Asphyxial complications in the term newborn with severe umbilical acidemia Thomas Murphy Goodwin, MD, Isaac Belai, MD, Patricia Hernandez, MD, Manuel Durand, MD, and Richard H. Paul, MD
Los Angeles, California OBJECTIVE: Our purpose was to determine the relationship of umbilical acid-base status and Apgar score to neonatal asphyxial sequelae in infants with severe acidemia (pH < 7.00). STUDY DESIGN: The obstetric and neonatal course of 129 term, nonanomalous singleton infants with umbilical pH < 7.00 was reviewed. RESULTS: There were three stillbirths (failed resuscitation). Seventy-two of 126 (57%) were admitted to the neonatal intensive care unit. Thirty-eight percent had pulmonary dysfunction, 26% renal dysfunction, 31% cardiac dysfunction, and 31% hypoxic ischemic encephalopathy (seizures and hypotonia, n = 29; seizures only, n = 3; hypotonia only, n = 10). There were five neonatal deaths. In 109 cases umbilical arterial values were available, and among these infants there was a significant increase in the incidence of seizures with declining pH from 9% (5/57), with a pH of 6.90 to 6.99, to 80% (8/10), with a pH of 6.61 to 6.70. Respiratory acidemia (Pco 2 > 65, base deficit < 10) was identified in 28 of 109 (26%), all but six occurring in the pH range above 6.90. Compared with infants with comparable umbilical artery pH, infants with respiratory acidemia did not differ significantly with respect to asphyxial end-organ injury in general (8/35 vs 6/22), but there was a trend toward a lower incidence of hypoxic ischemic encephalopathy (6/35 vs 1/22, P = 0.06). All infants with definite abnormal outcome (five neonatal deaths and 10 severe neurologic deficit) had seizures, hypotonia, and at least one other organ system dysfunction. Twenty-four of 29 infants (83%) who developed seizures had a 5-minute Apgar score 2 minutes) on admission, and 19 underwent emergency cesarean section. Overall, 113 (88%) patients were delivered because of a clinical diagnosis of fetal distress. Ninetyseven (76%) underwent emergency or urgent cesarean section, and 16 (12%) underwent instrumented vaginal delivery for fetal distress. There were three stillborn infants and five neonatal deaths. The findings of the postmortem examinations in these cases are summarized in Table II. The perinatal mortality rate for the study population was 62 per 1000 compared with our term uncorrected perinatal mortality rate of 1.5 per 1000. Fifty-four infants (43%) were admitted to the normal nursery and suffered no significant morbidity. Of the 72 infants admitted to the neonatal intensive care unit, 21 (17%) were observed or given supplemental oxygen but did not meet specific criteria for end-organ dysfunction. All 21 were normal at the time of discharge. Fifty-one of 126 infants (40%) had evidence of dysfunction in at least one organ system (Table III). Fifteen infants had non-cerebral organ dysfunction, and 14 of 15 were normal at discharge (n = 12) or follow-up (n = 2). One of these infants was lost to follow-up. Twenty-six infants had both seizures and prolonged hypotonia. Such infants constitute the principal risk group for permanent neurologic dysfunction l2 and are presented separately in the following discussion. Four infants who experienced seizures within 48 hours of life had factors other than hypoxic ischemic encephalopathy that may have contributed to the seizures. Two had seizures that were temporally related to intracranial hemorrhage occurring after heparinization for extracorporeal membrane oxygenation. One infant had congenital meningitis. These three neonates died.
6.90-6.99
Mixed acidemia (n = 25)
Metabolic acidemia (n = 10)
Respiratory acidemia (n = 22)
5 4
o
o
o
o o
20
9
21
1509
One infant with seizures had suffered a depressed skull fracture at delivery but was normal at follow-up. Seizures and hypotonia were seen in association with at least one other organ system dysfunction in 25 of 126 (20%). In Fig. 1 occurrence of seizures is stratified by the 5-minute Apgar score for the 126 liveborn infants. Mild d"pression at 5 minutes (Apgar score < 7) was noted in Z4 of 29 infants (83%) who developed seizures, but only 12 of 29 (41 %) had an Apgar score of :5 3 at 5 minutes. The positive and negative predictive value of a 5-minute Apgar score :5 3 for the occurrence of seizures were 75% and 84%, respectively. Two infants with Apgar scores of 6 and 7 at 5 minutes subsequently manifested profound neurologic deficits. Neither had evidence of neonatal asphyxia or other comorbidity to explain the poor neurologic outcome. To correlate the occurrence of asphyxial end-organ injury with the severity and type of acidemia, the data that follow refer to the 109 infants with documentable umbilical artery pH values. In Table IV umbilical artery pH values are arbitrarily stratified into ranges of 0.10 from a low of 6.61 to a maximum of 6.99. Each of the postasphyxial morbidities occurred with greater frequency as the degree of acidemia increased. Below a pH of 6.80, > 50% of infants had seizures and hypotonia. Twenty-two of 109 had seizures, hypotonia, and additional organ system dysfunction. The mean pH value of this group (6.79 ± 0.11, mean ± SD) differed significantly from the pH of the other 23 infants with Table VI. Preliminary outcome data (n live births) Neonatal deaths Normal at discharge* Suspect at discharge Follow-up of those suspect at discharge (n Normal Abnormal Major neurologic deficiu 10 Suspect§ 5 Lost to follow-up 8
=
=
126 5 (4%) 84 (66%) 37 (30%) 29)t 14 15
TOTAL
Normal Neonatal death Major neurologic deficit Suspect Lost to follow-up
98 (78%)
5 (4%) 10 (8%) 5 (4%) 8(6%)
*Infants lacking evidence of neonatal encephalopathy who had a normal neurologic examination result at discharge received no special follow-up. t Results refer to last examination, which ranged from 6 to 48 months of age. tTwo infants died before 18 months of age. §Mild tone abnormalities or cognitive delay.
1510 Goodwin et a\.
December 1992 Am J Obstet Gynecol
Table VII. Summary of cases with known abnormal outcome (N = 15) Apgar score Case No.
1 min
I
Major neurologic deficit* 1 1
Organ dysfunction
Pulmonary I Cardiac I dysfunction dysfunction
Blood pH
Gas Pco2
Base deficit
Cerebral dysfunction
5
6.61
153
-19
+
+
6.63
154
-18
+
+
5 min
I
10 min
+
2
0
2
3
2
4
6
6.78
111
-16
+
+
3
4
6.70
136
-17
+
+
6.67
148
-17
+
+
+
4
I
Renal dysfunction
+
+ +
5
2
7
6 7
4 0
6 0
3
6.64 6.78
139 114
-19 -16
+ +
+ +
+ +
+ +
8
2
4
6
6.91
100
-11
+
+
+
+
9
4
5
6.63
168
-17
+
+
+
+
10
2
4
6.71
169
-12
+
+
+
+
1 0 7
3 2
6.75 6.98 6.83
117 85 75
-17 -10 -19
+ + +
+ + +
+ + +
+ + +
8
6.84
87
-17
+
+
+
+
6.79
147
-10
+
+
+
+
Neonatal death 11 1 12 0 13 2
14
3
6
15
6
6
+, Positive; -, negative. *Cerebral palsy or severe hypotonia.
organ dysfunction (6.90 ± 0.08, P < 0.05) and the 64 infants with no organ system dysfunction (6.91 ± 0.07, p < 0.05). In Table V the incidence of seizures and hypotonia is stratified by pH and type of acidemia. Eleven of 109 (10%) had metabolic acidemia, and none developed seizures. None were abnormal at discharge. Twentyeight of 109 (26%) had respiratory acidemia, and seizures developed in 3 of28 (11%). Three were abnormal or suspect at discharge. Mixed acidemia was found in 70 of 109 (64%), and seizures developed in 24 (34%) of them. Thirty-one were abnormal or suspect at discharge. Overall, infants with respiratory acidemia were significantly less likely to develop seizures than were those with a metabolic component. Infants with respiratory acidemia, however, were uncommon below a pH of 6.90 (6/52). Among infants with a pH >6.90 there was a decreasing trend of developing hypoxic ischemic encephalopathy wth respiratory acidemia (1/22) com-
pared with metabolic or mixed acidemia (6/35,
p = 0.06). Seizures were uncommon in this range, and no significant difference could be demonstrated between infants with a respiratory acidemia and those with a metabolic component 0/22 vs 4/35). Below a pH of 6.90, two of 6 infants with respiratory acidemia developed hypoxic ischemic encephalopathy. Both of these had marked hypercarbia (Pco 2 128 and 169 torr). The relationship between pH, Pco 2 , and base deficit and the occurrence of seizures is shown in Fig. 2. Preliminary follow-up data on the 126 live-born infants are shown in Table VI. The results of examinations on infants who were suspected of neurologic abnormalities at discharge refer to the last available examination on record. All were between 6 and 48 months of age. The characteristics of those infants with known abnormal neurologic outcome or neonatal death are summarized in Table VII. All neonatal deaths and all cases of currently confirmed major neurologic dys-
Severe acidemia and asphyxia
Volume 167 "'umber 6
Neonatal comorbidities Meconium aspiration syndrome None None Neonatal aspiration day 5 Meconium aspiration syndrome None Meconium aspiration syndrome Meconium aspiration syndrome, nursery pH to 6.76 None None Congenital meningitis None Meconium aspiration syndrome, intracranial hemorrhage and seizure on extracorporeal membrane oxygenation Meconium aspiration syndrome, intracranial hemorrhage and seizure on extracorporeal membrane oxygenation Pulmonary hemorrhage
Abnormalities on arrival to hospital Oligohydramnios Bleeding previa, FHR bradycardia Massive maternal gastrointestinal bleeding Amnionitis, late decelerations Cocaine use, late decelerations None noted Prolapsed cord FHR bradycardia Motor vehicle accident with abruptio placentae Oligohydramnios Late decelerations FHR bradycardia Late decelerations
Oligohydramnios
Late decelerations
function occurred among infants who exhibited seizures, hypotonia, and other organ system dysfunction in the newborn period.
Comment We have shown a correlation between the degree of umbilical artery acidemia and evidence of asphyxial end-organ injury in the term newborn with severe acidemia (pH < 7.00). Because it is unlikely that a pH in this range would be found in the absence of fetal distress or some degree of newborn depression (the indications for umbilical blood sampling in this study), it is probable that the numbers here approximate the absolute risk for asphyxial injury associated with this degree of acidemia. Indeed, Goldaber et a1. II have reported a similar incidence of pH < 7.00 in a large population of term infants. Remarkably, 78% of infants were considered neurologically normal at discharge or at subsequent follow-up. This may represent an under-
1511
estimation. It is unlikely that infants with major deficits are among those "lost to follow-up." In contrast to other investigators" we found that a predominant respiratory acidemia was not uncommon, especially among infants with a pH ~ 6.90 (22/58, 38%). There was a trend toward a lower incidence of seizures and hypotonia among these infants. Below a pH of 6.90, this effect was not apparent. The profound hypercarbia seen with a respiratory or mixed acidemia in this pH range has few parallels in pediatric or adult medicine. Its particular contribution to the pathologic sequence in perinatal asphyxia is unknown, but it may act in synergy with hypoxemia to exacerbate tissue ischemia. A number of independent deleterious effects of hypercarbia has been described in both animal models and man, including altered cerebral blood flow, seizures, myocardial depression, dysrhythmias, pulmonary vasoconstriction, and decreased oxygen availability caused by a right shift in the oxyhemoglobin dissociation curve. 13. 16 The highest incidence of seizures in the current study was found among infants with a mixed acidemia, including a significant respiratory component, a pattern suggestive of chronic or subacute partial asphyxia followed by a predelivery episode of acute total asphyxia. It is noteworthy that no infants with a pure metabolic acidemia developed seizures or were abnormal at discharge. As Gilstrap et al. 8 have emphasized, other factors can predispose newborn seizures or result in neonatal hypoxia confounding the intrapartum contribution to neurologic morbidity. In the current study, for example, the incidence of infants delivering after term was more than twice the expected rate. Three of the five infants with seizures and neonatal death had specific confounding factors. Among survivors who developed hypoxic ischemic encephalopathy, however, the incidence of infection (1134), trauma (1/34), and distinct neonatal asphyxia (2/34) was low. In addition, the confluence of cardiopulmonary, renal, and cerebral injury manifesting shortly after birth identifies asphyxia as the probable major pathophysiologic factor. It is important to emphasize, however, that although a significant insult occurred during the intrapartum period, we do not suggest that the bad outcomes were necessarily preventable. In fact, 14 of 15 infants with confirmed abnormal outcome (five neonatal deaths and 10 major neurologic deficit) had evidence of possible fetal compromise (e.g., abnormal FHR, oligohydramnios) or preexisting pathologic process, usually of unknown duration, present on arrival in the labor and delivery area. The limitations of the Apgar score in diagnosing perinatal asphyxia have been well documented. It has been suggested, however, that among infants with a cord pH < 7.00 Apgar scores of =::; 3 should be observed to attribute neonatal cerebral dysfunction and subse-
1512 Goodwin et al.
quent permanent neurologic injury to intrapartum events.1O Our findings suggest that even in the pH range below 7.00, a 5-minute Apgar score :s; 3 has only moderate predictive value for hypoxic ischemic encephalopathy. This is not surprising, because some infants with hypoxic ischemic encephalopathy, in particular those with a history of intermittent hypoxia, may have injury limited to the cortex. This will affect tone but not brainstem functions controlling color, heart rate, and some reflexes. Although follow-up was not complete among the study subjects, it is possible to describe a limited profile of the infants who died in the neonatal period or survived with major neurologic deficit (Table VII). Excluding the three subjects who had significant neonatal disease not specifically related to the initial asphyxial injury, the most common pattern is that of a fetus with evidence of distress or compromise at initial evaluation (e.g., oligohydramnios, significant decelerations, infection; Table VII) who then experiences a near-total interruption of gas exchange, as suggested by the degree of hypercarbia. A profound acidemia (usually < 6.80) associated with marked hypercarbia is seen at birth. This is followed by multiorgan system dysfunction, including hypoxic ischemic encephalopathy.
December 1992 Am J Obstet Gynecol
4. 5. 6. 7.
8.
9.
10.
11. 12. 13.
REFERENCES 1. Ruth Vj, Raivo KO. Perinatal brain damage: predictive value of metabolic acidosis and the Apgar score. Br j Med 1988;297:24-7. 2. Yeomans ER, HauthjC, Gilstrap LC, et at. Umbilical cord pH, Pc02 , and bicarbonate following uncomplicated term vaginal deliveries. AM j OBSTET GYNECOL 1985;151:798800. 3. Wible jL, Petrie RH, Koons A, Perez A. The clinical use of
14. 15. 16.
umbilical cord acid-base determinations in perinatal surveillance and management. Clin Perinatol 1982;9;387-97. Thorpe jA, Sampson jE, Parisi VM, Creasy RK. Routine umbilical cord gas determinations. AM j OBSTET GYNECOL 1989;161:600-5. Marri M, Paes BA. Birth asphyxia: does the Apgar score have diagnostic value? Obstet Gynecol 1988;72:120-3. Perkins RP. Perspectives on perinatal brain damage. Obstet Gynecol 1987;69:807-19. Dijxhoorn Mj, Visser GHA, Hui*s Hj, et a1. The relation between umbilical pH values and neonatal neurological morbidity in full-term AFD infants. Early Hum Dev 1985; 11:33-42. Gilstrap LC, Leveno Kj, Burris j, Williams ML, Little BL. Diagnosis of birth asphyxia on the basis offetal pH, Apgar score, and newborn cerebral dysfunction. AM j OBSTET GYNECOL 1989;161:825-30. Winkler CL, HauthjC, Tucker M, Owenj, Brumfield CG. Neonatal complications at term as related to the degree of umbilical artery acidemia. AM j OBSTET GYNECOL 1991; 164: 637-41. Committee on Obstetrics: Maternal and Fetal Medicine (American College of Obstetricians and Gynecologists). Utility of umbilical cord blood acid-base assessment. Washington: American College of Obstetricians and Gynecologists, Feb 1991; ACOG committee opinion no 91. Goldaber KG, Gilstrap LC, Leveno Iq', Dax jS, McIntire DD. Pathologic fetal acidemia. Obstet Gynecol 1991;78; 1103-6. Robertson C, Finer N. Term infants with hypoxic ischemic encephalopathy: outcome at 3.5 years. Dev Child Neurol 1985;27:473-9. Lih L, Gonzalez-Mendez R, Severinghaus jW, et at. Cerebral intracellular changes during supercarbia: an in vivo 31p nuclear magnetic resonance study in rats. j Cereb Blood Flow Metab 1985;5:537-41. Manley ES, Nash CB, Woodbury RA. Cardiovascular responses to severe hypercapnia of short duration. Am j Physiol 1964;207 :634-8. Baile EM, Pare PD. Response of the bronchial circulation to acute hypoxemia and hypercarbia in the dog. Am j Physiol 1983;55:1474-80. Nunn jF. Applied respiratory physiology. 2nd ed. London: Butterworth, 1987 :366-8.
Los Angeles, California OBJECTIVE: Our purpose was to determine the relationship of umbilical acid-base status and Apgar score to neonatal asphyxial sequelae in infants with severe acidemia (pH < 7.00). STUDY DESIGN: The obstetric and neonatal course of 129 term, nonanomalous singleton infants with umbilical pH < 7.00 was reviewed. RESULTS: There were three stillbirths (failed resuscitation). Seventy-two of 126 (57%) were admitted to the neonatal intensive care unit. Thirty-eight percent had pulmonary dysfunction, 26% renal dysfunction, 31% cardiac dysfunction, and 31% hypoxic ischemic encephalopathy (seizures and hypotonia, n = 29; seizures only, n = 3; hypotonia only, n = 10). There were five neonatal deaths. In 109 cases umbilical arterial values were available, and among these infants there was a significant increase in the incidence of seizures with declining pH from 9% (5/57), with a pH of 6.90 to 6.99, to 80% (8/10), with a pH of 6.61 to 6.70. Respiratory acidemia (Pco 2 > 65, base deficit < 10) was identified in 28 of 109 (26%), all but six occurring in the pH range above 6.90. Compared with infants with comparable umbilical artery pH, infants with respiratory acidemia did not differ significantly with respect to asphyxial end-organ injury in general (8/35 vs 6/22), but there was a trend toward a lower incidence of hypoxic ischemic encephalopathy (6/35 vs 1/22, P = 0.06). All infants with definite abnormal outcome (five neonatal deaths and 10 severe neurologic deficit) had seizures, hypotonia, and at least one other organ system dysfunction. Twenty-four of 29 infants (83%) who developed seizures had a 5-minute Apgar score 2 minutes) on admission, and 19 underwent emergency cesarean section. Overall, 113 (88%) patients were delivered because of a clinical diagnosis of fetal distress. Ninetyseven (76%) underwent emergency or urgent cesarean section, and 16 (12%) underwent instrumented vaginal delivery for fetal distress. There were three stillborn infants and five neonatal deaths. The findings of the postmortem examinations in these cases are summarized in Table II. The perinatal mortality rate for the study population was 62 per 1000 compared with our term uncorrected perinatal mortality rate of 1.5 per 1000. Fifty-four infants (43%) were admitted to the normal nursery and suffered no significant morbidity. Of the 72 infants admitted to the neonatal intensive care unit, 21 (17%) were observed or given supplemental oxygen but did not meet specific criteria for end-organ dysfunction. All 21 were normal at the time of discharge. Fifty-one of 126 infants (40%) had evidence of dysfunction in at least one organ system (Table III). Fifteen infants had non-cerebral organ dysfunction, and 14 of 15 were normal at discharge (n = 12) or follow-up (n = 2). One of these infants was lost to follow-up. Twenty-six infants had both seizures and prolonged hypotonia. Such infants constitute the principal risk group for permanent neurologic dysfunction l2 and are presented separately in the following discussion. Four infants who experienced seizures within 48 hours of life had factors other than hypoxic ischemic encephalopathy that may have contributed to the seizures. Two had seizures that were temporally related to intracranial hemorrhage occurring after heparinization for extracorporeal membrane oxygenation. One infant had congenital meningitis. These three neonates died.
6.90-6.99
Mixed acidemia (n = 25)
Metabolic acidemia (n = 10)
Respiratory acidemia (n = 22)
5 4
o
o
o
o o
20
9
21
1509
One infant with seizures had suffered a depressed skull fracture at delivery but was normal at follow-up. Seizures and hypotonia were seen in association with at least one other organ system dysfunction in 25 of 126 (20%). In Fig. 1 occurrence of seizures is stratified by the 5-minute Apgar score for the 126 liveborn infants. Mild d"pression at 5 minutes (Apgar score < 7) was noted in Z4 of 29 infants (83%) who developed seizures, but only 12 of 29 (41 %) had an Apgar score of :5 3 at 5 minutes. The positive and negative predictive value of a 5-minute Apgar score :5 3 for the occurrence of seizures were 75% and 84%, respectively. Two infants with Apgar scores of 6 and 7 at 5 minutes subsequently manifested profound neurologic deficits. Neither had evidence of neonatal asphyxia or other comorbidity to explain the poor neurologic outcome. To correlate the occurrence of asphyxial end-organ injury with the severity and type of acidemia, the data that follow refer to the 109 infants with documentable umbilical artery pH values. In Table IV umbilical artery pH values are arbitrarily stratified into ranges of 0.10 from a low of 6.61 to a maximum of 6.99. Each of the postasphyxial morbidities occurred with greater frequency as the degree of acidemia increased. Below a pH of 6.80, > 50% of infants had seizures and hypotonia. Twenty-two of 109 had seizures, hypotonia, and additional organ system dysfunction. The mean pH value of this group (6.79 ± 0.11, mean ± SD) differed significantly from the pH of the other 23 infants with Table VI. Preliminary outcome data (n live births) Neonatal deaths Normal at discharge* Suspect at discharge Follow-up of those suspect at discharge (n Normal Abnormal Major neurologic deficiu 10 Suspect§ 5 Lost to follow-up 8
=
=
126 5 (4%) 84 (66%) 37 (30%) 29)t 14 15
TOTAL
Normal Neonatal death Major neurologic deficit Suspect Lost to follow-up
98 (78%)
5 (4%) 10 (8%) 5 (4%) 8(6%)
*Infants lacking evidence of neonatal encephalopathy who had a normal neurologic examination result at discharge received no special follow-up. t Results refer to last examination, which ranged from 6 to 48 months of age. tTwo infants died before 18 months of age. §Mild tone abnormalities or cognitive delay.
1510 Goodwin et a\.
December 1992 Am J Obstet Gynecol
Table VII. Summary of cases with known abnormal outcome (N = 15) Apgar score Case No.
1 min
I
Major neurologic deficit* 1 1
Organ dysfunction
Pulmonary I Cardiac I dysfunction dysfunction
Blood pH
Gas Pco2
Base deficit
Cerebral dysfunction
5
6.61
153
-19
+
+
6.63
154
-18
+
+
5 min
I
10 min
+
2
0
2
3
2
4
6
6.78
111
-16
+
+
3
4
6.70
136
-17
+
+
6.67
148
-17
+
+
+
4
I
Renal dysfunction
+
+ +
5
2
7
6 7
4 0
6 0
3
6.64 6.78
139 114
-19 -16
+ +
+ +
+ +
+ +
8
2
4
6
6.91
100
-11
+
+
+
+
9
4
5
6.63
168
-17
+
+
+
+
10
2
4
6.71
169
-12
+
+
+
+
1 0 7
3 2
6.75 6.98 6.83
117 85 75
-17 -10 -19
+ + +
+ + +
+ + +
+ + +
8
6.84
87
-17
+
+
+
+
6.79
147
-10
+
+
+
+
Neonatal death 11 1 12 0 13 2
14
3
6
15
6
6
+, Positive; -, negative. *Cerebral palsy or severe hypotonia.
organ dysfunction (6.90 ± 0.08, P < 0.05) and the 64 infants with no organ system dysfunction (6.91 ± 0.07, p < 0.05). In Table V the incidence of seizures and hypotonia is stratified by pH and type of acidemia. Eleven of 109 (10%) had metabolic acidemia, and none developed seizures. None were abnormal at discharge. Twentyeight of 109 (26%) had respiratory acidemia, and seizures developed in 3 of28 (11%). Three were abnormal or suspect at discharge. Mixed acidemia was found in 70 of 109 (64%), and seizures developed in 24 (34%) of them. Thirty-one were abnormal or suspect at discharge. Overall, infants with respiratory acidemia were significantly less likely to develop seizures than were those with a metabolic component. Infants with respiratory acidemia, however, were uncommon below a pH of 6.90 (6/52). Among infants with a pH >6.90 there was a decreasing trend of developing hypoxic ischemic encephalopathy wth respiratory acidemia (1/22) com-
pared with metabolic or mixed acidemia (6/35,
p = 0.06). Seizures were uncommon in this range, and no significant difference could be demonstrated between infants with a respiratory acidemia and those with a metabolic component 0/22 vs 4/35). Below a pH of 6.90, two of 6 infants with respiratory acidemia developed hypoxic ischemic encephalopathy. Both of these had marked hypercarbia (Pco 2 128 and 169 torr). The relationship between pH, Pco 2 , and base deficit and the occurrence of seizures is shown in Fig. 2. Preliminary follow-up data on the 126 live-born infants are shown in Table VI. The results of examinations on infants who were suspected of neurologic abnormalities at discharge refer to the last available examination on record. All were between 6 and 48 months of age. The characteristics of those infants with known abnormal neurologic outcome or neonatal death are summarized in Table VII. All neonatal deaths and all cases of currently confirmed major neurologic dys-
Severe acidemia and asphyxia
Volume 167 "'umber 6
Neonatal comorbidities Meconium aspiration syndrome None None Neonatal aspiration day 5 Meconium aspiration syndrome None Meconium aspiration syndrome Meconium aspiration syndrome, nursery pH to 6.76 None None Congenital meningitis None Meconium aspiration syndrome, intracranial hemorrhage and seizure on extracorporeal membrane oxygenation Meconium aspiration syndrome, intracranial hemorrhage and seizure on extracorporeal membrane oxygenation Pulmonary hemorrhage
Abnormalities on arrival to hospital Oligohydramnios Bleeding previa, FHR bradycardia Massive maternal gastrointestinal bleeding Amnionitis, late decelerations Cocaine use, late decelerations None noted Prolapsed cord FHR bradycardia Motor vehicle accident with abruptio placentae Oligohydramnios Late decelerations FHR bradycardia Late decelerations
Oligohydramnios
Late decelerations
function occurred among infants who exhibited seizures, hypotonia, and other organ system dysfunction in the newborn period.
Comment We have shown a correlation between the degree of umbilical artery acidemia and evidence of asphyxial end-organ injury in the term newborn with severe acidemia (pH < 7.00). Because it is unlikely that a pH in this range would be found in the absence of fetal distress or some degree of newborn depression (the indications for umbilical blood sampling in this study), it is probable that the numbers here approximate the absolute risk for asphyxial injury associated with this degree of acidemia. Indeed, Goldaber et a1. II have reported a similar incidence of pH < 7.00 in a large population of term infants. Remarkably, 78% of infants were considered neurologically normal at discharge or at subsequent follow-up. This may represent an under-
1511
estimation. It is unlikely that infants with major deficits are among those "lost to follow-up." In contrast to other investigators" we found that a predominant respiratory acidemia was not uncommon, especially among infants with a pH ~ 6.90 (22/58, 38%). There was a trend toward a lower incidence of seizures and hypotonia among these infants. Below a pH of 6.90, this effect was not apparent. The profound hypercarbia seen with a respiratory or mixed acidemia in this pH range has few parallels in pediatric or adult medicine. Its particular contribution to the pathologic sequence in perinatal asphyxia is unknown, but it may act in synergy with hypoxemia to exacerbate tissue ischemia. A number of independent deleterious effects of hypercarbia has been described in both animal models and man, including altered cerebral blood flow, seizures, myocardial depression, dysrhythmias, pulmonary vasoconstriction, and decreased oxygen availability caused by a right shift in the oxyhemoglobin dissociation curve. 13. 16 The highest incidence of seizures in the current study was found among infants with a mixed acidemia, including a significant respiratory component, a pattern suggestive of chronic or subacute partial asphyxia followed by a predelivery episode of acute total asphyxia. It is noteworthy that no infants with a pure metabolic acidemia developed seizures or were abnormal at discharge. As Gilstrap et al. 8 have emphasized, other factors can predispose newborn seizures or result in neonatal hypoxia confounding the intrapartum contribution to neurologic morbidity. In the current study, for example, the incidence of infants delivering after term was more than twice the expected rate. Three of the five infants with seizures and neonatal death had specific confounding factors. Among survivors who developed hypoxic ischemic encephalopathy, however, the incidence of infection (1134), trauma (1/34), and distinct neonatal asphyxia (2/34) was low. In addition, the confluence of cardiopulmonary, renal, and cerebral injury manifesting shortly after birth identifies asphyxia as the probable major pathophysiologic factor. It is important to emphasize, however, that although a significant insult occurred during the intrapartum period, we do not suggest that the bad outcomes were necessarily preventable. In fact, 14 of 15 infants with confirmed abnormal outcome (five neonatal deaths and 10 major neurologic deficit) had evidence of possible fetal compromise (e.g., abnormal FHR, oligohydramnios) or preexisting pathologic process, usually of unknown duration, present on arrival in the labor and delivery area. The limitations of the Apgar score in diagnosing perinatal asphyxia have been well documented. It has been suggested, however, that among infants with a cord pH < 7.00 Apgar scores of =::; 3 should be observed to attribute neonatal cerebral dysfunction and subse-
1512 Goodwin et al.
quent permanent neurologic injury to intrapartum events.1O Our findings suggest that even in the pH range below 7.00, a 5-minute Apgar score :s; 3 has only moderate predictive value for hypoxic ischemic encephalopathy. This is not surprising, because some infants with hypoxic ischemic encephalopathy, in particular those with a history of intermittent hypoxia, may have injury limited to the cortex. This will affect tone but not brainstem functions controlling color, heart rate, and some reflexes. Although follow-up was not complete among the study subjects, it is possible to describe a limited profile of the infants who died in the neonatal period or survived with major neurologic deficit (Table VII). Excluding the three subjects who had significant neonatal disease not specifically related to the initial asphyxial injury, the most common pattern is that of a fetus with evidence of distress or compromise at initial evaluation (e.g., oligohydramnios, significant decelerations, infection; Table VII) who then experiences a near-total interruption of gas exchange, as suggested by the degree of hypercarbia. A profound acidemia (usually < 6.80) associated with marked hypercarbia is seen at birth. This is followed by multiorgan system dysfunction, including hypoxic ischemic encephalopathy.
December 1992 Am J Obstet Gynecol
4. 5. 6. 7.
8.
9.
10.
11. 12. 13.
REFERENCES 1. Ruth Vj, Raivo KO. Perinatal brain damage: predictive value of metabolic acidosis and the Apgar score. Br j Med 1988;297:24-7. 2. Yeomans ER, HauthjC, Gilstrap LC, et at. Umbilical cord pH, Pc02 , and bicarbonate following uncomplicated term vaginal deliveries. AM j OBSTET GYNECOL 1985;151:798800. 3. Wible jL, Petrie RH, Koons A, Perez A. The clinical use of
14. 15. 16.
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