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Studies of global cognition in children born very preterm have been consistent in showing a greater risk of cognitive impairment with decreasing GA and

birthweight (Koller, Lawson, Rose, Wallace., & McCarton, 1997; Laptook, O'Shae, Shankaran, Bhaskar, & NICDH Neonatal Network, 2005; Vohr et al., 2000). Studies of executive function appear to replicate this trend. For example, when comparing children born ELBW (<750g) and children born VLBW (750-1500g) to a group of full term class peers at age 16 years, Taylor et al. (2004) found that children born

ELBW scored significantly lower than the full term group on several

neuropsychological measures. These included CANTAB measures of spatial working memory, planning and vigilance (Fray et al., 1996), the Rey Complex Figure

(Bernstein & Waber, 1996 ) and the Contingency Naming Test (Anderson, Anderson, Northam, & Taylor, 2000), a measure of set-shifting. In contrast, there were no significant differences between the performance of children born VLBW and full term, although visual inspection of the reported mean scores indicated a linear pattern, whereby the VLBW group achieved scores slightly lower than children in the full term group. This suggests a gradient effect, whereby lower birthweight may be associated with greater executive function difficulties.

There has been less evidence for a within-group effect of continuous measures of gestation and birthweight when only children born very preterm are considered (Anderson et al., 2004; Curtis et al., 2002; Rose & Feldman, 1996). For example, Rose and Feldman (1996) reported no correlation between birthweight or gestational age and scores on various measures of spatial working memory within a group of 11 year old children born VLBW. Similarly, although Anderson et al. (2004) found that there were some significant differences in the executive function performance of children born extremely preterm (<750g/<26 weeks GA) compared with those born at higher gestational ages (26-27 weeks GA, 750-1000g), there were only weak correlations between gestational age and these outcome measures (r=.001-0.19). One possible explanation for these findings may be the large variation in medical

experiences for children born very preterm. When they are considered as a group, it may be that gestation or birthweight acts as a good proxy for later impairments but further understanding of individual differences warrants a closer inspection of the impact of various individual clinical experiences within this group of children.

birth on later executive function is gender. Male gender is associated with a greater risk of very preterm birth, as well as higher mortality and morbidity (Elsmen, Pupp, & Hellstrom-Westas, 2004; Ingemarsson, 2003; Pollack & Birnbacher, 2004). Several studies have documented poorer cognitive and neurodevelopmental

outcomes in males born very preterm when compared with their female counterparts (Laptook et al., 2005; Marlow, 2004; Whitaker et al., 1997). In studies that have examined gender in relation to attention and executive function, there has also been some indication that males are at more risk than females from an early age (Elgen et al., 2004; Marlow et al., 2007; Martel, Lucia, Nigg, & Breslau, 2007; McGrath et al., 2005). Thus, there is a possibility that male gender interacts with the level of

prematurity or medical risk that children are exposed to, but these findings are in need of further investigation.

Added to this, several medical factors, including intrauterine growth restriction (IUGR), intrauterine infection, chronic lung disease (CLD) and respiratory distress, early (<72 hours after birth) or late onset (> 72 hours after birth) sepsis, patent ductus arteriosis (PDA), retinopathy of prematurity (ROP) and necrotising entercolitis (NEC) are associated with very preterm birth and rates of these medical morbidities are known to increase with decreasing gestation (Hack & Fanaroff, 2000).

Definitions of these medical complications are provided in Appendix A. Most of the extant literature relating to very preterm birth and cognitive outcome has considered groups of children born very preterm as homogeneous, with little regard to the different medical experiences that these children and families experience. In studies that have given some consideration to this issue, a common practice is to examine outcome in relation to medical risk indices, which consist of a composite of children’s exposures to neonatal complications (Girouard et al., 1998; Landry, Denson, & Swank, 1997; Laucht, Esser, & Schmidt, 1997). For example, Luciana et

al. (1999) used a composite risk score, summing infection, the degree of ventilation and neurological risk factors (IVH and PVL). This score was predictive of later spatial working memory (r=.36), spatial memory (r=-0.52), and strategy use in problem solving (r=0.36) in a group of children who had been in the NICU after birth. These findings suggest that level of overall illness may be a good marker for later difficulties in executive function.

However, a major limitation of this approach is that it does provide any information as to the specific factors that may make some children more vulnerable to later executive function difficulties. The most that can be concluded is that the sickest, most medically fragile infants are at greatest risk for later difficulties and that the effect of these risk factors is potentially additive. There is a need for the

identification of important constituent factors if findings are to assist in the provision of targeted intervention or the development of specific treatments for these children.

Studies that have examined the influence of specific medical risk factors have shown that very preterm children who experience CLD are more likely to achieve lower scores on standardised cognitive and achievement tests than those who do not (Hack & Fanaroff, 2000; Laucht et al., 1997; McGrath & Sullivan, 2002; Taylor et al., 2004; Vohr et al., 2000). Furthermore, continuous measures of the days that children spend on oxygen or ventilatory support have been shown to predict term neurobehavioural scores (Brown, Doyle, Bear, & Inder, 2006), as well as scores on complex executive function and visuo-spatial measures during childhood (Rose & Feldman, 2000) and adolescence (Taylor et al., 2004). Apart from this, further studies have revealed correlations between NEC, length of stay in hospital (Taylor et al., 2006), ROP (Bohm et al., 2004) and measures of executive function, suggesting that the influence of these clinical complications warrants further exploration.

In response to these medical complications, the modern era of neonatal intensive care has introduced a number of medical advancements; the increased use of antenatal steroids and surfactant therapy has had major repercussions in terms of survival and morbidity (Hack & Fanaroff, 2000; Meadow, Bell, & Unstein, 2003). Less is known about the long term consequences of these medical interventions for cognitive development. Studies to date show that the administration of a single course of antenatal steroids is not associated with impairments in attention and working memory in either children or adults (Dalziel et al., 2005; LeFlore, Salhab, Broyles, Engle, & 2002). Indeed, there is some evidence that antenatal steroids may be associated with better self-regulatory competence in infancy and early childhood (Brown et al., 2006; Clark, Woodward, Horwood, & Moor, In press). However, postnatal steroids may be associated with poorer neurodevelopmental outcomes. Follow-up studies have shown that infants who have received postnatal steroids achieve lower scores on standardised neuropsychological and executive function (NEPSY) measures later in childhood (Laptook et al., 2005; LeFlore et al., 2002; Taylor et al., 2006; Vohr et al., 2000). It is important to note the difficulty in separating the effects of these drugs from the medical risk factors they are designed to treat. Nonetheless, continued investigation into the later developmental outcomes of children treated with them will help to inform medical practice and intervention.

This brief review of literature relating to clinical factors that may increase the vulnerability of children born very preterm to impairments in executive function has highlighted several factors worthy of further evaluation. These include gender, the extent of immaturity and/or growth restriction, the use of ventilation and prolonged oxygen dependence, the infant’s exposure to infection as well as medical treatments administered to these infants. This study will therefore consider a range of clinical risk factors in relation to executive performance.