To minimize heterogeneity of the study population, we exclusively studied nonanomalous term infants in developed countries, with term defined as ≥ 37 weeks' gestation. Because the outcomes being examined were incidences rather than odds ratios with 95% confidence intervals, formal testing of heterogeneity could not be performed. We sought to identify English-language studies that measured the incidence of having an umbilical arterial pH < 7.0 at birth, the risk of neurologic morbidity and mortality associated with this degree of acidosis, the incidence of HIE, and the proportion of cerebral palsy cases associated with intrapartum hypoxia-ischemia. We searched Pubmed and Embase for English-language articles published from January 1966 to December 2007, using the following search terms as Medical Subject Headings (MeSH) and text words where appropriate: fetal hypoxia; asphyxia neonatorum; hypoxia-ischemia, brain; hypoxia, brain or umbilical artery; and incidence. Reference lists from relevant original research and review articles were manually searched for additional studies. The search was performed by 2 physicians and a medical school librarian. Studies that measured the incidence of an umbilical arterial pH < 7.0, the incidence of HIE, and the proportion of cerebral palsy associated with intrapartum asphyxia were reviewed. To determine the incidence of an umbilical arterial pH < 7.0, studies must have been in a population in which cord gases were routinely obtained at delivery, and a result was obtained in > 50%. When multiple studies used the same population to answer different research questions, only the most comprehensive study for answering our research questions was used. Data from 7 studies that measured the incidence and morbidity and mortality associated with an umbilical arterial pH < 7.0 at birth, 10 studies that measured the incidence of HIE, and 5 studies that measured the proportion of cerebral palsy associated with intrapartum asphyxia were combined to give aggregate incidences and percentages. Using an umbilical arterial pH < 7.0 as an objective measure of the presence of intrapartum hypoxia-ischemia, we identified 7 studies that measured the incidence of this degree of acidosis or that measured the proportion of these infants with neonatal neurologic morbidity and mortality (Table 1). A study of 109 neonates, with an umbilical arterial pH < 7.0 found a significant increase in the incidence of seizures with declining pH;11Goodwin T.M. Belai I. Hernandez P. Durand M. Paul R.H. Asphyxial complications in the term newborn with severe umbilical acidemia.Am J Obstet Gynecol. 1992; 167: 1506-1512Abstract Full Text PDF PubMed Scopus (201) Google Scholar 9% had seizures with a pH of 6.9-6.99, which increased to 80% when the pH was 6.61-6.70. Below a pH of 6.8, more than 50% of infants had seizures and hypotonia. When the cord pH was less than 7.0, the Apgar score was not highly predictive of asphyxial complications. In a study of 358 term infants, with an umbilical arterial pH < 7.20, there were 2 with pH < 7.0: 1 neonatal death in an eclamptic mother and 1 with neonatal seizures.12Winkler C.L. Hauth J.C. Tucker J.M. Owen J. Brumfield C.G. Neonatal complications at term as related to the degree of umbilical artery acidemia.Am J Obstet Gynecol. 1991; 164: 637-641Abstract Full Text PDF PubMed Scopus (140) Google Scholar Three studies performed at Parkland Memorial Hospital between 1987 and 1991 identified 144 term nonanomalous neonates, with an umbilical arterial pH < 7.0.13Gilstrap 3rd, L.C. Leveno K.J. Burris J. Williams M.L. Little B.B. Diagnosis of birth asphyxia on the basis of fetal pH, Apgar score, and newborn cerebral dysfunction.Am J Obstet Gynecol. 1989; 161: 825-830Abstract Full Text PDF PubMed Scopus (222) Google Scholar, 14Goldaber K.G. Gilstrap III, L.C. Leveno K.J. Dax J.S. McIntire D.D. Pathologic fetal acidemia.Obstet Gynecol. 1991; 78: 1103-1107PubMed Google Scholar, 15Perlman J.M. Risser R. Severe fetal acidemia: neonatal neurologic features and short-term outcome.Pediatr Neurol. 1993; 9: 277-282Abstract Full Text PDF PubMed Scopus (48) Google Scholar They found that the combination of a 1-minute Apgar ≤ 3 and pH < 7.0 was a sensitive predictor of all cases of serious neonatal morbidity.13Gilstrap 3rd, L.C. Leveno K.J. Burris J. Williams M.L. Little B.B. Diagnosis of birth asphyxia on the basis of fetal pH, Apgar score, and newborn cerebral dysfunction.Am J Obstet Gynecol. 1989; 161: 825-830Abstract Full Text PDF PubMed Scopus (222) Google Scholar When the umbilical arterial pH was less than 7.0 at birth, 67% had a metabolic component in their acidemia, compared with 14% for those with pH 7.0-7.2.14Goldaber K.G. Gilstrap III, L.C. Leveno K.J. Dax J.S. McIntire D.D. Pathologic fetal acidemia.Obstet Gynecol. 1991; 78: 1103-1107PubMed Google Scholar The statistically significant pH cutoff for all seizures was < 7.05 and for unexplained seizures was < 7.0, with 8 of 12 (67%) of the unexplained seizures occurring in the pH < 7.0 group. Having a pH < 7.0 was associated with a significantly increased frequency of low Apgar scores, early neonatal seizures, and neonatal deaths, but even at this low pH cutoff, nearly two-thirds of the newborn infants were admitted to the regular newborn nursery and had no apparent neurologic sequelae. For neonates with cord pH < 7.0 cardiopulmonary resuscitation and epinephrine intervention in the delivery room for persistent bradycardia identified those at greatest risk for short-term adverse outcome, and it was concluded that therapeutic strategies to preserve brain function in severe fetal acidemia should focus on such infants.15Perlman J.M. Risser R. Severe fetal acidemia: neonatal neurologic features and short-term outcome.Pediatr Neurol. 1993; 9: 277-282Abstract Full Text PDF PubMed Scopus (48) Google ScholarTABLE 1Studies measuring the incidence of an umbilical arterial pH < 7.0 at birth for nonanomalous term infants and neurologic morbidity and mortality associated with this degree of acidosisLocation and date of studyNumber with pH < 7.0Incidence of pH < 7.0 in nonanomalous term infants per 1000 live birthsNeurologic morbidity and mortalityLos Angeles, 1986-199021Graham E.M. Holcroft C.J. Rai K.K. Donohue P.K. Allen M.C. Neonatal cerebral white matter injury in preterm infants is associated with culture positive infections and only rarely with metabolic acidosis.Am J Obstet Gynecol. 2004; 191: 1305-1310Abstract Full Text Full Text PDF PubMed Scopus (80) Google Scholar1092.9 (202/69,340)aA cord gas was obtained at delivery for 10.6% of deliveries at this institution during this time, so their incidence was not used in calculating a population incidence for umbilical arterial pH < 7.0 at birth.33 (30.3%) HIE27 (24.8%) seizures5 (4.6%) deathsBirmingham, AL, 1987-198922Holcroft C.J. Blakemore K.J. Allen M. Graham E.M. Association of prematurity and neonatal infection with neurologic morbidity in very low birth weight infants.Obstet Gynecol. 2003; 101: 1249-1253Crossref PubMed Scopus (26) Google Scholar238.3 (23/2764)1 (4.3%) seizure1 (4.3%) deathDallas, TX, 1987-198823Graham E.M. Holcroft C.J. Blakemore K.J. Evidence of intrapartum hypoxia-ischemia is not present in the majority of cases of neonatal seizures.J Matern Fetal Neonatal Med. 2002; 12: 123-126PubMed Google Scholar186.6 (18/2738)2 (11.1%) seizuresDallas, TX, 1988-199024Badawi N. Kurinczuk J.J. Hall D. Field D. Pemberton P.J. Stanley F.J. Newborn encephalopathy in term infants: three approaches to population-based investigation.Semin Neonatol. 1997; 2: 181-188Abstract Full Text PDF Scopus (12) Google Scholar872.9 (87/30,000)9 (10.3%) seizures7 (8.0%) deathsDallas, TX, 1990-199125Nelson K.B. Ellenberg J.H. Apgar scores as predictors of chronic neurologic disability.Pediatrics. 1981; 68: 36-44Crossref PubMed Google Scholar392 (5.1%) neurologically abnormal at discharge6 (15.4%) seizures3 (7.7%) deathsThe Netherlands, 1991-199226Thornberg E. Thiringer K. Odeback A. Milsom I. Birth asphyxia: incidence, clinical course and outcome in a Swedish population.Acta Paediatr. 1995; 84: 927-932Crossref PubMed Scopus (235) Google Scholar214 (19.0%) Sarnat I2 (9.5%) Sarnat III and diedbThis study does not provide information on neonatal seizures.Ontario, Canada, 1995-200227Brown J.K. Purvis R.J. Forfar J.O. Cockburn F. Neurological aspects of perinatal asphyxia.Dev Med Child Neurol. 1974; 16: 567-580Crossref PubMed Scopus (176) Google Scholar714.0 (71/17,688)22 (31.0%) 5-min Apgar < 735 (49.3%) NICU admissioncThis study did not specifically measure neonatal neurologic morbidity.6 (8.5%) deathsTotal3863.7 (199/53,190)51/297 (17.2%) neurologic morbidity45/276 (16.3%) seizures24/407 (5.9%) deathsHIE, hypoxic-ischemic encephalopathy; NICU, neonatal intensive care unit.Graham. The role of intrapartum hypoxia-ischemia in the causation of neonatal encephalopathy. Am J Obstet Gynecol 2008.a A cord gas was obtained at delivery for 10.6% of deliveries at this institution during this time, so their incidence was not used in calculating a population incidence for umbilical arterial pH < 7.0 at birth.b This study does not provide information on neonatal seizures.c This study did not specifically measure neonatal neurologic morbidity. Open table in a new tab HIE, hypoxic-ischemic encephalopathy; NICU, neonatal intensive care unit. Graham. The role of intrapartum hypoxia-ischemia in the causation of neonatal encephalopathy. Am J Obstet Gynecol 2008. A review of the obstetric, neonatal, and pediatric records for all infants born with a pH < 7.0 over a 19-month period in Leiden found that 2 of 21 (9.5%) infants died in the neonatal period, but when the survivors were evaluated at 1-3 years, they had normal results on the Denver Developmental Screening Test.16Nagel H.T. Vandenbussche F.P. Oepkes D. Jennekens-Schinkel A. Laan L.A. Gravenhorst J.B. Follow-up of children born with an umbilical arterial blood pH < 7.Am J Obstet Gynecol. 1995; 173: 1758-1764Abstract Full Text PDF PubMed Scopus (52) Google Scholar They concluded that the umbilical arterial pH at birth is not predictive of serious developmental delay unless accompanied by clinical evidence of HIE. A study at a large tertiary hospital in Ontario, Canada, found a progression of risk in term infants for Apgar < 7 at 5 minutes, neonatal intensive care unit (NICU) admission, and need for assisted ventilation, with worsening acidosis at birth.17Victory R. Penava D. Da Silva O. Natale R. Richardson B. Umbilical cord pH and base excess values in relation to adverse outcome events for infants delivering at term.Am J Obstet Gynecol. 2004; 191: 2021-2028Abstract Full Text Full Text PDF PubMed Scopus (147) Google Scholar There were marginal but significant increases of 0.4- to 1.5-fold in the incidences of these outcomes beginning near the mean cord pH and more substantial increases of 3- to 10-fold with cord pH values 1 or 2 standard deviations (SD) below the mean (ie, pH of approximately 7.10-7.17, depending on the outcome studied). They concluded that the “near normal” cord pH at which adverse outcomes began to increase was 7.20. Combining data from these 7 studies, we found that the incidence of having an umbilical arterial pH < 7.0 at birth was 3.7 of 1000 (range, 2.9-8.3/1000), and of these infants, 17.2% (range, 5.1-30.3%) survived with neurologic morbidity, 16.3% (range, 10.3-24.8%) developed seizures, and 5.9% (range, 4.3-9.5%) died during the neonatal period (Table 1). The incidence of neonatal neurologic morbidity and mortality for nonanomalous term infants with an umbilical arterial pH < 7.0 at birth was 23.1%, with the remaining 76.9% being neurologically normal at the time of neonatal discharge. In 1 large Canadian study, when using an umbilical arterial base deficit > 12 mM to define intrapartum asphyxia, the prevalence was 26 of 1000 live term births (575/21,818), of whom 15% (3.9/1000) had moderate-severe encephalopathy.18Low J.A. Determining the contribution of asphyxia to brain damage in the neonate.J Obstet Gynaecol Res. 2004; 30: 276-286Crossref PubMed Scopus (123) Google Scholar The incidence of umbilical arterial pH < 7.0 at birth for all viable deliveries, both preterm and term, has been determined to be 12.2 of 1000 live births in The Netherlands19van den Berg P.P. Nelen W.L. Jongsma H.W. et al.Neonatal complications in newborns with an umbilical artery pH < 7.00.Am J Obstet Gynecol. 1996; 175: 1152-1157Abstract Full Text Full Text PDF PubMed Scopus (88) Google Scholar and 6.8 of 1000 in Philadelphia, PA.20Sehdev H.M. Stamilio D.M. Macones G.A. Graham E. Morgan M.A. Predictive factors for neonatal morbidity in neonates with an umbilical arterial cord pH less than 7.00.Am J Obstet Gynecol. 1997; 177: 1030-1034Abstract Full Text Full Text PDF PubMed Scopus (92) Google Scholar Data from this review agree with studies performed within our institution that have found metabolic acidosis to be present in a small proportion of cases of neonatal neurologic injury. Periventricular leukomalacia (PVL) is a major precursor of cerebral palsy, and in our institution, over a 7-year period, only 6% of PVL cases had an umbilical arterial pH < 7.0 or base deficit > 12 mM at the time of birth.21Graham E.M. Holcroft C.J. Rai K.K. Donohue P.K. Allen M.C. Neonatal cerebral white matter injury in preterm infants is associated with culture positive infections and only rarely with metabolic acidosis.Am J Obstet Gynecol. 2004; 191: 1305-1310Abstract Full Text Full Text PDF PubMed Scopus (80) Google Scholar Among neonates weighing < 1500 g at birth, with neurologic morbidity, we found that 5.8% had an umbilical arterial pH < 7.0.22Holcroft C.J. Blakemore K.J. Allen M. Graham E.M. Association of prematurity and neonatal infection with neurologic morbidity in very low birth weight infants.Obstet Gynecol. 2003; 101: 1249-1253Crossref PubMed Scopus (26) Google Scholar A study of all neonatal seizure cases born at our institution over an 11-year period found that 30% had a cord pH < 7.0 at birth.23Graham E.M. Holcroft C.J. Blakemore K.J. Evidence of intrapartum hypoxia-ischemia is not present in the majority of cases of neonatal seizures.J Matern Fetal Neonatal Med. 2002; 12: 123-126PubMed Google Scholar We identified 10 studies in developed countries that measured a population-based incidence of HIE at term (Table 2). The National Collaborative Perinatal Project involved more than 54,000 pregnant women delivering at 12 teaching hospitals in the United States between 1959 and 1966. There were 51,285 liveborn singletons, of whom outcome was known at age 7 years for 45,559 (11% of the population was lost to follow-up).24Badawi N. Kurinczuk J.J. Hall D. Field D. Pemberton P.J. Stanley F.J. Newborn encephalopathy in term infants: three approaches to population-based investigation.Semin Neonatol. 1997; 2: 181-188Abstract Full Text PDF Scopus (12) Google Scholar There were 189 cases of cerebral palsy. When intrapartum hypoxia-ischemia was defined as an Apgar score of 0-3 at 5 minutes, the incidence was 1.8 of 1000.25Nelson K.B. Ellenberg J.H. Apgar scores as predictors of chronic neurologic disability.Pediatrics. 1981; 68: 36-44Crossref PubMed Google Scholar Low Apgar score was a risk factor for cerebral palsy, but of the children with Apgar scores of 0-3 at 10 minutes or later and survived, 80% were free of major handicap at early school age. Of the children with cerebral palsy, 73% had Apgars of 7-10 at 5 minutes. One of the lowest incidences of HIE was found in a study from western Sweden that used a 5-minute Apgar < 7 to define intrapartum hypoxia-ischemia but excluded infants with opioid/anesthesia-related low Apgar scores, congenital malformations, chromosomal disorders, congenital infections, neuromuscular disorders, and subarachnoid hemorrhage.26Thornberg E. Thiringer K. Odeback A. Milsom I. Birth asphyxia: incidence, clinical course and outcome in a Swedish population.Acta Paediatr. 1995; 84: 927-932Crossref PubMed Scopus (235) Google Scholar A Scottish study performed over a 3-year period in the early 1970s attempted to objectively measure the presence of perinatal asphyxia by using a neonatal arterial pH < 7.2 and PCO2 > 60 mm Hg, but only 33 of 94 (35%) of neonates considered to be asphyxiated by other criteria had this degree of acidosis.27Brown J.K. Purvis R.J. Forfar J.O. Cockburn F. Neurological aspects of perinatal asphyxia.Dev Med Child Neurol. 1974; 16: 567-580Crossref PubMed Scopus (176) Google Scholar They noted that this underestimate occurred because some neonatal arterial blood gases were obtained after a buffer base was given as an immediate treatment.TABLE 2Studies measuring the incidence of hypoxic-ischemic encephalopathy in nonanomalous term infantsLocationYears of studyDefinition of asphyxiaIncidence of HIE per 1000 live births (cases/population)United States11Goodwin T.M. Belai I. Hernandez P. Durand M. Paul R.H. Asphyxial complications in the term newborn with severe umbilical acidemia.Am J Obstet Gynecol. 1992; 167: 1506-1512Abstract Full Text PDF PubMed Scopus (201) Google Scholar1959-1966Apgar 0-3 at 5 min.1.8 (81/44,517)Western Sweden12Winkler C.L. Hauth J.C. Tucker J.M. Owen J. Brumfield C.G. Neonatal complications at term as related to the degree of umbilical artery acidemia.Am J Obstet Gynecol. 1991; 164: 637-641Abstract Full Text PDF PubMed Scopus (140) Google Scholar1985-1991Apgar < 7 at 5 min. Excluded opioid/anesthesia-related low Apgar scores, congenital malformations, chromosomal disorders, congenital infections, neuromuscular disorders, and subarachnoid hemorrhage.1.8 (75/42,203)Edinburgh, Scotland13Gilstrap 3rd, L.C. Leveno K.J. Burris J. Williams M.L. Little B.B. Diagnosis of birth asphyxia on the basis of fetal pH, Apgar score, and newborn cerebral dysfunction.Am J Obstet Gynecol. 1989; 161: 825-830Abstract Full Text PDF PubMed Scopus (222) Google Scholar3-y period, published 1974Meconium, FHR > 170 or < 120 bpm or irregular FHR, Apgar < 3 at 1 min or < 5 at 5 min, need for intermittent positive pressure respiration, neonatal pH < 7.2 and PCO2 > 60 mm Hg.5.9 (83/14,020)Alberta, Canada15Perlman J.M. Risser R. Severe fetal acidemia: neonatal neurologic features and short-term outcome.Pediatr Neurol. 1993; 9: 277-282Abstract Full Text PDF PubMed Scopus (48) Google Scholar1974-1978Abnormal intrapartum FHR pattern, Apgar < 5 at 1 or 5 min, need for immediate neonatal resuscitation.3.3 (67/20,155)Western Australia16Nagel H.T. Vandenbussche F.P. Oepkes D. Jennekens-Schinkel A. Laan L.A. Gravenhorst J.B. Follow-up of children born with an umbilical arterial blood pH < 7.Am J Obstet Gynecol. 1995; 173: 1758-1764Abstract Full Text PDF PubMed Scopus (52) Google Scholar1993-1995Abnormal intrapartum FHR on cardiotocogram or auscultation and/or fresh meconium in labor, followed by 1 min Apgar < 3 and 5-min Apgar < 7.3.8 (164/43,160)Leicester, United Kingdom17Victory R. Penava D. Da Silva O. Natale R. Richardson B. Umbilical cord pH and base excess values in relation to adverse outcome events for infants delivering at term.Am J Obstet Gynecol. 2004; 191: 2021-2028Abstract Full Text Full Text PDF PubMed Scopus (147) Google Scholar1980-1983Retrospective review of neonates diagnosed with asphyxia, Abnormal intrapartum FHR tracing used to support the diagnosis, low Apgar score was noted but if depressed, not considered evidence of asphyxia.6.0 (126/20,975)Derby, United Kingdom19van den Berg P.P. Nelen W.L. Jongsma H.W. et al.Neonatal complications in newborns with an umbilical artery pH < 7.00.Am J Obstet Gynecol. 1996; 175: 1152-1157Abstract Full Text Full Text PDF PubMed Scopus (88) Google Scholar1976-19801984-19881992-1996Same as Levene et al.31Levene M.L. Kornberg J. Williams T.H. The incidence and severity of post-asphyxial encephalopathy in full-term infants.Early Hum Dev. 1985; 11: 21-26Crossref PubMed Scopus (234) Google Scholar7.7 (189/24,824)4.6 (112/24,265)1.9 (48/24,804)Pittsburgh, PA20Sehdev H.M. Stamilio D.M. Macones G.A. Graham E. Morgan M.A. Predictive factors for neonatal morbidity in neonates with an umbilical arterial cord pH less than 7.00.Am J Obstet Gynecol. 1997; 177: 1030-1034Abstract Full Text Full Text PDF PubMed Scopus (92) Google Scholar1970-1975Requiring > 1 min positive pressure ventilation before spontaneous respiration occurred.4.9 (149/30,621)South West Thames, United Kingdom10Stroup D.F. Berlin J.A. Morton S.C. et al.Meta-analysis of observational studies in epidemiology: a proposal for reporting. Meta-analysis Of Observational Studies in Epidemiology (MOOSE) group.JAMA. 2000; 283: 2008-2012Crossref PubMed Scopus (16529) Google Scholar1993-1995No a priori definition of birth asphyxia, but range of definitions used.2.5 (149/60,000)Trent, United Kingdom10Stroup D.F. Berlin J.A. Morton S.C. et al.Meta-analysis of observational studies in epidemiology: a proposal for reporting. Meta-analysis Of Observational Studies in Epidemiology (MOOSE) group.JAMA. 2000; 283: 2008-2012Crossref PubMed Scopus (16529) Google Scholar1990-1997One or more of the following: low Apgars, thick meconium, midwife diagnosis of fetal distress, FHR abnormality, decreased fetal movement, low cord pH; other cases discussed individually.1.2 (358/300,000)Total2.5 (1601/649,544)bpm, beats per minute; FHR, fetal heart rate; HIE, hypoxic-ischemic encephalopathy.Graham. The role of intrapartum hypoxia-ischemia in the causation of neonatal encephalopathy. Am J Obstet Gynecol 2008. Open table in a new tab bpm, beats per minute; FHR, fetal heart rate; HIE, hypoxic-ischemic encephalopathy. Graham. The role of intrapartum hypoxia-ischemia in the cau
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