Background: Children born very preterm are at risk for cognitive deficits and motor impairment. Enhanced protein intake immediately after very preterm birth has been associated with favorable growth and improved neurodevelopment. It is unknown whether increased protein intake after discharge from the hospital affects long-term neurodevelopment. Objective: The primary objective was to assess neurodevelopment from infancy to 8 years in pretermborn children who received either protein-enriched formula (PDF), standard term formula (TF), or human milk (HM) after discharge. The secondary objective was to assess the correlation between outcomes obtained at 24 months corrected age (CA) and at 8 years. Methods: This RCT included 152 children born very preterm (gestational age <= 32 weeks) and/or with a very low birth weight (<= 1500 g) of whom 102 were randomly assigned to receive PDF (n = 54) or TF (n = 48) from term age to 6 months CA. A control group of infants fed HM (n = 50) was also included. Neurodevelopmental outcomes were assessed at 24 months CA (cognitive and motor functioning; n = 123) and at 8 years (estimated Full Scale Intelligence Quotient, visual-motor skills, verbal memory, attention, and motor functioning; n = 76). Results: The PDF and TF groups were not significantly different in neurodevelopmental outcomes. The HM group had a better cognitive score compared with the PDF group: at 24 months CA 92.9 +/- 12.5 vs. 105.2 +/- 18.6, P < 0.001 and at 8 years 98.1 +/- 11.3 vs. 105.8 +/- 9.1, P = 0.017 (P = 0.002 and P = 0.080, respectively, after adjustment for parental educational level). Correlations between outcomes at 24 months CA and 8 years were weak: r = 0.35 and r = 0.37 for cognitive and motor outcomes, respectively. Conclusions: PDF did not improve long-term neurodevelopmental outcomes as compared with TF. However, these results should be interpreted with caution considering the substantial attrition at follow-up. Furthermore, the correlation between outcomes at different ages was weak, emphasizing the need for long-term follow-up of nutritional intervention studies in preterm-born children. (C) 2018 European Society for Clinical Nutrition and Metabolism. Published by Elsevier Ltd. All rights reserved.

Background Increasing numbers of preterm-born children survive nowadays, and improving long-term health and neurodevelopment is becoming more important. Early-life growth has been linked to neurodevelopmental outcomes. We aimed to study whether this association has changed with time. Methods We studied two cohorts of preterm-born children (gestational age ≤32 weeks and/or birth weight ≤1500 g) from 1983 ( n = 708) and 2003–2006 ( n = 138), respectively. We distinguished four early-life growth patterns at 3 months corrected age: appropriate for gestational age (AGA) with or without growth restriction (AGA GR+/AGA GR−), and small for gestational age (SGA) with or without catch-up growth (SGA CUG+/SGA CUG−). Intelligence quotient (IQ), neuromotor function, and behavior were assessed at ages 19 and 8 years, respectively, for the cohorts. Results In the 2003–2006 cohort, less children had early-life GR. In both cohorts, SGA CUG− subjects had unfavorable growth trajectories and neurodevelopmental outcomes (IQ β −6.5, 95% confidence interval (CI) −9.8; −3.2, P < 0.001; neuromotor score β −1.9%, 95% CI −3.2; −0.6, P = 0.005), while SGA CUG+ subjects were comparable to adequately grown subjects. Conclusion Although the incidence of adverse growth patterns decreased between the cohorts, possibly indicating improvements in care over time, the impact of these growth patterns on neurodevelopmental outcomes was not significantly different. Achieving adequate early-life growth may be crucial for improving neurodevelopmental outcomes, especially for preterms born SGA.

BACKGROUND:Very preterm birth has a detrimental impact on the developing brain, including widespread white matter brain abnormalities that threaten efficient sensory processing. Yet, sensory processing difficulties in very preterm children are scarcely studied, especially at school age.AIMS:To investigate somatosensory registration, multisensory integration and sensory modulation.PARTICIPANTS:57 very preterm school-age children (mean age=9.2years) were compared to 56 gender and age matched full-term children.METHODS:Group differences on somatosensory registration tasks (Registration of Light Touch, Sensory Discrimination of Touch, Position Sense, Graphestesia), a computerized multisensory integration task, and the parent-reported Sensory Profile were investigated using t-tests and Mann-Whitney U tests.RESULTS:In comparison to full-term children, very preterm children are less accurate on somatosensory registration tasks, including Registration of Light Touch (d=0.34), Position Sense (d=0.31) and Graphestesia (d=0.42) and show more sensory modulation difficulties (d=0.41), including both behavioral hyporesponsivity (d=0.52) and hyperresponsivity (d=0.56) to sensory stimuli. Tactile discrimination and multisensory integration efficiency were not affected in very preterm children. Aspects of sensory processing were only modestly related.CONCLUSION:Very preterm children show sensory processing difficulties regarding somatosensory registration and sensory modulation, and preserved multisensory (audio-visual) integration. Follow-up care for very preterm children should involve screening of sensory processing difficulties at least up to school age.

Background: Very preterm (VP) children face a broad range of neurodevelopmental sequelae, including behavioral problems. Aim: To investigate prevalence, pervasiveness and co-occurrence of symptoms of attention deficit hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) in school-age children born very preterm. Methods: Using questionnaire and diagnostic interview data, parent and teacher reported symptoms of ADHD and ASD of 57 VP-children (mean age = 9.2 years) were compared with 57 gender and age matched full-term children using t-tests. Intra-class correlation coefficients quantified parent-teacher agreement. Correlation analysis investigated co-occurrence of ADHD/ASD symptoms. ADHD/ASD measures were aggregated using principal component analysis. Regression analyses investigated the contribution of perinatal risk factors, sex and SES to ADHD/ASD symptoms. Results: VP-children showed higher levels of parent and teacher reported attention problems, social impairment and compromised communication skills. Fair to strong agreement was found between parent and teacher reported ADHD and ASD symptoms, indicating pervasiveness of observed difficulties. Co-occurrence of ADHD and ASD symptoms in VP-children was found. Lower gestational age was associated with higher ADHD and ASD symptom levels, male sex with higher ADHD symptom levels and lower SES with higher ASD symptom levels. Conclusion: School-age VP-children show higher levels of ADHD and ASD symptoms, and attention, socialization and communication difficulties in particular. Routinely screening for these problems is recommended in follow-up care.

BackgroundNeurodevelopmental sequelae in preterm born children are generally considered to result from cerebral white matter damage and noxious effects of environmental factors in the neonatal intensive care unit (NICU). Cerebral white matter damage is associated with sensory processing problems in terms of registration, integration and modulation. However, research into sensory processing problems and, in particular, sensory modulation problems, is scarce in preterm children.AimThis review aims to integrate available evidence on sensory modulation problems in preterm infants and children (<37 weeks of gestation) and their association with neurocognitive and behavioral problems.MethodRelevant studies were extracted from PubMed, EMBASE.com and PsycINFO following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Selection criteria included assessment of sensory modulation in preterm born children (<37 weeks of gestation) or with prematurity as a risk factor.ResultsEighteen studies were included. Results of this review support the presence of sensory modulation problems in preterm children. Although prematurity may distort various aspects of sensory modulation, the nature and severity of sensory modulation problems differ widely between studies.ConclusionsSensory modulation problems may play a key role in understanding neurocognitive and behavioral sequelae in preterm children. Some support is found for a dose-response relationship between both white matter brain injury and length of NICU stay and sensory modulation problems.

Tactile defensiveness (TD) is a disturbance in sensory processing and is observed in some children with attention-deficit-hyperactivity disorder (ADHD). TD has been examined in male children with ADHD and in children with ADHD without differentiating by sex. As males and females with ADHD may differ in the clinical expression of the disorder and associated deficits, the aim of this study was to examine sex differences in TD in males and females with ADHD. Non-affected siblings were also examined to investigate familiality of TD. The Touch Inventory for Elementary-School-Aged Children was administered to 47 children with ADHD (35 males, 12 females; mean age 9y 8mo [SD 1y 11mo]), 36 non-affected siblings (21 males, 15 females; mean age 8y 10mo [SD 2y 4mo]), and 35 control children (16 males, 19 females; mean age 9y 5mo [SD 6mo]). Results indicated that females with ADHD displayed higher levels of TD than males with ADHD (who did not differ from control males). This suggests that TD is sex specific and may contribute to the identification of ADHD in females, thus improving diagnostic and therapeutic strength in this under-referred group. Non-affected siblings were unimpaired, regardless of sex, which suggests that TD is specific to the disorder and not part of a familial risk for ADHD.

BACKGROUND:An issue somewhat overlooked in children with Attention Deficit/Hyperactivity Disorder (ADHD) is somatosensory functioning. Some studies show a deficit in the processing of tactile and kinesthetic stimuli, but more research is needed to confirm these findings. A related topic, namely the subjective experience of pain, has not been investigated. Also unknown is the somatosensory functioning and experienced pain of non-affected siblings of children with ADHD, which may shed light on the familiality of possible alterations in somatosensory functioning and experienced pain. Therefore, the present study aimed to investigate these aspects in children with ADHD and their non-affected siblings, and to investigate how these aspects were related to each other.METHOD:Somatosensory functioning (tactile perception and kinesthesia) and subjective intensity and emotionality of pain experiences were examined in 50 children with ADHD, their 38 non-affected siblings and 35 normal controls.RESULTS:Both children with ADHD and their non-affected siblings showed deficits in tactile perception, though kinesthesia appeared unimpaired. Non-affected siblings reported a significant lower intensity and emotionality of past experienced pain than controls. The 'objective' tests of somatosensory functioning did not relate to the subjective sensation of pain.CONCLUSIONS:Alterations in tactile perception may relate to a familial susceptibility for ADHD. Clinicians should be aware of possible under reportage of experienced pain in siblings of children with ADHD. The intensity and emotionality of pain appears difficult to objectify with somatosensory test.