In these models, 19% of the variance in CP at 12–36 months and 26% of the variance in low PDI at 24 months is explained by specific NNNS summary scores and low birth weight. A combination of NNNS summary scores explains 2–3 times more of the variance in motor outcome than low birth weight.
Multiple investigators have attempted to identify predictors for CP and poor motor outcome in preterm infants. Low birth weight has been identified as perhaps the most important contributor to neurologic and motor outcomes in multiple previous publications. Other factors associated with poor motor outcomes include sociodemographic (maternal education < 12th
grade, 5, 8, 10
), biologic (male sex, plurality, low birth weight),5, 7, 10
perinatal (prolonged premature rupture of membranes, maternal bleeding, chorioamnionitis, delivery at a hospital with a Level 1 nursery only), 13
neonatal (5 minute Apgar, 5, 12
bronchopulmonary dysplasia (BPD), 2, 5, 7–12
postnatal Steroids, 2, 5, 10, 11
necrotizing enterocolitis, 2
infection, 5, 13
pneumothorax, 7, 13
Though risk factors for poor neurologic outcome have been identified, attempts to predict neurologic morbidity based on identifiable risk factors has proven largely unsuccessful. Several investigators have used univariate and/or multiple logistic regression analyses to identify a combination of important predictors for CP or poor motor outcome.4, 12, 13, 41
Ambalavanan used both regression analysis and neural networks to attempt to predict a Bayley PDI < 68 at 12–18 months corrected age using perinatal and neonatal characteristics. Less than 15% of the variance in low PDI was explained by IVH grade, PVL, BPD, chorioamnionitis, and low maternal education.8
Although abnormalities on neuroimaging are important in identifying infants at risk for abnormal neurologic outcomes in preterm infants, both cranial ultrasound and MRI are flawed in their predictive abilities.20–22
Evidence suggests that MRI is superior to ultrasound in identifying white matter abnormalities, but the significance of these findings is not clear. The largest study to date of MRI and neurodevelopmental impairment found that 22% of preterm infants with no or mild white matter injury on MRI at term equivalent have neurodevelopmental impairment at 2 years of age, and 50% of preterm infants with moderate to severe white matter injury at term equivalent have no neurodevelopmental impairment at 2 years.22
Neurologic or neurobehavioral assessment has been studied as a potentially more accurate way to predict outcome in ELBW infants. In 1997 Prechtl reported high sensitivity (95%) and specificity (96%) of one hour of videotaped spontaneous movements in predicting 2 year neurologic outcome in a cohort of term and preterm infants with fidgety movements.25
More recently, Garcia demonstrated less positive results.42
In their cohort of 40 preterm infants, 20 minute videotaped observations of gross motor movements varied in accuracy for predicting abnormal neurologic outcome by timing of exam (prior to 37 weeks adjusted age, 37–42 weeks adjusted age, and >42 weeks adjusted age). Sensitivity ranges from 75–100%, specificity from 44–67%, positive predictive value from 36–60% and negative predictive value from 80–100%.
Spittle et al described a significant correlation between videotaped assessments of general movements at 1 and 3 months post-term and white matter abnormalities on MRI at term equivalent,43
but no data from neurologic follow-up of these infants was reported.
The Neurobehavioral Assessment of the Preterm Infant (NAPI) was used to predict outcome at 12, 18 and 30 months corrected age.23, 24
Infants who went on to diagnosis of CP had lower NAPI scores for alertness and orientation at 36 weeks but no difference in NAPI motor scores compared with infants without CP. The association between NAPI score and poor motor outcome as measured by low PDI score was not explored.
Several authors have described the neurobehavioral assessment of the preterm infant using various neurobehavioral assessment tools.44–49
Miller-Loncar et al described an association between NNNS summary scores, Bayley27
PDI at 12 months and Motor scales performed at 4 and 18 months in term neonates.28
Brown et al described significant differences in NNNS summary scores between term and preterm infants.29
In an unpublished study of a small group of preterm infants NNNS scores were associated with white matter abnormalities on MRI and motor outcomes at 24 months.30
This study demonstrated an association between neurobehavioral assessment using the NNNS and poor motor outcome at 24 months as defined by PDI <70 and /or CP in a large cohort of preterm infants. Specific summary scores were identified in these models as significant predictors of poor motor outcome (CP and /or low PDI) at 12–36 months. These summary scores, low movement, high lethargy, low handling, and hypotonia, describe an infant with significant underarousal.
As the original MLS Study was designed to look at the effects of prenatal cocaine exposure, a large number of infants in this study were exposed to cocaine (and other substances) in utero. It is not clear whether these results will generalize to all preterm infants, the majority of whom are not exposed to these substances in utero. In addition, our follow-up rate was low as only 68% of the infants in our cohort had a Bayley at 24 months. Thus further prospective work is needed to determine the predictive ability of the NNNS for all preterm infants.
Neonatal correlates to cerebral palsy have long been known and frequently involve a clinical picture of decreased tone and/or movement.50
Thus the association between performance on the NNNS, a comprehensive assessment of neurologic integrity, behavioral functioning, and stress behavior, and cerebral palsy is not surprising. These findings imply that neurobehavioral assessment can and should be added to our assessment of risk for poor motor outcome in all preterm infants. Findings of underarousal on the NNNS at term equivalent provide additional information about the risk of poor motor outcome. The addition of these findings to those of chronic lung disease, intraventricular hemorrhage and periventricular leukomalacia will increase our ability to predict cerebral palsy and improve our ability to counsel families of preterm and low birth weight infants.