Aim
To review systematically studies examining the development of social competence in children born very preterm (VPT) (gestation <33wks) and identify neonatal and family predictors.
Method
...Peer‐reviewed original articles were extracted from PubMed and PsycINFO following Preferred Reporting Items for Systematic Reviews and Meta‐Analyses (PRISMA) guidelines. Selection criteria included children born VPT and comparison children born at term, sample born after 1990, and children assessed between 0 and 17 years on at least one measure of social competence spanning social adjustment, performance, and/or social skills.
Results
Twenty‐three studies were included. Seven focused on social competence and another 16 examined social competence within a range of outcomes. Study quality was low. Limitations included reliance on single informant data, cross‐sectional measurement, use of brief screening tools, absence of child or peer report, and no conceptual model. In terms of social adjustment, 16 out of 21 studies found children born VPT had more peer problems and social withdrawal. Findings of social performance were mixed, with some studies suggesting differences in prosocial behavior (4/14) and others not. Social skills were assessed in four studies and showed children born VPT had poorer skills than children born at term. Predictors of social competence included gestational age, neonatal brain abnormalities, and family socio‐economic status.
Interpretation
Children born VPT have poorer social competence. These difficulties emerge early and persist throughout childhood.
What this paper adds
Two out of seven primary social competence studies and three out of 16 with a more general focus were considered to have high quality methodology.
Children born very preterm are at increased risk of social competence difficulties.
These difficulties emerge early and persist throughout childhood.
Social difficulties include more peer problems and social skill deficits.
Predictors include extremely preterm birth, neonatal cerebral abnormalities and lower socio‐economic status.
This article is commented on by Johnson on page 890 of this issue.
Cerebral white matter abnormalities on term MRI are a strong predictor of motor disability in children born very preterm. However, their contribution to cognitive impairment is less certain.
Examine ...relationships between the presence and severity of cerebral white matter abnormalities on neonatal MRI and a range of neurocognitive outcomes assessed at ages 4 and 6 years.
The study sample consisted of a regionally representative cohort of 104 very preterm (≤32 weeks gestation) infants born from 1998-2000 and a comparison group of 107 full-term infants. At term equivalent, all preterm infants underwent a structural MRI scan that was analyzed qualitatively for the presence and severity of cerebral white matter abnormalities, including cysts, signal abnormalities, loss of white matter volume, ventriculomegaly, and corpus callosal thinning/myelination. At corrected ages 4 and 6 years, all children underwent a comprehensive neurodevelopmental assessment that included measures of general intellectual ability, language development, and executive functioning.
At 4 and 6 years, very preterm children without cerebral white matter abnormalities showed no apparent neurocognitive impairments relative to their full-term peers on any of the domain specific measures of intelligence, language, and executive functioning. In contrast, children born very preterm with mild and moderate-to-severe white matter abnormalities were characterized by performance impairments across all measures and time points, with more severe cerebral abnormalities being associated with increased risks of cognitive impairment. These associations persisted after adjustment for gender, neonatal medical risk factors, and family social risk.
Findings highlight the importance of cerebral white matter connectivity for later intact cognitive functioning amongst children born very preterm. Preterm born children without cerebral white matter abnormalities on their term MRI appear to be spared many of the cognitive impairments commonly associated with preterm birth. Further follow-up will be important to assess whether this finding persists into the school years.
Preterm birth is associated with a significantly increased risk for childhood and adolescent psychopathology relative to full-term birth, with an inverse relationship between gestational age at birth ...and later risk for psychopathology. The manifestation of symptomatology and comorbidity profiles of emotional and behavioral adjustment problems in this high-risk group have been shown to be distinct from the broader pediatric population. Acknowledging these differences, a preterm behavioral phenotype has been proposed and increasingly recognized, highlighting the unique, frequent co-occurrence of symptomatology associated with attention-deficit/hyperactivity disorder, autism spectrum disorder, and anxiety disorders. The current state-of-the-art review provides a comprehensive characterization of this phenotype to date and further highlights key knowledge gaps primarily regarding the evolution of symptoms, co-occurrence of disorders and/or symptomatology within the phenotype, and associations of the phenotype with chronological age and degree of prematurity.
Objectives To document associations between confirmed and suspected neonatal infection and motor, cognitive, educational, and mental health outcomes of very preterm (VPT)-born children at 9 years of ...age; to examine the potential intervening role of cerebral white matter abnormalities (WMAs) and structural development on term magnetic resonance imaging. Study design A regional cohort of 110 infants born VPT in Christchurch, New Zealand were studied from birth to age of 9 years. Confirmed infection was defined as positive blood, cerebrospinal fluid or urine culture, and/or necrotizing enterocolitis ≥stage 2. Suspected infection was defined as ≥5 days of antibiotics with evidence of clinical correlates. At term gestational equivalence, infants underwent structural magnetic resonance imaging. At age 9 years, neuromotor function, IQ, educational achievement, and mental health were assessed. Results During hospitalization, 25% of VPT infants had confirmed and 23% had suspected infection. Longer-term neurodevelopmental impairments were largely confined to infants with confirmed infection (relative risk 1.4-3.1, vs uninfected). After accounting for other neonatal factors, these infants were at increased risk of severe motor impairment (OR 3.3, 95% CI 1.3-8), attention deficit hyperactivity disorder (ADHD) (OR 3.6, 95% CI 1.6-8), and IQ delay (OR 2.0, 95% CI 1-3.9). Cerebral WMAs contributed to associations between confirmed infection and motor and IQ impairments but not to ADHD ( P = .005). Conclusions Confirmed neonatal infection heightens VPT infants' risk for neurodevelopmental impairment. WMA appears to be an important intervening factor linking infection and severe motor and IQ impairments. Further analysis of the neurologic mechanism accounting for ADHD in infants with infection is needed.
Low- and middle-income countries account for the greatest burden of preterm birth globally; however, there is limited understanding of neurodevelopmental outcomes of survivors within these ...resource-constrained settings. To accelerate progress, current priorities are to generate more high-quality data; engage with diverse local stakeholders including families of infants born preterm to identify neurodevelopmental outcomes meaningful to them within their contexts; and develop sustainable, scalable, high-quality models of neonatal follow-up, codesigned with local stakeholders, addressing the unique needs of low- and middle-income countries. Advocacy is critical to recognize optimal neurodevelopment as an "outcome of priority" along with the reduction in mortality.
Abstract Purpose Donor breastmilk (DBM) has gained popularity as an alternative to formula when mother’s own milk (MOM) is unavailable. The objective of this study was to evaluate the effects of a ...predominantly DBM diet on growth and subsequent neurodevelopment in preterm infants at a level 3 neonatal intensive care unit (NICU). Methods This single-center, observational cohort study compared data from preterm infants supplemented with predominantly (>50%) DBM to those from age- and weight-matched infants fed only MOM or supplemented with predominantly (>50%) preterm formula (PF). The primary outcome was in-hospital weight gain, and the secondary outcome was neurodevelopment, as assessed by the Bayley III scale at 1 and 2 years’ corrected age. Exclusion criteria were major congenital defects, death prior to discharge from the NICU, or supplementation volumes of <50% over the first month of life. We compared the outcomes among the 3 feeding groups with the χ2 test, ANOVA, and ANCOVA, with post hoc pairwise comparisons after adjustment for the following confounders: bronchopulmonary dysplasia, multiple births, and social work involvement. Findings In the entire cohort, the mean gestational age was 27.1 weeks and the mean birthweight was 914 g. The DBM (n = 27) and PF (n = 25) groups were similar with regard to socioeconomic characteristics. DBM infants regained birthweight more slowly over the first month of life compared with infants fed MOM (n = 29) or PF (mean SD, 17.9 5.7, 22.0 6.8, and 20.3 5.7 g/kg/d, respectively; P = 0.05); however, this growth difference was attenuated at later time points. In a fully adjusted model, the DBM group scored significantly lower in cognition at both 1 year ( P = 0.005) and 2 years ( P = 0.03) of age compared with the infants fed non-DBM diets. Implications The findings from this study suggest that in this NICU, preterm infants supplemented with predominantly DBM had compromised early in-hospital weight gain and, possibly, early cognitive delays compared with infants fed only MOM or infants supplemented with predominantly PF. These findings reinforce the need for further research on the optimal use of DBM in the preterm population and a continued need for promoting breastfeeding efforts to supply MOM.
•MRI morphometrics of very preterm infants were obtained between 29-35 weeks PMA.•Cortical GM volume and shape predict motor and cognitive outcomes at 2 years.•Demonstrates utility of early neonatal ...brain MRI for estimating 2-year outcomes.
Infants born very preterm face a range of neurodevelopmental challenges in cognitive, language, behavioural and/or motor domains. Early accurate identification of those at risk of adverse neurodevelopmental outcomes, through clinical assessment and Magnetic Resonance Imaging (MRI), enables prognostication of outcomes and the initiation of targeted early interventions. This study utilises a prospective cohort of 181 infants born <31 weeks gestation, who had 3T MRIs acquired at 29-35 weeks postmenstrual age and a comprehensive neurodevelopmental evaluation at 2 years corrected age (CA). Cognitive, language and motor outcomes were assessed using the Bayley Scales of Infant and Toddler Development – Third Edition and functional motor outcomes using the Neuro-sensory Motor Developmental Assessment. By leveraging advanced structural MRI pre-processing steps to standardise the data, and the state-of-the-art developing Human Connectome Pipeline, early MRI biomarkers of neurodevelopmental outcomes were identified. Using Least Absolute Shrinkage and Selection Operator (LASSO) regression, significant associations between brain structure on early MRIs with 2-year outcomes were obtained (r = 0.51 and 0.48 for motor and cognitive outcomes respectively) on an independent 25% of the data. Additionally, important brain biomarkers from early MRIs were identified, including cortical grey matter volumes, as well as cortical thickness and sulcal depth across the entire cortex. Adverse outcome on the Bayley-III motor and cognitive composite scores were accurately predicted, with an Area Under the Curve of 0.86 for both scores. These associations between 2-year outcomes and patient prognosis and early neonatal MRI measures demonstrate the utility of imaging prior to term equivalent age for providing earlier commencement of targeted interventions for infants born preterm.
Children born very preterm (VPT) are at high risk of educational delay, yet few guidelines exist for the early identification of those at greatest risk. Using a school readiness framework, this study ...examined relations between preschool neurodevelopmental functioning and educational outcomes to age 9 years.
The sample consisted of a regional cohort of 110 VPT (≤ 32 weeks' gestation) and 113 full-term children born during 1998-2000. At corrected age 4 years, children completed a multidisciplinary assessment of their health/motor development, socioemotional adjustment, core learning skills, language, and general cognition. At ages 6 and 9, children's literacy and numeracy skills were assessed using the Woodcock-Johnson III Tests of Achievement.
Across all readiness domains, VPT children were at high risk of delay/impairment (odds ratios 2.5-3.5). Multiple problems were also more common (47% vs 16%). At follow-up, almost two-thirds of VPT children were subject to significant educational delay in either literacy, numeracy or both compared with 29% to 31% of full-term children (odds ratios 3.4-4.4). The number of readiness domains affected at age 4 strongly predicted later educational risk, especially when multiple problems were present. Receiver operating characteristic analysis confirmed ≥ 2 readiness problems as the optimal threshold for identifying VPT children at educational risk.
School readiness offers a promising framework for the early identification of VPT children at high educational risk. Findings support the utility of ≥ 2 affected readiness domains as an effective criterion for referral for educational surveillance and/or additional support during the transition to school.
Background
Attention problems are among the most prevalent neurobehavioral morbidities affecting very preterm (VPT) born children. The first study aim was to document rates of persistent ...attention/hyperactivity problems from ages 4 to 9 years in a regional cohort of VPT born children. The second aim was to examine the extent to which persistent problems were related to cerebral white matter abnormality and structural development on neonatal MRI.
Methods
Data were drawn from a prospective longitudinal study of 110 VPT (≤32 weeks gestation) and 113 full‐term (FT) children born from 1998 to 2000. At term equivalent, all VPT and 10 FT children underwent cerebral structural MRI, with scans analyzed qualitatively for white matter abnormalities and quantitatively for cortical and subcortical gray matter, myelinated and unmyelinated white matter, and cerebrospinal fluid volumes. At ages 4, 6, and 9 years, each child's parent and teacher completed the Inattention/Hyperactivity subscale of the Strengths and Difficulties Questionnaire.
Results
VPT born children had a fivefold increased risk of persistent attention/hyperactivity problems compared with FT children (13.1% vs. 2.8%; p = .002). No association was found between neonatal white matter abnormalities and later persistent inattention/hyperactivity risk (p ≥ .24). In contrast, measures of cerebral structural development including volumetric estimates of total cerebral tissue and cerebrospinal fluid relative to intracranial volume were associated with an increased risk of persistent attention/hyperactivity problems in VPT born children (p = .001). The dorsal prefrontal region showed the largest volumetric reduction (↓3.2–8.2 mL). These brain‐behavior associations persisted and in some cases, strengthened after covariate adjustment for postmenstrual age at MRI, gender, and family socioeconomic status.
Conclusions
Just over one in 10 VPT born children are subject to early onset and persistent attention/hyperactivity problems during childhood. These problems appear to reflect, at least in part, neonatal disturbances in cerebral growth and development rather than the effects of white matter injury.
The Taste And Smell To Enhance nutrition (TASTE) trial investigated the effects of smell and taste of milk with tube feeding compared to routine care on the growth of preterm infants. There was no ...difference between groups in growth (weight, head circumference, length) z-scores at discharge from the hospital. Infants in the intervention group had higher head circumference and length z-scores at 36 weeks postmenstrual age, both secondary outcomes. The objective of this follow-up study is to assess 2-year neurodevelopmental and growth outcomes after exposure of preterm infants to the smell and taste of milk with tube feeding compared to routine care.
This is a neurodevelopmental follow-up study of a two-center, placebo-controlled randomized trial. Infants born before 29 weeks postmenstrual age and/or with a birth weight of less than 1250 g were randomized to smell and taste of milk with each tube feed or routine care. The current follow-up assessed the 2-year neurodevelopmental and growth outcomes of participants of the TASTE trial discharged from the hospital (n = 334). The primary outcome is survival free of any major neurodevelopmental impairment comprising any moderate/severe cerebral palsy (Gross Motor Function Classification System score II-V), Bayley Scales of Infant and Toddler Development, Third/Fourth Edition (Bayley-III/Bayley-4) motor, cognitive, or language scores < -2SD, blindness, or deafness at 2 years of age. Other outcomes include death, breastfeeding within the first year, and respiratory support, oral feeding, and anthropometric parameters at 2 years of age. The Human Research Ethics Committees of Mater Misericordiae Limited and the Royal Women's Hospital approved the TASTE trial including the neurodevelopmental follow-up described in this protocol.
For patients and their families, the neurodevelopmental outcomes of preterm infants are of utmost importance. Consequently, they should be investigated following any interventional study performed during the newborn period. Furthermore, improved weight gain and head growth in the hospital are associated with better long-term neurodevelopmental outcomes. Smelling and tasting of milk is an uncomplicated and cost-effective intervention that may improve the growth and neurodevelopmental outcomes of preterm infants. Potential limitations affecting this follow-up study, caused by the COVID-19 pandemic, are anticipated and discussed in this protocol.
Name of the registry: Australian and New Zealand Clinical Trials Registry; Registration number: ACTRN12617000583347 ; Registration date: 26 April 2017.
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