Early Human Development,
135
25 (1991) 135-148
Elsevier Scientific Publishers Ireland Ltd.
EHD 01140
Acute neonatal morbidity and long-term central nervous system sequelae of perinatal asphyxia in term infants* Seetha Shankaran,
Department
of Pediatrics,
Eunice Woldt, Thomas Koepke, and Raja Nandyal
Mary P. Bedard
Wayne State University School of Medicine, and Children’s Hospital of Michigan, Detroit, MI (U.S.A.)
(Received 26 March 1990; revision received 18 February 1991; accepted 1 March 1991)
Summary Twenty-eight term neonates with severe perinatal asphyxia were referred to a tertiary neonatal intensive care unit (NICU). The morbidity of asphyxia included involvement of the pulmonary (n = 24 infants), central nervous system (n = 22), renal (n = 15), cardiac (n = 14), metabolic (n = 13) and hematologic (n = 10) systems. The majority of neonates had more than three organ systems involved. Twenty-four neonates survived the neonatal course and at NICU discharge all system effects other than the central nervous system had resolved. At 5 years (60 months), 14 children had a normal neurologic examination, 9 had spastic quadriplegia and one had hemiplegia. Nine children had a McCarthy General Cognitive Index (GCI) 1 84, 3 had a GCI between 68 and 83 and 12 scored < 67. Neonatal seizures, renal problems, microcephaly at 3 months, and post-neonatal seizures were associated with an abnormal neurologic outcome or a GCI < 67. A neurologic examination during the first year of life may reveal whether children with birth asphyxia will be relatively normal at age 5 years or whether they will show considerable delay.
asphyxia; multisystem involvement; neurodevelopmental
sequelae.
Correspondence to: Seetha Shankaran, Children’s Hospital of Michigan, 3901 Beaubien Blvd., Detroit, MI 48201, U.S.A. *Supported by a grant from the Department of Mental Health, State of Michigan.
0378-3782/91/$03.50 0 1991 Elsevier ScientificPublishers Published and Printed in Ireland
Ireland Ltd.
136
Introduction Perinatal asphyxia affects multiple organ systems in the term neonate, including the cardiac, pulmonary, central nervous, renal and hematological systems [l-9]. The effects of asphyxia on the term infant following the neonatal period have been investigated in only one organ system, the central nervous system (CNS) [l&-16]. The CNS sequelae of asphyxia include cerebral palsy, seizures and developmental delay. The predictors of outcome have included low Apgar scores, presence of encephalopathy, seizures, and abnormalities in the computerized tomographic (CT scan) of the head revealing areas of hypodensities [l&16]. The purpose of this prospective study was to evaluate the long-term sequelae of asphyxia in term neonates in an outborn population. Our hypothesis was that asphyxia results in acute multisystem effects followed by recovery in all organ systems except the CNS. Materials and Methods The study patients were full term neonates with a gestational age between 38 and 42 weeks of age who were transferred to the Neonatal Intensive Care Unit at the Children’s Hospital of Michigan with a diagnosis of perinatal asphyxia between January 1980 and December 1982. Neonates were eligible for study entry if they were admitted at less than 24 h of age. Asphyxia was defined as fetal distress documented on fetal heart rate monitoring (late or variable decelerations), the presence of meconium stained amniotic fluid with the neonate in the vertex position, the need for endotracheal intubation at delivery, and the occurrence of abnormal muscle tone and seizures within 24 h of age. Neonates were eligible for study entry if they fulfilled three out of the above four criteria. Exclusion criteria included the presence of a congenital abnormality, clinical or laboratory evidence of intrauterine infection, intrauterine growth retardation and an abnormal head size at birth (< 5 or >95 percentile). The clinical course prior to admission to the neonatal unit was recorded. The neonatal hospital course was followed prospectively and data recorded on predetermined flow sheets. The neurologic status was classified using the stages of Sarnat and Sarnat [4]. An echoencephalogram of the head was performed within 24 h and a CT scan of the head was performed at one week of age. An electroencephalogram was performed on all neonates with seizures. Seizures were treated with anticonvulsant therapy using phenobarbital and dilantin. Neonates with hypotension or cardiomegaly on chest radiograph were evaluated by echocardiogram and measurement of cardiac enzymes. The renal status of the infants was noted by measuring hourly urine output, blood urea nitrogen (BUN) and serum creatinine and the presence of red cells or casts in the urine. Oliguria was treated with fluid restriction. The pulmonary status of each neonate was followed by assessing the need for assisted ventilation, serial blood gas measurements and chest radiographs. Persistent pulmonary hypertension was diagnosed by the presence of hypoxemia and a right to left shunt in the absence of a structural heart defect on echocardiography. The pulmonary
137
hypertension was treated with hyperventilation and tolazoline. The metabolic status of each neonate was assessed by measurement of blood gases, serum electrolytes, blood sugar, calcium or magnesium as needed. Metabolic acidosis that was persistent after 24 h was considered abnormal. A coagulation profile was performed if there was evidence of a bleeding disorder. The course of the disturbance of each organ system was noted daily during the first week and weekly thereafter. The disturbance of the organ system was reported as normal when the clinical status and laboratory data were normal. An attempt was made to obtain an autopsy in neonates who did not survive. All surviving infants were followed longitudinally in the developmental assessment clinic after discharge from the Neonatal Intensive Care Unit. Neurological examinations were performed at 3, 6 and 12 months of age and yearly thereafter. The height, weight and head circumferences were measured at each visit. The Bayley Scales of Infant Development [17] were performed on each child at each visit between 12 and 30 months of age and the McCarthy Scales of Children’s Abilities [ 181 were performed at each visit after 30 months until 5 years of age. An ophthalmologic, audiologic and language assessment was performed at yearly intervals. The ophthalmologic evaluation consisted of a clinical examination of extraocular movements, optic nerve and fundi, refraction and examination for strabismus and amblyopia. The audiologic examination consisted of tympanometry and observation of behavior during distraction testing with a variety of noisemakers. In a selected group of infants brain stem auditory evoked responses were performed. Language testing included the Receptive Emergent Language Scale in infants 2 S.D. less than the mean (567). The parents’ marital status, educational status and health care insurance were recorded. The socioeconomic status of each family was determined using the Hollingshead Four Factor Index of Social Position [ 191
Statistical methods The Chi square and the Kruskal-Wallis one way analysis of variance (ANOVA) were employed to analyze the differences at five years of age between those children who had a normal neurological examination and those who had sequelae, and children with a McCarthy GCI >84 as compared to
0
(01 = u) P8
135
25 (1991) 135-148
Elsevier Scientific Publishers Ireland Ltd.
EHD 01140
Acute neonatal morbidity and long-term central nervous system sequelae of perinatal asphyxia in term infants* Seetha Shankaran,
Department
of Pediatrics,
Eunice Woldt, Thomas Koepke, and Raja Nandyal
Mary P. Bedard
Wayne State University School of Medicine, and Children’s Hospital of Michigan, Detroit, MI (U.S.A.)
(Received 26 March 1990; revision received 18 February 1991; accepted 1 March 1991)
Summary Twenty-eight term neonates with severe perinatal asphyxia were referred to a tertiary neonatal intensive care unit (NICU). The morbidity of asphyxia included involvement of the pulmonary (n = 24 infants), central nervous system (n = 22), renal (n = 15), cardiac (n = 14), metabolic (n = 13) and hematologic (n = 10) systems. The majority of neonates had more than three organ systems involved. Twenty-four neonates survived the neonatal course and at NICU discharge all system effects other than the central nervous system had resolved. At 5 years (60 months), 14 children had a normal neurologic examination, 9 had spastic quadriplegia and one had hemiplegia. Nine children had a McCarthy General Cognitive Index (GCI) 1 84, 3 had a GCI between 68 and 83 and 12 scored < 67. Neonatal seizures, renal problems, microcephaly at 3 months, and post-neonatal seizures were associated with an abnormal neurologic outcome or a GCI < 67. A neurologic examination during the first year of life may reveal whether children with birth asphyxia will be relatively normal at age 5 years or whether they will show considerable delay.
asphyxia; multisystem involvement; neurodevelopmental
sequelae.
Correspondence to: Seetha Shankaran, Children’s Hospital of Michigan, 3901 Beaubien Blvd., Detroit, MI 48201, U.S.A. *Supported by a grant from the Department of Mental Health, State of Michigan.
0378-3782/91/$03.50 0 1991 Elsevier ScientificPublishers Published and Printed in Ireland
Ireland Ltd.
136
Introduction Perinatal asphyxia affects multiple organ systems in the term neonate, including the cardiac, pulmonary, central nervous, renal and hematological systems [l-9]. The effects of asphyxia on the term infant following the neonatal period have been investigated in only one organ system, the central nervous system (CNS) [l&-16]. The CNS sequelae of asphyxia include cerebral palsy, seizures and developmental delay. The predictors of outcome have included low Apgar scores, presence of encephalopathy, seizures, and abnormalities in the computerized tomographic (CT scan) of the head revealing areas of hypodensities [l&16]. The purpose of this prospective study was to evaluate the long-term sequelae of asphyxia in term neonates in an outborn population. Our hypothesis was that asphyxia results in acute multisystem effects followed by recovery in all organ systems except the CNS. Materials and Methods The study patients were full term neonates with a gestational age between 38 and 42 weeks of age who were transferred to the Neonatal Intensive Care Unit at the Children’s Hospital of Michigan with a diagnosis of perinatal asphyxia between January 1980 and December 1982. Neonates were eligible for study entry if they were admitted at less than 24 h of age. Asphyxia was defined as fetal distress documented on fetal heart rate monitoring (late or variable decelerations), the presence of meconium stained amniotic fluid with the neonate in the vertex position, the need for endotracheal intubation at delivery, and the occurrence of abnormal muscle tone and seizures within 24 h of age. Neonates were eligible for study entry if they fulfilled three out of the above four criteria. Exclusion criteria included the presence of a congenital abnormality, clinical or laboratory evidence of intrauterine infection, intrauterine growth retardation and an abnormal head size at birth (< 5 or >95 percentile). The clinical course prior to admission to the neonatal unit was recorded. The neonatal hospital course was followed prospectively and data recorded on predetermined flow sheets. The neurologic status was classified using the stages of Sarnat and Sarnat [4]. An echoencephalogram of the head was performed within 24 h and a CT scan of the head was performed at one week of age. An electroencephalogram was performed on all neonates with seizures. Seizures were treated with anticonvulsant therapy using phenobarbital and dilantin. Neonates with hypotension or cardiomegaly on chest radiograph were evaluated by echocardiogram and measurement of cardiac enzymes. The renal status of the infants was noted by measuring hourly urine output, blood urea nitrogen (BUN) and serum creatinine and the presence of red cells or casts in the urine. Oliguria was treated with fluid restriction. The pulmonary status of each neonate was followed by assessing the need for assisted ventilation, serial blood gas measurements and chest radiographs. Persistent pulmonary hypertension was diagnosed by the presence of hypoxemia and a right to left shunt in the absence of a structural heart defect on echocardiography. The pulmonary
137
hypertension was treated with hyperventilation and tolazoline. The metabolic status of each neonate was assessed by measurement of blood gases, serum electrolytes, blood sugar, calcium or magnesium as needed. Metabolic acidosis that was persistent after 24 h was considered abnormal. A coagulation profile was performed if there was evidence of a bleeding disorder. The course of the disturbance of each organ system was noted daily during the first week and weekly thereafter. The disturbance of the organ system was reported as normal when the clinical status and laboratory data were normal. An attempt was made to obtain an autopsy in neonates who did not survive. All surviving infants were followed longitudinally in the developmental assessment clinic after discharge from the Neonatal Intensive Care Unit. Neurological examinations were performed at 3, 6 and 12 months of age and yearly thereafter. The height, weight and head circumferences were measured at each visit. The Bayley Scales of Infant Development [17] were performed on each child at each visit between 12 and 30 months of age and the McCarthy Scales of Children’s Abilities [ 181 were performed at each visit after 30 months until 5 years of age. An ophthalmologic, audiologic and language assessment was performed at yearly intervals. The ophthalmologic evaluation consisted of a clinical examination of extraocular movements, optic nerve and fundi, refraction and examination for strabismus and amblyopia. The audiologic examination consisted of tympanometry and observation of behavior during distraction testing with a variety of noisemakers. In a selected group of infants brain stem auditory evoked responses were performed. Language testing included the Receptive Emergent Language Scale in infants 2 S.D. less than the mean (567). The parents’ marital status, educational status and health care insurance were recorded. The socioeconomic status of each family was determined using the Hollingshead Four Factor Index of Social Position [ 191
Statistical methods The Chi square and the Kruskal-Wallis one way analysis of variance (ANOVA) were employed to analyze the differences at five years of age between those children who had a normal neurological examination and those who had sequelae, and children with a McCarthy GCI >84 as compared to
0
(01 = u) P8
