Neurodevelopmental outcomes following very preterm birth: What clinicians need to know

Introduction

The vast majority of children born very preterm (<32 weeks’ gestation) now survive, with survival rates increasing significantly over the past three decades due to advances in obstetric and neonatal care. While important, survival is only one outcome, and it is possible that reductions in mortality are associated with increases in short- and long-term morbidity. Long-term outcome studies of children born very preterm are essential for determining the true benefits and consequences of new interventions and changes to management practices. Reliable outcome data is critical for clinical decision-making, counseling families, and structuring surveillance programs for individual children and their families. As such, it is recommended that perinatal health professionals have a strong understanding of the long-term outcomes following very preterm birth; however, this is not the case with health professionals tending to overestimate major disability in children born extremely preterm. ^,

While there is undeniable evidence that children born very preterm are at risk for a spectrum of developmental challenges, reviewing the literature can be daunting given the thousands of published papers on this topic. This chapter will begin with a brief summary of the long-term neurodevelopmental impairments associated with very preterm birth, followed by a discussion on how group-based data can often portray an overly negative perception of long-term outcomes. We propose that more emphasis should be given to interpreting the true rates of impairment, individual differences in severity and profile of impairments, whether or not impairments persist or diminish with increasing age, and consideration of the changes in long-term outcomes as a result of improved medical care.

Neurodevelopmental outcomes following very preterm birth

General cognitive functioning is the most common domain assessed in long-term outcome studies of children born very preterm, and this is typically done by administering a measure of general intelligence, or IQ. A recent meta-analysis found that at a group level, the IQ of children born very preterm was 13 points lower than children born at term, representing a group difference of approximately 0.9 standard deviation (SD). The authors also performed a meta-regression examining the standardized mean difference according to the birth year of the pooled cohorts (1990–2017), and found no evidence that the IQ discrepancy between children born very preterm and term is reducing in more recent cohorts. While IQ tests are generally sensitive at identifying cognitive problems, these measures are not particularly helpful for determining the nature of the cognitive deficits. Neuropsychological evaluations are required to establish the profile of cognitive strengths and weaknesses in children born very preterm, which is critical for determining appropriate remediate strategies.

Sensory and motor systems are impacted following very preterm birth. Meta-analyses report poorer performance in children born very preterm of 0.6 to 0.9 SD across tasks assessing visual perception and visual-motor integration when compared with term peers, with the rate of impairment being 2 to 3 times higher for those born extremely preterm when compared with children born at term. With regards to performance on standardized tests of motor functioning, the performance of children born very preterm is approximately 0.5 to 0.9SD below term peers. In contrast to a rate of 0.1% to 0.2% in the general population, the prevalence of cerebral palsy (CP) is approximately 15% for infants born before 28 weeks’ gestation and 6% for those born between 28 and 31 weeks’ gestation. Furthermore, it has been reported that approximately half of 5-year-olds born very preterm have functionally impaired motor coordination and balance which is not related to CP, and meeting criteria for developmental coordination disorder (DCD).

Inattention is often noted to be an area of concern for children born very preterm by parents and teachers, which is supported by numerous neuropsychological studies that have identified poorer performance by children born very preterm on formal tests of attention compared with term controls. In a cohort of children born extremely preterm, it was estimated that 75% had at least a mild attention impairment. Deficits have been reported across all facets of attention functioning including selective, sustained, shifting, and divided attention, ^, and while there is inter-individual variability, at a group level, the evidence suggests that very preterm birth is associated with a generalized attention impairment.

Executive function refers to those cognitive processes that are critical for goal-directed behavior and includes inhibitory control, working memory, cognitive flexibility, planning, and reasoning ability. Meta-analyses have reported deficits across all elements of executive functioning, with the magnitude of the group differences with term controls ranging from 0.3 to 0.9 SD. ^{, ,} Executive dysfunction has been reported in preschoolers born very preterm, but there is no evidence that these difficulties decline with age. ^,

Less research has studied memory following very preterm birth, but the evidence to date suggests that memory is also an area of concern. The rate of verbal and visuospatial episodic deficits was approximately three-fold in a cohort of 7-year-olds born very preterm compared with term born controls. Similar findings were reported in an older cohort (13-year-olds), although this study found the recall of visuospatial information to be particularly problematic for children born very preterm with a six-fold higher rate of impairment. Prospective memory is also more likely to be impaired in children born very preterm, especially time-based tasks in which children are required to remember to perform a future action at a specific time.

Language delay is common in infants and toddlers born very preterm, however, language challenges are ongoing with a meta-analysis revealing that school-aged children perform 0.6 SD below term controls for expressive language and 0.8 SD below for receptive language. Children born extremely preterm seem particularly vulnerable, with reports of a 10-fold higher odds of a moderate to severe language impairment.

Long-term outcome studies of children born very preterm often assess behavior and emotional status using parent-reported questionnaires. While differences are rarely found between children born very preterm and term on scales of externalizing behavior problems (i.e., aggression, conduct problems, defiance), there is a tendency for parents of children born very preterm to report more internalizing (i.e., anxiety, depression, social withdrawal) and attention problems. Similarly, in adulthood, those born very preterm self-report more internalizing difficulties and fewer externalizing difficulties than term born peers. Consistent with these findings, higher rates in specific psychiatric disorders have been reported in those born very preterm when structured clinical interviews have been conducted. ^, In a recent individual participant meta-analysis, those born very preterm were 10 times more likely to meet criteria for a diagnosis of autism spectrum disorder (ASD), 5 times more likely to meet criteria for attention-deficit hyperactivity disorder (ADHD), and twice as likely to meet criteria for anxiety.

Given the increased risk for deficits across cognitive, motor, and behavioral domains, it is not surprising that children born very preterm are more likely to have academic difficulties. Multiple meta-analyses have reported poorer performance on standardized tests of reading and maths in children born preterm compared with term controls, especially those born very and extremely preterm, with group differences ranging from 0.5 SD to 0.8 SD. ^{, ,} Related to these findings, studies have reported a marked increase in the rate of children born very preterm who are receiving extra support and resources at school. ^,

This summary of the long-term outcomes following very preterm birth focuses on group-level findings and paints a pretty grim picture. However, it is important to note that the profile and severity of neurodevelopmental impairments for each child are unique. For example, a child may present with CP and intellectual impairment, another with ADHD and learning impairment, and a third with DCD and language impairment. There is also a significant proportion of children born very preterm who present with no developmental concerns. To demonstrate the considerable variability in outcomes at the individual level, the next two sections will highlight the importance of (1) analyzing the true rate of impairments and not just focusing on mean group differences and odds ratios and (2) utilizing person-centered analyses to examine profiles of functioning.