EBNEO COMMENTARY: Parent-Guided Developmental Intervention for Infants with Very Low Birth Weight
MANUSCRIPT CITATION
Silveira RC, Valentini NC, O’Shea TM, et al. Parent-Guided Developmental Intervention for Infants with Very Low Birth Weight: A Randomized Clinical Trial. JAMA Netw Open. 2024;7(7): e2421896. Published 2024 Jul 1. doi:10.1001/jamanetworkopen.2024.21896 PMID: 39018071.
REVIEWED BY
1. Srishti Jayakumar, MD MPH. Neonatal-Perinatal Medicine Fellow.
Johns Hopkins University School of Medicine
srishtijayakumar@jhu.edu
2. Heather Burris, MD, MPH. Associate Professor of Pediatrics.
University of Pennsylvania Perelman School of Medicine
Children’s Hospital of Philadelphia
burrish@chop.edu
3. Andrea Duncan, MD, MSCR. Professor of Pediatrics.
University of Pennsylvania Perelman School of Medicine
Children’s Hospital of Philadelphia
duncana2@chop.edu
4. Sara B. DeMauro, MD MSCE. Associate Professor of Pediatrics
University of Pennsylvania Perelman School of Medicine
Children’s Hospital of Philadelphia
demauro@chop.edu
TYPE OF INVESTIGATION
Randomized Controlled Trial
QUESTION
Among infants with a birth weight less than 1500 grams or gestational age less than 32 weeks, born at the study hospital and residing within 40 km of the hospital (P), does a parent-guided enhanced developmental intervention consisting of usual care of lactation support, kangaroo care and routine developmental therapies, plus infant massage, enhanced visual stimulation, auditory stimulation, social interactions, and support for motor development, instructed by developmental therapists (I) compared to those receiving usual care (C) lead to better neurodevelopmental outcomes on the Bayley Scales of Infant and Toddler Development-Third Edition (O) at 18 months of age adjusted for prematurity (T).
METHODS
• Design: Single center randomized control trial
• Allocation: Parents of infants recruited at 48 hours of life, for randomization beginning on postnatal day 7 to usual care, consisting of support for lactation, kangaroo care, and routine developmental therapies, or to a parent-guided enhanced developmental intervention, consisting of usual care plus infant massage and enhanced visual stimulation, auditory stimulation, social interactions, and support for motor development, instructed by developmental therapists.
• Blinding: Participants and clinicians caring for participants in the NICU at the study institution were aware of their randomization assignments given the nature of the intervention. Individuals who evaluated the primary outcome, the Bayley Scales of Infant and Toddler Development–Third Edition (BSID-III) score, were masked to randomization assignment.
• Follow-up period: Up to 18 months corrected age. Follow-up exams performed between November 1, 2017, and May 31, 2022.
• Setting: The neonatal intensive care unit (NICU) and follow-up clinic at Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil.
• Patients:
o Inclusion Criteria: Infants born at the study hospital with a birth weight less than 1500 grams or gestational age less than 32 weeks, and residing within 40 km of the hospital.
o Exclusion Criteria: Major congenital malformations or inborn errors of metabolism; congenital infections, including syphilis, toxoplasmosis, varicella-zoster virus, parvovirus B19, rubella, cytomegalovirus, herpes simplex virus, and HIV; or autoimmune conditions.
• Intervention:
o Usual Care Group (Controls): Consisted of lactation support, kangaroo care and routine developmental therapies in the NICU. Follow-up visits with developmental evaluation were scheduled after NICU discharge every month up to 6 months corrected age, bimonthly from 7 to 12 months corrected age, and every 3 months thereafter until 24 months corrected age. If a developmental delay was detected, the infant was referred for early intervention services provided by the Brazilian Unified Health System.
o Enhanced Developmental Intervention: Consisted of usual care of lactation support, kangaroo care and routine developmental therapies, plus infant massage, enhanced visual stimulation, auditory stimulation, social interactions, and support for motor development, instructed by developmental therapists. Home-based intervention was provided by a multidisciplinary team at 10 visits after discharge to reinforce education catered to adult learners and record delivery of the intervention to inform additional counselling.
• Primary outcome: Cognitive scores on the BSID-III at 18 months corrected age.
• Secondary outcomes:
o Child neurodevelopmental outcomes: Assessed at 18 months corrected age using BSID-III language and motor scales and Alberta Infant Motor Scales (AIMS). Delayed language or motor on BSID-III was defined as score below 80. Delay on AIMS was defined as score below 5.
o Measures of the home environment and parental practice and knowledge: Assessed at 12 months corrected age using the Interaction Rating Scale, the Affordance in the Home Environment for Motor Development–Infant Scale, the Daily Activities of Infant Scale, the Knowledge of Infant Development Inventory adapted for Brazilian children and Daily Activities of Infant Scale
o Opportunities at home: Assessed using the Affordance in the Home Environment for Motor Development- Infant Scale
• Analysis and Sample Size: A sample size of 100 was selected toward the goal of obtaining the primary outcome, the BSID-III score, for at least 84 study participants. This sample size was estimated to provide 80% power to detect a difference of 3 points (equal to 0.2 SDs in the normative sample) in BSID-III scores. 207 infants were assessed for eligibility; 69 were excluded, 138 were randomized in the first 48 hours of life, of which 38 either withdrew or died following randomization. 50 were randomized to usual care, 50 were randomized to enhanced developmental intervention. One way analysis of variance (ANOVA) test was used to compare continuous variables between the groups and Chi square test used for comparison of categorical variables.
MAIN RESULTS
The enhanced developmental intervention and usual care groups were similar with respect to maternal, family, and neonatal characteristics. The primary outcome, the BSID-III cognitive score at 18 months of corrected age was higher in the enhanced developmental intervention group (mean [SD], 101.8 [11.9] vs 97.3 [13.5]; mean difference, 4.5 [95% CI, 0.1-8.9]). In terms of the secondary outcomes, increased language (mean [SD], 99.3 [12.0] vs 91.6 [14.4]; mean difference 7.7 [95% CI, 2.1 – 13.3]) and motor scores (mean [SD], 102.5 [13.3] vs 92.7 [17.9]; mean difference, 9.8 [95% CI, 3.2 – 16.5]) were seen in the enhanced developmental intervention group on the BSID-III. A similar trend was seen with the AIMS score (mean [SD], 53.7 [17.0] vs 30.3 [12.1]; mean difference, 23.4 [95% CI, 16.8 – 30.0), demonstrating a greater effect of the intervention on motor development, compared to cognitive and language development. The enhanced developmental intervention group had higher scores for the overall Interaction Rating Scale scores that served as a measure of the quality of parent-infant interaction; most effect sizes were moderate. No differences were found on measures of development opportunities available at home, parental care practices, or parental knowledge regarding infant development.
CONCLUSION
This randomized clinical trial employing parent-guided developmental intervention for very preterm or very low birth weight infants in an LMIC found an improvement in very preterm infants’ cognitive, language and motor outcomes at 18 months in the group that received the intervention compared to the usual care group.
COMMENTARY
Very preterm birth is associated with injury in the developing brain and subsequent impairments in cognitive, motor, behavioral and emotional skills.1,2 Early childhood provides a critical window for neurorestorative interventions, including developmental interventions, in the hospital and after discharge.3
Developmental interventions vary widely in their component elements, intensity, target domains, parental involvement, and cost. A majority of studies evaluating these interventions have been based in high-income countries.4 Given the heterogeneity of medical systems and access to follow-up care across the globe, results from prior studies may not be generalizable to low-to-middle-income (LMIC) countries. The randomized trial by Silveira et al, based in Brazil, addressed this critical gap and demonstrated that a parent-guided developmental intervention administered to high-risk preterm infants in a LMIC improved cognitive, language, and motor development through 18 months corrected age.
Silveira, et al. observed a stronger effect of enhanced developmental support on motor outcomes compared to cognitive outcomes. While it is plausible that early motor developmental skills are more amenable to improvement with the study intervention, this finding is in contrast to many prior studies which show greater improvements in cognitive domains with early developmental intervention programs.5. Notably, the effect on motor skills strengthened between 4 and 18 months, suggesting a sustained or even increasing intervention effect over time.
Strengths of this study include parental training beginning in the first week after birth and the assessment of numerous factors influencing neurodevelopment, including parents’ childhood experiences and socioeconomic status. Testing in the participants’ homes allowed for assessment of child neurodevelopment in a comfortable, familiar setting. The use of multiple scales measuring non-overlapping aspects of development allowed for a holistic evaluation of the child and their environment. The randomized design, use of blinded outcomes assessments, and robust sample size are additional strengths of the study.
This study could have been further strengthened by inclusion of validated measures of infant state control, parent-infant bonding, parental mental health and self-efficacy. The Bayley Scales of Infant and Toddler Development, Third Edition (Bayley-III), used to assess the primary outcome, is known to overestimate development.6,7,8, 9 Notably, the intensity of follow-up care provided to the control group is markedly higher than in many other settings, including some high-income countries. Therefore, similar interventions in settings with less robust follow-up might yield even greater effects and will be important to study the scalability of this intervention. While the authors acknowledge the burdens of extended follow-up, longer-term assessments will be essential for demonstrating persistence of intervention effects.
Dr. Silveira’s trial represents an essential contribution to the literature describing the important impact of neurodevelopmental interventions on outcomes of high-risk infants and demonstrates the success of a parent-guided intervention in a LMIC. While LMICs are a varied group, the study offers a low-cost intervention that could be applied to numerous resource-limited settings, with potentially greater impact depending on the intensity of their follow-up services. This trial sets a benchmark for future studies of developmental interventions and provides a template for evidence-based developmental care of high-risk infants around the world.
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