Functional electrical stimulation (FES)-assisted rowing combined with zoledronic acid, but not alone, preserves distal femur strength and stiffness in people with chronic spinal cord injury.

We investigated the effect of 12 months of functional electrical stimulation-assisted rowing with and without zoledronic acid (ZA) on computationally estimated bone strength and stiffness in individuals with spinal cord injury. We found that rowing with ZA, but not rowing alone, improved stiffness at the distal femur, but not the proximal tibia. INTRODUCTION: People with spinal cord injury (SCI) have high fracture risk at the knee after the injury. Therapies that prevent bone loss or stimulate an anabolic response in bone have been proposed to reduce fractures. Zoledronic acid (ZA) is a potent bisphosphonate that inhibits osteoclastic resorption. Functional electrical stimulation (FES)-assisted rowing is a potentially osteogenic exercise involving mechanical stimulation to the lower extremities. Here, we investigated the effect of FES-assisted rowing with and without ZA on bone strength and stiffness in individuals with SCI. METHODS: Twenty individuals from a cohort of adults with SCI who participated in a clinical trial were included in the study. CT scans of their knees before and after the intervention were converted to finite element models. Bone failure strength (Tult) and stiffness were calculated at the proximal tibia and distal femur. RESULTS: Tult at the distal femur increased 4.6% among people who received rowing + ZA and decreased 13.9% among those with rowing only (p < 0.05 for group). Torsional and compressive stiffness at the femur metaphysis increased in people with rowing + ZA (+ 3 to +4%) and decreased in people with rowing only (- 7 to -8%; p < 0.05). Tult in the proximal tibia decreased in everyone, but the loss was attenuated in the rowing + ZA group. People with initially stronger bone tended to lose more strength. CONCLUSION: Overall, we observed increases in bone strength at the distal femur but not the proximal tibia, with FES-assisted rowing combined with ZA treatment. Rowing alone did not significantly prevent bone loss at either site, which might be attributed to insufficient mechanical loading.

Combination Therapy With Zoledronic Acid and FES-Row Training Mitigates Bone Loss in Paralyzed Legs: Results of a Randomized Comparative Clinical Trial.

Spinal cord injury (SCI) results in rapid, severe osteoporosis and an increased risk of lower extremity fractures. Despite the medical complications associated with these fractures, there is no standard of care to prevent osteoporotic fractures following SCI. Functional electrical stimulation- (FES-) assisted rowing is a promising intervention to improve bone health in SCI because of its ability to generate a muscular contraction in conjunction with mechanical loading of the lower extremity long bones. Combination therapy consisting of FES-rowing plus zoledronic acid (ZA) may be a superior treatment via inhibition of bone resorption and stimulation of new bone formation. We studied participants enrolled in a randomized clinical trial comparing FES-rowing alone with FES-rowing plus ZA to improve bone health in SCI. Volumetric CT scans at the distal femur and proximal tibial metaphyses were performed. Bone geometric properties (cortical thickness index [CTI], cortical compressive strength index [CSI], buckling ratio [BR], bending strength index) and mineral (cortical bone volume [CBV], cortical bone mineral density, cortical bone mineral content) indices were determined. In models adjusting for baseline values, we found that the CBV (p = 0.05 to 0.006), the CTI (p = 0.009), and the BR (p = 0.001) at both the distal femoral and proximal tibial metaphyses were greater in the ZA plus rowing group compared with the rowing-only group. Similarly, there was a significant positive association between the total rowing work completed and the BR at the proximal tibia (p = 0.05). A subgroup analysis of the rowing-only arm showed that gains in the CSI at the tibial metaphysis varied in a dose-dependent fashion based on the total amount of exercise performed (p = 0.009). These findings demonstrate that the osteogenic response to FES-rowing is dose-dependent. Combination therapy with ZA and FES-row training has therapeutic potential to improve bone quality, and perhaps reduce fracture risk at the most common fracture site following SCI. © 2019 The Authors. JBMR Plus Published by Wiley Periodicals, Inc. on behalf of the American Society for Bone and Mineral Research.

Serial aEEG recordings in a cohort of extremely preterm infants: feasibility and safety.

OBJECTIVE: Amplitude-integrated electroencephalography (aEEG) monitoring is increasing in the neonatal population, but the safety and feasibility of performing aEEG in extremely preterm infants have not been systematically evaluated. STUDY DESIGN: Inborn infants 23(0/7) to 28(6/7) weeks gestation or birth weight 401 to 1000 g were eligible. Serial, 6-h aEEG recordings were obtained from first week of life until 36 weeks postmenstrual age. Adverse events were documented, and surveys evaluated the impact of the aEEGs on routine care. Success of performing aEEGs according to protocol and aEEG quality were assessed. RESULT: A total of 102 infants were enrolled, with 755 recordings performed. 83% of recordings were performed according to schedule, and 96% were without adverse event. Bedside nurses reported no interference with routine care for 89% of recordings. 92% of recordings had acceptable signal quality. CONCLUSION: Serial aEEG monitoring is safe in preterm infants, with few adverse events and general acceptance by nursing staff.

Outcomes of extremely preterm infants following severe intracranial hemorrhage.

OBJECTIVE: Severe intracranial hemorrhage (ICH) is an important prognostic variable in extremely preterm (EPT) infants. We examined imaging and clinical variables that predict outcomes in EPT infants with severe ICH. STUDY DESIGN: Retrospective analysis of 353 EPT infants with severe ICH. Outcomes were compared by examining: (i) unilateral vs bilateral ICH; and (ii) presence vs absence of hemorrhagic parenchymal infarction (HPI). Regression analyses identified variables associated with death or neurodevelopmental impairment (NDI). RESULT: Bilateral ICH and HPI had higher rates of adverse outcomes and were independently associated with death/NDI. HPI was the most important variable for infants of lower birth weight, and bilateral ICH for larger infants. For infants surviving to 36 weeks, shunt placement was most associated with death/NDI. CONCLUSION: Bilateral ICH and the presence of HPI in EPT infants with severe ICH are associated with death/NDI, though the importance depends on birth weight and survival to 36 weeks.

Influence of gestational age on death and neurodevelopmental outcome in premature infants with severe intracranial hemorrhage.

OBJECTIVE: To determine whether death and/or neurodevelopmental impairment (NDI) after severe intracranial hemorrhage (ICH; grade 3 or 4) differs by gestational age (GA) at birth in extremely low birth weight (ELBW) infants. STUDY DESIGN: Demographic, perinatal and neonatal factors potentially contributing to NDI for ELBW infants (23 to 28 weeks gestation) were obtained retrospectively; outcome data came from the ELBW Follow-up Study. NDI was defined at 18 to 22 months corrected age as moderate/severe cerebral palsy, Bayley Scales of Infant Development II cognitive or motor score <70, and/or blindness or deafness. Characteristics of younger versus older infants with no versus severe ICH associated with death or NDI were compared. Generalized linear mixed models predicted death or NDI in each GA cohort. RESULT: Of the 6638 infants, 61.8% had no ICH and 13.6% had severe ICH; 39% of survivors had NDI. Risk-adjusted odds of death or NDI and death were higher in the lower GA group. Lower GA increased the odds of death before 30 days for infants with severe ICH. Necrotizing enterocolitis (particularly surgical NEC), late onset infection, cystic periventricular leukomalacia and post-natal steroids contributed to mortality risk. NDI differed by GA in infants without ICH and grade 3, but not grade 4 ICH. Contributors to NDI in infants with severe ICH included male gender, surgical NEC and post-hemorrhagic hydrocephalus requiring a shunt. CONCLUSION: GA contributes to the risk of death in ELBW infants, but not NDI among survivors with severe ICH. Male gender, surgical NEC and need for a shunt add additional risk for NDI.

Necrotizing enterocolitis in infants with periventricular hemorrhagic infarction: associations and outcomes.

BACKGROUND: Necrotizing enterocolitis (NEC) and periventricular hemorrhagic infarction (PVHI) are complications of prematurity associated with poor neurodevelopmental outcomes. OBJECTIVES: We characterized temporal and causal associations between NEC and type of PVHI as well as associations with outcomes. METHODS: This was a multicenter retrospective study of infants with birth weight <1,500 g and diagnosis of PVHI by a pediatric radiologist at 3 neonatal intensive care units in North Carolina, USA, between January 1998 and December 2004. NEC was confirmed using radiological and surgical pathology findings. Infants were assessed by 3 years using the Bayley Scales of Infant Development, second edition. RESULTS: 35 of 112 (31%) of study patients developed NEC. NEC was diagnosed subsequent to PVHI by a median of 16.6 days (95% CI [9.5, 24.9], p < 0.0001). Indomethacin use and the presence of bilateral PVHI were associated with an increased risk of subsequent NEC (OR 2.8, 95% CI [1.1, 7.2] and OR 2.4, 95% CI [1.1, 5.7], respectively). Having bilateral versus unilateral PVHI was associated with a 2.34-fold increased risk of death (95% CI [1.27, 4.33], p = 0.007). NEC was not associated with worse motor outcomes in this population. Overall, the probability of a mental development index >70 was greatest for infants with unilateral PVHI versus bilateral PVHI, although the presence of NEC was associated with worse cognitive outcomes in both groups. CONCLUSIONS: Premature infants with PVHI often subsequently develop NEC, especially if they have bilateral PVHI and are exposed to indomethacin. While NEC results in worse neurodevelopmental outcomes, PVHI severity appears more important to the outcome of these infants.

Long-term morbidities associated with vocal cord paralysis after surgical closure of a patent ductus arteriosus in extremely low birth weight infants.

OBJECTIVE: Determine associations between left vocal cord paralysis (LVCP) and poor respiratory, feeding and/or developmental outcomes in extremely low birth weight (ELBW) infants following surgical closure of a patent ductus arteriosus (PDA). STUDY DESIGN: ELBW infants who underwent PDA ligation between January 2004 and December 2006 were identified. We compared infants with and without LVCP following ligation to determine relationships between LVCP and respiratory morbidities, feeding and growth difficulties and neurodevelopmental impairment at 18 to 22-month follow-up. Student's t-test, Fisher's exact test and multivariable regression analyses were used to determine associations. RESULT: In all, 60 ELBW infants with a mean gestational age of 25 weeks and mean birth weight of 725 g had a PDA surgically closed. Twenty-two of 55 survivors (40%) were diagnosed with LVCP post-operatively. Infants with LVCP were significantly more likely to develop bronchopulmonary dysplasia (82 vs 39%, P=0.002), reactive airway disease (86 vs 33%, P<0.0001), or need for gastrostomy tube (63 vs 6%, P<0.0001). CONCLUSION: LVCP as a complication of surgical ductal ligation in ELBW infants is associated with persistent respiratory and feeding problems. Direct laryngoscopy should be considered for all infants who experience persistent respiratory and/or feeding difficulties following PDA ligation.

Neurodevelopmental and health outcomes in term infants treated with surfactant for severe respiratory failure.

OBJECTIVE: Analysis of health, neurodevelopmental, and school performance outcomes in a pilot study of term and near-term infants with respiratory failure due to pneumonia or meconium aspiration treated with surfactant. STUDY DESIGN: Retrospective review of medical records, neurodevelopmental and psychosocial evaluations, and parent and teacher surveys. RESULTS: Of the 14 patients enrolled, only one was rehospitalized, for pneumonia. Three were reported to have episodes of wheezing, two of whom required bronchodilators. One patient had unilateral hearing loss, one had a full-scale intelligence quotient that was below normal, and all but one patient for whom complete results were obtained were performing at or above grade level. CONCLUSION: Term and near-term newborns with moderately severe respiratory failure treated with surfactant can, in general, be expected to recover completely and have normal general health, neurodevelopmental outcome, and school performance.

Infant arousal in an en-face exchange with a new partner: effects of prematurity and perinatal biological risk.

Very low birth weight (VLBW) infants of higher (n = 18) and lower (n = 29) perinatal biological risk were contrasted at 4 months adjusted age with healthy full-term infants (n = 32) in their arousal during a standardized peekaboo game with an examiner. VLBW infants showed less positive arousal, more negative arousal, and 3 mixtures of behavioral cues across the peekaboo game seldom seen for full-term infants-strong cues of both positive and negative arousal, strong cues of negative arousal alone, and no strong cues of either positive or negative arousal. Contrary to expectations, perinatal biological risk did not strongly predict variations in arousal within the VLBW group. Possible changes in how internal and external sources of arousal are integrated provide one explanation for the presence of strong relationships between perinatal biological risk and social responsiveness near term age and their disappearance by 4 months of age.

Studies of DNA dumbbells VII: evaluation of the next-nearest-neighbor sequence-dependent interactions in duplex DNA.

Melting experiments were conducted on 22 DNA dumbbells as a function of solvent ionic strength from 25-115 mM Na(+). The dumbbell molecules have short duplex regions comprised of 16-20 base pairs linked on both ends by T(4) single-strand loops. Only the 4-8 central base pairs of the dumbbell stems differ for different molecules, and the six base pairs on both sides of the central sequence and adjoining loops on both ends are the same in every molecule. Results of melting analysis on the 22 new DNA dumbbells are combined with our previous results on 17 other DNA dumbbells, with stem lengths containing from 14-18 base pairs, reported in the first article of this series (Doktycz, Goldstein, Paner, Gallo, and Benight, Biopoly 32, 1992, 849-864). The combination of results comprises a database of optical melting parameters for 39 DNA dumbbells in ionic strengths from 25-115 mM Na(+). This database is employed to evaluate the thermodynamics of singlet, doublet, and triplet sequence-dependent interactions in duplex DNA. Analysis of the 25 mM Na(+) data reveals the existence of significant sequence-dependent triplet or next-nearest-neighbor interactions. The enthalpy of these interactions is evaluated for all possible triplets. Some of the triplet enthalpy values are less than the uncertainty in their evaluation, indicating no measurable interaction for that particular sequence. This finding suggests that the thermodynamic stability of duplex DNA depends on solvent ionic strength in a sequence-dependent manner. As a part of the analysis, the nearest-neighbor (base pair doublet) interactions in 55, 85, and 115 mM Na(+) are also reevaluated from the larger database.

Is size discordancy an indication for delivery of preterm twins?

OBJECTIVE: Our goal was to determine the clinical significance of size discordancy in preterm twins. STUDY DESIGN: A retrospective study was performed to review outcomes of twins delivered between Jan. 1, 1988, and June 30, 1995. Maternal and neonatal records were assessed for demographic data, maternal medical history, and neonatal mortality and morbidity outcomes. Discordancy was defined as > or = 20% difference in birth weight. The chi 2 analysis was performed. RESULTS: There were 42 sets of discordant twins and 77 sets of concordant twins in the final analysis. The distribution of gestational ages in both groups was similar. We found no difference in maternal morbidity between the groups. Discordant sets had a significantly longer hospital stay (p = 0.003) and more cases of hyperbilirubinemia (p = 0.01), but there were no other differences in morbid outcomes. There were no differences in outcome variables between the two twins within discordant sets with respect to gender, size, birth order, growth restriction, or route of delivery. There were no stillbirths among any of the 238 infants. Of the 15 neonatal deaths, none occurred in infants delivered after 32 weeks' gestation or in infants weighing > 2000 gm at birth. Infants who were small for gestational age had a higher incidence of sepsis (p = 0.043) and longer hospital stays (p = 0.005) compared with infants who were appropriate for gestational age. CONCLUSIONS: Size discordancy alone does not appear to be an indication for preterm delivery of twins. When results of antenatal testing are normal and growth restriction is absent, attempts should be made to achieve a gestational age > 32 weeks and weight > 2000 gm before delivery is considered.

Developmental outcome of very low birth weight infants at four years of age as a function of biological risk and psychosocial risk.

The continuing contribution of early biological and psychosocial risk factors to developmental outcome of 55 very low birth weight infants (< or = 1500 g) was assessed at 4 years of age. Biological risk, assessed by the Neurobiologic Risk Score, accounted for significant portions of the variance in the perceptual-performance (17%) and motor (35%) dimensions of the McCarthy Scales of Children's Abilities. Psychosocial risk, reflected in maternal appraisals of daily stress during the newborn period, did not account for a significant portion of variance in any of the McCarthy Scales. Maternal education level, however, another measure of psychosocial risk, accounted for significant portions of variance (from 6% to 34%) on each of the McCarthy Scales. Movement from low neurobiologic risk status to poor outcome status at 4 years of age was associated with a number of psychosocial variables, including maternal education and early levels of maternal daily stress. The findings are discussed in terms of early markers for very low birth weight infants who require careful follow-up and of potential intervention targets to promote developmental outcome.

Behavioral characteristics of very-low-birth-weight infants of varying biologic risk at 6, 15, and 24 months of age.

OBJECTIVE: To explore the relationship between developmental outcome and behavior of very-low-birth-weight (VLBW) infants (< or = 1500 g) at high and low biologic risk. DESIGN: Descriptive, ex post facto. SETTING: Clinic for follow-up of infants at high risk. PARTICIPANTS: A convenience sample of 102 VLBW infants, free of major congenital anomalies, who completed 6-, 15-, and 24-month developmental testing and who were part of a larger study of 274 VLBW infants. MAIN OUTCOME MEASURE: Bayley Scales of Infant Development. RESULTS: Infants at high biologic risk, versus infants at low biologic risk, were less attentive and active through age 15 months and were less adept in gross and fine motor skills through age 24 months (p < or = 0.05-0.001). Infants with continuous delay were less attentive than infants with no delay or late delay through age 24 months, less active through age 15 months (p < or = 0.001-0.001), and less skilled in motor behaviors through age 24 months (p < or = 0.05-0.001). CONCLUSION: Infants at high biologic risk and infants with developmental delays are less attentive, less active, and less skilled in motor tasks during the first 15-24 months of life, suggesting an association between biologic risk and behavior and developmental delay and behavior.

Delayed development of sensorineural hearing loss after neonatal hyperbilirubinemia: a case report with brain magnetic resonance imaging.

Sensorineural hearing loss has long been known to be a clinical consequence of kernicterus. Brainstem auditory evoked potentials (BAEPs) that occur in hyperbilirubinemic infants, can be reversed in the neonatal period by exchange transfusion. The case was reported in an infant with neonatal hyperbilirubinemia from hemolysis due to glucose-6-phosphate dehydrogenase (G6PD) deficiency and napthalene exposure. BAEPs showed that the baby had normal hearing at 30 decibels at 13 days of age, after exchange transfusions, but had developed profound bilateral sensorineural hearing loss by 7 months of age. The brain magnetic resonance imaging (MRI) findings at 7 months are also presented.

Cerebral blood flow and carbon dioxide reactivity in neonates during venoarterial extracorporeal life support.

OBJECTIVES: a) To determine if cerebral blood flow is symmetric after internal carotid artery and ipsilateral internal jugular vein ligation in infants during venoarterial extracorporeal life support. b) To determine the cerebral CO2 reactivity (delta cerebral blood flow/delta torr CO2) of neonates during venoarterial extracorporeal life support and its correlation to neurodevelopmental outcome. DESIGN: Prospective, clinical study. SETTING: University hospital pediatric intensive care unit. PATIENTS: Fourteen neonates with respiratory failure who were receiving venoarterial extracorporeal life support. INTERVENTIONS: PaCO2 was altered by adjusting the CO2 gas flow through the membrane oxygenator. Cerebral blood flow was measured over both parietal-temporal regions at three PaCO2 values using xenon-133 clearance methodology. Cerebral blood flow measurements were made early (< or = 12 hrs of extracorporeal life support, n = 10) or late (> or = 48 hrs of extracorporeal life support, n = 10). In six of 14 infants, both early and late cerebral blood flow rates were measured. PaO2, mean arterial pressure, pump flow rate, and temperature were stable during each study period. Neurodevelopmental outcome was assessed in the neonatal follow-up clinic. MEASUREMENTS AND MAIN RESULTS: Right and left hemispheric cerebral blood flow rates were significantly correlated with each other during early and late extracorporeal life support (p = .0001; r2 = .91). Overall, hemispheric cerebral blood flow was statistically symmetric. There was no association of CO2 reactivity (delta cerebral blood flow/delta torr PCO2, range 0.04 to 1.36 mL/min/100 g/torr) with short-term neurodevelopmental outcome. Infants with normal neurodevelopmental outcome had variable CO2 reactivity (range 0.04 to 0.67 mL/min/100 g/torr). Normal short-term neurodevelopmental outcome was observed in two infants with cerebral blood flow of < 10 mL/min/100 g. CONCLUSIONS: Hemispheric cerebral blood flow was symmetric in infants during early and late venoarterial extracorporeal life support. Some subgroups showed a trend toward decreased right hemispheric cerebral blood flow, but the small number of patients limited interpretation of this finding. CO2 reactivity and cerebral blood flow were highly variable in this population, and were not predictive of short-term neurodevelopmental outcome. Stressed neonates with extremely low cerebral blood flow rates may have relatively normal short-term neurodevelopmental outcome after venoarterial extracorporeal life support.

Influence of acidosis, hypoxemia, and hypotension on neurodevelopmental outcome in very low birth weight infants.

OBJECTIVE: We previously demonstrated that acidosis (pH < 7.15) predicts poor motor outcome in very low birth weight (VLBW) infants. The present study was undertaken to examine the association between acidosis and developmental outcome in more detail and to better understand the interrelationship of acidosis with related factors such as hypoxemia and hypotension. METHODS: The nursery records of 191 infants enrolled in our VLBW follow-up study were reviewed to identify the type of acidosis (metabolic or respiratory) present, measure the duration of single and cumulative episodes, and examine the interaction of acidosis with hypoxemia and hypotension. The Bayley Scales of Infant Development and a detailed neurologic examination were performed at 6 (n = 158) and 24 (n = 106) months corrected age. RESULTS: At 6 months, both respiratory and metabolic acidosis as well as the total duration and longest single episode of acidosis were significantly correlated with cognitive, motor, and neurologic outcome (P < .0001). By 24 months, only the association of the metabolic component of acidosis with all three outcome measures remained significant. Duration of hypotension independently correlated with outcome at both testing periods (P < .002) but isolated hypoxemia did not. The metabolic component of acidosis and isolated hypotension contributed significantly to the variance in all three outcome measures (P < .05). Duration of hypoxemia, but not hypotension, contributed significantly (53%) to the variance in the metabolic component of acidosis. CONCLUSION: We conclude that it is the metabolic component of acidosis that is important in predicting poor developmental outcome in VLBW infants. The detrimental effect of hypoxemia appears to be closely related to the occurrence of metabolic acidosis while hypotension has an independent effect on outcome.

Developmental outcome of very low birth weight infants as a function of biological risk and psychosocial risk.

The relative contribution of biological and psychosocial risk factors to developmental outcome of 102 very low birth weight infants (< 1500 g) was delineated through 24 months corrected age. Biological risk, assessed by the Neurobiologic Risk Score (NBRS), accounted for significant amounts of variance in Bayley Mental Developmental Index (MDI) and Psychomotor Developmental Index (PDI) at the 6-, 15-, and 24-month assessment points. Psychosocial risk, reflected in maternal appraisals of daily stress, accounted for a significant increment in cognitive outcome (MDI), over and above that accounted for by the NBRS, at each assessment point. Cognitive functioning at each assessment point differed as a function of biological risk and psychosocial risk status. The findings are discussed in terms of maternal stress as a marker of, and salient intervention target for, caregiving environments that can maximize or minimize the effects of biological vulnerability.

Efficient rotamer elimination applied to protein side-chains and related spin glasses.

Folded proteins and spin glasses share various properties, such as seemingly random interactions between residues (spins), and one might presume that some generic behaviors of spin glasses would also be exhibited in a general way by proteins. But a comparison here shows that the side-chain conformation systems of apo-myoglobin and lysozyme are qualitatively different from specific closely related spin glass systems. This difference is manifest in the number of rotamers that can be identified as definitely not contributing to the global energy minimum. This identification is effected by using a significantly enhanced version of the Dead End Elimination theorem (Desmet, J., M. De Maeyer, B. Hazes, and I. Lasters. 1992. The dead-end elimination theorem and its use in protein side-chain positioning. Nature. 356:539-542), which is much more effective and efficient in eliminating rotamers. In several cases (for proteins, although not for spin glasses) this improved Dead End Elimination theorem succeeded in identifying the absolute global minimum of rotamer conformations, with no statistical uncertainty. The difference between protein and spin glass is due to correlations between the interactions of one residue pair with another pair, and probably will play an important role in the thermodynamic behavior of the protein system.

Nursery neurobiologic risk score: levels of risk and relationships with nonmedical factors.

This study compares the Neurobiologic Risk Score (NBRS) with developmental outcome in 199 infants < or = 1500 g birth weight to determine levels of risk and to investigate the relative contributions of the NBRS and nonmedical factors to developmental outcome. The NBRS correlated significantly (p < .0001) with the Bayley Mental (MDI) and Psychomotor (PDI) Indexes, and neurologic examination score (NS) at 6, 15, and 24 months. Three risk groups were identified: low, NBRS < or = 4; intermediate, NBRS 5 to 7; and high, NBRS > or = 8 with an incidence of major handicaps at 24 months of 7%, 32%, and 50%, respectively. Of eight factors considered, the NBRS accounted for the greatest variance: MDI, 14 to 27%; PDI, 25 to 29%; NS, 34 to 42%. Additional increments of variance were contributed by gender (MDI, PDI, NS), maternal intelligence and race (MDI), and maternal education (PDI). The NBRS is a useful tool for identifying risk for developmental abnormalities due to neonatal medical events.