Alterations in Preterm Brain Development: Relation to Developmental Assessment and Prediction.

Infants born extremely preterm are at risk for compromised cognitive and motor outcome. There are various possibilities as to why this occurs. The "two-hit" hypothesis consists of interrelated developmental disruptions and insults. Both specifically affect the transient subplate neuronal layer (SNL) and the early development of brain circuitry. The SNL, analogous to a switchboard, is critical in connecting cortical and lower brain centers and is highly susceptible to disruptions and insults, producing dysfunctional neural networks. Damage to the SNL provides the putative link between atypical early brain development and later cognitive and academic function that require complex neural circuitry. This, in turn, has major ramifications for developmental assessment and prediction. KEY POINTS: · Preterm brains are highly susceptible to disruptions and insults, this being the two-hit hypothesis.. · There is a variation in which low-grade stressors "sensitize" the infant increasing susceptibility to a second stressor-causing brain damage.. · Subplate neuronal layer damage compromises outcome by interfering with thalamocortical connections.. · Combining neuroimaging and developmental testing is the best way to gain insight into these processes.. · Atypical early brain development may not be evident until the network is mature and challenged..

Assessment of Executive Function in Infants and Toddlers: A Potential Role of the Bayley-4.

OBJECTIVE: The development of executive function (EF) in infants and toddlers has received increased interest by clinicians and researchers. Higher rates of deficits in EF have been reported in at-risk groups of infants such as those born extremely preterm. These deficits play an important role in the etiology of early neurodevelopmental problems and are predictive of subsequent nonoptimal educational outcomes. In this study, the Bayley-4 is used to follow the developmental course of EF and to determine whether EF is a unitary concept or can be parsed into discrete components over the first 42 months. METHOD: All 81 cognitive items from the Bayley-4 normative sample of 1700 infants and toddlers were classified a priori into 6 EFs, and then, 5 age groups derived from Bayley-4 start points were factor analyzed to determine at what age EFs emerge and to address the controversy of whether the factor structure of the cognitive items for each of 5 age groups reflect a single factor or multiple factors. RESULTS: Bayley-4 items form 1 to 5 EF factors for each age group, accounting for 59% to 74% of the variance. There is a developmental progression in EF as well. The results indicate EF constructs can be identified early. CONCLUSION: Executive function tasks in infants and toddlers are interrelated with task content either remaining the same or changing with advancing age (i.e., content that is homotypic or heterotypic, respectively). EFs measured by Bayley-4 items are useful clinically and become more complex with increasing age, corresponding to more advanced brain development and integration. The findings have the potential of providing additional information in the assessment of infants at risk such as those born preterm.

Is It Correct to Correct for Prematurity? Theoretic Analysis of the Bayley-4 Normative Data.

OBJECTIVE: To determine whether correction for prematurity is appropriate for cognitive, language, and motor function at varying degrees of prematurity and at different baseline functional levels. METHODS: The newly published Bayley-4 normative data on 1700 normal children were used. Raw scores for baseline levels of function (-2 SD, -1 SD, and M) were identified at 6, 12, 24, and 36 months for receptive communication, expressive communication, fine motor, and gross motor scaled scores and cognitive, language, and motor composite scores. Differences between the baseline and uncorrected scores at 4, 3, 2, and 1 months of prematurity were evaluated at each age. RESULTS: Using a cutoff of 3 points (1/5 SD), correction is needed for cognitive composite scores at all gestational ages for the first 2 years and in those born 4 months premature at 3 years of age; language and motor composite scores should be corrected to 3 years at all degrees of prematurity. CONCLUSION: Not correcting for prematurity in cognitive, language, and motor function at 3 years and younger places preterm infants at a distinct disadvantage when compared to peers with few exceptions, suggesting that such correction should be routine.

What Are We Measuring as Outcome? Looking Beyond Neurodevelopmental Impairment.

Outcomes of neonatal intensive care unit (NICU) graduates have been categorized by rates of neurodevelopmental impairment at 2 years old. Although useful as metrics for research, these early childhood assessments may underestimate or overestimate later functional capabilities. Often overlooked are less severe but more prevalent neurobehavioral dysfunctions seen later in childhood, and chronic health concerns that may impact the child's quality of life (QoL). Comprehensive NICU follow-up should include measures of less severe cognitive/learning delays, physical/mental well-being, and the promotion of resilience in children and families. Studies are needed to identify QoL measures that will optimize children's assessments and outcomes.

Neurodevelopmental outcomes of infants born prematurely.

Long-term follow-up of infants born prematurely is necessary to determine neurodevelopmental outcomes, particularly with the expansion of interest from major disabilities to high prevalence/low severity dysfunctions. Models of pathogenesis include changes due to developmental disruptions and to injury, the magnitude and type of change influenced by the infant's age, and central nervous system recovery and reorganization. Alterations in neurogenesis, migration, myelination, cell death, and synaptogenesis occur even in the absence of insult. Despite increased knowledge regarding these processes, the functional significance of brain abnormalities is unclear. Because of methodologic problems in follow-up studies, it is difficult to characterize outcome definitively. Nonetheless, an acceptable degree of agreement across studies is found with regard to specific neurodevelopmental outcomes: motor/neurologic function, visuomotor integrative skills, IQ, academic achievement, language, executive function, and attention-deficit hyperactivity disorder/behavioral issues. In general, children born prematurely have more problems in these areas than do their normal birth weight counterparts. Suggestions for improved analyses and clarification of outcomes include use of cluster analysis, structural equation modeling, growth curve analysis, developmental epidemiologic approaches, and better control of background variables using risk indexes and factor scores. Better assessment techniques measuring functions documented to be at higher risk of problems are discussed.

Application of neurodevelopmental screening to a sample of South American infants: the Bayley Infant Neurodevelopmental Screener (BINS).

OBJECTIVE: To evaluate the utility of the Bayley Infant Neurodevelopmental Screener (BINS), standardized in the US, for South American infants, 3-24 months of age. METHODS: Thirty-five physicians administered the BINS to 2471 South American infants recruited during routine well-child visits, 578 (23%) from Brazil and 1893 (77%) from six other South American countries. The BINS was translated into Spanish and Portuguese and participating physicians were trained to administer the BINS. Physician inter-rater agreement with training tapes was 84.4%; test-retest reliability for age item sets ranged from 0.80 to 0.93 (Pearson's r). Infants were classified into being at low, moderate, or high risk for developmental delay or neurological impairment based on their total BINS score. The sample was stratified by infant's age, sex and language (Spanish and Portuguese). The BINS scores were compared to the scores of the US infant sample used to standardize the BINS. RESULTS: Female infants performed higher than male at 16-20 months and 21-24 months; male infant scores were more variable at 5-6 months. Scores on only two items were significantly different between Spanish and Portuguese speaking participants. South American scores were typically significantly higher than the US sample, and a lower proportion of infants were classified as being at high risk in the South American sample than in the US standardization sample. CONCLUSION: Overall, the results of this study indicate that the BINS is feasible and appropriate for neurodevelopmental screening in South America. Further studies are needed to confirm the BINS utility in South America, including its use with a clinical sample.

The changing yardstick in measurement of cognitive abilities in infancy.

There are concerns regarding accurate measurement of cognitive function in infants, particularly those at biologic risk. Herein we discuss these issues and make recommendations. Concerns include: 1) secular changes in test norms, referred to as the Flynn effect; 2) changes in the content of revised test versions; 3) recent findings of higher mean scores in newer test versions when compared to previous scores; and 4) correction for prematurity. Caution is necessary when comparing the same test scores over extended periods of time, and using different versions of the same test when mean scores of the tests vary or evaluate different areas of functioning. Ideal solutions are not readily apparent and thus we provide several suggestions: control groups are essential for longitudinal studies; clinicians should not rely totally on cognitive scores; and further investigation of the Flynn effect in different subgroups of children at different ages is necessary.

Comparison of caretaker report and hands-on neurodevelopmental screening in high-risk infants.

Caretaker report in developmental screening of high-risk infants has not been investigated adequately. We compare a caretaker-completed neurodevelopmental prescreening questionnaire (NPQ) to a hands-on screener (Bayley Infant Neurodevelopmental Screener; BINS) and attempt to identify factors that influence agreement in a high-risk sample. From 1,436 infants drawn from 5 centers, 471 were prospectively evaluated at 6-months corrected age, 376 at 12-months, and 244 at 24-months. Fifty-five percent were male; 28% African American, 70% Caucasian, 3% other; M gestational age = 31.2 weeks, M birth weight = 1568 g. Caretakers completed the NPQ (based on the BINS) while watching a video depicting infants engaged in items. The BINS was subsequently administered. Sensitivity ranged from 80%-91%, specificity 57%-82%, and overall agreement 70%-83%, depending on age. Mean NPQ summary scores were lower than the BINS. Agreement varied depending on BINS risk status, being best in the high-risk group, and worst in the moderate risk group. Background variables had minimal impact at 6 and 12 months with BINS risk status being the primary influence; at 24-months, race, intraventricular hemorrhage, and respiratory distress syndrome were influential. Caretaker report is useful in a high-risk population, although the infant's neurodevelopmental status influences such early on; ethnic background and biomedical variables become more important at 2 years.

Associations between cognitive function, blood lead concentration, and nutrition among children in the central Philippines.

OBJECTIVE: Because little is known about its effects on cognitive function among children in less-developed countries, we determined the impact of lead exposure from other nutritional determinants of cognitive ability. STUDY DESIGN: Data were from a cross-sectional population-based stratified random sample of 877 children (age 6 months-5 years) participating in the Quality Improvement Demonstration Study we are conducting in the Philippines. With data from validated psychometric instruments, venous blood samples, and comprehensive survey instruments, we developed multi-stage models to account for endogenous determinants of blood lead levels (BLLs) and exogenous confounders of the association between BLLs and cognitive function. RESULTS: A 1 microg/dL increase in BLL was associated with a 3.32 point decline in cognitive functioning in children aged 6 months to 3 years and a 2.47 point decline in children aged 3 to 5 years olds. BLL was inversely associated with hemoglobin and folate levels. Higher folate levels mitigated the negative association between BLL and cognitive function. CONCLUSIONS: These population-based data suggest greater lead toxicity on cognitive function than previously reported. Our findings also suggest that folate and iron deficient children are more susceptible to the negative cognitive effects of lead. Folate supplementation may offer some protective effects against lead exposure.

Long-term neurodevelopmental outcome and brain volume after treatment for hydrops fetalis by in utero intravascular transfusion.

OBJECTIVE: We tested the hypothesis that long-term neurodevelopmental outcomes of successfully treated fetuses with immune hydrops are similar to their unaffected siblings according to a protocol that addresses the underlying pathophysiologic condition. STUDY DESIGN: Sixteen of 18 consecutive hydropic fetuses (89%) who were treated in a dedicated fetal medicine unit between July 1985 and October 1995 survived. The transfusion protocol used a 2-step correction over a 2 to 4 day interval, combined with umbilical venous pressure measurements to avoid over transfusion and bicarbonate administration to assure a posttransfusion UV pH of >7.30. Survivors were evaluated at a mean age of 10 years. Statistical analyses included t-test, Wilcoxon rank-sum test, Fisher's exact test, and Pearson coefficients. RESULTS: Overall, death or major neurologic morbidity occurred in 4 of 18 of the fetuses (22%) who were treated (2/16 of survivors [12.5%]). Among the survivors, the children with immune hydrops had physical, neurologic, and cognitive outcomes statistically similar to their siblings, except for a measure of visual attention. Two of the children (12%) had major neurologic sequelae. Brain volumes were statistically smaller than unrelated control subjects by 8.8%, but these control subjects were not matched for height at testing or gestational age at birth. Both groups had brain volumes within the normal range. CONCLUSION: Intravascular transfusion of fetuses with profoundly anemic immune hydrops results in high survival rates and favorable long-term neuropsychological outcomes.

Neurodevelopmental outcomes of infants born prematurely.

Long-term follow-up of infants born prematurely is necessary to determine neurodevelopmental outcomes, particularly with the expansion of interest from major disabilities to high prevalence/low severity dysfunctions. Models of pathogenesis include changes due to developmental disruptions and to injury, the magnitude and type of change influenced by the infant's age, and central nervous system recovery and reorganization. Alterations in neurogenesis, migration, myelination, cell death, and synaptogenesis occur even in the absence of insult. Despite increased knowledge regarding these processes, the functional significance of brain abnormalities is unclear. Because of methodologic problems in follow-up studies, it is difficult to characterize outcome definitively. Nonetheless, an acceptable degree of agreement across studies is found with regard to specific neurodevelopmental outcomes: motor/neurologic function, visuomotor integrative skills, IQ, academic achievement, language, executive function, and attention-deficit hyperactivity disorder/behavioral issues. In general, children born prematurely have more problems in these areas than do their normal birth weight counterparts. Suggestions for improved analyses and clarification of outcomes include use of cluster analysis, structural equation modeling, growth curve analysis, developmental epidemiologic approaches, and better control of background variables using risk indexes and factor scores. Better assessment techniques measuring functions documented to be at higher risk of problems are discussed.