Attention development following preterm birth and its relationship to stress and white matter microstructure

Abstract

Preterm infants, those born before 37 weeks of gestation, are at increased risk for a range of neurocognitive difficulties, including problems with attention, but outcomes are extremely heterogenous. Understanding the profile of attention difficulties and the mechanistic underpinnings of attention development following prematurity may go some way towards early identification of vulnerable infants. Altered development of the stress response system is one candidate mechanism since preterm infants experience a high burden of early life stress and have dysregulated stress hormone levels. In addition, the developing brain is vulnerable to the effects of stress with consequences for brain structure, and preterm birth is strongly associated with generalised dysconnectivity of white matter. I hypothesised that difficulties with attention in preterm infants are associated with variances in the stress response system which may relate to alterations in white matter microstructure. Parent perspectives are important for guiding this and future research and practices surrounding outcomes of prematurity.

I reviewed the recent literature measuring life course attention outcomes following preterm birth. Parent perspectives and preferences for research were captured by a survey including 148 parents of preterm children between the ages of 0 and 12 years. A separate sample of 53 preterm and 67 full-term infants were recruited and assessed at 9 months of age (corrected age for the preterm group). Infants participated in two eye-tracking tasks of attention that measured switching, disengagement and sustained attention. Infants were exposed to a socio-emotional stressor, the still-face procedure. Recordings of this were behaviourally coded for infant negative affect and self-comforting behaviours. Saliva was collected from a subset (20 preterm, 24 term infants) at three timepoints: pre-, 20- and 30-minutes post stressor and cortisol concentrations were quantified. Diffusion MRI data was collected at term equivalent age.

The literature revealed that attention is commonly but not consistently impaired across the life course and a clear preterm attention profile could not be delineated from the available literature. Survey findings confirmed that attention is a priority area for parents of preterm children. Findings from a cohort of 9-month-old infants revealed no significant differences in attention switching, disengagement or sustained attention between full-term and preterm infants. There was no significant difference in duration of self-comforting behaviours between preterm and term infants, but preterm infants displayed significantly less negative affect. Salivary cortisol was significantly higher in the preterm compared to the term group 30 minutes post stressor, though findings were no longer significant after adjusting for covariates. Greater negative affect was correlated with higher cortisol concentration 30 minutes post stressor in the full-term but not the preterm group. Attention was not associated with cortisol stress response though it was associated with emotion regulation in preterm infants and with white matter microstructure in term infants.

Findings suggest that prematurity does not have a large effect on visual attention abilities in 9-month-old preterm infants. Altered functioning of the stress response system in preterm infants manifests as reduced emotion regulation, less efficient cortisol recovery and a lack of synchrony between biological and behavioural stress response. However, a lack of association between sustained attention and measures of cortisol indicates that disruptions to the stress response system do not directly underlie attention development. Nonetheless, associations between emotion regulation and attention indicate that emotion regulation could be a potential marker for stratification and target for intervention. Attention was significantly associated with brain microstructure in the term but not the preterm group suggesting that these relationships also warrant further investigation such as mediation analyses to determine whether these relationships are causal.