Resting state functional MRI in infants with prenatal opioid exposure-a pilot study

PURPOSE: Exposure to prenatal opioids may adversely impact the developing brain networks. The aim of this pilot study was to evaluate alterations in amygdalar functional connectivity in human infants with prenatal opioid exposure. METHODS: In this prospective IRB approved study, we performed resting state functional MRI (rs-fMRI) in 10 infants with prenatal opioid exposure and 12 infants without prenatal drug exposure at < 48 weeks corrected gestational age. Following standard preprocessing, we performed seed-based functional connectivity analysis with the right and left amygdala as the regions of interest after correcting for maternal depression and infant sex. We compared functional connectivity of the amygdala network between infants with and without prenatal opioid exposure. RESULTS: There were significant differences in connectivity of the amygdala seed regions to the several cortical regions including the medial prefrontal cortex in infants who had prenatal opioid exposure when compared with opioid naïve infants. CONCLUSION: This finding of increased amygdala functional connectivity in infants with in utero opioid exposure suggests a potential role of maternal opioid exposure on infants' altered amygdala function. This association with prenatal exposure needs to be replicated in future larger studies

Identifying Autism Spectrum Disorder in a High-risk Follow-up Program through Quality Improvement Methodology

Introduction: Children born prematurely are at increased risk for autism spectrum disorder (ASD). ASD can be diagnosed between 18 and 24 months of age, but access barriers and medical complexity can delay diagnosis. ASD screening was implemented in a high-risk infant follow-up program using QI methodology. The project aimed to screen 60% of children and refer 90% of those with positive screens. Methods: The team developed a standardized workflow to administer the M-CHAT-R/F to HRIF patients between the ages of 16-22 months. Telehealth ASD assessment, using the TELE-ASD-PEDS, was conducted for those who screened positive. Monthly team meetings were held to implement change cycles and review the impact of the previous month's change. Results: Within 7 months of program implementation, ASD screening exceeded the 60% aim. The program referred 72% of patients who screened as medium/high risk on the M-CHAT-R/F. The remaining patients were not referred per provider discretion. Twenty-seven percent of patients who received an autism evaluation received an ASD diagnosis. The average age at diagnosis was 22.5 months. Conclusions: An ASD screening protocol was implemented for patients enrolled in a high-risk infant follow-up program. Patients identified as at risk for ASD received an expedited telehealth ASD evaluation. The screening protocol was maintained for 13 months and is now part of the standard workflow. Screening has been expanded to other HRIF clinics, and evaluation appointments have been added to meet access needs. QI methodology is an effective tool for implementing ASD screening and referral in multidisciplinary HRIF programs

Cultural adaptation of the Bayley Scales of Infant and Toddler Development, 3rd Edition for use in Kenyan children aged 18-36 months: A psychometric study

Background: The Bayley Scales of Infant and Toddler Development, 3rd Edition (Bayley-III) is frequently used in international child development research. No studies examine its psychometric properties when culturally adapted within the Kenyan context. Aims: To culturally adapt the Bayley-III for use in Kenya and evaluate its validity and reliability. Methods and procedures: Forward and backward translation, cognitive interviews, and a brief pilot of culturally adapted items were performed. This psychometric study was part of another study on children born to mothers with HIV in Eldoret, Kenya. One hundred seventy-two children aged 18-36 months were assessed for cognition, receptive/expressive communication, and fine/gross motor domains using the Bayley-III. Confirmatory factor analysis (CFA), inter-scale Pearson correlations, internal consistency, t-tests, and test-retest reliability were performed. Outcomes and results: The mean age of children was 22.8 (SD 4.5) months old; 52.7 % (n = 89) were male. CFA revealed that both two- and three-factor indices had good and comparable fit. Pearson correlations were high between fine motor and receptive communication (r \u3e0.70). Internal consistency was very strong for all of the subtests, with Cronbach coefficient alpha scores ranging from 0.88 to 0.96. Known groups/convergent validity was confirmed with stunting and parental concern for delays. Test-retest reliability was good and did not differ substantially across groups. Conclusions and implications: The Kenyan adapted Bayley-III is a psychometrically acceptable tool to assess child development. The scaled and composite scores should not be used to define Kenyan developmental norms, but it can be useful for comparing groups within research settings

Virtual Developmental Screening After Invasive Mechanical Ventilation in Children: A Prospective Cohort Pilot Study

OBJECTIVES: With decreasing PICU mortality, survivor morbidity has increased. This study aims to evaluate feasibility of virtual PICU-led follow-up of patients at risk for pediatric postintensive care syndrome. DESIGN: Prospective cohort study. SETTING: Single-center, quaternary children's hospital. PATIENTS: Children less than or equal to 4 years without known preexisting neurodevelopmental deficits requiring greater than or equal to 12 hours mechanical ventilation. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Age-appropriate Ages and Stages Questionnaires, Third Edition (ASQ-3) were administered via a web-based system at 3, 6, and 12 months following PICU discharge. Primary-care physicians were notified of results; at-risk patients were referred to early developmental intervention. Forty-eight patients enrolled with median age 11.5 months (interquartile range [IQR], 2-19.5 mo) and median mechanical ventilation duration 92.5 hours (IQR, 40.5-147 hr). Fifty-eight percent completed greater than or equal to 1 ASQ-3. Lower caregiver educational achievement, lower income, and single-caregiver status were associated with lower ASQ-3 completion rates. Of those completing any ASQ-3, 50% flagged as at-risk for developmental delay and referred to early developmental intervention. There was no association between patient characteristics and abnormal ASQ-3. CONCLUSIONS: Virtual caregiver-completed surveillance is a promising method to screen children for neurodevelopmental abnormalities following PICU hospitalization and facilitate early referral for developmental intervention, but special attention must be dedicated to families with limited resources for follow-up

Virtual Developmental Screening After Invasive Mechanical Ventilation in Children: A Prospective Cohort Pilot Study

OBJECTIVES: With decreasing PICU mortality, survivor morbidity has increased. This study aims to evaluate feasibility of virtual PICU-led follow-up of patients at risk for pediatric postintensive care syndrome. DESIGN: Prospective cohort study. SETTING: Single-center, quaternary children's hospital. PATIENTS: Children less than or equal to 4 years without known preexisting neurodevelopmental deficits requiring greater than or equal to 12 hours mechanical ventilation. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Age-appropriate Ages and Stages Questionnaires, Third Edition (ASQ-3) were administered via a web-based system at 3, 6, and 12 months following PICU discharge. Primary-care physicians were notified of results; at-risk patients were referred to early developmental intervention. Forty-eight patients enrolled with median age 11.5 months (interquartile range [IQR], 2-19.5 mo) and median mechanical ventilation duration 92.5 hours (IQR, 40.5-147 hr). Fifty-eight percent completed greater than or equal to 1 ASQ-3. Lower caregiver educational achievement, lower income, and single-caregiver status were associated with lower ASQ-3 completion rates. Of those completing any ASQ-3, 50% flagged as at-risk for developmental delay and referred to early developmental intervention. There was no association between patient characteristics and abnormal ASQ-3. CONCLUSIONS: Virtual caregiver-completed surveillance is a promising method to screen children for neurodevelopmental abnormalities following PICU hospitalization and facilitate early referral for developmental intervention, but special attention must be dedicated to families with limited resources for follow-up

Hydrocortisone to Improve Survival without Bronchopulmonary Dysplasia

BACKGROUND Bronchopulmonary dysplasia is a prevalent complication after extremely preterm birth. Inflammation with mechanical ventilation may contribute to its development. Whether hydrocortisone treatment after the second postnatal week can improve survival without bronchopulmonary dysplasia and without adverse neurodevelopmental effects is unknown. METHODS We conducted a trial involving infants who had a gestational age of less than 30 weeks and who had been intubated for at least 7 days at 14 to 28 days. Infants were randomly assigned to receive either hydrocortisone (4 mg per kilogram of body weight per day tapered over a period of 10 days) or placebo. Mandatory extubation thresholds were specified. The primary efficacy outcome was survival without moderate or severe bronchopulmonary dysplasia at 36 weeks of postmenstrual age, and the primary safety outcome was survival without moderate or severe neurodevelopmental impairment at 22 to 26 months of corrected age. RESULTS We enrolled 800 infants (mean [±SD] birth weight, 715±167 g; mean gestational age, 24.9±1.5 weeks). Survival without moderate or severe bronchopulmonary dysplasia at 36 weeks occurred in 66 of 398 infants (16.6%) in the hydrocortisone group and in 53 of 402 (13.2%) in the placebo group (adjusted rate ratio, 1.27; 95% confidence interval [CI], 0.93 to 1.74). Two-year outcomes were known for 91.0% of the infants. Survival without moderate or severe neurodevelopmental impairment occurred in 132 of 358 infants (36.9%) in the hydrocortisone group and in 134 of 359 (37.3%) in the placebo group (adjusted rate ratio, 0.98; 95% CI, 0.81 to 1.18). Hypertension that was treated with medication occurred more frequently with hydrocortisone than with placebo (4.3% vs. 1.0%). Other adverse events were similar in the two groups. CONCLUSIONS In this trial involving preterm infants, hydrocortisone treatment starting on postnatal day 14 to 28 did not result in substantially higher survival without moderate or severe bronchopulmonary dysplasia than placebo. Survival without moderate or severe neurodevelopmental impairment did not differ substantially between the two groups. (Funded by the National Institutes of Health; ClinicalTrials.gov number, NCT01353313.