Abstract
Neonatal care is continually changing. There is increasing evidence that these advances work together to produce incremental improvements in outcome, promoting survival of children without serious impairment. Thus major neurosensory deficits, such as cerebral palsy or vision and hearing impairment, are decreasing in frequency among survivors, but medical services need to remain alert to their presentation and need for support. Recognition of the pervasive effects that prematurity has on brain and, therefore, functional development over childhood has led to increased research activity in the field. However, effective strategies to ameliorate some of the developmental disadvantages in a significant proportion of very preterm children remain elusive. The impact of core neurologic functions, such as slower processing speed and working memory compared with children born at term, has wide-ranging effects on neurologic function and behavior. This may affect the ability to socialize and integrate for some children, adolescents, and adults. Recognition and support remain critically important functions for follow-up services in the foreseeable future. For the future, it is essential that development of accurate biomarkers in infancy of later cognitive problems so that these can be identified early, leading to earlier intervention and acting as short-term outcomes to reduce the time required to study their prevention. In addition, identification of the optimal developmental intervention timing and strategy to prevent later neuropsychological problems are urgently required
Keywords
behavioral impairment, cerebral palsy, cognitive impairment, hearing loss, language impairment, sensory outcomes, very preterm graduates, visual impairment
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Very preterm graduates may develop complex and subtle deficits of neuropsychological function that have implications for health and well-being across childhood.
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Major neurosensory deficits, such as cerebral palsy or vision and hearing impairment, are decreasing in frequency among survivors, but medical services need to remain alert to their presentation and need for support.
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Recognition and support over infancy may be effective in ensuring optimal outcomes.
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Very preterm children at school are at risk of key executive function deficits that may lead to poor performance in the classroom and in behavior.
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These issues have importance for attainment and wealth as adults.
The continuum of perinatal casualty extends to adverse neuropsychological outcomes after very preterm (VPT) birth, which consist of an important spectrum of impairments that has become more apparent with increasing academic study over the past 20 years. Increasing survival without severe impairment at extremely low gestational ages has fueled increasing intervention in the perinatal period and a recognition that “less” intervention may be “more” in terms of outcomes. Birth at extremely low gestations is nonetheless attended with a high risk of neurologic injury and complex sequelae. Outcome evaluation has resulted in an explosion of interest in this area that has contributed to our current understanding of the problems faced by VPT children through infancy to adolescence and into adult life. This chapter focuses on the child and the support necessary to ensure optimal outcomes as a result of our perinatal investment.
Most follow-up services are associated with individual neonatal programs and fulfill two roles: first, as individual family-infant support and detection of atypical neurodevelopment so that families can receive appropriate services, and second, collecting information for quality assurance and research. Support may be most intensive over the first year as the child develops and anxiety is highest for families. Most serious impairment should be detected during this time, including cerebral palsy (CP), and significant developmental delay, and issues with feeding, regulation, and growth should be addressed. As the infant develops, respiratory function improves, and supplemental oxygen and feeding support can be withdrawn. Over the second year the intensity of support required lessens, and most services now carry out a formal assessment at 18 to 24 months to categorize outcome for quality assurance purposes. Services then may transfer children to the care of their family medical support team or continue to monitor progress intermittently. As will be noted, continuing support helps to support families in decision-making—for example, about education—and can provide advice and direction when new problems arise. Research into the neuropsychological impairments found in middle childhood is important in helping us to understand the educational and wider support needs of VPT children.
The Major Sequelae of Very Preterm Birth
Key neurosensory adverse outcomes found among VPT survivors include:
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CP
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Cognitive impairment
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Visual impairment
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Hearing loss
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Behavioral problems
These outcomes are inversely related to gestational age at birth, best exemplified by the exponential rise of educational special needs with increasing immaturity and the similar relationship between mean intelligence quotient (IQ) of studies and gestational age.
Cerebral Palsy
Classically, CP following VPT birth is described as bilateral spastic in type, tending to be worse in the lower limbs and associated with periventricular leukomalacia (spastic diplegia). However, with increasing immaturity, the pattern of CP is complex and more mixed in distribution among more modern cohorts. Among infants with birth weights between 1000 and 1500 g, there is some evidence that CP rates are falling in Europe and a suggestion that rates for infants weighting less than 1000 at birth are following the trend. There is also evidence in multiple studies that less severe motor problems are more common among VPT survivors. Strong prognostic risk factors for CP and motor problems are intraventricular hemorrhage and periventricular leukomalacia, together with use of postnatal or nonuse of antenatal steroids for CP. Male sex and lower gestational age are also related to the prevalence of CP, but in studies with restricted study size or gestational range this may not be as clear.
The definition of CP varies from physician to physician. Various classification systems are in place, such as that from the Surveillance of Cerebral Palsy in Europe group (SCPE; www.scpenetwork.eu ). Their simple classification tree provides for consistent classification into spastic (bilateral, unilateral), dyskinetic (dystonic, choreoathetoid), ataxic, or other. Functional outcome in children with CP is increasingly important. Simple classifications, such as the Gross Motor Function Classification System (GMFCS) and Manual Ability Classification System (MACS), are valuable schemes to maintain some consistency between reports and are often used in published studies. However, functional outcome extends beyond motor outcomes to other aspects of daily living and societal integration, as described by Bax and colleagues in their extended definition of CP.
Early detection of CP is challenging before discharge. Critical imaging findings may indicate high risk but distribution and severity are hard to predict. Most nonambulatory CP can be identified using sequential cranial ultrasound, supplemented by assessment of the posterior limb of the internal capsule on magnetic resonance imaging (MRI). All VPT infants should have a formal structured neurologic examination before discharge. Many services, particularly in Europe, find a video recording of general movements, classified as suggested by Prechtl, to be valuable. Most predictive of later problems is a repeat video at 3 months postterm, in particular evaluating for the normal presence or absence of fidgety movements. Classic persistence of primitive reflexes and ongoing neurologic abnormalities raise suspicion. When there is anxiety about evolving neurologic signs, early referral to neurodisability services is important to provide enhanced surveillance and monitoring, with intervention as indicated.
During follow-up in infancy, VPT children may display what are considered abnormal patterns of neurologic development, mainly related to persisting trunk extension and shoulder retraction. Such a pattern is not associated with the typical evolving pattern of spastic CP; on occasions it may masquerade as such when it is severe. Such transient dystonias or transient neurologic abnormalities are well described and they tend to resolve over the second year; hence distinguishing them from evolving CP may be of great importance. First described by Drillien, such findings may be associated with persisting periventricular echodensities on sequential neonatal ultrasound and may signal children at risk of later educational challenges. Recognition should nonetheless initiate support from neurodisability services to encourage optimal posture and facilitate development.
Cognitive Impairment in Infancy
Developmental progress should be monitored as part of routine follow-up. Repeated formal assessments may provide a suitable framework on which to counsel parents, but are not strictly necessary. Most follow-up programs will develop key assessment points. National recommendations in the United Kingdom are to make a single formal assessment point at 24 months of age corrected for preterm birth. At this age, there are a range of screening and assessment tools available. Choice of tools will depend on resources. In the United Kingdom, there is a proposal to use a parental questionnaire (Parent Report of Children’s Abilities-Revised [PRCA-R] ) at 2 years but to supplement this by a formal general cognitive score in the preschool period. Other schemes include assessment using formal comprehensive assessments, such as the Bayley Scales of Toddler and Infant Development (Bayley-III). Formally assessed developmental scores underpin much outcome research activity. There is some evidence that the second edition of the Bayley Scales has a high predictive value for IQ over childhood to 19 years, emphasizing the importance of accurate and well-conducted assessments in the third postnatal year. It is too early to review the predictive value of the third edition, but concerns have been raised over the rather higher-than-anticipated scores, possibly because of overscoring of performance at lower scores.
Children who are causing developmental concern or who score poorly on screening or developmental testing should be referred to early intervention services, which can provide longitudinal monitoring and support. Early intervention programs may show early benefit through to the preschool period, but there is little evidence the effects persist into childhood from current studies. Parental support and reassurance are equally important in the early months when uncertainty and anxiety may compromise maternal-infant interaction but are rarely assessed.
Sensory Outcomes
Neonatal screening for hearing impairment and vision screening will identify those children with severe or profound impairment; formal testing where good population screening and intervention services exist is not necessary. Because the increased prevalence of acquired hearing loss and milder degrees of visual impairment are very common in VPT children, in the absence of specialized screening programs formal assessment is an important part of follow-up services for this group.
Behavior
Assessing behavior at 2 years of age is fraught with problems. Most disability classifications (see later text) at around 2 years of age do not include behavioral criteria.
However, there is little doubt that the prevalence of autistic symptoms is increased after very preterm birth and detection before 2 years may help with intervention, if it is deemed necessary. Screening is recommended by the American Academy of Pediatrics at 18 months followed by referral. Screening for autistic symptoms is frequently undertaken in many follow-up programs, but the screening tools available, designed to identify at-risk children in the general population, are confounded by their reliance on developmental questions and the obligatory telephone follow-up and clinical assessment are rarely reported. Very high rates of positive screening results have been reported but the necessary screening is not followed by diagnostic testing. Later follow-up indicates that the proportion with a diagnosis of autism may be considerably less than these estimates. Screening tools should be used with caution and follow-up diagnostic assessments undertaken before disclosure. Some of the newer screening tools may be better in this respect, but further work is required in the preterm population to define their performance.
Classification of Impairment
For the purposes of research and audit, several classification systems are in use. The most common reports include children with what are called “moderate or severe impairments” or “neurodevelopmental impairment.” Such data are frequently used to support counseling without real reference to their predictive validity. Other systems use a more graded approach, separating severe and moderately disabling impairments. The prevalence of “severe impairment” in some situations is a useful construct, such as delivery room decisions about active care and decisions concerning palliative care, and forms part of the widely used the U.K. National Institute for Health Research (NIHR) prognostic calculator. In contrast, most individuals with “moderate impairment” at 2 years will achieve independent living. Although on an individual basis the categorization of impairment at 2 to 3 years is a relatively poor predictor of childhood status, on a population basis it provides a good estimate of risk throughout childhood; children with borderline results frequently move between categories in both directions.
Abigail was born to a 33-year-old primigravid Afro-Caribbean mother following spontaneous preterm labor at 26 weeks. Her mother presented with 6-cm dilatation and proceeded to deliver without steroids. Abigail was ventilated for 2 weeks and then received continuous positive airway pressure/supplemental oxygen until 32 weeks of postmenstrual age (PMA). Her course was complicated by feeding difficulties and several episodes of neonatal sepsis ( Staphylococcus epimermidis ). She was discharged home at 38 weeks PMA. Results of neurologic examination were normal, and ultrasound revealed mild ventriculomegaly (+2 standard deviations bilaterally). No brain MRI scanning was performed.
Prechtl video assessment at 3 months corrected age (CA) (i.e., postterm) was inconclusive as to the presence of fidgety movements; neurologic and developmental examinations were unremarkable. Feeding was slow and weight gain borderline. Working with the speech and language team, solids foods were introduced but no developmental interventions were planned.
At 6 months CA Abigail was just starting to roll over, with tendency to go into extension, but limb tone and reflexes were unremarkable. The parents were resistant to intervention at this stage, so early review was planned but this appointment was missed.
Abigail was evaluated again at 12 months CA when generalized hypertonia was evident. She was not sitting and reflexes were generally brisk. Hand function was poor without pincer grasp. She was bright and communicative, with three clear words. Assessment by physiotherapy confirmed the hypertonia, and referral was made to the community disability team, who confirmed our findings and organized support with physiotherapy as the lead professional team. Formal disclosure of a diagnosis of CP was made, which the parents denied.
Over the next 6 months Abigail made rapid progress and was walking at 18 months CA. When seen formally at 24 months CA, her motor developmental score was 95 and her cognitive score 106. Neurologic assessment demonstrated a resolution of her hypertonia, and her overall classification was unimpaired.
Learning Points
The early clinical course included the evolution of mild bronchopulmonary dysplasia (BPD), sepsis, and the absence of treatment with antenatal steroid—all risk factors for poor outcomes. Despite normal neurologic examination results at discharge, two factors point to the need for close surveillance: the presence of ventriculomegaly and subsequently the lack of convincing fidgety movements at 3 months CA. Interestingly Abigail appears to have developed transient dystonia, a condition well described in very preterm children. Important clues that this might not be severe CP at 6 months were the lack of tonal changes in the lower limbs (one might expect severe CP to demonstrate hypertonicity in ankle flexion and abduction, with hyperreflexia, upgoing plantar responses, and perhaps even clonus). However, by 12 months this had progressed to cause widespread professional concern that this was indeed CP. The rapid resolution over the second year is typical of transient dystonia and indeed at 24 months CA she was classed as unimpaired. In view of the history, however, the team considered it prudent to continue observation.
Transition to School
VPT children are increasingly followed up through to school age. In the transitional preschool period, there is a focusing of cognitive development into recognizable patterns of executive processing, and accessing general cognitive function (IQ) becomes more reliable. Over this period children frequently attend nursery education in preparation for learning in the school environment. Behavior changes alongside this, as the relative overactivity of the 2-year-old is replaced by the emerging internalized phenotype seen across school age and into adult life. Language and socialization develop rapidly at this time.
Starting School
In some settings, school readiness is assessed to help determine when children appear ready to go to school. Such structured assessments can inform follow-up programs. In other settings, neonatal follow-up services may provide support over this transition. When school entry is age dependent, there is controversy whether former VPT children should be held back to be allowed to catch up, particularly if their birthday and due date would place them in different school intakes (e.g., see the Bliss website at www.bliss.org.uk/starting-school ). There is little evidence either way. In the EPICure study, children born before 26 weeks’ gestation who were in school in the correct year by due date had attainment similar to that of children who had gone to school in an earlier intake, but the children received more special needs support to do so. Decisions may be better made considering the social development of the child, bearing in mind that keeping a child back a year will not necessarily improve this.
Emerging Impairments at Early School Age
Over the period of transition to school, difficulties in learning, behavior, and motor function may evolve or appear de novo. It is important that such issues are detected early, so that strategies can be put in place to support and optimize learning. Formal assessments by follow-up teams may be structured to assist in this and to inform educational teams.
Cognitive Function
General cognitive scores for very preterm children are, on average, lower than those of children whose pregnancies deliver at full term. As gestation decreases below around 32 weeks, mean scores at each gestational week are progressively lower. Traditionally the scores for school age children are calculated on chronological age, rather than age corrected for prematurity, for two reasons—firstly, the school age child is compared to their peers in the school year and, secondly, proportionately the correction is less. More recently this has been challenged with the suggestion that correction should continue, but there appears to be little consensus.
General cognitive scores are the product of a range of executive processes, which themselves may be impaired. The size of the discrepancy, compared with individuals born at term, depends on the process and the postnatal and gestational age of the child. Some executive functions will catch up during childhood—for example, selective or sustained attention—whereas others may diverge—for example, planning or phonemic fluency. Hence the pattern of cognitive problems changes as the children grow through school. At 8 to 10 years of age, key functions such as working memory or information-processing speed appear to underpin the cognitive, learning, and behavioral problems seen in VPT children, which point to foci that may provide opportunity for intervention.
School Attainment
Very preterm children at school are more frequently reported to have special needs, with increasing proportions as gestation decreases. At 24 weeks’ gestation around 50% of children will have some special needs in the classroom, varying from 1:1 or small group teaching, to support from therapists. In the EPICure study 13% of children born at less than 26 weeks were in non-mainstream schools because of special needs. Attainment is lower across all educational domains but seems particularly problematic with mathematics, scores in which are depressed more than in other domains. Mathematics difficulties may have a different origin in the VPT child compared with children born at term; more often the problem is related more frequently to underlying executive and working memory problems rather than number estimation, which is most often the cause for children born at term. Key strategies to optimize learning in VPT children may be the presentation of sequential information (i.e., breaking tasks down into smaller steps) and careful monitoring of attention in the classroom.
Behavior
Over the past 20 years there has been increasing recognition of common behavioral and psychiatric morbidity in cohorts of VPT and extremely preterm children. Current estimates suggest that VPT 7-year-olds have 3 times the odds of being assigned a psychiatric diagnosis. The most frequent diagnosis is attention deficit disorder, which is most commonly of the inattentive subtype, consistent with the working memory and processing deficits observed. Autism is currently of interest and has been recognized for some time in association with prematurity. Eight percent of an extremely preterm cohort was assigned a diagnosis of autism using a standardized assessment protocol. The literature on preterm infants is somewhat confusing because making a formal diagnosis and scoring high on screening tests are different things. Indeed, symptoms of attention deficit (as scored using the DuPaul RS4 Rating Scale [RS-IV] ) or of autistic traits (Social Communication Questionnaire, Social Responsiveness Scale ) are much more frequently found in VPT children compared with diagnoses. Comorbid with symptoms of anxiety in early adolescence, this excess of symptoms has led to the definition of a preterm behavioral phenotype consisting of internalized individuals with common symptoms within the domains of anxiety, inattention, and social communication. There is some evidence that this may be exacerbated by bullying, which is reported more frequently in preterm populations. It is important that teachers and follow-up teams are aware of these risks if they are to be detected early and support provided to minimize the impact they have on the child and family.
Motor Problems
CP aside, VPT children are frequently reported to have impairments of motor function, referred to variously in the literature. The commonest assessment tool is the Movement Assessment Battery for Children, which is a test of motor impairment as opposed to a motor performance test. Rates of scores above the 5th or 15th percentiles (higher scores reflect more impairment) are significantly higher in VPT populations. In a recent study 28% of VPT children scored at or above the 5th percentile at 8 years, which was a similar proportion to their findings at 4 years. The proportion scoring above these thresholds has not changed appreciably for some time and seems to be related to both perinatal risk and comorbid cognitive scores. These impairments may need assessment and support from physical or occupational therapists. When assessed alongside a detailed neurologic examination—for example, as described by Touwen —motor problems also may be comorbid with a range of soft neurologic signs and seem to reflect a less well-organized motor system.
Changes Over Time for Individual Children
Assessments in infancy are often considered relatively poor predictors of school age outcomes. Particularly when categorical outcomes are used, children may shift between categories. Within the EPICure study at 6 years, only 65% of children classified as having a severe disability at 30 months were still classified as such. In other categories movement was greater. Hence it can be difficult to be certain from even earlier assessments of the likely outcomes if emphasis is placed on categorization. There is often uncertainty about population scores catching up over school age, but such data are very challenging to interpret as the tests will have changed and may measure slightly different mixtures of functions. Generally, in our cohorts mean cognitive scores have remained the same and, although scores in individual children may rise, in others they fall. Cognitive scores in particular appear to be conserved over childhood and adolescence, particularly in those with impairments.
Related posts:
Cerebral Circulation and Hypotension in the Premature Infant: Diagnosis and Treatment
Hypothermia for Neonatal Hypoxic-Ischemic Encephalopathy: Different Cooling Regimens and Infants Not Included in Prior Trials
General Supportive Management of the Term Infant With Neonatal Encephalopathy Following Intrapartum Hypoxia-Ischemia
Neonatal-Onset Epilepsies: Early Diagnosis and Targeted Treatment
Neonatal Meningitis: Current Treatment Options
Amplitude-Integrated EEG and Its Potential Role in Augmenting Management Within the NICU
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