Potharst et al.1 report an interesting study evaluating a range of preschool age executive functions in a large group of very preterm children against a term-born comparison group. As in many other studies, they show significant differences in a whole range of functions that underpin school attainment and behaviour, as well as interaction with learning. These important areas of function are highly interrelated. Trying to tease out these processes is important because interventions that access and lead to improvements in these functions should produce generalizable benefits for the individual child. That is the holy grail of outcomes research relating to preterm birth, but one that has been elusive. Early childhood interventions ought to work, but in practice show variable benefit in outcomes and none has been confirmed as long-lasting. None has really been targeted within preterm populations at particular high risk. Success here is important as delivering such interventions is expensive, in addition to the considerable financial and resource costs attributable to preterm birth. The educational system is being continually stretched as survival at the lowest gestations increases and there is an increasing willingness to intervene in extremely low gestational age births in many countries.

The effect sizes revealed by studies of executive tasks are highly dependent on the age at which they are assessed and the gestational age of the cohort.2 Sensibly, Potharst et al. evaluate a wide spectrum of functions at an age when most show a large effect size, and then try to determine the key impairments. They use principal component analysis to derive four groupings, outside of which sit working memory deficits. This is an interesting finding as it resonates with other work and has been the subject of interventional trials in preterm children (unpublished) and other groups, e.g. attention-deficit–hyperactivity disorder.3 These studies are difficult to do because recruitment is essentially difficult and targeting critical. Those children who will fail at school and benefit from such interventions are those often lost to follow-up.

Most such studies include a whole population of preterm children. Many preterm children perform well in the classroom setting, so why apply such interventions to them? Studies such as this help to focus on which areas we need to target and determine those ‘at risk’. In this present study those who were very growth-restricted at birth and those with bronchopulmonary dysplasia are clearly at risk. What is it about these markers that confer such outcomes?

With the current state of knowledge, preventing progressive brain injury following fetal growth restriction seems challenging. One trial failed to show differences4 and another is on the way, but neuroprotection for these children seems to be far off and early detection and treatment earlier in pregnancy is probably necessary.

Bronchopulmonary dysplasia seems a reasonable risk factor – how it is mediated is more difficult to say. These children have the most complex neonatal courses, are exposed to hypoxia, often have associated brain injuries, are fed later and have greater nutritional deficits, have poorer brain and somatic growth, and are at greater risk for sepsis and inflammation – all of which are putative causal pathways for the ‘encephalopathy of prematurity’.5

So where to go from here? Can we identify these problems earlier in infancy and use them as key biomarkers on which to base more individualized intervention? Can we identify the important neonatal mediators of these subtle changes in brain structure and organization, and intervene there?

Developmental research to target executive function is required and needs multidisciplinary input to succeed. Several funders are keen on this area as it benefits patients and is truly experimental medicine. Very preterm children at preschool age deserve close assessment and stratification of risk, and better interventions are clearly needed. Follow-up should not stop at 2 years of age simply because there are no major issues with development!


  1. Top of page
  2. Acknowledgements
  3. References

NM receives part funding from the Department of Health’s NIHR Biomedical Research Centre’s funding scheme at UCLH/UCL.


  1. Top of page
  2. Acknowledgements
  3. References
  • 1
    Potharst ES, Van Wassenaer-Leemhuis AG, Houtzager BA, et al. Perinatal risk factors for neurocognitive impairments in preschool children born very preterm. Dev Med Child Neurol. DOI: 10.1111/dmcn.12018.
  • 2
    Mulder H, Pitchford NJ, Hagger MS, Marlow N. Development of executive function and attention in preterm children: a systematic review. Dev Neuropsychol2009; 34: 393421.
  • 3
    Klingberg T, Fernell E, Olesen PJ, et al.Computerized training of working memory in children with ADHD – a randomized, controlled trial. J Am Acad Child Adoles Psychiatry2005; 44: 17786.
  • 4
    Walker DM, Marlow N, Upstone L, et al.The growth restriction intervention trial: long-term outcomes in a randomized trial of timing of delivery in fetal growth restriction. Am J Obstet Gynecol2011; 204: 34.
  • 5
    Volpe JJ. Brain injury in premature infants: a complex amalgam of destructive and developmental disturbances. Lancet Neurol2009; 8: 11024.