Interventions to improve executive functions in children aged 3 years and under: A systematic review.

BACKGROUND: Early executive functioning (EF) skills are foundational capabilities that predict school readiness, academic development and psychiatric risk. Early interventions enhancing these capabilities could have critical import in improving outcomes. However, to develop interventions, it is necessary to identify specific EF skills that will vary with child age. Thus, we aimed to examine the characteristics and efficacy of interventions targeting EF in infancy and early childhood up to age 3. METHODS: A comprehensive search of PubMed, Embase, CINAHL and APA PsycINFO databases was performed for studies published before December 2022. Randomized and non-randomized studies of interventions designed to improve at least one EF skill in children ≤3 years were included. EF skills included attentional control, inhibition/self-regulation, activity initiation, working memory, cognitive flexibility, planning ability, problem-solving and performance monitoring. We independently extracted data, used the revised Cochrane Risk-of-Bias tool to assess the quality of the evidence and conducted Synthesis Without Meta-analysis (SWiM). The overall quality of the evidence and the strength of recommendations was determined using elements of the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. RESULTS: Thirty-five studies met inclusion criteria (original n = 7467). Studies were highly variable in the EF skill targeted, target subject (i.e., child, parent and teacher), nature and dosage of the intervention, and timing of outcome assessment. Most interventions focused on improving impulse control and self-regulation. The overall quality of evidence was low to moderate with a high risk of bias, though six studies had low risk of bias but yielded mixed findings of efficacy. CONCLUSIONS: The relatively small number of early EF intervention studies uses such variable methods that there is currently no converging evidence of efficacy to recommend a specific intervention. Thus, findings support the need for a more systematic, targeted approach to the design and implementation of early EF interventions for target populations.

Bayley trajectories predict school readiness better than single assessments in formerly very preterm preschoolers.

BACKGROUND: Development of children born very preterm (VPT) is evaluated using the Bayley Scales of Infant Development. Early Bayley scores may not predict later outcomes. We studied whether VPT Bayley trajectories in the early years predicted school readiness better than single assessments. METHODS: We prospectively evaluated 53 VPT at 4-5 years using standardized measures of school readiness, including the domains of cognition, early mathematical and literacy abilities, and motor skills. Predictors were Bayley-III scores obtained 1-5 times/child between 6 and 35 months. Linear mixed models (LMM) with random effects extracted estimated random effect for slope (change in Bayley score/1 year) and fixed+random effect sum for the intercept (initial Bayley score) for each participant, to then evaluate 4-5-year outcomes prediction. RESULTS: Variability of individual trajectories prevailed across developmental domains. For the initial LMM, adding Bayley change to models with only initial score improved model fits for several Bayley-III domains. Models containing estimates for initial Bayley scores and Bayley change explained significantly more variability in school readiness scores (21-63%) than either variable alone. CONCLUSION: Neurodevelopmental follow-up of VPT is more relevant to school readiness when children are assessed multiple times in the first 3 years. Neonatal intervention research could use early trajectories rather than single timepoints as outcomes. IMPACT: This study is the first to examine individual Bayley scores and trajectories to predict school readiness of formerly preterm children at 4-5 years. Modeling demonstrated extreme variability of individual trajectories compared to the group's average trajectories. Models containing initial Bayley scores and Bayley change over time explained more variability in preschool readiness than either variable alone. Using the Bayley to predict future school readiness is enhanced by administration across multiple follow-up visits and inclusion of change across the first 3 years. Follow-up care models and clinical trial design for neonatal interventions may benefit from a trajectory-based approach to outcomes evaluation.

Associations of Parental Distress and Behavior with School Readiness in Children Born Very Preterm.

OBJECTIVE: Children born very preterm (VPT; gestational age [GA] <31 weeks) have robust school readiness difficulties relative to children born full-term (FT; GA ≥37 weeks). This study examined whether four aspects of parental well-being and behavior-distress, harshness, responsiveness and positive control, and cognitive stimulation-were linked to school readiness in a sample of children born VPT <31 weeks GA and whether these characteristics similarly impact VPT and FT children. METHODS: Parents of 4-year-olds born VPT (n = 55) and FT (n = 38) reported on parental distress, behavior, and cognitive stimulation. Children's cognition, executive function, motor skills, preacademic abilities, and behavior were assessed via neuropsychological tests and parent-report questionnaires. RESULTS: For both groups of children, higher psychological distress and harshness were associated with more behavior problems, and more cognitive stimulation was associated with higher scores on tests of cognitive, motor, and preacademic abilities. More parental distress was associated with lower cognitive ability only for children born VPT and more harshness was associated with lower preacademic skills only for children born FT. CONCLUSIONS: Identifying modifiable family factors associated with school readiness in children born VPT is essential for informing family-based interventions to improve school readiness in this population. Findings suggest that distress, harshness, and cognitive stimulation may be reasonable targets for interventions to improve school readiness in children born VPT.

Intrauterine drug exposure as a risk factor for cerebral palsy.

AIM: To determine whether infants with intrauterine drug exposure (IUDE) are similarly at risk for cerebral palsy (CP) as other high-risk populations, whether CP classification differs based on IUDE status, and describe the association of CP with specific substances among exposed infants. METHOD: This was a retrospective analysis of infants in a high-risk follow-up program (n=5578) between January 2014 and February 2018 with a history of IUDE or who received a CP diagnosis. CP rates were compared using two-sample z-tests. CP classification was assessed using Fisher's exact, Cochran-Armitage, and Wilcoxon rank-sum tests. Models for CP risk were assessed using multivariable logistic regression. RESULTS: Among all infants with IUDE (n=1086), 53.8% were male with a mean (SD) birth gestational age of 36.8 (3.6) weeks. Among unexposed infants with CP (n=259), 54.4% were male with a mean (SD) birth gestational age of 29.9 (5.7) weeks. Opioids were the most common exposure (93.7%) of all infants with IUDE. The CP rate in the IUDE (5.2%) and unexposed (5.7%) high-risk populations were not significantly different (p=0.168), nor were there differences in CP typology, topography, or severity between exposed (n=57) and unexposed (n=259) infants (all p>0.05). In patients with IUDE and after controlling for established CP risk factors, the observed odds of CP varied among substances. INTERPRETATION: We suggest that IUDE should be considered a 'newborn-detectable risk' in the guidelines for the early detection of CP.

Regional anesthesia in neonates and infants outside the immediate perioperative period: A systematic review of studies with efficacy and safety considerations.

This review examines the quality and quantity of literature regarding methods that measure efficacy in the context of reported safety of regional anesthesia techniques in preterm and term infants <1 year of age. Because the role of anesthesiologists continues to expand outside the operating room, we focused on all relevant settings with assessments that extend beyond 24 hours from the intraoperative period. All study designs were included from a search of MEDLINE, EMBASE, CINAHL, Scopus, and Cochrane databases from 1946 to the end of 2019. A total of 31 studies were included (n = 1038 participants), consisting of five randomized controlled trials and 26 observational studies. Twenty-three studies examined neuraxial procedures, seven studies examined peripheral procedures, and one study examined both. Efficacy measures included pain assessment tools, analgesic use, and factors pertaining to the recovery of patients. Safety was assessed in multiple systems (neurological, cardiovascular, respiratory, pathological) and with vital signs and/or measures of systemic toxicity. Evidence in this review establishes that neuraxial and peripheral anesthesia treatments may be applied to neonates and infants with a high degree of safety. However, large gaps in the consistency of methods used to assess pain in these studies underline the need for rigorous prospective efficacy studies of these techniques in this population. This systematic review was registered on PROSPERO (CRD42018114466).

Neonatal Multisensory Processing in Preterm and Term Infants Predicts Sensory Reactivity and Internalizing Tendencies in Early Childhood.

Multisensory processes include the capacity to combine information from the different senses, often improving stimulus representations and behavior. The extent to which multisensory processes are an innate capacity or instead require experience with environmental stimuli remains debated. We addressed this knowledge gap by studying multisensory processes in prematurely born and full-term infants. We recorded 128-channel event-related potentials (ERPs) from a cohort of 55 full-term and 61 preterm neonates (at an equivalent gestational age) in response to auditory, somatosensory, and combined auditory-somatosensory multisensory stimuli. Data were analyzed within an electrical neuroimaging framework, involving unsupervised topographic clustering of the ERP data. Multisensory processing in full-term infants was characterized by a simple linear summation of responses to auditory and somatosensory stimuli alone, which furthermore shared common ERP topographic features. We refer to the ERP topography observed in full-term infants as "typical infantile processing" (TIP). In stark contrast, preterm infants exhibited non-linear responses and topographies less-often characterized by TIP; there were distinct patterns of ERP topographies to multisensory and summed unisensory conditions. We further observed that the better TIP characterized an infant's ERPs, independently of prematurity, the more typical was the score on the Infant/Toddler Sensory Profile (ITSP) at 12 months of age and the less likely was the child to the show internalizing tendencies at 24 months of age. Collectively, these results highlight striking differences in the brain's responses to multisensory stimuli in children born prematurely; differences that relate to later sensory and internalizing functions.

Randomized controlled trial protocol to improve multisensory neural processing, language and motor outcomes in preterm infants.

BACKGROUND: Premature infants are at risk for abnormal sensory development due to brain immaturity at birth and atypical early sensory experiences in the Neonatal Intensive Care Unit. This altered sensory development can have downstream effects on other more complex developmental processes. There are currently no interventions that address rehabilitation of sensory function in the neonatal period. METHODS: This study is a randomized controlled trial of preterm infants enrolled at 32-36 weeks postmenstrual age to either standard care or standard care plus multisensory intervention in order to study the effect of multisensory intervention as compared to standard care alone. The study population will consist of 100 preterm infants in each group (total n = 200). Both groups will receive standard care, consisting of non-contingent recorded parent's voice and skin-to-skin by parent. The multisensory group will also receive contemporaneous holding and light pressure containment for tactile stimulation, playing of the mother's voice contingent on the infant's pacifier sucking for auditory stimulation, exposure to a parent-scented cloth for olfactory stimulation, and exposure to carefully regulated therapist breathing that is mindful and responsive to the child's condition for vestibular stimulation. The primary outcome is a brain-based measure of multisensory processing, measured using time locked-EEG. Secondary outcomes include sensory adaptation, tactile processing, speech sound differentiation, motor and language function, measured at one and two years corrected gestational age. DISCUSSION: This is the first randomized controlled trial of a multisensory intervention using brain-based measurements in order to explain the causal effects of the multisensory intervention on neural processing changes to mediate neurodevelopmental outcomes in former preterm infants. In addition to contributing a critical link in our understanding of these processes, the protocolized multisensory intervention in this study is therapist administered, parent supported and leverages simple technology. Thus, this multisensory intervention has the potential to be widely implemented in various NICU settings, with the opportunity to potentially improve neurodevelopment of premature infants. TRIAL REGISTRATION: NIH Clinical Trials ( clinicaltrials.gov ): NCT03232931 . Registered July 2017.

Parenting style associations with sensory threshold and behaviour: a prospective cohort study in term/preterm infants.

AIM: Early-life atypical sensory functioning and behavioural profiles are often associated with long-term developmental problems, especially in former preterm infants. We tested whether parenting style is associated with atypical sensory threshold or behavioural outcomes in preterm and term infants assessed during early childhood. METHODS: We prospectively evaluated parenting style for a cohort of term and preterm infants who had previous assessments of sensory development and behaviour. We used standardised tools to evaluate parenting style, sensory neurological threshold at one year, and internalising and externalising behavioural tendencies at two years. Covariates included gestational age, sex and maternal education. RESULTS: For the entire cohort (n = 82), children of more permissive parents were 2.7 times more likely to demonstrate abnormal sensory neurological thresholds compared to children of parents with less permissive styles (CI: 1.4-4.9). More permissive parenting scores were also associated with 2.4 times increased internalising (CI: 1.3-4.2) and 3.0 times increased externalising (CI: 1.6-5.6) tendencies. In the preterm group only, higher authoritative parenting scores were associated with fewer behavioural problems. CONCLUSION: Permissive parenting is associated with worse infant sensory and behavioural outcomes. Authoritative parenting is associated with fewer behavioural problems in preterm children. Modification of parenting style may improve sensory development and behavioural outcomes.

Comparing parent and provider priorities in discussions of early detection and intervention for infants with and at risk of cerebral palsy.

BACKGROUND: Although literature suggests that parents need support when their child is diagnosed with cerebral palsy (CP), it is unclear to what extent providers implement these supports in practice and what parental perspectives surround provider early diagnosis and management of CP. Therefore, we aimed to characterize and compare experiences of providers and parents of children with CP with regards to early detection and intervention. METHOD: Seventeen parents participated in day-long world-café style workshops focused on categories extracted from the International Classification of Function framework and recent systematic reviews of early detection for CP. Thirty regional providers (generalists, specialists, and therapists) caring for infants with CP completed surveys with scaled score and open-ended questions. Quantitative and qualitative data were independently assessed by two reviewers to identify prominent themes. RESULTS: All parents (100%) stated early diagnosis or high risk for CP classification was beneficial compared with only 50% of providers who often gave early CP diagnoses before 12 months. Top parent priorities were honesty and positively phrased messages. Providers most often addressed cognition, primary care need, motor, and feeding issues (80%, 62%, 54%, 54% frequently/sometimes). Matching priorities for discussion were neuroimaging timing/risk/benefit, cognition, primary care, motor, and feeding/nutrition. Discordance occurred for participation, parent well-being, pain and vision, with parents wanting more education and resources. CONCLUSIONS: Receiving early diagnoses or high-risk for CP classification is a parent priority. Alignment between parents and providers exists for International Classification of Function domains of body functions/structures and activity, but less for those of environment, personal, and participation.

School Readiness Predictors of Early Academic Achievement in Children Born Very Preterm.

OBJECTIVE: This study examined associations of school readiness measures obtained before school entry with academic achievement at early school age in children born very preterm (VPT, gestational age ≤ 30 weeks) and children born full term (FT, GA ≥ 37 weeks). METHOD: The sample included 38 children born VPT and 30 born FT recruited at age 4 years and followed to early school age. Measures of readiness included tests of global cognition, executive function, motor abilities, and preacademic skills, as well as caregiver behavior ratings. Tests of math, reading, and spelling were administered to assess school-age achievement. Analyses that controlled for socioeconomic status and accounted for inclusion of siblings compared the groups on the achievement tests and identified measures of readiness related to school-age achievement. RESULTS: Achievement difficulties were more pronounced in the VPT group and associated with problems in multiple readiness domains. Effect sizes for these associations were largest for measures of spatial ability, executive function, and preacademic skills. Some associations remained significant when controlling for global cognitive ability at age 4 years, and others were significant only for the VPT group. CONCLUSION: Findings suggest that deficits on tests in multiple readiness domains assessed before school entry in children born VPT or FT are associated with early school-age achievement. The most pronounced readiness deficits in the VPT group at age 4 years were also among those most closely associated with later difficulties in achievement. Further research is needed to refine assessment of school readiness in children born VPT.

Parenting Style Interventions in Parents of Preterm and High-Risk Infants: Controversies, Cost, and Future Directions.

This review highlights the current state of evidence on interventions whose primary purpose is to change parenting style in parents of preterm, and other-high risk, infants. To date, interventions for parents of preterm infants are heterogeneous with variability in intervention timing, measured outcomes, program components, and cost. Most interventions target parental responsivity/sensitivity. Most reported outcomes are short-term, measured at age less than 2 years. The few studies that report later child outcomes in prekindergarten/school-aged children are encouraging, overall indicating improved cognition and behavior in the children of parents who received a parenting style intervention.

Behavioral and neural measures of infant responsivity increase with maternal multisensory input in non-irritable infants.

INTRODUCTION: Parents often use sensory stimulation during early-life interactions with infants. These interactions, including gazing, rocking, or singing, scaffold child development. Previous studies have examined infant neural processing during highly controlled sensory stimulus presentation paradigms. OBJECTIVE: In this study, we investigated infant behavioral and neural responsiveness during a mother-child social interaction during which the mother provided infant stimulation with a progressive increase in the number of sensory modalities. METHODS: We prospectively collected and analyzed video-coded behavioral interactions and electroencephalogram (EEG) frontal asymmetry (FAS) from infants (n = 60) at 2-4 months born at ≥ 34 weeks gestation. As the number of sensory modalities progressively increased during the interaction, infant behaviors of emotional connection in facial expressiveness, sensitivity to mother, and vocal communication increased significantly. Conversely, infant FAS for the entire cohort did not change significantly. However, when we accounted for infant irritability, both video-coded behaviors and EEG FAS markers of infant responsiveness increased across the interaction in the non-irritable infants. The non-irritable infants (49%) demonstrated positive FAS, indicating readiness to engage with, rather than to withdraw from, multisensory but not unisensory interactions with their mothers. RESULTS: These results suggest that multisensory input from mothers is associated with greater infant neural approach state and highlight the importance of infant behavioral state during neural measures of infant responsiveness.

Contingent Mother's Voice Intervention Targeting Feeding in Hospitalized Infants with Critical Congenital Heart Defects.

Infants with critical congenital heart defects (CCHD) are at high risk for feeding challenges and neurodevelopmental delays; however, few interventions promoting the neurodevelopmental progression of feeding have been studied with this population. Contingent mother's voice has been successfully used as positive reinforcement for non-nutritive suck (NNS) in studies with preterm infants, leading to improved weight gain and more rapid cessation of tube feedings; however, this type of intervention has not been studied in infants with CCHD. This study aimed to determine whether an NNS-training protocol using the mother's voice as positive reinforcement and validated in preterm infants could improve oral feeding outcomes in hospitalized infants with CCHD undergoing cardiac surgical procedures. Infants were randomized to receive the contingent mother's voice intervention before or after cardiac surgery, with a control comparison group receiving passive exposure to the mother's voice after surgery. There were no significant differences in discharge weight, PO intake, length of stay, time to full feeds, or feeding status at 1-month post-discharge between infants who received contingent mother's voice compared to those who did not. There were significant differences in PO intake and time to full feeds following surgery based on infants' pre-enrollment PO status and severity of illness. At 1-month post-discharge, parents of infants in the intervention group expressed a higher rate of positive feelings and fewer concerns regarding their infant's feeding compared to parents of infants in the control group. While the current protocol of 5 sessions was not associated with improved feeding outcomes in infants with CCHD, it empowered parents to contribute to their infant's care and demonstrated the feasibility of using the mother's voice as positive reinforcement for infants with CCHD. Further study of timing, intensity, and duration of interventions leveraging the mother's voice in this population is needed. ClinicalTrials.gov Identifier: NCT03035552.

ezPreemie study protocol: a randomised controlled factorial trial testing web-based parent training and coaching with parents of children born very preterm.

INTRODUCTION: Children born very preterm (VPT; gestational age <32 weeks) are twice as likely to demonstrate behaviour problems such as aggression, non-compliance, temper tantrums and irritability compared with their term-born peers. While behavioural parent training (BPT), also referred to as behaviour therapy is a gold standard for prevention and treatment of childhood problem behaviours, there are limited accessible and effective BPT interventions for families with children born VPT. The purpose of this paper is to describe a multicentre, randomised controlled protocol for a factorial design trial evaluating the independent and combined effects of the ezParent BPT intervention plus brief, weekly coaching calls on parent and child outcomes for families with toddlers born VPT. METHODS AND ANALYSIS: The study employs a 2×2 factorial randomised design. Parents (n=220) of children aged 20-30 months corrected age who were born VPT (<32 weeks) will be recruited from two large metropolitan Neonatal Intensive Care Units follow-up clinics and randomised to one of four conditions: (1) ezParent (2) ezParent +coach, (3) Active control or (4) Active Control +coach. Data on parenting and child behaviour outcomes will be obtained from all participants at baseline and 3, 6 and 12 months postbaseline. All analyses will use an intention-to-treat approach, independent of their actual dose of each intervention. ETHICS AND DISSEMINATION: The study protocol has been approved by The Ohio State University Institutional Review Board (IRB) using a single IRB. Study results will be disseminated through presentations at regional and national conferences, publications in peer-reviewed journals, and sharing research reports with participating families and recruiting sites. TRIAL REGISTRATION NUMBER: NCT05217615.

School Readiness in 4-Year-Old Very Preterm Children.

The aims of this study were to identify the aspects of school readiness that best distinguish very preterm (VPT) preschoolers from full-term (FT) controls, determine the extent to which readiness problems in the VPT group reflected global cognitive weaknesses or more specific deficits, and identify distinct profiles of readiness problems. Fifty-three VPT (gestational age ≤ 30 weeks) 4-year-olds were compared to 38 FT (gestational age ≥ 37 weeks) controls on measures of global cognitive ability, executive function, motor skills, early literacy and numeracy, and psychosocial functioning. Latent class analysis (LCA) was also conducted to identify individual readiness profiles. The VPT group had the most pronounced difficulties on tests of spatial and nonverbal cognitive abilities, executive function, motor skills, phonological processing, and numeracy. The VPT group also had sex-related difficulties in processing speed, social functioning, and emotion regulation. These differences were evident in analyses of both continuous scores and rates of deficits. The VPT group's difficulties in motor skills, and VPT females' difficulties in social functioning and emotion regulation, were evident even when controlling for global cognitive ability. LCA suggested four profiles of readiness, with the majority of the VPT group assigned to profiles characterized by relative weaknesses in either cognitive abilities or psychosocial functioning or by more global readiness problems. The findings support the need to evaluate multiple aspects of school readiness in VPT preschoolers and inform efforts to design more targeted early educational interventions.

Exceeding expectations after perinatal risks for poor development: associations in term- and preterm-born preschoolers.

OBJECTIVE: To define parenting/social characteristics associated with better-than-expected cognitive and motor outcomes in preschoolers at similar perinatal biological risk-level including various gestational ages at birth (GA) and perinatal complications. STUDY DESIGN: Prospective cohort study (n = 87) of children at four years, median GA 29 weeks (IQR 26, 38). Assessments included Differential Ability Scales, Movement Assessment Battery, parenting styles, and social risk scores. Perinatal risk factors were weighted based on regression models for each outcome; individual calculated risk scores became predictors to extract standardized residuals from the mean (>1 SD above mean = better-than-expected). Mixed-effect regressions examined associations between positive adaptation and parenting/social factors. RESULT: Perinatal risk scores explained 21-53% outcome variability. Children across all GA displayed positive adaptation. Children of parents with higher authoritarian scores had higher odds of better-than-expected outcomes (OR 1.17, p = 0.0002). CONCLUSION: Parental structure may promote positive adaptation at preschool age in children with perinatal risk factors for poor development, including extreme prematurity.

Resilience and vulnerability in very preterm 4-year-olds.

OBJECTIVE: The primary goal was to determine the prevalence and correlates of adaptive competence in 51 very preterm (VPT, gestational age ≤30 weeks) 4-year-old children compared to a group of 35 term-born (Term) children of the same age. Methods: Adaptive competence, or "resilience" in the VPT group, was defined as age-appropriate scores on tests of early literacy and numeracy and an absence of clinical elevations on parent ratings of problems in behavior and development. Analyses were conducted to compare groups in the prevalence of adaptive competence, determine how adaptively competent VPT children differed from children who were not adaptively competent (i.e. the "maladaptive" subset) and from adaptively competent Term children, and identify family factors related to competence independent of group. Results: Controlling for sociodemographic background, fewer VPT children compared to Term participants (31% vs. 71%) were adaptively competent (p = .026). Compared to the maladaptive subset of the VPT group, adaptive VPT children had higher scores on cognitive tests and more positive parent ratings of executive function and self-regulation. The adaptive VPT subset had outcomes similar to adaptive Term children on many measures but poorer outcomes in specific domains. Higher home stimulation for learning and lower parent distress were also related to adaptive competence. Conclusion: Although a substantial minority of VPT children display adaptive competence, these children may have weaknesses in cognitive skills and executive functioning that present developmental challenges. Associations of adaptive competence with supportive home environments suggest that early family intervention may improve outcomes in this population.