See

discussions, stats, and author profiles for this publication at:

https://www.researchgate.net/publication/8547970

Low Apgar scores and the

definition of birth asphyxia

Article in Pediatric Clinics of North America · July 2004

DOI: 10.1016/j.pcl.2004.01.016 · Source: PubMed

CITATIONS READS

46 10,277

2 authors, including:

Steven R Leuthner
Medical College of Wisconsin
66 PUBLICATIONS 1,163 CITATIONS

SEE PROFILE

All content following this page was uploaded by Steven R Leuthner on 25 May 2017.

The user has requested enhancement of the downloaded file.

 Pediatr Clin N Am 51 (2004) 737 – 745

Low Apgar scores and the definition of

birth asphyxia
Steven R. Leuthner, MD, MA*,
Utpala (‘‘Shonu’’) G. Das, MD
Division of Neonatology, Medical College of Wisconsin, 8701 Watertown Plank Road, MS 213,
Milwaukee, WI 53226, USA

More than 4 million babies are born in thousands of hospitals across the
United States [1]. Most of these hospitals do not have neonatal facilities; how-
ever, most deliveries are attended by medical personnel with various levels of
training. Virtually every baby born is assigned an Apgar score. The Apgar score
has come under criticism for its inability to predict accurately perinatal asphyxia
and long-term neurodevelopmental disabilities. The goal of this article is to
define perinatal or birth asphyxia, review the Apgar score and its function, and
review other predictors of perinatal or birth asphyxia.

Birth asphyxia
Being called to attend the emergent delivery of a term infant in distress is
something many pediatricians or other medical personal will be required to do.
Although it is beyond the scope of this article to review the neonatal resuscitation
program guidelines, there are a few key points to make [2]. The first is to ap-
preciate that although this is a distressing situation, one must keep calm and
realize that neonatal resuscitation is much easier when one is calm. Although this
is much easier said than done, we can review the simple steps to take when an
infant is born with a low rate or no heart beat. We should first think of the ABCs.
A is to establish an airway and B is to establish breathing. These can be done
through bag and mask ventilation or intubation. If an infant is born with a heart
rate, proper positive pressure ventilation makes it rare to have to begin chest
compressions. C is to maintain circulation via chest compressions or medications.
For the infant who has no heart beat, if the airway is established and chest
compressions are being done, the recommendation is to administer epinephrine

* Corresponding author.
E-mail address: leuthner@mcw.edu (S.R. Leuthner).

0031-3955/04/$ – see front matter D 2004 Elsevier Inc. All rights reserved.
doi:10.1016/j.pcl.2004.01.016
738 S.R. Leuthner, U.G. Das / Pediatr Clin N Am 51 (2004) 737–745

via endotracheal tube or umbilical venous line once every 5 minutes. This means
that once epinephrine is given, one simply continues to provide positive pressure
ventilation and chest compressions in a calm manner. During this time, one could
provide volume expansion, but it is important to keep track of time. With ap-
propriate resuscitation there is a 40% to 50% chance of survival. Almost two
thirds of infants who survive have normal neurologic outcome. The neonatal
resuscitation program currently recommends that resuscitation be discontinued if
there is an absent heart rate at 15 minutes of appropriate resuscitation [2]. This is
based on data that newborns who are asystolic at 10 minutes of life usually die,
and if they survive, they have severe disabilities [3– 6].
Once an infant is born and resuscitated, often the next question is ‘‘will my
baby be all right’’? It is important for those pediatricians involved to be knowl-
edgeable about and begin to determine if an infant may have birth asphyxia.
Asphyxia is defined as a condition of impaired gas exchange that leads to three
biochemical components: hypoxemia, hypercapnia, and metabolic acidosis [7].
Because of uterine contraction during the normal birth process, all fetuses
experience some asphyxia. The fetus who experiences a significant asphyxial
episode is at risk of developing hypoxic-ischemic encephalopathy or other end-
organ sequelae. Hypoxic-ischemic encephalopathy should be diagnosed only
when an infant has clinical findings of an encephalopathy, such as neurologic
depression or seizures, and the infant has experienced a severe asphyxiating
event. A diagnosis of an asphyxiating event should not be made without some
evidence of an interruption of oxygen supply or blood flow to the fetus. These
events can be secondary to problems from the mother (eg, hypotension, toxemia,
uterine tetany, uterine rupture), the placenta or umbilical cord (eg, abruption,
infection or inflammation, or umbilical cord compression or occlusion), or the
fetus or infant (eg, central nervous system depression, anomalies, infection) [8].
The term ‘‘asphyxia’’ should not be used unless the neonate meets all of the
following conditions: (1) umbilical cord arterial pH less than 7 (whether meta-
bolic or mixed), (2) Apgar score of 0 to 3 for longer than 5 minutes, (3) neuro-
logic manifestations (eg, seizures, coma, or hypotonia), and (4) multisystemic
organ dysfunction [9].
To label an infant with hypoxic-ischemic encephalopathy from birth asphyxia
without these criteria may not only cause one to miss the real cause of a neuro-
logic problem, such as infections or metabolic abnormalities, but also unfairly
incriminate a colleague.
Communication with a family is critical in these scenarios because we must be
truthful yet fair to obstetric colleagues in ‘‘labeling’’ an infant with a diagnosis
that has a perceived poor outcome. It is common to label an infant initially as
having perinatal depression until the previously noted criteria are met. The first
goal is to let the family know that concerns exist about the infant’s status, but one
can say honestly that predicting outcome shortly after birth is not appropriate.
Collecting data, including Apgar scores, umbilical cord gas values, and infant
blood gas values and observing the infant are important, yet these values are still
far from perfect at predicting long-term outcome.
 S.R. Leuthner, U.G. Das / Pediatr Clin N Am 51 (2004) 737–745 739

The Apgar score

The Apgar score was first developed in 1952 by Dr. Virginia Apgar, an
obstetric anesthesiologist. Her goal was to develop a scoring system using signs
traditionally observed by anesthesiologists that would assess a neonate’s transi-
tion after birth, particularly in relation to fetal presentation, mode of delivery, and
anesthetics used in obstetrics [10 – 12]. It was developed as an objective tool that
measures five signs of physiologic adaptation (Table 1). A score is a sum of the
values assigned to the infant at 1 and 5 minutes of life, with a score of 7 or more
indicating that the baby is in good to excellent condition. The scoring system
quickly gained near universal acceptance after it was shown to predict survival,
particularly at 5 minutes [3,4,13]. The Apgar score is even common knowledge
for families, and they often ask what the Apgar score was after they inquire after
the baby’s weight.
The value of the Apgar score has been criticized for its usefulness in clini-
cal assessment and predictive abilities. It has been suggested to be antiquated
because of the modern prompt application of resuscitation and neonatal care [14].
The score does not take into account preterm infants or intubated infants, who
often get lower scores based on these situations [15]. It is most controversial
when it is used as a predictor of birth asphyxia and long-term neurologic outcome
[16,17]. This controversy is not surprising because the initial intent of the Apgar
was to predict survival and not perinatal asphyxia [18,19]. The report by Casey
et al [19] supports the collaborative study on cerebral palsy 40 years earlier,
which stated that an Apgar score of 3 or less at 5 minutes of life does predict a
higher rate of mortality [4,11]. Casey’s retrospective analysis of 151,891 neonates
born over a 10-year period revealed a mortality rate of 24.4% verses a mortality
rate of 0.02% if the Apgar was 7 or higher. Although the Apgar can somewhat
predict mortality, it is not a tool to be used alone in determining neurologic
outcomes of infants who survive.

Cord blood gas

The normal cord blood gas values of the fetus are important to know to
interpret gases after delivery (Table 2) [20]. During the course of normal labor,

Table 1
Apgar score
Sign 0 1 2
Heart rate Absent Below 100 Above 100
Respiratory effort Absent Slow, irregular Good, crying
Muscle tone Flaccid Some flexion of extremities Active motion
Reflex irritability No response Grimace Vigorous cry
Color Pale Cyanotic Completely pink
740 S.R. Leuthner, U.G. Das / Pediatr Clin N Am 51 (2004) 737–745

Table 2
Cord blood gases
pH PaO2 (mm Hg) PaCO2 (mm Hg) HCO3 (mEq/L)
Umbilical artery 7.27 ± 0.08 25 ± 19 45 ± 10 22 ± 3.7
Umbilical vein 7.34 ± 0.07 36 ± 10 40 ± 6 23 ± 2.2

the PaO2 drops, the PaCO2 rises, and the base deficit rises. In most centers, a pH of
more than 7.2 is considered normal and a pH of 7 to 7.2 is considered mild or
moderate acidemia. Severe acidemia is when the pH is below 7 and there is a base
deficit of more than 12 nM.
As controversy arose regarding the value of the Apgar score in predicting or
defining birth asphyxia, investigators turned to the umbilical cord blood gas as a
tool to assess asphyxia. Just as the Apgar score alone is a poor predictor of
outcome, metabolic acidosis in isolation also proved to be a poor predictor of
significant perinatal brain injury. Ruth and Raivio [21] compared Apgar scores,
cord blood pH, and cord lactate levels in more than 900 infants and looked at
outcome. They found that 11% of the infants with cord blood acidosis had an
Apgar score below 7, whereas 41% of infants with an Apgar of less than 7 had an
acidosis. In the end, the sensitivity and positive predictive value of a low pH for
adverse outcome were 21% and 8%, respectively. Cord blood lactate levels were
no better at 12% and 5%, respectively. The sensitivity and positive predictive
value of the Apgar score values were 12% and 19%, respectively.
Other studies also have not shown an acidosis to be predictive. Some studies
suggest that neurologic injury is more likely to occur in an infant who is
depressed but has a normal pH [22,23]. Hermansen [24] suggested there is an
acidosis paradox, or a beneficial effect of a mild to moderate acidosis. One of the
possible beneficial effects is that hypercarbia may result in cerebral vasodilation
and increased cerebral blood flow. Second, acidosis has been shown to decrease
cerebral metabolism and lower the oxidative needs of the brain. Finally, acidosis
promotes the unloading of oxygen from the fetal hemoglobin by shifting the
oxygen dissociation curve. These three mechanisms theoretically lead to an
adequate amount of oxygen delivery to the brain tissue, which potentially limits
damage. These protective effects would be lost, however, with severe acidosis,
which can lead to decreased cardiac output and cerebral ischemia [25]. One study
suggested that the risks of neonatal seizures and long-term motor or cognitive
functions worsen as the pH decreases further below 7 [26].

Clinical presentation and examination

Once an infant is resuscitated, the Apgar scores assigned, and the cord blood
gas results returned, the pediatrician must observe the infant and monitor for end-
organ dysfunction. The cardiorespiratory systems often provide the first signs or
 S.R. Leuthner, U.G. Das / Pediatr Clin N Am 51 (2004) 737–745 741

symptoms of end-organ damage. The respiratory system may require support for
respiratory distress syndrome or pulmonary hypertension. The goal in manage-
ment of the respiratory system is moderation in oxygen and carbon dioxide
levels. Hypoxia and hyperoxia can lead to further neuronal injury. Hypercarbia
can lead to cerebral vasodilation and hemorrhage, whereas hypocarbia can lead to
decreased cerebral blood flow.
The cardiovascular system may need support because of myocardial ischemia
or cardiac stun, poor contractility from the acidosis, tricuspid insufficiency often
from pulmonary hypertension, and hypotension. Moderation is best; it helps to
avoid hypotension and hypertension because the cerebral vasculature is pressure
passive. Infants with any cardiorespiratory conditions need neonatal intensive
care and require transport for management.
Gastrointestinal damage might include injury to the bowel wall, which can be
mucosal or full thickness and even involve perforation. The extent of the damage
influences the nutritional management, in particular when to begin feedings once
recovery occurs. It might be prudent to allow 3 days of healing for mucosal injury
and 7 days for more extensive damage before attempting enteral feeding. The
liver can be injured, as measured by elevated transaminases. The liver and bowel
typically heal over time and cannot be treated other than through cardiorespira-
tory support and time.
The hematologic system also can be affected. In the first hours to days of life,
this is manifest through disseminated intravascular coagulation. The infant might
need to be supported with blood products over the first few days of life to prevent
pulmonary or intracranial hemorrhage. If the bone marrow itself had an ischemic
injury, the first sign of marrow suppression would be thrombocytopenia at ap-
proximately 5 to 7 days of age, because platelets have the shortest half-life of the
marrow products. The marrow recovers over time.
Metabolic abnormalities that are often seen include hypoglycemia, hypocal-
cemia, myoglobinuria, and inappropriate secretion of antidiuretic hormone, which
leads to hyponatremia. These abnormalities must be treated to prevent wors-
ening seizures.
The kidney often has been thought to be the window to the brain in this
disease. One study revealed that if an infant had good urine output, the chances of
mortality and neurologic injury were 5% and 10%, respectively, whereas oligu-
ria beyond 24 hours resulted in rates of mortality and neurologic injury of 33%
and 67%, respectively [27]. Acute tubular necrosis has not proved to be as good a
predictor of mortality and neurologic injury as initially believed [28]. Manage-
ment of acute tubular necrosis is through fluid restriction once volume status has
been maximized.
The central nervous system is the central focus when discussing asphyxia.
Injury can occur through focal intracranial hemorrhage or infarction or the more
global injury of hypoxic-ischemic encephalopathy. These injuries typically are
evaluated by neurologic examination, electroencephalography (EEG), and imag-
ing (either CT scan or MRI). Three clinical stages of encephalopathy, known as
the Sarnat stages, have been characterized and can predict outcome [29]. Stage 1
742 S.R. Leuthner, U.G. Das / Pediatr Clin N Am 51 (2004) 737–745

lasts less than 24 hours and is characterized by hyperalertness, uninhibited Moro

and stretch reflexes, sympathetic effects, and a normal electroencephalogram.
Stage 2 is marked by obtundation, hypotonia, strong distal flexion, and multifocal
seizures. Infants in stage 3 are stuporous and flaccid, and brain stem and auto-
nomic functions are suppressed.
The severity of the neurologic syndrome, the presence of seizures, and the
duration of the abnormalities provide the best prediction of prognosis. Sarnat and
Sarnat [29] found that infants who have signs of stage 2 for less than 5 days have
normal outcome. Persistence of stage 2 for more than 7 days or stage 3 at any
time is associated with later neurologic impairment or death [18]. Other re-
searchers have confirmed that although the overall incidence of death or sequelae
is 27%, if the neurologic syndrome is mild there are no later deficits. When the
neurologic syndrome was severe, 80% of infants died and the remaining 20% had
significant sequelae [30,31].
Seizures increase the risk of neurologic sequelae two- to fivefold. Phenobar-
bitol is the first line drug most often used with a loading dose of 20 mg/kg,
followed by a maintenance dose of 5 mg/kg every 24 hours. If the seizures are
persistent or recalcitrant to anticonvulsant medications, they are nearly uniformly
associated with death or significant neurologic deficits [32]. Recalcitrant seizures
often require high levels of phenobarbital, often loading with 40 mg/kg and
reaching a blood level of 40 to 60. Often a second drug, fosphenytoin, must be
added for the first 2 to 3 days. The loading dose is 10 – 20 mg/kg, followed by a
maintenance dose of 5 mg/kg divided twice a day. Typically by the third day the
seizures seem to stop or are at least controlled. Often and infant can cease taking
fosphenytoin and receive a normal phenobarbital dose and level. This must be
done to ensure a reliable encephalography result.
Finally, the duration of the neurologic abnormalities predicts outcome. Re-
searchers have said that the two factors that predict long-term neurologic outcome
are the neurologic examination at discharge and the parents’ socioeconomic
status. Data support the theory that if a newborn’s neurologic examination returns
to normal by 1 to 2 weeks, the infant likely will be normal at follow-up [18,29,
31,33].

Testing
EEG evaluation is a useful tool to help in the management of these infants,
particularly for treatment of nonclinical seizures. EEG, like the neurologic
examination, can predict outcome based on severity and duration of abnormali-
ties. At any time, a burst-suppression or an isoelectric pattern is associated with
poor outcome. If there is only mild depression early, there can be normal out-
come. If there is depression after 12 days, poor outcome is expected. A normal
EEG at 7 days predicts normal outcome [31]. Visual- and somatosensory-evoked
potentials have been reported to predict outcome and can be done within 6 hours
of birth. If there is a normal response, there will likely be normal outcome. If
 S.R. Leuthner, U.G. Das / Pediatr Clin N Am 51 (2004) 737–745 743

there is a delayed response, there will likely be sequelae. If there is no response,

death is the likely outcome [34].
Imaging of the brain includes ultrasound, CT scan, and MRI. Although the
ultrasound is often the easiest study to perform, it is not as valuable in the early
stages as CT or MRI. The CT scan (without contrast) is valuable in showing
hypoattenuation or a lack of differentiation between the gray-white matter. This is
a sign of diffuse cerebral edema. Although an early scan may have some prog-
nostic value, a scan at 2 to 6 weeks is more valuable because it reveals what
damage remains after the swelling resolves [35]. If the results of a CT scan are
normal, it is rare for an infant to have any long-term problems. If there is marked
diffuse hypoattenuation, infants are rarely normal at follow-up. MRI imaging
may be the best imaging to predict prognosis [36]. One study reported that an
abnormal signal in the posterior limb of the internal capsule alone predicts poor
neurologic status at follow-up [37].

Neuroprotective measures
There have been several attempts to find the magic medical treatment during a
possible window of opportunity to protect the injured brain. Although it is
important to stop seizures to protect the central nervous system from further
injury, prophylactic phenobarbital has been tried but not supported by improve-
ment in death or disability outcomes. Calcium channel blockers have been pro-
posed, with the theory being that neuronal death occurs through elevated
cytosolic calcium. They have not been fully tested, and cardiovascular risks
may be involved [38]. Magnesium sulfate may have those same risks, and trials
have been inadequate. The free radical scavenger, allopurinol, has shown some
promise in trends to better outcome in one study, but results were not statistically
significant [39]. More recently, the concept of mild, local hypothermia has been
proposed. The evidence from animal studies that posthypoxic mild hypothermia
reduces brain injury is controversial [40,41]. In humans, one small, randomized
trial of mild hypothermia found no adverse effects, but it was too small to
examine death or disability [42]. The authors concluded that therapeutic hypo-
thermia should not be used outside of stringent, multicenter trials. There are
reports of a large, randomized trial of selective head cooling and several large,
ongoing trials of systemic mild hypothermia [43]. Until results of these re-
ports are published and reproducible, this should not be considered standard of
care therapy.

Summary
Nonreassuring fetal heart rate patterns, prolonged labor, meconium-stained
fluid, a low 1-minute Apgar score, and mild to moderate acidemia have no
predictive value for long-term neurologic injury without signs of encephalopathy
744 S.R. Leuthner, U.G. Das / Pediatr Clin N Am 51 (2004) 737–745

and seizures. It is important to provide proper resuscitation, support infants, and

allow time for evaluation. We have time and the tools to provide fairly predic-
tive information to families. It is important to use this knowledge wisely in
communicating honestly with families, because difficult decisions undoubtedly
will arise.

References
[1] Arias E, MacDorman MF, Strobino DM, Guyer B. Annual summary of vital statistics: 2002.
Pediatrics 2003;112:1215 – 30.
[2] American Heart Association/American Academy of Pediatrics. Textbook of neonatal resuscita-
tion. 4th edition. Elk Grove Village (IL): American Academy of Pediatrics; 2000.
[3] Jain L, Ferre C, Vidyasager D, et al. Cardiopulmonary resuscitation of apparently stillborn
infants: survival and long-term outcome. J Pediatr 1991;118:778 – 82.
[4] Scott H. Outcome of very severe birth asphyxia. Arch Dis Child 1976;51:712 – 6.
[5] Steiner H, Neligan G. Perinatal cardiac arrest: quality of the survivors. Arch Dis Child 1975;
50:696 – 702.
[6] Thomson AJ, Searle M, Russel G. Quality of life after severe birth asphyxia. Arch Dis Child
1977;52:620 – 6.
[7] Low JA. Intrapartum fetal asphyxia: definition, diagnosis, and classification. Am J Obstet
Gynecol 1997;100:1004 – 14.
[8] Nelson KB. Defining hypoxic-ischemic birth events. Dev Med Child Neurol 2003;45:71 – 2.
[9] American Academy of Pediatrics and American College of Obstetricians and Gynecologists.
Care of the neonate. In: Gilstrap LC, Oh W, editors. Guidelines for perinatal care. 5th edition. Elk
Grove Village (IL): American Academy of Pediatrics; 2002. p. 196 – 7.
[10] Apgar V. A proposal for a new method of evaluation of the newborn infant. Presented at the
27th Annual Congress of Anesthetists, Joint Meeting of the International Anesthesia Research
Society and International College of Anesthetists. Virginia Beach, September 22 – 25, 1952.
[11] Apgar V. A proposal for a new method of evaluation of the newborn infant. Curr Res Anesth
Analg 1953;32:260 – 7.
[12] Apgar V, James LS. Further observations on the newborn scoring system. Am J Dis Child
1962;104:419 – 28.
[13] Drage JS, Kennedy C, Schwarz BK. The Apgar score as an index of neonatal mortality: a report
from the Collaborative Study of Cerebral Palsy. Obstet Gynecol 1964;24:222 – 30.
[14] Anonymous. Is the Apgar score outmoded? Lancet 1989;1:591 – 2.
[15] Catlin EA, Carpenter MW, Brann IV BS, et al. The Apgar score revisited: influence of gesta-
tional age. J Pediatr 1986;109:865 – 8.
[16] Nelson KB, Ellenberg JH. Apgar scores as predictors of chronic neurologic disability. Pediatrics
1981;68:36 – 44.
[17] American Academy of Pediatrics, American College of Obstetricians and Gynecologists. Use
and abuse of the Apgar score. Pediatrics 1996;98:141 – 2.
[18] Papile LA. The Apgar score in the 21st century. N Engl J Med 2001;344(7):519 – 20.
[19] Casey BM, McIntire DD, Leveno KJ. The continuing value of the Apgar score for the assess-
ment of newborn infants. N Engl J Med 2001;344:467 – 71.
[20] Maher JT, Conti JA. A comparison of umbilical cord blood gas values between newborns with
and without true knots. Obstet Gynecol 1996;88(5):863 – 6.
[21] Ruth VJ, Raivio KO. Perinatal brain damage: predictive value of metabolic acidosis and the
Apgar score. BMJ 1988;297:24 – 7.
[22] Dijxhoorn MJ, Visser GHA, Fidler VJ, Touwen BCL, Huisjes HJ. Apgar score, meconium and
acidaemia at birth in relation to neonatal neurological morbidity in term infants. Br J Obstet
Gynaecol 1986;93:217 – 22.
 S.R. Leuthner, U.G. Das / Pediatr Clin N Am 51 (2004) 737–745 745

[23] Johnson DJ, Mutch L, Yudkin P, Johnson P. Acid-base status at birth and neurodevelopmental
outcome at four and one-half years. Am J Obstet Gynecol 1989;161:213 – 20.
[24] Hermansen MC. The acidosis paradox: asphyxial brain injury without coincident academia.
Dev Med Child Neurol 2003;45:353 – 6.
[25] Downing SE, Talner NS, Garndner TH. Influences of hypoxemia and academia on left ventricu-
lar function. Am J Physiol 1966;210:1327 – 34.
[26] Andres RI, Saade G, Gilstrap LC, Wilkins I, Wiltin A, Zlatnic F, et al. Association between
umbilical blood gas parameters and neonatal morbidity and death in neonates with pathologic
fetal acidemia. Am J Obstet Gynecol 1999;181:867 – 71.
[27] Perlman JM, Tack ED. Renal injury in the asphyxiated newborn infant: relationship to neuro-
logic outcome. J Pediatr 1988;113:875 – 9.
[28] Goodwin TM, Belai I, Hernandez P, Durand M, Paul RH. Asphyxial complications in the term
newborn with severe umbilical acidemia. Am J Obstet Gynecol 1992;167(6):1506 – 12.
[29] Sarnat HB, Sarnat MS. Neonatal encephalopathy following fetal distress: a clinical and electro-
encephalographic study. Arch Neurol 1976;33(10):696 – 705.
[30] Roberson C, Finer N. Term infants with hypoxic-ischemic encephalopathy: outcome at 3.5 years.
Dev Med Child Neurol 1985;27:473 – 84.
[31] Thornberg E, Thiringer K, Odeback A, Milsom I. Birth asphyxia: incidence, clinical course and
outcome in a Swedish population. Acta Pediatr 1995;84:927 – 32.
[32] Volpe JJ, editor. Hypoxic-ischemic encephalopathy: clinical aspects. In: Neurology of the new-
born. 4th edition. Philadelphia: WB Saunders Co.; 2001. p. 331 – 94.
[33] Scott H. Outcome of very severe birth asphyxia. Arch Dis Child 1976;51:712 – 6.
[34] Eken P, Toet MC, Groendendaal F, Devries LS. Predictive value of early neuroimaging, pulsed
Doppler and neurophysiology in full term infants with hypoxic-ischemic encephalopathy. Arch
Dis Child 1995;73:F75 – 80.
[35] Lipp-Zwahlen AE, Deonna T, Chrzanowski R, et al. Temporal evolution of hypoxic-ischemic
brain lesions in asphyxiated full-term newborns as assessed by computerized tomography.
Neuroradiology 1985;27:138 – 44.
[36] Kuenzle C, Baenziger O, Martin E, et al. Prognostic value of early MR imaging in term infants
with severe perinatal asphyxia. Neuropediatrics 1994;25:191 – 200.
[37] Rutherford MA, Pennock JM, Counsell SJ, et al. Abnormal magnetic resonance signal in the
internal capsule predicts poor neurodevelopmental outcome in infants with hypoxic-ischemic
encephalopathy. Pediatrics 1998;102:323 – 8.
[38] Leven MI, Gibson NA, Fenton AC, et al. The use of a calcium-channel blocker, nicardipine, for
severely asphyxiated newborn infants. Dev Med Child Neurol 1990;32:567 – 74.
[39] Van Bel F, Shadid M, Moison RM, et al. Effect of allopurinol on postasphyxial free radical
formation, cerebral hemodynamics, and electrical brain activity. Pediatrics 1998;101:184 – 93.
[40] Gunn AJ, Bennet L, Gunning MI, Gluckman PD, Gunn TR. Cerebral hypothermia is not
neuroprotective when started after postischemic seizures in fetal sheep. Pediatr Res 1999;
46(3):274 – 80.
[41] Agnew DM, Koehler RC, Guerguerian AM, Shaffner DH, Traystman RJ, Martin LJ, et al.
Hypothermia for 24 hours after asphyxic cardiac arrest in piglets provides striatal neuroprotec-
tion that is sustained 10 days after rewarming. Pediatr Res 2003;54(2):253 – 62.
[42] Battin MR, Dezoete JA, Gunn TR, Gluckman PD, Gunn AJ. Neurodevelopmental outcome of
infants treated with head cooling and mild hypothermia after perinatal asphyxia. Pediatrics
2001;107(3):480 – 4.
[43] Whitelaw A, Thoresen M. Clinical trials of treatments after perinatal asphyxia. Curr Opin Pe-
diatr 2002;14(6):664 – 8.

View publication stats