Very Preterm Early Motor Repertoire and Neurodevelopmental Outcomes at 8 Years

One hundred and eighteen infants born <30 weeks’ gestation between January 2005 and September 2006 and admitted to the Royal Women’s Hospital, Melbourne, Victoria, Australia, participated in an early intervention trial over the first 12 months after birth.¹²  Survivors were invited for follow-up assessments at 2, 4, and 8 years’ corrected age (Fig 1). Because no substantial differences in motor and cognitive outcomes related to the intervention were found at 2, 4 and 8 years,^9,13,14  groups were combined for the current study, which is focused on the 8-year outcomes. The Royal Women’s Hospital and Royal Children’s Hospital Human Research Ethics Committees approved the study. Written informed consent was obtained from all parents. Families were classified as lower or higher social risk on the basis of 6 aspects of social status, as previously reported.¹⁵ 

At 3 months’ corrected age, 20- to 30-minute video recordings of spontaneous movements were made in 97 infants. The recordings were scored according to Prechtl’s method by 2 independent assessors who were blinded to the infants’ clinical history and had completed formal training with the General Movement Trust (90.9% agreement; Cohen’s ĸ = 0.77, SE = 0.21), with the MOS-R completed by 1 assessor.^6,13,16  An infant’s FMs were classified as normal when continuous small-amplitude, moderate-speed movements of shoulders, wrists, hips, and ankles in all directions and of variable accelerations were seen. In case of an exaggeration of movements in terms of speed and amplitude, FMs were judged abnormal. If FMs were not observed, they were judged as absent.¹⁶  In addition, the MOS-R was determined on the basis of the following subscales: observed movement patterns, age-adequacy, observed postural patterns, and movement character. Each subscale consists of 3 categories on the basis of which scores of 1, 2 or 4 were given, in ascending order of normality. FMs are an exception and scores of 1 (absent), 4 (abnormal), and 12 (normal) were used. As a result, a MOS-R ranging from 5 to 28 points was possible, with higher scores reflecting better performance.^6,7,11,17 

At 8 years, children were administered a test battery assessing various neurocognitive developmental domains.¹⁸ 

To assess general cognition, the Differential Ability Scale - Second edition (DAS-II) was administered. Indices of interest include the General Conceptual Ability scale, which is a composite scale from the verbal, nonverbal, and spatial reasoning scales.¹⁹  A normative mean of 100 (SD = 15) applies to all scales.

Attention was assessed by using the Score! (sustained attention) and Sky Search (selective attention) subtests of the Test of Everyday Attention for Children, which have a mean of 10 (SD = 3).²⁰ 

Working memory was assessed by using subtests from the Working Memory Test Battery-Children. Digit Recall was used to assess immediate verbal memory, whereas Backward Digit Recall was used to assess verbal working memory. A normative mean of 100 (SD = 15) applies to both subtests.²¹ 

The Tower of London was administered to assess planning ability. The measure of interest was the number of items correctly solved within 60 seconds.²² 

Motor outcome was determined by using the Movement Assessment Battery for Children-II. A total score and scores for manual dexterity, aiming and catching, and balance tasks were obtained. A normative mean of 10 applies to all scales (SD = 3).²³ 

Data were analyzed by using SPSS Statistics for Windows, Version 23 (IBM SPSS Statistics, IBM Corporation). Baseline characteristics of participating children were compared with those lost to follow-up. Statistical tests used were independent t test, Mann-Whitney U test, χ² test, and Fisher’s exact test. Associations between the various neurodevelopmental outcomes and the total score on the MOS-R and with the subscales were calculated by using linear regression analysis. The subscales FMs, observed movement patterns, observed postural patterns, and movement character were analyzed as normal versus the remainder and coded as 1 or 0, respectively. The subscale age-adequate repertoire was analyzed based on the 3 categories “present,” “reduced,” and “absent” and coded as 2, 1, or 0, respectively. To correct for multiple testing, a false discovery rate of 5% was applied. Multivariable linear regression analysis was used when covariates (gestational age, z scores of birth weight, presence of white matter injury, and social status) were incorporated.

At 8 years, 78 of 97 (80%) of those with general movements at 3 months from the initial cohort participated in neurodevelopmental follow-up assessments. There was evidence that children who were assessed at 8 years had a higher birth weight than those who were not but little evidence of a difference in proportions who were extremely low birth weight between the groups. (Table 1). Furthermore, there was evidence that participating mothers more often received antenatal corticosteroids than nonparticipating mothers. The was little evidence for differences in other patient characteristics between groups. Follow-up assessments were performed at a mean corrected age of 8.0 (0.7 SD) years.

Most children had normal FMs, a higher number of normal than abnormal observed movement patterns, higher number of normal than abnormal observed postural patterns, and smooth and fluent movement character, but only a minority had an age-adequate repertoire. (Table 2). The median MOS-R was 23.5 (25th and 75th percentile: 23.0, 28.0).

Scores on neurodevelopmental tests are presented in Table 3. Four children diagnosed with CP earlier in childhood were unable to complete all tests because of their physical impairment.

There was strong evidence for positive associations between a higher score on the MOS-R itself, as well as on all of its subscales, with better scores for all DAS-II composites including verbal, nonverbal, spatial reasoning, and General Conceptual Ability scores (Fig 2). After excluding 4 children with CP, the evidence for all associations remained except for those between observed postural patterns and verbal and nonverbal reasoning (Supplemental Table 4). When adjusted for covariates (ie gestational age, z scores of birth weight, presence of white matter injury, and social status), the evidence for positive associations remained strong, except for the association between the subscale observed postural patterns and verbal and nonverbal reasoning (Fig 2).

For a higher MOS-R, as well as for higher scores on observed movement patterns, there was strong evidence for associations with better sustained and selective attention (Fig 3). For the other MOS-R subscales, results were more heterogeneous. There was strong evidence that children who had normal FMs in infancy had better sustained attention than their peers in whom FMs had been absent, but no evidence for differences in selective attention was found. Furthermore, evidence was found that better performance on the age-adequate repertoire and observed postural patterns subscales were associated with higher scores for selective attention but not for sustained attention. After excluding children with CP and after adjusting for covariates, evidence for the aforementioned associations remained (Supplemental Table 4; Fig 3).

There was strong evidence for positive relations between the MOS-R and all its subscales except observed postural pattern with verbal memory and verbal working memory (Fig 4). When children with CP were excluded, the evidence weakened for the associations between the quality of FMs and verbal working memory as well as observed movement patterns and verbal working memory (Supplemental Table 4). After adjusting for covariates, the associations between the quality of FMs and both memory test scores weakened (Fig 4).

There was evidence that higher scores on the subscales of observed movement patterns and movement character were related to better performance on the spatial planning and behavioral inhibition task (Fig 5). There was little evidence for associations of the MOS-R, FMs, age-adequate repertoire, or observed postural patterns subscales with performance on the spatial planning and behavioral inhibition task, before and after excluding children with CP, and after adjusting for covariates (Supplemental Table 4; Fig 5).

There was strong evidence that a higher MOS-R, presence of normal FMs, presence of an age-adequate repertoire, and a smooth and fluent movement character were associated not only with better total motor performance but also with its components of manual dexterity, aiming and catching, and balance (Fig 6). After excluding children with CP and after adjustment for covariates, the strength of the evidence for the relationships remained strong (Supplemental Table 4; Fig 6).

In this study, we demonstrate that the early motor repertoire ∼3 months’ corrected age is strongly associated with many areas of neurodevelopment at 8 years in children born <30 weeks’ gestational age, including cognition, attention, working memory, executive function, and motor function. It is consistent with findings of previous follow-up measurements in the same cohort that studied the association between FMs only and neurodevelopmental outcome up until 4 years. Unique to the current report is that it extends those positive associations to aspects of the MOS-R other than just FMs, and also into school-age.

Better performance on all subscales of the MOS-R, as well as the total MOS-R, were associated with higher scaled scores for general cognition at 8 years (eg, children with normal FMs had higher scores by 17 to 25 points compared with children who did not have normal FMs). In our cohort at the 2- and 4 year follow-up time points, group differences for these scaled scores were only 7.4 (95% confidence interval [CI]: 0.9–13.9) and 14.3 (95% CI: 5.1–23.9), respectively.⁹  This widening group difference might be attributed to the ongoing emergence of specific cognitive skills. In addition, it should be noted that at 2 years, cognition was tested using the Bayley Scales of Infant Development-III, which is known to overestimate neurodevelopmental performance.²⁴ 

We found evidence that selective and sustained attention were associated with the MOS-R and various subscales. Researchers in 2 studies who addressed the same associations in preterm and healthy term infants did not provide any conclusive evidence.^25,26  Further research is needed to identify associations with attention in other groups of infants.

Better immediate and working memory were associated with a higher MOS-R and higher scores on all subscales, except observed postural patterns. This is consistent with findings of Grunewaldt et al, who found that extremely low birth weight children with an abnormal movement character in infancy had a poorer working memory at 10 years compared with those who had a normal movement character.²⁷ 

Evidence was found that better performance on the spatial planning and behavioral inhibition task was associated with higher scores for observed movement patterns and movement character. Compared with the other neurodevelopmental domains investigated in our study, this subdomain of executive function was less associated with the early motor repertoire. Research into associations of early motor repertoire with other domains of executive function is required.

Favorable motor performance was strongly associated with a higher MOS-R and higher scores on most subscales. Our findings are consistent with those of Bruggink et al, who reported that in preterm children, the combination of normal FMs with an abnormal movement character increases the risk for developmental coordination disorder.²⁸  Fjørtoft et al came to a similar conclusion on the basis of a study in infants who were at high-risk for poor neurodevelopment. They also found that a poor motor outcome could be identified by an abnormal movement character in the presence of normal FMs at 14 weeks’ corrected age.²⁹ 

Although group means for the whole cohort are close to expected values, they are performing worse than Australian children who were not born preterm. When we assessed the cohort at 4 years of age, they were 6 to 10 points below term-born children in the control group on DAS-II composite scales.¹⁸  The reductions in cognitive scores for those with abnormalities on the GMA in the current study put them further into impaired ranges compared with the majority of children in Australia, and hence our findings are clinically important.

Most associations remained strong after excluding 4 children with CP and after adjusting for perinatal and social factors, which implies that the associations between the early motor repertoire and neurodevelopment in VP children are robust.

Our findings may be explained by neuronal changes occurring in infancy. Approximately 2 to 3 months’ corrected age, neuronal activity of the cortex, cerebellar cortex, and basal ganglia increases markedly.³⁰  At the same time, the early motor repertoire with age-specific spontaneous movements and postures emerges. This early motor repertoire is considered to reflect the integrity of the central nervous system. Based on that, any disruption to the central nervous system may result in abnormalities in the early motor repertoire.^6,31  Because VP infants are at risk for perinatal brain alterations such as white matter injury that often results in poor neurodevelopment,^13,32  studying their early motor repertoire may help in predicting their neurodevelopmental outcome.

The broad range of neurodevelopmental domains that were tested in childhood, using validated and normed tests, was a strength of our study. The follow-up was ∼80%, which was high considering the infants were initially recruited at birth with no school-age follow-up planned. A limitation is the inability to account for all factors influencing and interfering with neurodevelopment up until 8 years. However, we were able to allow for some important perinatal variables and the child’s social risk status.

Favorable early motor repertoire at 3 months’ corrected age is strongly associated with better neurodevelopment at 8 years in VP children. These findings indicate that the early motor repertoire may be useful in identifying infants at risk for poor neurodevelopment.

We acknowledge Merilyn Bear, research nurse, who has coordinated recruitment and follow-up of this cohort.

CI

confidence interval

CP

cerebral palsy

DAS-II

Differential Ability Scale

FM

fidgety movement

MOS-R

motor optimality score-revised

VP

very preterm