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A Proposed Evidence-Based Neonatal Work-up to Confirm or Refute Allegations of Intrapartum Asphyxia

Muraskas, Jonathan K. MD; Morrison, John C. MD

doi: 10.1097/AOG.0b013e3181e7d267
Original Research

OBJECTIVE: To propose a clinical work-up in term and near-term newborns to address the nine American College of Obstetricians and Gynecologists (the College) and American Academy of Pediatrics criteria to define an acute intrapartum event sufficient to cause cerebral palsy.

METHODS: We examined our experience as neonatal expert witnesses in 103 closed claims of alleged intrapartum asphyxia with poor newborn outcome over a 21-year period from 1987 to 2008. We estimated how often the clinical components of this proposed work-up were not obtained or recorded in the medical record.

RESULTS: Cord arterial blood gases and placental pathology were not obtained or sent in 38% and 32% of the 103 cases, respectively. Routine neonatal laboratory tests, including a complete blood count with differential, nucleated red blood cells, electrolytes, calcium, coagulation profile, and renal and liver function tests, were frequently absent. Cranial imaging in ultrasonograms, computed tomography, and magnetic resonance imaging were absent in more than 50% of the cases reviewed and were often not scheduled at optimal times.

CONCLUSION: The medical record of newborns with poor outcomes frequently has a paucity of objective, evidence-based data. This leads to speculation and unethical expert testimony. The protocol will assist in confirming or refuting allegations of intrapartum asphyxia.


A protocol is proposed to confirm or refute allegations of obstetric professional liability resulting in poor newborn outcomes.

From the Division of Neonatal-Perinatal Medicine, Loyola University Medical Center, Maywood, Illinois; and the Department of Obstetrics and Gynecology, University of Mississippi Medical Center, Jackson, Mississippi.

Corresponding author: Jonathan Muraskas, MD, Division of Neonatal-Perinatal Medicine, Loyola University Medical Center, 2160 South 1st Avenue, 107-5810, Maywood, IL 60153; e-mail:

Financial Disclosure John Morrison is a consultant for Alere, Christus Healthcare, and Atley Pharmaceuticals. He is on the speakers bureau for Adeza Bio-Medical, Wyeth, Omegatech, and Proctor and Gamble and has received grants from Kimberly Clark, Upjohn, Argent, Lupitold, and Matria Healthcare. The other author did not report any potential conflicts of interest.

The professional liability crisis remains a common problem for obstetricians. Approximately 89% of the American College of Obstetricians and Gynecologists (the College) fellows have been sued at least once, and 15% have ceased obstetric practice because of exorbitant premiums and the prevalence of nonmeritorious claims in this field of practice.1,2 The average age at which an obstetrician–gynecologist stops providing obstetric care is currently 48 years, an age at which most physicians approach the peak of judgment and experience. Efforts aimed at tort reform, award caps, and the policing of junk science have not been uniformly successful.3 The average award for “alleged medical negligence” in child birth cases is $2.3 million.4 The global cerebral palsy (CP) rate is approximately one to two cases per 1,000 live births. Cerebral palsy attributable to hypoxic ischemic encephalopathy in the singleton term (37 or more weeks of gestation) and near-term (34 or more weeks of gestation) newborns is even more rare, with a reported incidence of approximately one in 12,500 live births.5 The rate of CP has not decreased in developed countries over the past 30 years, despite the widespread use of electronic fetal heart rate monitoring and a fivefold increase in cesarean delivery rate.6 In 2003, the College/American Academy of Pediatrics task force on Neonatal Encephalopathy and Cerebral Palsy identified four essential and five suggestive criteria to define an acute intrapartum event sufficient to cause CP in term/near-term newborns.7 Acute intrapartum events account for approximately 10% of cases of CP. The focus is too often on the last 3 hours of a typical 7,000-hour term gestation. It is common for plaintiffs' attorneys to be willing to pursue litigation against physicians and hospitals even when causation criteria are not fully met. The use of junk science, unethical expert witness testimony, and speculation is all too common in medical litigation involving the obstetrician and compromised newborn. A routine clinical work-up in these newborns with alleged intrapartum asphyxia is proposed that will address these nine criteria.

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Over a 21-year period (1987–2008), 109 consecutive cases of alleged intrapartum asphyxia in the term/near-term newborn were requested to be reviewed by a neonatal expert witness (J.M.). Of these, six were not reviewed because of a conflict of interest with the institution or physician. Twenty-nine of 103 (28%) of the cases reviewed occurred since the the College criteria were published in 2003. Eighty-one of 103 (79%) were reviewed for the defense and 22 of 103 (21%) for the plaintiff. Including 71 cases from Illinois, a total of 89 of 103 (86%) were from the Midwest and 14 cases from seven other states. Singleton gestation and male gender made up 88% and 58% of the cases, respectively. In defense cases, 69 of 81 (85%) were deemed defensible and 14 of 22 (64%) for the plaintiff were deemed nonmeritorious by the author. All 103 cases have been resolved, with18 of 103 (17%) dismissed and 85 of 103 (83%) settled. Eight of 103 (8%) cases went to trial, with six of eight (75%) resulting in a favorable verdict for the defense. The computation of percentages and confidence intervals were used for data analysis. The analysis describes only the percentage of tests not available in the medical record in each of the proposed clinical work-up categories. We propose a clinical work-up to address the nine College criteria to define an acute intrapartum event and estimated how often the various components of this work-up were not obtained or recorded in the medical record.

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A routine clinical work-up in term and near-term newborns to address all nine College criteria is proposed (Table 1). Table 2 illustrates a clinical template in the first 7 days of life to best follow the progression of the neurotoxic cascade in acute intrapartum asphyxia. In the 103 cases reviewed, Table 3 gives the percentage of proposed clinical data not obtained or reported in the medical record of 103 cases of alleged intrapartum asphyxia. From the obstetric point of view, it is noteworthy that an arterial cord gas was not obtained 38% of the time, and placental pathology was absent in 32% of these cases. Microcephaly at birth was present in seven of 103 (7%) of the cases reviewed but was not documented in the medical record. In 77% of cases reviewed, no 10- and 15-minute Apgar scores were assigned despite an Apgar score of less than 6 at 5 minutes. Serial nucleated red blood cell counts during the first 3 days of life were not obtained in 91% of cases we reviewed. Routine neonatal laboratory examinations and cranial imaging were frequently not part of the neonatal work-up in the medical record.

Table 1

Table 1

Table 2

Table 2

Table 3

Table 3

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Each case of alleged intrapartum asphyxia is unique and no single test can time an alleged event. The College criteria have been criticized as being too restrictive and potentially not being able to identify many cases of intrapartum asphyxia. Perlman8 considers a sentinel event to be a critical and essential first step in linking intrapartum asphyxia to neonatal encephalopathy. Aside from a sentinel event during labor, the College criteria are postdelivery assessments.8 Despite the controversy, we feel this proposed work-up will provide significantly more objective data in the medical record to support or refute allegations of intrapartum asphyxia. We have demonstrated that obstetricians do not consistently obtain cord arterial blood gases or send placental pathology in eventful deliveries. Routine neonatal laboratory studies, such as a complete blood count with differential, nucleated red blood cells, electrolytes, calcium, coagulation profile, and renal or hepatic function test, are frequently absent. In more than 50% of the cases reviewed, cranial imagings by ultrasonography, computed tomography, or magnetic resonance imaging were absent and often not optimally scheduled to assist in the timing of the insult. The criteria to define an acute intrapartum event sufficient to cause CP modified from the international Cerebral Palsy Task Force in relation to this work-up are described.

Umbilical cord blood gas assessments are the most objective determinants of the fetal metabolic condition at the moment of birth.9 Umbilical arterial blood reflects fetal status more directly and umbilical venous blood more closely reflects whether the oxygen exchange of the uteroplacental unit is optimal. Westgate et al10 recommend obtaining cord blood from the artery and vein. However, in clinical practice this is not practical and an umbilical cord arterial gas is most often obtained. Fetal scalp blood sampling has been virtually eliminated in clinical practice without an increase in adverse newborn outcomes.11

An ongoing dilemma with the College criteria is the requirement of metabolic acidemia to determine whether an insult occurred intrapartum. Many term newborns who are delivered in the presence of fetal acidemia are not recognized by intrapartum events and are triaged to the regular nursery with an uneventful hospital course.12 Studies have demonstrated when the umbilical artery pH was less than 7.0 at birth, 67% had a metabolic component in their acidemia compared with 14% for those with pH of 7.0 to 7.2.13 One study showed with an umbilical arterial pH less than 7.0 at birth, neurologic damage was found in 23%, with the remaining 77% being neurologically normal at the time of neonatal discharge.14 The pH is a direct measurement, whereas the base deficit is a calculated value obtained by the Siggard-Andersen alignment nomogram. This nomogram can confirm the biochemical authenticity of arterial cord blood gases.15 Umbilical arterial pH decreases and the base deficit increases during the course of normal labor, because a buffer base is depleted before the pH declines.16 The pH decreases approximately 0.07 units for every 10-mm Hg increment increase in PCO2.17 The respiratory component of acidosis cannot damage the newborn, and when present, the onset of hypoxia can be established because this component cannot last more than 20 to 30 minutes.18 In our experience, the absence of a cord arterial blood gas leads to more speculation between the plaintiff and defense experts than any other laboratory value and should be drawn in all deliveries and sent for analysis when clinically indicated.

Neonatal encephalopathy is a clinically defined syndrome of disturbed neurological function in the earliest days of life, manifested by depression of tone and reflexes, subnormal levels of consciousness, and often times, seizures. After intrapartum asphyxia, hypotonia is the norm and, in general, early hypertonia or absence of hypotonia (normal tone) point to other neurological abnormalities.19 The grading of neonatal encephalopathy as mild, moderate, or severe was originally described by Sarnat and Sarnat.20 The presence of seizures is required to meet the Sarnat criteria for moderate to severe encephalopathy. Neonatal seizures can be subtle, often presenting with oxygen desaturations and focal motor abnormalities such as eye deviation, smacking of lips, and staring. Also, the presence of atypical apnea with desaturations frequently was not identified as seizures and delayed appropriate therapy. An electroencephalogram can be used to confirm the presence of seizures. Seizures soon after birth (1–6 hours or more than 24 hours of life are not consistent with acute intrapartum asphyxia).19 When seizures occurred within 24 hours, 48% of newborns were significantly negatively affected compared with when the seizures occurred after 24 hours.21

Cerebral palsy is most often not diagnosed until well after the first year of life. White matter lesions such as cystic periventricular leukomalacia is a common lesion of prematurity (less than 34 weeks of gestation), often results in spastic diplegia, and is usually not associated with intrapartum asphyxia in the term infant.22 However, focal noncystic white matter injury is increasingly recognized in term newborns with neonatal encephalopathy.23 In term newborns, the gray matter is the most metabolically active and therefore most vulnerable to an acute intrapartum event. Although spastic quadriplegia with a dyskinetic, chorioathetoid component is the most common subtype of CP associated with an acute profound hypoxic intrapartum event, it is not specific to intrapartum hypoxia.24,25

The majority of cases involving neonatal encephalopathy and CP are associated with maternal and antenatal factors such as intrauterine infection, maternal/fetal coagulation problems, antenatal hemorrhage, abnormal presentation, preterm birth, and developmental/chromosomal abnormalities. Plotting out weight, length, and head circumference is a vital component of the initial newborn assessment. The presence of microcephaly at birth can be consistent with an earlier pregnancy insult and usually results in a poor neurological outcome.26,27 The presence of intrauterine growth restriction and status of small for gestational age at birth can be associated with poor neurodevelopmental outcomes.28–30

The placenta can be an excellent source of information to confirm alternate etiologies such as metabolic disorders, adverse growth events, and infections.31 Intraamniotic infection is the most common antecedent to birth depression, low Apgar scores, and neonatal encephalopathy in term newborns.32 The presence of chorioamnionitis and funisitis are significant risk factors for CP in term/near-term newborns.33–36 Fetal inflammatory response syndrome caused by cytokine expression in the fetus after exposure to maternal infection can also result in neonatal encephalopathy, often with negative cultures, cord arterial pH more than 7.0, and Apgar scores more than 3 to 5 at 5 minutes.37 Infection, inflammation, thrombosis, and coagulopathy are recognized as being associated with white matter-mediated damage caused by the elevated fetal cytokines and are ultimately associated with periventricular leukomalacia and encephalopathy. A newborn with neutropenia (absolute neutrophil count less than 2,000) and a band-to-segmented neutrophils ratio of more than 0.2 on a complete blood count more probably than not has clinical sepsis despite negative cultures.38,39 Newborn blood cultures should be obtained any time sepsis is suspected. A genetic work-up may be helpful to direct postnatal testing. Newborn thrombophilias also can be a congenital cause of abnormal neonatal outcome and may present as a hemorrhagic or thrombotic lesion. Many known thrombophilias, such as antithrombin III deficiency, protein C or S deficiency, prothrombin genetic deficiencies, hyperhomocystinemia, and factor V Leiden mutation, can all lead to strokes in the newborn, which can cause neonatal encephalopathy with CP and mental retardation and/or fetal/neonatal death.40 Meconium-stained amniotic fluid is often erroneously associated with intrapartum fetal distress. In reality, 15% of the 4,000,000 annual births in the United States have meconium-stained amniotic fluid.41

Nonspecific criteria collectively suggestive of intrapartum timing include sentinel hypoxic intrapartum event. Cord prolapse, ruptured uterus, maternal shock amniotic fluid embolus, and acute bleeding can result in catastrophic intrapartum asphyxia.

Vaginal bleeding during labor can signal trauma, such as a ruptured uterus, abruptio placenta/placenta previa, or fetal bleeding from a vasoprevia. When bleeding leads to fetal damage, it is usually associated with a significantly abnormal electronic fetal heart rate tracing such as bradycardia (usually less than100 beats per minute for more than 10 minutes) and/or repetitive late decelerations with absent fetal heart rate variability. Bleeding can also be concealed and such fetal heart rate tracings may be the only suggestion of fetal compromise.

The presence of anemia in the newborn at birth also can point to nonpreventable etiologies such as maternal–fetal transfusion as well as chronic abruption. Unexplained anemia in the newborn should prompt the pediatrician/neonatologist to request a maternal Kleihauer-Betke test. In the newborn, a complete blood count with differential and a platelet count at birth as well as nucleated red blood cell often can be helpful in differentiating the patient with intrapartum asphyxia from other causes of encephalopathy.

The presence of thrombocytopenia (less than 150,000) as well as an elevated hemoglobin (greater than 18 g/dL) and hematocrit (greater than 55%) in the newborn can be consistent with chronic hypoxia in utero.42–44 Serial nucleated red blood cell counts in the first 3 days of life can provide helpful information because an elevated nucleated red blood cell count at birth with delayed clearance (greater than 72 hours) does not support a diagnosis of acute intrapartum asphyxia.45 The proportion of CP associated with intrapartum hypoxia-ischemia is 8% to 14.5%.9,46 Certain preexisting conditions such as perinatal ischemic stroke, neuromuscular disorders, and certain in-born errors of metabolism can present at birth with a clinical picture not unlike intrapartum asphyxia.47 Likewise, elevated lymphocyte counts in the fetus may be predictive of earlier hypoxia that antedates labor.48 Finally, a detailed note by the obstetrician after delivery that summarizes the intrapartum course may be helpful in ruling out asphyxia in labor as the cause of newborn depression.

The National Institute of Child Health in Human Development's Research Planning Workshop on electronic fetal heart rate monitoring offers standardized definitions for such tracings.49 The participants agreed that tracings with a normal fetal heart rate pattern including baseline heart rate within the normal range and normal fetal heart rate variability with the presence of accelerations and absent of decelerations (type I) confers an extremely high likelihood of a normally oxygenated fetus. At the other end of the spectrum, when there is bradycardia or repetitive (greater than 50% of contractions) late or significant variable decelerations, each with absent fetal heart rate variability (type III), there is a substantial risk of impending damaging asphyxia. However, the false-positive rates of these patterns (type III) are very high, and the majority of nonreassuring fetal tracings during labor are associated with normal outcomes. Thus, none of these patterns can be used to predict CP and mental retardation as an outcome ascribed to intrapartum asphyxia. However, if accelerations occur above a normal baseline and variability of any degree is present, then it frequently rules out intrapartum acidosis or asphyxia as a cause of neonatal encephalopathy and CP. An in-depth review of the fetal heart rate tracing is helpful in confirming or refuting asphyxia as the cause of newborn depression.

Apgar scores can be subjective. Numerous factors can affect the Apgar scores, including intrapartum maternal sedation or anesthesia, congenital malformations, the individual assigning the score, resuscitative efforts, and the presence of an infection.50 This can result in speculation on the quality and response to resuscitation. Although low Apgars are poor predictors of long-term neurologic outcome, there is a good correlation with extremely low Apgars (0, 1, and 2) at 15 to 20 minutes and subsequent neurologic dysfunction. For example, Apgar score of less than 3 at 15 minutes was associated with a 53% neonatal mortality rate and a 36% CP incidence.51 Conversely, it is also true that 75% of children with CP have normal Apgar scores. The fine details of resuscitation require documentation or they could be used erroneously to support intrapartum asphyxia. Inability to achieve an adequate airway in a depressed newborn or failure of a previously damaged fetus to transition to extrauterine life are common etiologies of low Apgar scores and can erroneously lead to the assumption that this depression is attributable to the obstetric care. This is also important because the 30-minute decision–incision guideline may impact Apgar scores, as well as umbilical and neonatal blood gas sampling.52 It is paradoxical to note, however, that in 50% to 65% of cases, the decision–incision interval exceeds 30 minutes, but the lower Apgar scores and blood gases are usually found in those who have an interval of less than 30 minutes and often less than 15 minutes.53

Multisystem organ dysfunction is physiologically related to the diving reflex. In the majority of cases, intrapartum asphyxia deprives all other organs of oxygenated blood before the flow of oxygen to the brain is diminished. Studies have demonstrated that a cord pH 6.92 or less is the threshold linked with neonatal organ dysfunction at 72 hours of birth.54 Many expert witnesses erroneously consider a transient decrease in urine output (less than 2 mL·kg-1·h-1) or a slight elevation in liver enzymes to be signs of multiorgan failure. The presence of pulmonary hypertension, tricuspid insufficiency, hypocalcemia, hypoglycemia, abnormal cardiac enzymes, and coagulopathy may be more supportive of multiorgan failure after a significant intrapartum event if other causes cannot be ruled out.55

Several patterns of brain injury may result from hypoxic-ischemic episodes in the fetus and depend on the severity of cerebral hypotension, the maturity of the brain at the time of injury, and the duration or recurrence of the event. Cerebral edema usually appears approximately 24 hours after a significant asphyxial episode and resolves in 3 to 5 days.56,57 The presence of cerebral edema on an ultrasonogram on the first day of life would not be consistent with an acute intrapartum asphyxial event. The evolution of cystic periventricular leukomalacia in preterm newborns takes 2 to 3 weeks after an insult to be visualized using conventional imaging studies such as computed tomography and ultrasonography scans.58 Magnetic resonance imaging has emerged as a valuable tool for determining the timing and etiology of neonatal brain injury.59 Hypoxia-ischemia in term newborns typically results in one of two characteristic patterns of brain injury: 1) a basal ganglia distribution pattern involving deep gray nuclei, hippocampi, and perirolandic cortex with additional cortical involvement when severe, and 2) a watershed distribution pattern involving intervascular boundary-zone white matter plus cortical gray matter when severe.60 Acute total asphyxia mainly involves the brain stem nuclei, thalami, and basal ganglia and is associated with dystonic CP and brain stem deficits. Prolonged partial asphyxia involves mainly the cerebral cortex, especially parasagittal regions, and is associated with spastic quadriplegia and microcephaly.61,62 In term newborns, basal ganglia and thalamic lesions evolve through a neurotoxic cascade during the first week after the insult. Imaging studies obtained too early after birth may appear normal even when there has been severe injury to the brain.63 It is important to consider not only which imaging studies to obtain but also when to schedule them to optimize the results in attempting to determine the timing of the alleged insult. Neuroimaging can be helpful in approximating a window of time when the injury might have occurred.

Although tort reform in some states has reduced nonmeritorious legal suits, professional liability involving the obstetrician and compromised newborn continues to be a crisis. The medical record of the mother and newborn frequently has a paucity of data. This leads to the use of junk science, unethical expert witness testimony, and speculation in child birth litigation. The proportion of CP associated with intrapartum hypoxia-ischemia is 8% to 14.5%. We developed a clinical work-up for newborns based on our experience in reviewing 103 cases of alleged intrapartum asphyxia. These suggested clinical data are directly related to the four essential and five suggestive criteria proposed in defining an acute intrapartum event sufficient to cause CP. In this litigious society with tort reform still being debated, this work-up can favorably affect the current malpractice crisis. The evolution of a malpractice case can take years before a trial date is set. This protocol will result in significant objective data in the medical record and provide both defense and plaintiff expert evidence-based medicine to decide on the meritorious nature of the allegations. We recommend this protocol be considered in any depressed term/near-term newborn, as well as in newborns with the onset of seizures in the first 24 hours of life when the etiology is not clear. We emphasize that none of these observations sets the standard of care or reflects an exclusive standard of care.

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1. Chauhan SP, Chauhan VB, Cowan BD, Hendrix NW, Magann EF, Morrison JC. Professional liability claims and Central Association of Obstetricians and Gynecologists members: Myth versus reality. AJOG 2005;192:1820–8.
2. MacLennan A, Nelson KB, Hankins G, Speer M. Who will deliver our grandchildren? Implications of cerebral palsy litigation. JAMA 2005;294:1688–90.
3. Clark SL, Belfort MA, Dildy GA, Meyers JA. Reducing obstetric litigation through alterations in practice patterns. Obstet Gynecol 2008;112:1279–83.
4. Hankins GD, MacLennan AH, Speer ME, Strunk A, Nelson K. Obstetric litigation is asphyxiating our maternity services. Obstet Gynecol 2006;107:1382–5.
5. Phelan JP, Martin GI, Korst LM. Birth asphyxia and cerebral palsy. Clin Perinatol 2005;32:61–76, vi.
6. Clark SL, Hankins GD. Temporal and demographic trends in cerebral palsy—fact and fiction. Am J Obstet Gynecol 2003;188:628–33.
7. The American College of Obstetricians and Gynecologists and American Academy of Pediatrics. Neonatal encephalopathy and cerebral palsy: defining the pathogenesis and pathophysiology. Washington, DC: The American College of Obstetricians and Gynecologists, American Academy of Pediatrics; 2003.
8. Perlman J. Intrapartum asphyxia and cerebral palsy: is there a link? Clin Perinatal 2006;33:335–53.
9. ACOG Committee on Obstetric Practice. Umbilical cord blood gas and acid-base analysis. Obstet Gynecol 2006;108:1319–22.
10. Westgate J, Garibaldi JM, Greene KR. Umbilical cord blood gas analysis at delivery: a time for quality data. Br J Obstet Gynaecol 1994;101:1054–63.
11. Goodwin TM, Milner-Masterson L, Paul RH. Elimination of fetal scalp blood sampling on a large clinical service. Obstet Gynecol 1994;83:971–4.
12. Clark SJ, Belfort MA, Byrun SL, et al. Improved outcomes, fewer cesarean deliveries, and reduced litigation: results of a new paradigm in patient safety. Am J Obstet Gynecol 2008;199:105 e1–7.
13. Goldaber KG, Gilstrap LC III, Leveno KJ, Dax JS, McIntire DD. Pathologic fetal acidemia. Obstet Gynecol 1991;78:1103–7.
14. Graham EM, Ruis KA, Hartman AL, Northington FJ, Fox HE. A systematic review of the role of intrapartum hypoxia-ischemia in the causation of neonatal encephalopathy. Am J Obstet Gynecol 2008;199:587–95.
15. Practical Neonatal Respiratory Care. In: Schreiner RL, Kisling JA (eds). New York (NY): Raven Press; 1982. p. 248.
16. Riley RJ, Johnson JW. Collecting and analyzing cord blood gases. Clin Obstet Gynecol 1993;36:13–23.
17. Schreiner RL, Kisling JA, editors. Practical neonatal respiratory care. New York (NY): Raven Press; 1982. p. 246.
18. Blickstein I, Green T. Umbilical cord blood gases. Clin Perinatol 2007;34:451–9.
19. Volpe J. Hypoxic-ischemic encephalopathy: clinical aspects. In: Volpe J, editor. Neurology of the Newborn. 5th ed. Philadelphia (PA): W. B. Saunders; 2008. p. 400–80.
20. Sarnat HB, Sarnat MS. Neonatal encephalopathy following fetal distress. A clinical and electroencephalographic study. Arch Neurol 1976;33:696–705.
21. Finer NN, Robertson CM, Richards RT, Pinnell LE, Peters KL. Hypoxic-ischemic encephalopathy in term neonates: perinatal factors and outcome. J Pediatr 1981;98:112–7.
22. Baud O, d'Allest AM, Lacaze-Masmonteil T, Zupan V, Nedelcoux H, Boithias C, et al. The early diagnosis of periventricular leukomalacia in premature infants with positive rolandic sharp waves on serial electroencephalography. J Pediatr 1998;132:813–7.
23. Li AM, Chau V, Poskitt KJ, Sargent MA, Lupton BA, Hill A, et al. White matter injury in term newborns with neonatal encephalopathy. Pediatr Res 2009;65:85–9.
24. Rutherford M, Counsell S, Allsop J, Boardman J, Kapellou O, Larkman D, et al. Diffusion-weighted magnetic resonance imaging in term perinatal brain injury: a comparison with site of lesion and time from birth. Pediatrics 2004;114:1004–14.
25. Pasternak JF, Gorey MT. The syndrome of acute near-total intrauterine asphyxia in the term infant. Pediatr Neurol 1998;18:391–8.
26. Levine MI, Chervenak FA, Whittle M. Congenital structural defects of the brain. In: Bennett MF, Punt J, editors. Fetal and neonatal neurology and neurosurgery. 3rd ed. Harcourt: London (UK): Churchill Livingston; 2001. p. 211–2.
27. Vargas JE, Allred EN, Leviton A, Holmes LB. Congenital microcephaly: phenotypic features in a consecutive sample of newborn infants. J Pediatr 2001;139:210–4.
28. Geva R, Eshel R, Leiner Y, Valevski AF, Harel S. Neuropsychological outcome of children with intrauterine growth restriction: a 9-year prospective study. Pediatrics 2006;118: 91–100.
29. Larroque B, Bertrais S, Czernichow P, Leger J. School difficulties in 20-year-olds who were born small for gestational age at term in a regional cohort study. Pediatrics 2001;108:111–5.
30. Strauss RS. Adult functional outcome of those born small for gestational age: twenty-six-year follow-up of the 1970 British birth cohort. JAMA 2000;283:625–32.
31. Baergen RN. The placenta as witness. Clin Perinatol 2007;34:393–407.
32. Hermansen MC, Hermansen MG. Perinatal infections and cerebral palsy. Clin Perinatol 2006;33:315–33.
33. Neufeld MD, Frigon C, Graham AS, Nueller BA. Maternal infection and risk of cerebral palsy in term and preterm infants. J Perinatol 2005;25:108–113; doi:10.1038/ 7211219.
34. Wu YW, Escobar GJ, Grether JK, Croen LA, Greene JD, Newman TB. Chorioamnionitis and cerebral palsy in term and near-term infants. JAMA 2003;290:2677–84.
35. Shalak LF, Laptook AR, Jafri HS, Ramilo O, Perlman JM. Clinical chorioamnionitis, elevated cytokines, and brain injury in term infants. Pediatrics 2002;110:673–80.
36. Grether JK, Nelson KB. Maternal infection and cerebral palsy in infants of normal birth weight. JAMA 1997;278:207–11.
37. Cornette L. Fetal and neonatal inflammatory response and adverse outcome. Semin Fetal Neonat Med 2000;9:459–70.
38. Papoff P. Use of hematologic data to evaluate infections in neonates. In: Christensen, editor. Hematologic problems of the neonate. Philadelphia (PA): W.B. Saunders; 2000. p. 389–404.
39. Arnon S, Litmanovitz I, Regev RH, Bauer S, Shainkin-Kestenbaum R, Dolfin T. Serum amyloid A: an early and accurate marker of neonatal early-onset sepsis. J Perinatol 2007;27:297–302.
40. Rodger MA, Paidas M, McLintock C, Claire M, Middeldorp S, Kahn S, et al. Inherited thrombophilia and pregnancy complications revisited. Obstet Gynecol 2008;112:320–4.
41. Gelfand SL, Fanaroff JM, Walsh MC. Controversies in the treatment of meconium aspiration syndrome. Clin Perinatol 2004;31:445–52.
42. Naeye RL, Shaffer ML. Postnatal laboratory timers of antenatal hypoxemic-ischemic brain damage. J Perinatol 2005;25:664–8.
43. Buonocore G, Perrone S. Biomarkers of hypoxic brain injury in the neonate. Clin Perinatol 2004;31:107–16.
44. Korst LM, Phelan JP, Wang YM, Ahn MO. Neonatal platelet counts in fetal brain injury. Am J Perinatol 1999;16:79–83.
45. Korst LM, Phelan JP, Ahn MO, Martin GI. Nucleated red blood cells: an update on the marker for fetal asphyxia. Am J Obstet Gynecol 1996;175:843–6.
46. Freeman RK. Medical and legal implications for necessary requirements to diagnose damaging hypoxic-ischemic encephalopathy leading to later cerebral palsy. Am J Obstet Gynecol 2008;199:585–6.
47. Kirton A, deVeber G. Cerebral palsy secondary to perinatal ischemic stroke. Clin Perinatol 2006;33:367–86.
48. Phelan JP, Korst LM, Ahn MO, Martin GI. Neonatal nucleated red blood cell and lymphocyte counts in fetal brain injury. Obstet Gynecol 1998;91:485–9.
49. Macones GA, Hankins GD, Spong CY, Hauth J, Moore T. The 2008 National Institute of Child Health and Human Development Workshop Report on Electronic Fetal Monitoring: update on definitions, interpretation, and research guidelines. Obstet Gynecol 2008;112:661–6.
50. American College of Obstetricians and Gynecologists, American Academy of Pediatricians. Chapter 5: Neonatal assessment. In: Van Eerden P, Bernstein PS (eds). Neonatal encephalopathy and cerebral palsy. Washington, DC: American College of Obstetricians and Gynecologists; 2003. p. 53–62.
51. Nelson KB, Ellenberg JH. Apgar scores as predictors of chronic neurologic disability. Pediatrics 1981;2:181–8.
52. Bloom SL, Leveno KJ, Spong CY, Gilbert S, Hauth JC, Landon MB, et al. Decision-to-incision times and maternal and infant outcomes. Obstet Gynecol 2006;108:6–11.
53. Chauhan SP, Magann EF, Scott JR, Scardo JA, Hendrix NW, Martin JN Jr. Emergency cesarean delivery for nonreassuring fetal heart rate tracings. Compliance with ACOG guidelines. J Reprod Med 2003;48:975–81.
54. Chauhan SP, Hendrix NW, Magann EF, Sanderson M, Bofill JA, Briery CM, et al. Neonatal organ dysfunction among newborns at gestational age 34 weeks and umbilical arterial pH <7.00. J Matern Fetal Neonatal Med 2005;17:261–8.
55. Johnston MV, Donn SM. Hypoxic-ischemic encephalopathy and traumatic intracranial injuries. In: Donn SM, Fisher CW, editors. Risk management techniques in perinatal and neonatal practice. New York (NY): Futura Publishing Company, Inc.; 1996. p. 453.
56. Rutherford MA. The asphyxiated term infant. In: Rutherford MA, editor. MRI of the neonatal brain. London (UK): W.B. Saunders; 2002. p. 101.
57. Hayakawa F, Okumura A, Kato T, Kuno K, Watanabe K. Determination of timing of brain injury in preterm infants with periventricular leukomalacia with serial neonatal electroencephalography. Pediatrics 1999;104:1077–81.
58. Okereafor A, Allsop J, Counsell SJ, Fitzpatrick J, Azzopardi D, Rutherford MA, Cowan FM. Patterns of brain injury in neonates exposed to perinatal sentinel events. Pediatrics 2008;121:906–15.
59. Miller SP, Ramaswamy V, Michelson D, Barkovich AJ, Holshouser B, Wycliffe N, et al. Patterns of brain injury in term neonatal encephalopathy. J Pediatr 2005;146:453–60.
60. Steinman KJ, Gorno-Tempini ML, Glidden DV, Kramer JH, Miller SP, Barkovich AJ, Ferriero DM. Neonatal watershed brain injury on magnetic resonance imaging correlates with verbal IQ at 4 years. Pediatrics 2009;123:1025–30.
61. Shah P, Perlman M. Time courses of intrapartum asphyxia: neonatal characteristics and outcomes. Am J Perinat 2009;26:39–44.
62. Ferriero DM. Neonatal brain injury. N Engl J Med 2004;351:1985–95.
63. Rutherford M. Neuroimaging. In: Donn SM, Sinha SK, Chiswick ML, editors. In: Birth asphyxia and the brain: basic science and clinical implications. New York (NY): Futura Publishing Company, Inc.; 2002. p. 320–321.
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