Nursery Neurobiologic Risk Score: Important factors in predicting outcome in very low birth weight infants J a n e E. Brazy, MD, C a r o l O. E c k e r m a n , PhD, Jerri M. O e h l e r , PhD, Ricki F. Goldstein, MD, a n d A n g e l a M. O ' R a n d , Phb From the Departments of Pediatrics, Psychology, and Sociology, Duke University, Durham, North Carolina, and the Department of Pediatrics, University of Wisconsin, Madison We d e v e l o p e d a nursery N e u r o b i o l o g i c Risk Score (NBRS) based on potential mechanisms of brain cell injury in preterm infants a n d correlated it with develo p m e n t a l o u t c o m e at the c o r r e c t e d ages of 6, 15, a n d 24 months. The NBRSwas d e t e r m i n e d at 2 weeks of a g e and at the time of discharge from intensive care in 58 preterm infants with birth weights ~4500 gm. The NBRS correlated significantly with the Bayley Scales of Infant Development, Mental D e v e l o p m e n t Index (MDI) (r = -0.61 to - 0 . 4 0 ) and Psychomotor D e v e l o p m e n t Index (PDI) (r = - 0 . 5 9 to -0.46), and with abnormal neurologic e x a m i n a t i o n findings (r = 0.59 to 0.73) at the three testing periods. Although 12 of the 13 items c o m p o s i n g the NBRS individually correlated with o n e or more o u t c o m e variables, seven items (infection, b l o o d pH, seizures, intraventricular hemorrhage, assisted ventilation, periventricular l e u k o m a l a c i a , and h y p o g l y c e m i a ) a c c o u n t e d for almost all of the e x p l a i n e d variance. Logistic regression of individual items demonstrated intraventrlcular h e m o r r h a g e to be the most important item for predicting the MDI at 24 months; pH was the most influential item for predicting the PDI at every testing period. A shorter, revised NBRS that i n c l u d e d only the seven significant items demonstrated as strong a correlation with d e v e l o p m e n t a l o u t c o m e as the original NBRS. A revised 2-week score of > 5 or a discharge score of > 6 demonstrated 100% specificity and had a 100% positive predlctlve value for an abnormal o u t c o m e at 24 months of a g e in this group of infants. We c o n c l u d e that the NBRS identifies during the intensive care nursery stay those infants at highest risk for an abnormal o u t c o m e related to nursery events. In addition, analysis of NBRS items provides insight into the relative importance of individual factors for influencing mental, motor, and n e u r o l o g i c outcome. (J PEDIATR1991;118:783-92)
Many approaches and scoring systems have been developed in an attempt to define the effect of neonatal illness on subsequent outcome. Several early methods focused largely on the presence of specific problems that occur during pregnancy or the neonatal period), 2 The scores, based on the assumption that a specific disease has equal impact on each fetus or infant, were not successful in predicting outcome. Submitted for publication July 26, 1990; accepted Dec. 28, 1990. Reprint requests: Jane E. Brazy, MD, Meriter-Madison General 6C, 202 S. Park St., Madison, WI 53715. 9/23/27626
Subsequent investigators took a more general approach, that of measuring the duration and/or intensity of care needed by each infant) As expected, the smallest infants and those with the most extensive care requirements were at greatest risk for neurodevelopmental problems. A more direct approach has been to try to predict outcome by looking at the target organ, the brain and nervous system. Head growth can be used as an index of overall brain development.4-6 Gross et al. 4 and Eckerman et al. 5 demonstrated that infants with poor head growth in the first 6 weeks of life have significantlypoorer outcomes than those with normal head growth. Dubowitz et al. 7 and Allen and
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IVH MDI NBRS NBRS-2 NBRS-D PDA PDI
Intraventricular hemorrhage Mental Development Index Neurobiologic Risk Score NRBS administered at 2 weeks of age NRBS administered at time of discharge from intensive care Patent ductus arteriosus Psychomotor Development Index
Capute 8 chose neurologic assessment and noted significant correlations between abnormal neurologic findings at 40 or 44 weeks of corrected age and subsequent neuromotor disabilities. The most specific approach has been to identify a brain lesion on cranial sonograms and to determine its impact on outcome; investigators demonstrated the importance of severe intraventricular hemorrhage and periventricular echodensities in determining neurodevelopmental risk. 915 However, not all infants with subsequent disabilities have brain hemorrhage or cysts identifiable on cranial sonograms, and most infants with IVH are normal at follow_up.9, 11-13There remains a need for an assessment tool that not only provides for early identification of those infants at highest risk for neurodevelopmental abnormalities but also contributes insight into the causes of these disabilities. The primary purpose of this study was to develop a risk assessment scoring system focused on mechanisms of brain cell injury. The concept is based on two premises: (1) if a neonatal medical event is going to be significant enough to alter the infant's subsequent development, it must have the potential to cause cell injury; and (2) the duration and number of adverse events are important determinants of injury. We hypothesized that cell injury would occur predominantly through four mechanisms: hypoxemia, insufficient blood flow, inadequate substrate for cellular metabolism, or direct tissue damage. Thus we designed the Neurobiologic Risk Score on the basis of 13 items involving events or conditions with the potential to alter cell survival through these mechanisms. The severity and duration of adverse events were weighted by a geometric progression of scores within each item. A second goal in creating the NBRS was to develop a scoring system that was simple, rapid, and objective. Acquisition of data would not require any special medical skills or depend on the cooperation of the infant during an examination. The final goal was to determine whether risk for abnormal outcome could be assessed early in the neonatal course. METHODS Neurobiologic Risk Score. The NBRS is based on 13 items. Zero points are given if a risk item is absent. If the
The Journal of Pediatrics May 1991
item is present, the item is graded 1, 2, or 4. A geometric rather than arithmetic progression of scores is used to weight the severity or duration of an event more heavily. A score of 4 is reserved for the most severe and potentially injurious conditions and is possible in only 10 categories. Each item is scored by cumulative events; for example, all hours in which hypoglycemia was present are counted before a score is assigned. The final score for each item is either 0, 1, 2, or 4. The total NBRS is the sum of the scores for each item. By design, three items (hypotension, hypoxia, and pH) can be assessed either as duration in hours or by number of recorded events. The former is more precise and is used whenever abnormal values are repeated at a frequency of more than one per hour. The duration of an event is calculated from the time when the first value that meets the scoring criteria was obtained to the time when the first subsequent value that exceeds the scoring cutoff point was obtained. Items and rationale for inclusion Apgar score. The Apgar score is included in the assessment to account for those events that occur in the delivery room during the first minutes of the infant's life: 0 -- Score >5 at 1 and 5 minutes 1 = Score -5 at 5 minutes 2 -- Score -
Many approaches and scoring systems have been developed in an attempt to define the effect of neonatal illness on subsequent outcome. Several early methods focused largely on the presence of specific problems that occur during pregnancy or the neonatal period), 2 The scores, based on the assumption that a specific disease has equal impact on each fetus or infant, were not successful in predicting outcome. Submitted for publication July 26, 1990; accepted Dec. 28, 1990. Reprint requests: Jane E. Brazy, MD, Meriter-Madison General 6C, 202 S. Park St., Madison, WI 53715. 9/23/27626
Subsequent investigators took a more general approach, that of measuring the duration and/or intensity of care needed by each infant) As expected, the smallest infants and those with the most extensive care requirements were at greatest risk for neurodevelopmental problems. A more direct approach has been to try to predict outcome by looking at the target organ, the brain and nervous system. Head growth can be used as an index of overall brain development.4-6 Gross et al. 4 and Eckerman et al. 5 demonstrated that infants with poor head growth in the first 6 weeks of life have significantlypoorer outcomes than those with normal head growth. Dubowitz et al. 7 and Allen and
783
78 4
Brazy et al.
IVH MDI NBRS NBRS-2 NBRS-D PDA PDI
Intraventricular hemorrhage Mental Development Index Neurobiologic Risk Score NRBS administered at 2 weeks of age NRBS administered at time of discharge from intensive care Patent ductus arteriosus Psychomotor Development Index
Capute 8 chose neurologic assessment and noted significant correlations between abnormal neurologic findings at 40 or 44 weeks of corrected age and subsequent neuromotor disabilities. The most specific approach has been to identify a brain lesion on cranial sonograms and to determine its impact on outcome; investigators demonstrated the importance of severe intraventricular hemorrhage and periventricular echodensities in determining neurodevelopmental risk. 915 However, not all infants with subsequent disabilities have brain hemorrhage or cysts identifiable on cranial sonograms, and most infants with IVH are normal at follow_up.9, 11-13There remains a need for an assessment tool that not only provides for early identification of those infants at highest risk for neurodevelopmental abnormalities but also contributes insight into the causes of these disabilities. The primary purpose of this study was to develop a risk assessment scoring system focused on mechanisms of brain cell injury. The concept is based on two premises: (1) if a neonatal medical event is going to be significant enough to alter the infant's subsequent development, it must have the potential to cause cell injury; and (2) the duration and number of adverse events are important determinants of injury. We hypothesized that cell injury would occur predominantly through four mechanisms: hypoxemia, insufficient blood flow, inadequate substrate for cellular metabolism, or direct tissue damage. Thus we designed the Neurobiologic Risk Score on the basis of 13 items involving events or conditions with the potential to alter cell survival through these mechanisms. The severity and duration of adverse events were weighted by a geometric progression of scores within each item. A second goal in creating the NBRS was to develop a scoring system that was simple, rapid, and objective. Acquisition of data would not require any special medical skills or depend on the cooperation of the infant during an examination. The final goal was to determine whether risk for abnormal outcome could be assessed early in the neonatal course. METHODS Neurobiologic Risk Score. The NBRS is based on 13 items. Zero points are given if a risk item is absent. If the
The Journal of Pediatrics May 1991
item is present, the item is graded 1, 2, or 4. A geometric rather than arithmetic progression of scores is used to weight the severity or duration of an event more heavily. A score of 4 is reserved for the most severe and potentially injurious conditions and is possible in only 10 categories. Each item is scored by cumulative events; for example, all hours in which hypoglycemia was present are counted before a score is assigned. The final score for each item is either 0, 1, 2, or 4. The total NBRS is the sum of the scores for each item. By design, three items (hypotension, hypoxia, and pH) can be assessed either as duration in hours or by number of recorded events. The former is more precise and is used whenever abnormal values are repeated at a frequency of more than one per hour. The duration of an event is calculated from the time when the first value that meets the scoring criteria was obtained to the time when the first subsequent value that exceeds the scoring cutoff point was obtained. Items and rationale for inclusion Apgar score. The Apgar score is included in the assessment to account for those events that occur in the delivery room during the first minutes of the infant's life: 0 -- Score >5 at 1 and 5 minutes 1 = Score -5 at 5 minutes 2 -- Score -
