Early developmental intervention programmes provided post hospital discharge to prevent motor and cognitive impairment in preterm infants

Background Infants born preterm are at increased risk of cognitive and motor impairments compared with infants born at term. Early developmental interventions for preterm infants are targeted at the infant or the parent‐infant relationship, or both, and may focus on different aspects of early development. They aim to improve developmental outcomes for these infants, but the long‐term benefits remain unclear. This is an update of a Cochrane review first published in 2007 and updated in 2012 and 2015. Objectives Primary objective To assess the effect of early developmental interventions compared with standard care in prevention of motor or cognitive impairment for preterm infants in infancy (zero to < three years), preschool age (three to < five years), and school age (five to < 18 years). Secondary objective To assess the effect of early developmental interventions compared with standard care on motor or cognitive impairment for subgroups of preterm infants, including groups based on gestational age, birthweight, brain injury, timing or focus of intervention and study quality. Search methods We searched CENTRAL, MEDLINE, Embase, CINAHL, PsycINFO and trial registries in July 2023. We cross‐referenced relevant literature, including identified trials and existing review articles. Selection criteria Studies included randomised, quasi‐randomised controlled trials (RCTs) or cluster‐randomised trials of early developmental intervention programmes that began within the first 12 months of life for infants born before 37 weeks' gestational age (GA). Interventions could commence as an inpatient but had to include a post discharge component for inclusion in this review. Outcome measures were not prespecified, other than that they had to assess cognitive outcomes, motor outcomes or both. The control groups in the studies could receive standard care that would normally be provided. Data collection and analysis Data were extracted from the included studies regarding study and participant characteristics, timing and focus of interventions and cognitive and motor outcomes. Meta‐analysis using RevMan was carried out to determine the effects of early developmental interventions at each age range: infancy (zero to < three years), preschool age (three to < five years) and school age (five to < 18 years) on cognitive and motor outcomes. Subgroup analyses focused on GA, birthweight, brain injury, time of commencement of the intervention, focus of the intervention and study quality. We used standard methodological procedures expected by Cochrane to collect data and evaluate bias. We used the GRADE approach to assess the certainty of evidence. Main results Forty‐four studies met the inclusion criteria (5051 randomly assigned participants). There were 19 new studies identified in this update (600 participants) and a further 17 studies awaiting outcomes. Three previously included studies had new data. There was variability in the focus and intensity of the interventions, participant characteristics, and length of follow‐up. All included studies were either single or multicentre trials and the number of participants varied from fewer than 20 to up to 915 in one study. The trials included in this review were mainly undertaken in middle‐ or high‐income countries. The majority of studies commenced in the hospital, with fewer commencing once the infant was home. The focus of the intervention programmes for new included studies was increasingly targeted at both the infant and the parent‐infant relationship. The intensity and dosages of interventions varied between studies, which is important when considering the applicability of any programme in a clinical setting. Meta‐analysis demonstrated that early developmental intervention may improve cognitive outcomes in infancy (developmental quotient (DQ): standardised mean difference (SMD) 0.27 standard deviations (SDs), 95% confidence interval (CI) 0.15 to 0.40; P < 0.001; 25 studies; 3132 participants, low‐certainty evidence), and improves cognitive outcomes at preschool age (intelligence quotient (IQ); SMD 0.39 SD, 95% CI 0.29 to 0.50; P < 0.001; 9 studies; 1524 participants, high‐certainty evidence). However, early developmental intervention may not improve cognitive outcomes at school age (IQ: SMD 0.16 SD, 95% CI ‐0.06 to 0.38; P = 0.15; 6 studies; 1453 participants, low‐certainty evidence). Heterogeneity between studies for cognitive outcomes in infancy and preschool age was moderate and at school age was substantial. Regarding motor function, meta‐analysis of 23 studies showed that early developmental interventions may improve motor outcomes in infancy (motor scale DQ: SMD 0.12 SD, 95% CI 0.04 to 0.19; P = 0.003; 23 studies; 2737 participants, low‐certainty evidence). At preschool age, the intervention probably did not improve motor outcomes (motor scale: SMD 0.08 SD, 95% CI ‐0.16 to 0.32; P = 0.53; 3 studies; 264 participants, moderate‐certainty evidence). The evidence at school age for both continuous (motor scale: SMD ‐0.06 SD, 95% CI ‐0.31 to 0.18; P = 0.61; three studies; 265 participants, low‐certainty evidence) and dichotomous outcome measures (low score on Movement Assessment Battery for Children (ABC) : RR 1.04, 95% CI 0.82 to 1.32; P = 0.74; 3 studies; 413 participants, low‐certainty evidence) suggests that intervention may not improve motor outcome. The main source of bias was performance bias, where there was a lack of blinding of participants and personnel, which was unavoidable in this type of intervention study. Other biases in some studies included attrition bias where the outcome data were incomplete, and inadequate allocation concealment or selection bias. The GRADE assessment identified a lower certainty of evidence in the cognitive and motor outcomes at school age. Cognitive outcomes at preschool age demonstrated a high certainty due to more consistency and a larger treatment effect. Authors' conclusions Early developmental intervention programmes for preterm infants probably improve cognitive and motor outcomes during infancy (low‐certainty evidence) while, at preschool age, intervention is shown to improve cognitive outcomes (high‐certainty evidence). Considerable heterogeneity exists between studies due to variations in aspects of the intervention programmes, the population and outcome measures utilised. Further research is needed to determine which types of early developmental interventions are most effective in improving cognitive and motor outcomes, and in particular to discern whether there is a longer‐term benefit from these programmes.