Neonatal encephalopathy – the ACOG and AAP criteria
Radek Bukowski MD, PhD
and
Gary D. V. Hankins, M.D.
Division of Maternal Fetal Medicine
The University of Texas Medical Branch
Galveston, Texas
Introduction
The American College of Obstetricians and Gynecologists created a multidisciplinary Task
Force to review and consider the current state of scientific knowledge about the mechanisms,
timing, and etiologies of neonatal encephalopathy and cerebral palsy. Jointly sponsored by both
the American College of Obstetricians and Gynecologists (ACOG) and by the American
Academy of Pediatrics (AAP), a consensus document was developed and circulated to many
other professional societies and governmental agencies for their critique, input, and endorsement.
Ultimately four criteria were identified, all of which were felt to be required to accurately define
an acute intrapartum hypoxic event as sufficient to cause cerebral palsy. (Table I) Additionally,
it was recognized that there are other criteria that suggest an intrapartum timing for the
occurrence of the injury, but which by themselves are not sufficiently specific. (Table II)
Many nonspecific markers have been used to represent intrapartum asphyxia or birth asphyxia.
Included among these have been such markers as meconium stained amniotic fluid,
abnormalities of the electronic fetal monitor strip, or condition of the baby as described by Apgar
scores or time to spontaneous respirations at birth. Given the lack of equivalence of any of these
criteria, in addition to their lack of specificity, the potential for diagnostic misclassification has
been enormous. 1 As one illustration, in the very recent past the International Classification for
Disease Manual used the Apgar score to define not only birth asphyxia, but the degree of birth
asphyxia. Unfortunately, once this diagnosis was entered onto the newborn’s chart, it tended to
be perpetuated until it artificially achieved a status of reality. In contrast, epidemiological
studies have suggested that in only 6-10% of cases of neonatal encephalopathy of a moderate to
severe degree was the cause in fact isolated intrapartum hypoxia. 2-6 Some studies suggested that
hypoxia may be superimposed upon other antepartum risk factors in as many as another 25% of
cases of moderate to severe newborn encephalopathy. Ultimately, however, about 70% of
moderate to severe newborn encephalopathy would appear to have no relationship whatsoever
with intrapartum hypoxia or asphyxia. Among the host of variables that account for the at least
70% that are not intrapartum hypoxia or asphyxia are intrauterine growth restriction, intrauterine
infection, maternal or fetal coagulation disorders, multiple pregnancies, antepartum hemorrhage,
abnormal presentations, and chromosomal or congenital abnormalities. 4;7-36 Infections and
inflammations along with thromboses and coagulopathies are recognized as being associated
with white matter damage and cerebral palsy. Research in animals and humans has shown an
association between inflammatory markers, elevated fetal cytokines in both amniotic fluid and
fetal blood. 21-24 and periventricular leukomalacia and neonatal encephalopathy. 20 Coagulation
disorders such as antithrombin III and protein C or protein S deficiencies, and prothrombin gene
and factor V Leiden mutation can lead to stroke. 17;25-27 Occlusion of either arterial supply or
venous return can also cause permanent focal damage. Such damage may rarely be secondary to
trauma in pregnancy, especially if in conjunction with an existing coagulation disorder.
Early imaging studies may be useful in identifying and evaluating a specific etiology.
Additionally, numerous genetic and metabolic disorders can present clinically as neonatal
encephalopathy. Although there exists an ever expanding list of genetic causes, in most infants
with neonatal encephalopathy the condition does not result from an identifiable genetic cause.
Diagnosis of a genetic cause is unlikely unless there is heightened clinical suspicion based on
specific findings or based upon family history. The provider should nonetheless attempt to
identify such disorders by taking a detailed family history, performing a thorough examination of
the infant for dysmorphic features consistent with a genetic etiology, and ordering appropriate
laboratory studies if warranted. Additionally, the obstetric provider should remain in close
contact with the pediatrician or neonatologist providing care to the child. Sharing of accurate
information is of utmost importance to all concerned. Knowledge has certainly advanced to the
point that today it is not plausible to hypothesize that cerebral palsy can be the result of
intrapartum asphyxia absent the development of neonatal encephalopathy. Pathophysiologically
it simply is not possible for intrapartum asphyxia to result in brain injury yet have an infant with
a normal newborn course! 6;36
What then does this mean for the practicing obstetrician? First and foremost, there is a need for
all of us to use precision in terminology. In those instances where one has delivered a baby that
is significantly depressed, it is recommended that umbilical arterial and umbilical venous cord
blood be analyzed for pH, blood gases, and buffering capacity and levels. Similarly,
histopathologic examination of the placenta and placental membranes and umbilical cord may be
enlightening as regards the cause of the newborn’s condition. The importance of early
neuroimaging studies and collection of appropriate specimens to look for multiple organ system
injuries to include the liver, coagulation system, and kidneys should be discussed with the
infant’s caregiver. In regards to providing care to the severely growth restricted infant, Badawi
and associates have shown that if the fetus is at less than the third percentile it will carry a 38fold increase in risk of manifesting moderate to severe encephalopathy. Such growth restricted
fetuses are also usually intolerant of labor. Accordingly, we discuss the delivery options with the
parents in advance and encourage them to accept a cesarean section delivery timed such that the
neonatal team can be available to receive and treat the infant. This concept is not original
inasmuch as Sigmund Freud hypothesized long ago that the previously injured fetus is unable to
adapt to the usual stresses of labor. In the instance of such a severely growth restricted fetus, one
can almost be guaranteed of abnormal fetal heart rate tracings which will then be blamed as
causal of injury, when in fact most often they have absolutely nothing to do with the injury. This
practice recommendation has certainly not been tested in an interventional randomized trial,
however, when the product of the pregnancy has a demonstrated risk of moderate to severe
encephalopathy of above 10% it seems prudent to optimize the outcome for all concerned – fetus
as well as obstetrician.
Finally, we would commend to all a thorough review of the document Neonatal Encephalopathy
and Cerebral Palsy – Defining the Pathogenesis and Pathophysiology, co-published by the
American College of Obstetricians and Gynecologists and the American Academy of Pediatrics,
and endorsed by a host of other organizations to include the Centers for Disease Control and
Prevention, the March of Dimes Birth Defects Foundation, the National Institutes of Child
Health and Human Development, the Royal Australian and New Zealand College of
Obstetricians and Gynaecologists, the Society for Maternal Fetal Medicine, and the Society of
Obstetricians and Gynaecologists of Canada. This has resulted in one of the most highly peerreviewed and scientifically rigorous documents ever published on the topic.
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