In this group of VPT young adults, we have demonstrated an increase in neurological abnormalities compared to a term‐born control group. Total, primary, and integrative abnormalities were all increased relative to the term group. The VPT group also had increased rates of left or mixed handedness. These results confirm that neurological signs associated with VPT birth persist into adulthood.
The pattern of individual neurological signs may suggest links to underlying pathologies. For example, eye movement abnormalities have been reported in association with periventricular leukomalacia and damage to the optic radiation.18
Mirror movements were more common in the VPT group, and are an indication of abnormalities of sensorimotor and interhemispheric interaction. They are a normal finding in young children and disappear with maturation, as well as being associated with genetic conditions (Klippel‐Feil syndrome, X‐linked Kallman syndrome) or occurring as an isolated finding. Mirror movements are also seen after brain damage in early life19
and occur more frequently in left handers.20
The anatomical basis for bilateral motor encoding is still debated and may depend on the aetiology of the mirror movements. Maegaki et al21
studied two individuals with congenital mirror movements and concluded that there is bilateral activation of sensorimotor cortex. Others have proposed the existence of extra ipsilateral corticospinal pathways.22
Still others have proposed that both mechanisms may be acting in the same individuals.19
The corpus callosum has also been implicated,20
the theory being that maturational myelination of the corpus callosum allows transcallosal inhibition of the ipsilateral pathways.
The increase in mirror movements in VPT individuals shown here may thus reflect a delay in neurological maturation. The normal mirror movements of childhood would be expected to disappear by 10 years of age,23
so this would imply a significant motor delay in our VPT 18–19 year olds. If the disappearance of normal mirror movements depends on corpus callosum myelination, it may be that VPT individuals are experiencing a delay in this process. There is considerable evidence that perinatal white matter lesions, in particular periventricular leucomalacia, result in delayed myelination.24,25
Additionally, the corpus callosum has been shown to be both structurally26
abnormal in VPT individuals.
Gaze impersistence, also increased in this VPT group, is another sign that is associated with callosal pathology. Heilman and Adams28
reported the onset of gaze impersistence after callosal transection (for treatment of epileptic seizures) in a patient with a pre‐existing right hemisphere lesion. Bae and Pincus29
found that periventricular white matter damage (in term‐born adults) was associated with abnormalities of visual tracking and with three‐step motor sequencing. Gaze impersistence has also been attributed to disordered CNS maturation and occurs with increased frequency among patients with early onset schizophrenia.30
The VPT group also had increased rates of right‐left (R‐L) confusion, which classically occurs in Gerstmann's syndrome (along with finger agnosia, agraphia, and acalculia) in association with lesions of the dominant angular gyrus.31
R‐L confusion is also, of course, an everyday phenomenon recognised by many people who do not have a neurological condition and is reported to be more common in men and in left handers.32
It is possible that this sign also represents a deficit of interhemispheric information transfer.
We also found an increased rate of neurological signs in the term males compared to term females. This may reflect a general increased susceptibility to neurodevelopmental insult in boys, or that girls are more developmentally robust. There is evidence for a male disadvantage, for example, perinatal mortality for very low birth weight (VLBW) boys is significantly greater than for girls, and surviving boys have a higher risk of adverse outcomes.33,34
Our results did not show a clear difference in neurological outcome between male and female VPT 18 year olds; in fact, both groups were equally impaired. We therefore cannot rule out the possibility that the difference between male and female controls reflects a bias in our term comparison group. Such a bias would be likely to have reduced the chance of finding differences between the two groups. It should also be pointed out that the term‐born comparison group was made up of individuals from two sources: a birth cohort from UCLH and individuals recruited at age 18 from press advertisements.
In this group of VPT young adults, we found associations between neurological dysfunction and gestational age, and a weak association with birth weight. This is consistent with Foulder‐Hughes and Cooke12
who reported weak correlations between childhood neurological abnormality and birth weight and gestational age. Perinatal indicators of hypoxia and acidosis showed no significant associations with neurological abnormalities in any domain. This is surprising, in that hypoxia/ischaemia is often assumed to be the cause of many of the brain lesions associated with preterm birth. It may be that the lesions which cause neurological compromise are those that affect white matter (such as periventricular leukomalacia) and are not adequately described by perinatal Apgar scores or blood pH.
There were strong associations between integrative neurological abnormalities and full scale, verbal, and performance IQ at 18 years of age in the VPT group. This is in agreement with the large body of literature that suggests that neurological dysfunction, even if mild, is associated with reduced academic performance. It suggests that neurological signs, possibly of relatively trivial importance in themselves, are potentially markers of a real cognitive disability. Olsen et al35
found that “minor neurodevelopmental dysfunction” in preterm children was associated with reduced neuropsychological performance. Sullivan and McGrath36
suggested that early motor delay contributes to later cognitive disability and refer to this as “hidden morbidity”. Several studies have found that neurological signs in LBW children are associated with reduced IQ and specific learning disabilities.37,38
We found a relatively high rate of neurological deviance in the term control group. However, estimates of rates of neurological signs in the normal adult population vary widely from 26%30
and rates of neurological abnormalities increase with age. In young people there is generally a higher rate of neurological signs, for example Kennard40
reported neurological signs in 60% of a group of 72 normal children. Buchanan and Heinrichs,14
using a very similar rating scale to that used here, found rates of abnormalities very similar to those in our study in a control group of 50 healthy adults.
In comparing the frequencies of individual neurological signs between the groups (table 4), we have not made a statistical adjustment to compensate for multiple comparisons. It thus remains possible that some of these findings are due to chance, so caution should be used in their interpretation. For example, the difference between left and right sides for signs such as cranial nerve palsy and mirror movements may be indicative of chance effects. However, most individual signs are found to be more frequent in the VPT group, regardless of the level of statistical significance.
Another potential weakness of this study is the reliability of assessments of neurological signs.41
Inter‐rater reliability has been shown to be poor for rare signs, for example those occurring in less than 10% of subjects.13,14
Reliability has been shown in various studies to be lowest for sensory signs,42
and primitive reflexes (grasp, suck, snout).30
Summing the individual scores, as we have done here, improves their reliability.42
A further limitation of this study is the relatively low follow‐up rate of the VPT group (48%). This drop out rate is a problem common to many long term follow‐up studies12
and may limit the generalisability of our findings. Additionally, the VPT group was 7 months younger than the term group, and it is not clear how much this might have contributed to group differences. It is certainly known that structural brain changes continue into young adulthood and beyond, including progressive changes in relative amounts and distribution of grey and white matter43
and in the size of the corpus callosum.44
However, little is known about changes in neurological signs over this time.