Cognitive Development Trajectories in Preterm Children With Very Low Birth Weight Longitudinally Followed Until 11 Years of Age

Background: There is a high prevalence of cognitive dysfunction in very low birthweight (500–1250 g) infants (VLBW). Understanding long-term risk factors associated with cognitive development in preterm children requires longitudinal characterization. Thus, follow-up evaluations, including identification of risks and resilience influences–are important to promote health and cognitive abilities of children born preterm.Aim: To examine changes in cognitive development from birth until 11 years of age in preterm children with very low birthweight.Methods: 24 VLBW infants, at the Karolinska University Hospital, Stockholm, were assessed with regards to cognitive functioning at three times during development at 18 months, 5 and 11 years of age using standardized tests. Longitudinal data were analyzed using Generalized Estimating Equation (GEE) univariate and multivariate models.Results: The follow-up rate was 100%. Level of cognitive functioning at 18 months and at 11 years was similar. Females had higher cognitive scores than males at all three timepoints. We found that intraventricular hemorrhage (IVH) and prolonged invasive ventilatory support (>7 days) had a negative effect on cognitive functioning. Higher levels of parental education had a favorable influence on cognitive functioning over time.Conclusion: Level of cognitive development at 18 months was highly predictive of level of cognitive function at 11 years of age and differences in assessment scores between male and female VLBW infants persisted. Additional longitudinal studies, performed before school entry and across childhood, are needed to further elucidate the cognitive trajectories of preterm children

Risk and resilience in children born preterm : Cognitive and executive functioning at 5½ 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

Preschool outcome in children born very prematurely and cared for according to the Newborn Individualized Developmental Care and Assessment Program (NIDCAP)

Aim: Care based on the Newborn Individualized Developmental Care and Assessment Program (NIDCAP) has been reported to exert a positive impact on the development of prematurely born infants. The aim of the present investigation was to determine the effect of such care on the development at preschool age of children born with a gestational age of less than 32 wk. Methods: All surviving infants in a randomised controlled trial with infants born at a postmenstrual age less than 32 wk (11 in the NIDCAP group and 15 in the control group) were examined at 66.3 (6.0) mo corrected for prematurity [mean (SD)]. In the assessment we employed the Wechsler Preschool and Primary Scale of Intelligence-Revised (WPPSI-R) for cognition, Movement Assessment Battery for Children (Movement ABC) for motor function, subtests of the NEPSY test battery for attention and distractibility, and the WHO definitions of impairment, disability and handicap. Exact binary logistic regression was employed. Results: There were no significant differences between the intervention group in Full-Scale IQ 93.4 (14.2) [mean (SD)] versus the control group 89.6 (27.2), Verbal IQ 93.6 (16.4) versus 93.7 (26.8) or Performance IQ 94.3 (14.7) versus 86.3 (24.8). In the NIDCAP group 8/13 (62%) survived without disability and for the children with conventional care this ratio was 7/19 (37%). The corresponding ratios for surviving without mental retardation were 10/13 (77%) and 11/19 (58%), and for surviving without attention deficits 10/13 (77%) and 10/19 (53%). Overall, the differences were not statistically significant, although the odds ratio for surviving with normal behaviour was statistical significant after correcting for group imbalances in gestational age, gender, growth retardation and educational level of the parents. Conclusion: Our trial suggests a positive impact by NIDCAP on behaviour at preschool age in a sample of infants born very prematurely. However, due to problems of recruitment less than half of the anticipated subjects were included in the study, which implies a low power and calls for caution in interpreting our findings. Larger trials in different cultural contexts are warranted

Visual-motor functions are affected in young adults who were born premature and screened for retinopathy of prematurity.

AIM: To assess visual-motor integration in young adults previously included in a prospective study on the incidence of retinopathy of prematurity (ROP). METHODS: The study encompassed 59 preterm individuals, born 1988-1990, with a birth weight ≤1500 g, and 44 full-term controls, aged 25-29 years. Ophthalmological examination, including visual acuity and contrast sensitivity, and the Beery Visual-Motor Integration (VMI) with supplemental tests of visual perception and motor coordination, were performed. A short questionnaire was filled in. RESULTS: The preterm individuals had significantly lower scores than the controls in all VMI tests, median values and interquartile ranges: Beery VMI 87 (21) vs 103 (11), visual perception 97 (15) vs 101 (8) and motor coordination 97 (21) vs 102 (15), respectively. Within the preterm group, no correlations were found between the VMI tests and ROP, gestational age, birth weight or visual acuity. Contrast sensitivity was correlated to visual perception. Neurological complication at 2.5 years was a risk factor for lower scores on Beery VMI. The preterm subjects reported six times as many health problems as compared to the controls. CONCLUSION: Being born preterm seemed to have life-long effects. This study shows that visual-motor integration was affected in young adults born preterm

Average 2.5-year neurodevelopmental test results in children born very preterm did not rule out cognitive deficits at 6.5 years of age

Aim The aim of the study was to investigate cognitive outcomes at 6.5 years in children born very preterm, in relation to neonatal characteristics and 2.5-year neurodevelopment. Methods A prospective cohort, with gestational age 22.3-31.9 weeks, born 2004-2007, were examined at 2.5 years with the Bayley Scales of Infant and Toddler Development (Bayley-III) (n = 100) and at 6.5 years with the Wechsler Intelligence Scales (n = 91). Results Neonatal factors independently related to 6.5-year outcome were gestational age, retinopathy of prematurity and treated persistent ductus arteriosus. The Bayley-III cognitive scores explained only 44% of the Full-Scale Intelligence Quotient result at 6.5 years, and 22% of the children had Wechsler index results below −1 SD, indicating cognitive impairment, after average test results at 2.5 years. The relative risk to score below −1 SD on the Full-Scale IQ was 2.83 (95% CI 1.45-5.53) in children with gestational age below 28 weeks and 2.22 (95% CI 1.18-4.17) at gestational age 28-31 weeks. Conclusion Very preterm infants born in the 2000s had increased risks for impaired cognition at 6.5 years, but individual predictions based on neonatal risks and 2.5-year test results were not enough to identify all high-risk children

Neonatal magnetic resonance imaging and outcome at age 30 months in extremely preterm infants

OBJECTIVE: To examine associations between brain white matter abnormalities, including diffuse excessive high signal intensities, detected on neonatal magnetic resonance imaging (MRI) with neurodevelopmental outcome at age 30 months. STUDY DESIGN: This was a prospective, population-based study of infants born at <27 weeks gestation (n=117) undergoing conventional MRI at term equivalent age (n=107). At age 30 months corrected, 91 of the preterm infants (78%) and 85 term-born controls were assessed with the Bayley Scales of Infant and Toddler Development, Third Edition (BSID-III). RESULTS: Cerebral palsy (CP) was present in 7% of the preterm group. On the BSID-III, mean composite scores were 96±9.5 for the cognitive scale, 97±14 for language scales, and 103±15 for motor scales, all within the normal range for age. Compared with the term-born controls, however, the preterm infants did not perform as well on all 3 scales, also when MRI was normal. Significant associations were seen between moderate to severe white matter abnormalities and CP (P<.001). The presence of diffuse excessive high signal intensities was not associated with performance on the BSID-III or with CP. CONCLUSION: This 3-year cohort of extremely preterm infants had low rates of major brain injury and impaired outcome. Neonatal MRI provides useful information, but this information needs to be treated with caution when predicting outcome

Social variables predict gains in cognitive scores across the preschool years in children with birth weights 500 to 1250 grams

OBJECTIVE To determine the extent that social variables influence cognitive development of very low birth weight (VLBW) infants across the preschool years. STUDY DESIGN Participants were VLBW (500-1250 g) children enrolled in the Caffeine for Apnea of Prematurity randomized trial between 1999 and 2004. We investigated the relationships between 4 potential social advantages: higher maternal education, higher paternal education, caregiver employment, and 2 biologic parents in the same home--and gain in cognitive scores. Cognitive assessments were performed at the corrected ages of 18 months (Mental Development Index score on the Bayley Scales of Infant Development II) and 5 years (Full Scale IQ on the Wechsler Preschool and Primary Scale of Intelligence III). Cognitive gain was computed by subtracting each individual 18-month Mental Development Index score from the corresponding Full Scale IQ at 5 years. RESULTS Data were available for 1347 children. Mean (SD) cognitive scores were 90.8 (15.7) at 18 months and 98.9 (14.5) at 5 years. Multivariable regression showed that higher maternal education, higher paternal education, and caregiver employment had independent and additive effects of similar size on cognitive gain (P < .001); the mean cognitive gain between 18 months and 5 years increased by 3.6 points in the presence of each of these advantages. When all 3 were present, cognitive scores improved on average by 10.9 points compared with children without any of these advantages. CONCLUSION In VLBW children, a count of 3 social advantages strongly predicts gains in cognitive scores across the preschool years