The NICU Network Neurobehavioral Scale (NNNS) was developed as an assessment for the at-risk infant. The purpose of this article is to describe the NNNS, provide video examples of the NNNS procedures and discuss the ways in which the exam has been used.
There has been a long-standing interest in the assessment of the neurobehavioral integrity of the newborn infant. The NICU Network Neurobehavioral Scale (NNNS) was developed as an assessment for the at-risk infant. These are infants who are at increased risk for poor developmental outcome because of insults during prenatal development, such as substance exposure or prematurity or factors such as poverty, poor nutrition or lack of prenatal care that can have adverse effects on the intrauterine environment and affect the developing fetus. The NNNS assesses the full range of infant neurobehavioral performance including neurological integrity, behavioral functioning, and signs of stress/abstinence. The NNNS is a noninvasive neonatal assessment tool with demonstrated validity as a predictor, not only of medical outcomes such as cerebral palsy diagnosis, neurological abnormalities, and diseases with risks to the brain, but also of developmental outcomes such as mental and motor functioning, behavior problems, school readiness, and IQ. The NNNS can identify infants at high risk for abnormal developmental outcome and is an important clinical tool that enables medical researchers and health practitioners to identify these infants and develop intervention programs to optimize the development of these infants as early as possible. The video shows the NNNS procedures, shows examples of normal and abnormal performance and the various clinical populations in which the exam can be used.
There has been a long-standing interest in the assessment of the neurobehavioral integrity of the newborn infant. From a scientific point of view, the study of newborn neurobehavior could inform models of the developmental origins of later behavioral outcomes. From a practical point of view, the early detection of infants with poor developmental outcome would invite the study of preventive interventions that could ameliorate or reduce the severity of long term developmental deficits.
The NICU Network Neurobehavioral Scale (NNNS)1 was developed as an assessment for the at-risk infant and is used in research and clinical practice. These are infants who are at increased risk for poor developmental outcome because of insults during prenatal development, such as substance exposure or prematurity or factors such as poverty, poor nutrition or lack of prenatal care that can have adverse effects on the intrauterine environment and affect the developing fetus. However, its formulation was based on a developmental perspective emphasizing normative neurobehavior and its variation, and derailing effects of risk conditions. Thus, the NNNS was meant to have broad applicability. It assesses the full range of infant neurobehavioral performance including neurological integrity, behavioral functioning, and signs of stress/abstinence. The neurologic component includes active and passive tone, primitive reflexes, and items that reflect the integrity of the central nervous system and maturity of the infant.2, 3 The behavior component adapted items from the Neonatal Behavioral Assessment Scale (NBAS).4 The stress/abstinence component is a checklist of ‘yes’ or ‘no’ items organized by organ system based on the work of Finnegan5 and observations of behavioral signs in at-risk infant populations such as preterm infants. These neurobehavioral items are framed by the concept of behavioral states of organization (sleep to distress) because of their moderating effect on behavior and because they in and of themselves and their dynamics index central nervous system integrity. By including evaluations of classical reflexes, tone, posture, social and self-regulatory competencies, as well as signs of stress and withdrawal, and state organization, the NNNS examination is sensitive to a broad range of behaviors that high-risk infants present and can be used for a variety of infants and for infants of varying gestational ages.
The exam should be performed on medically stable infants in an open crib/isolette. It is probably not appropriate for infants less than 28-32 weeks gestational age; the upper age limit may also vary, with a reasonable upper limit of 46 weeks (corrected for conceptional age, i.e., weeks gestational age at birth plus weeks since birth).
In the NNNS, items are administered in packages with each package beginning with a change in focus or position. The order of administration is relatively invariant. Here we present a summary of the exam followed by the protocol shown in the video. During the Pre-Examination Observation the infant is asleep, prone, undressed and covered. Initial State is scored using the traditional 1-6 criteria described by Prechtl.2 The Response Decrement items (habituation) are administered with infant in state 1 or 2 and coded on scales that include criteria for when the infant stops responding ('shutdown'), and criteria for when the item is discontinued. During Unwrap and Supine, the infant's posture, skin color, and movement are observed and scored on scales that include, where appropriate, criteria for normal, hypo-responsivity and hyper-responsivity. Skin texture is also scored for the presence of specific conditions. The seven lower extremity reflexes, nine upper extremity reflexes, four upright and three prone responses are administered with the infant in states 3, 4 or 5 and include classic reflexes, measures of tone and angles, scored on scales that also include, where appropriate, criteria for normal, hypo-responsivity and hyper-responsivity. The infant, in state 4 or 5, is picked up and cuddled and scored separately for cuddle in arm and shoulder. The six orientation items are then administered with the infant still in state 4 or 5, on the examiner’s lap. The types of handling procedures used to keep the infant in a state 4 or 5 during the orientation package are scored along with the orientation responses. The infant is picked up for the vestibular items, returned to the crib for the final set of reflexes and observed for the post examination period.
1. Pre-examination Observation
2. Habituation
3. Unwrap and Supine
4. Lower Extremity Reflexes
5. Upper Extremity Reflexes and Face
6. Upright Responses
7. Infant Prone
8. Pick up Infant
9. Orientation/Attention
Administer the orientation items as you sit in a chair with the infant resting on your lap. Have the infant at a slight upward angle.
10. Infant Spin
11. Infant Supine in Crib
12. Stress/Abstinence
Summary Items
Throughout the exam, observe and record the following: quality of infant’s alertness and responsiveness, general tone, motor maturity, consolability maneuvers required, level of arousal, irritability, spontaneous and elicited activity, amount of tremors and startles, lability of skin color and state, predominate state, hand to mouth efforts and self-quieting efforts.
Summary Scores
Analysis of the NNNS is based on previously established summary scores1 or scales measuring habituation, attention, need for handling, quality of movement, self-regulation, non-optimal reflexes, asymmetric reflexes, arousal, hypertonicity, hypotonicity, excitability, lethargy, and stress/abstinence. The requisite psychometric properties of these scales have been well documented including inter-examiner reliability, internal consistency, discriminant, construct, and predictive validity1 including norms for healthy term infants.6, 7 The summary scores have also been consolidated into profiles or typologies (described below) that classify infants into discrete categories.8-10
Overview of Research and Clinical Applications of the NNNS
Research
Here we provide a summary of published studies using the NNNS for research across a wide range of infant populations. Infants with prenatal exposure to a wide range of substances consistently show poorer performance on the NNNS. Illegal and legal substances of abuse include cocaine,11, 12 opiates,11 methamphetamine,13, 14 marijuana,15 alcohol,11 and tobacco.16-18 Both prenatal tobacco and postnatal exposure to secondary smoke were related to poorer NNNS scores and ethnicity.19 Infants with prenatal cocaine and opiate exposure show low respiratory sinus arrhythmia during visual attention on the NNNS.20 The exam is also sensitive to more subtle prenatal exposures, such as bisphenol A, phthalates and chemicals used in the production of synthetic materials found in normal populations.21
Other prenatal exposure studies are treatment studies. Infants who required pharmacologic treatment for NAS (neonatal abstinence syndrome or withdrawal symptoms) showed more dysregulated behavior on the NNNS than those without NAS.22, 23 Infants treated for NAS with opiates and phenobarbital had better NNNS scores than those treated with opiates alone.24 Performance on the NNNS was better in infants with NAS due to treatment during pregnancy with buprenorphine vs. methadone in heroin addicted mothers.23, 24 Maternal depression during pregnancy is often treated with serotonin reuptake inhibitors (SRIs) resulting in negative findings on the NNNS.25 Thus the NNNS is capable of detecting not only strong (e.g., opiate) drug effects but subtle drugs effects as well, discriminating, infants who develop NAS from those who will not, infants who show milder withdrawal-like (SRIs) signs as well as effects of chemicals in the normal environment.
In preterm infants, medical problems result in compromised neurobehavior on the exam.26 Even in the absence of medical problems, preterm infants at term gestational age have deficits on the NNNS when compared with term infants. 27 In a brain imaging study, preterm infants with decreased regional brain volumes showed deficits on the NNNS.28 Better developmental care in the NICU (Neonatal Intensive Care Unit) improves developmental outcome on the NNNS in preterm infants when they are discharged from the hospital.29 In addition, NNNS findings in preterm infants shortly before NICU discharge are more positive when there is more family centered care, developmental care and parent satisfaction and less maternal depression and parenting stress.30 The NNNS may be useful in implementing developmental models of care in the NICU and identifying infants who may be at high risk for poor developmental outcome even without medical problems. The latter is supported by the long term predictive validity of the NNNS.
The long term predictive validity of the NNNS has been reported in several studies. In preterm infants, performance on the NNNS has been related to mental and motor outcomes at 18 months31 and motor status at 24 months28 and to the later development of cerebral palsy and impaired motor function.32 In drug exposed infants33 motor scores on the NNNS predicted motor outcomes at 18 months. In a path model, prenatal substance exposure was related to worse NNNS neurobehavior which was, in turn, related to behavior problems at ages 3 and 7.34
NNNS summary scores can be converted to profiles which can then be used for long term prediction. Each infant is assigned to a mutually exclusive profile or category based on their pattern of scores across the summary scores. Figure 1A shows five profiles identified from a sample of over 1,200 infants at risk due to factors such as prenatal substance exposure and prematurity in which the summary scores are presented as standardized scores (standard deviation units).8 Infants in profile 5 showed an abnormal pattern. These infants had poor attention that required extensive handling, poor regulation, they were highly aroused and excitable, with poor quality of movement and a high number of stress signs. As shown in Figure 1B, infants with profile 5 were more likely to show abnormalities between 2 and 4 ½ years on the Bayley Scales, behavior problems on the Child Behavior Checklist (CBCL), deficits in school readiness (DIAL-R) and low IQ. NNNS profiles have also been used to predict developmental outcome in a low risk sample9 and are related to epigenetic changes in placental genes.10 These studies raise the possibility of using the NNNS to identify which infants are at highest risk for poor outcome and develop interventions early enough to prevent or reduce the severity of later deficits.
Figure 1. In studies of other at risk populations, the NNNS has been shown to be sensitive to intrauterine growth restriction35 cardiac surgery,36 maternal depression in mothers who used cocaine during pregnancy,25 and infants of adolescent mothers.37 Please click here to view a larger version of this figure.
Although we have been able to link prenatal factors to newborn neurobehavior we do not know the mechanisms responsible for these effects. One possibility is through epigenetic mechanisms such as DNA methylation that regulate gene expression. For example, reduced activity of the glucocorticoid receptor gene in the placenta due to DNA methylation can increase fetal exposure to cortisol and alter newborn neurobehavior. In recent work, NNNS scores have been related to epigenetic alterations of several candidate genes in the placenta,10, 38-40 as well as genome wide epigenetic effects.41 Growth restriction42 and maternal depression during pregnancy43 are also related to epigenetic alterations in placental genes that in turn affect NNNS scores. These studies provide insight into molecular mechanisms related to newborn neurobehavior that could have long term implications for behavioral development30, 44, 45 including the development of mental health disorders.46, 47
The NNNS has also been used with normal, healthy infants to examine methodological issues7, 48 and describe the range of variability of newborn neurobehavior in this population.6, 7 These studies provide normative data for comparisons with other populations. They are also key because they show that normal healthy infants are not a homogeneous population; that their neurobehavioral organization is affected by factors in environments not usually associated with risk. In other normative samples, the exam has been used in relation to fetal behavior,49 and infant temperament.50, 51 Thus, although the NNNS was designed for high risk infants it also appears to be sensitive to neurobehavioral variability in low risk populations as well.
Clinical Applications
In clinical settings such as hospital nurseries, neonatal follow-up clinics, drug treatment programs and early intervention programs, the NNNS examination can be used to help with the management and developmental care plan of the infant and to inform caregivers of specific strengths and vulnerabilities of high risk infants. In our hospital (Women and Infants Hospital of Rhode Island) and increasingly in other hospitals, the exam is part of standard care in the NICU and some hospitals, including ours, use the assessment as part of standard care for infants undergoing neonatal abstinence syndrome due to maternal use of opiates during pregnancy. The importance of the NNNS for nursing has been well described by Sullivan et al.52 They note that newborn assessment has become more critical with the increased acuity and complex care needed especially in the NICU. Suggestions for clinical interpretation of NNNS summary scores are available,34 along with various formats for reporting clinical observations. Summary scores can be calculated and compared with percentile scores and/or described in a clinical narrative with recommendations for treatment. Initial NNNS observations provide a baseline for developing a symptom oriented care plan to help with the management of the infant and empower the caregiver’s parenting ability. The exam provides an excellent opportunity for professionals to partner with parents in observing the infant’s competencies and needs, and in formulating a plan for developmental intervention. Thus, consultation with the NNNS is a collaborative process, that is driven by the infants neurobehavioral functioning. Since the medical and neurobehavioral status of the infant is evolving, it is preferable for the NNNS examination to be repeated over time or for consultation sessions to be done in a regularly scheduled series. An exam near to the time of discharge can be particularly helpful to families as they are better prepared to take the infant home when they appreciate the strengths and vulnerabilities of the infant. This helps them read the infant’s cues and signals, bolsters their confidence in parenting and helps in the developing parent-infant relationship. An exam at this time is also useful to inform discharge planning with recommendations for follow up clinics, community pediatricians and early intervention programs.53
Approximately 5 to 10% of the pediatric population has a developmental disability.54 The NNNS can identify infants at high risk for abnormal developmental outcome and is an important clinical tool that enables medical researchers and health practitioners to identify these infants and develop intervention programs to optimize the development of these infants as early as possible.
The NNNS is a noninvasive neonatal assessment tool that has shown to be sensitive to a wide range of populations including risk for poor developmental outcome, treatment, quality of developmental care in the NICU, epigenetic changes and variability in normal newborn neurobehavior. The exam has predictive validity, not only of medical outcomes such as cerebral palsy, neurological abnormalities, and diseases with risks to the brain, but also of developmental outcomes such as mental and motor functioning, behavior problems, school readiness, and IQ.
The American Academy of Pediatrics has called for a referral to early intervention or special education following a positive screening result. A diagnosis is not required for such a referral.55 The NNNS profiles specify the neurobehavioral deficits associated with poor outcome that could serve as target behaviors for the development of preventive interventions to reduce or ameliorate these deficits. The NNNS profiles enable us to identify, from the larger pool of infants who are already at risk, which infants are at highest risk and affording better use of increasingly limited resources.
The authors have nothing to disclose.
The development of the NNNS was supported by NIH grants U10 DA 024119-01 and U10HD27904 and contract N01-HD-2-3159 to Dr Lester. ARTICLES: PEDIATRICS Volume 125, Number 1, January 2010 e90-e98.