Risk and resilience in children born preterm : cognitive and executive functioning at 5 1/2 years of age

• We investigated the intellectual outcome of two cohorts of preterm children, born from 1988 to 1993 and 1994 to 1997, respectively. A population-based follow-up study (the Stockholm Neonatal Project) included 182 children with a birth weight of 1500 g or less (very-low-birthweight: VLBW) and a control group of 125 children born healthy at term who were examined with the Wechsler Preschool and Primary Scale-Revised (WPPSI-R) and a neuropsychological test battery (Nepsy) at 5½ years of age ((paper I-IV). Paper V includes the results from 11 preterm children treated according to the Newborn Individualized Developmental Care and Assessment Program (NIDCAP) and a control group of 15 likewise preterm children who had a conventional care at the NICU. The test design was the same in the two studies. The WPPSI-R results of the VLBW children fell well within the normal range: WPPSI-R full scale (FSIQ) 95.7, verbal subscale (VIQ) 99.9 and 91.6 for the performance subscale (PIQ).The term born control group had significantly better results than the VLBW group. This could partly be attributed to the greater variability of the VLBW group, with a larger proportion falling in the lower area of the IQ distribution, specifically for PIQ. Paternal education was equal in the two groups and was found to be the single most important predictor of IQ for all children. The frequency of bilingualism was the same in the VLBW and control groups and was negatively associated with verbal and full scale IQ, but to a minor degree. Visual impairment was inversely associated with all three IQ scores. The severe form of retinopathy of prematurity (ROP), visual impairment and intrauterine growth retardation turned out to be negatively related to FSIQ and PIQ, while paternal education acted as a protective factor. With a small sample of the VLBW and control children we used diffusion tensor imaging to show the white matter microstructure, as preterm birth frequently involves white matter injury affecting long-term neurological and cognitive outcomes. We found that the preterm group had lower fractional anisotropy values in the posterior corpus callosum and bilaterally in the internal capsules. In the posterior corpus callosum, this difference may partially be related to a difference in white matter volume between the groups. The analysis failed to indicate a group difference in the axonal organization. These results are in agreement with previous diffusion tensor imaging findings in newborn preterm children and indicate that ex-preterm children with attention deficits have white matter disturbances that are not compensated for, or repaired, before 11 years of age. To explore whether children born preterm have deficient executive functions (EF) in comparison with children born at full term, we analysed the results from several of the Nepsy tests. We found that the controls surpassed the VLBW children on tests of EF, even after controlling for intelligence (IQ). EF was associated with retinopathy of prematurity (ROP), and with visual impairment as a whole. In both groups, girls surpassed boys on test outcome .We conclude that it is possible to analyse executive functions already in pre-school age. Preterm infants with chronic lung disease (CLD) had impaired cognitive development and poorer eye-hand coordination at 10 months of age. We examined whether this effect of CLD persisted until school age and whether the severity of CLD affected the outcome. The group included 32 VLBW without known brain insult and 28 controls. The groups did not differ significantly in cognitive outcome;. FSIQ of 94.4 and 99.1, VIQ of 99.6 and 101.5, and PIQ 90.9 and 96.7 respectively. Similarly, no difference was found in tests of eye-hand control. The children with the most severe form of CLD had significantly lower PIQ,(84.8), and FSIQ, 87.6 and worse visual-motor performance than the controls. CLD grade III, together with visual impairment had a significant relation to IQ. NIDCAP was evaluated as a positive alternative to conventional care of very preterm infants. We studied the 5 years development in children treated and there were no significant differences between the groups in FSIQ: 93.4 vs. 89.6; VIQ 93.6 vs. 93.7 or PIQ 94.3 vs. 86.3 Overall, the differences in survival, attention and cognition were in favour of the NIDCAP children. Our trial suggests a positive impact by NIDCAP on attention behaviour at preschool age, but the small samples, which implies a low power, calls for caution in interpreting our findings. Larger trials in different cultural contexts are warranted.

Nyckelord

Preterm birth, intelligence, chronic lung disease, executive functions, MRI, NIDCAP

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