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.

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.

Randomized Trial to Increase Speech Sound Differentiation in Infants Born Preterm.

OBJECTIVE: To test whether infant-directed foreign language active learning would specifically increase speech sound differentiation to the intervention language while not decreasing differentiation in response to English. STUDY DESIGN: Pilot randomized controlled trial of stable infants born preterm in the newborn intensive care unit with normal auditory brainstem responses, whose parents spoke only English and had no musical training or familial hearing abnormality. Assignment was to 1 of 3 groups: passive exposure to English infant-directed lullabies and readings (English-enrichment, control group) and contingent exposure by active sucking on a sensor-equipped pacifier to either infant-directed French lullabies and readings (English environment, French-contingent learning group) or infant-directed Mandarin lullabies and readings (English environment, Chinese-contingent learning group). The main outcome measures were preintervention and postintervention event-related potentials (ERPs) in response to standardized speech syllables in each language. RESULTS: Forty-one subjects completed the study, including 15 in the English-enrichment control group and 13 each in the French-contingent and Chinese-contingent groups. The median gestational age at birth was 34 weeks (IQR, 8.75 weeks); postmenstrual age at intervention ranged from 36 to 46 weeks and was similar across the 3 groups. Postintervention mean ERP amplitude to pairs of English speech sounds did not differ across the 3 groups; however, ERP amplitude in French sound differentiation was greater in the French-contingent group than in the Chinese-contingent or English-enrichment groups, and ERP amplitude greater in Chinese sound differentiation was greater in the Chinese-contingent group compared with the other 2 groups. CONCLUSION: Contingent infant-directed foreign language exposure increased speech sound differentiation specific to the intervention language and did not decrease differentiation in response to English. TRIAL REGISTRATION: ClinicalTrials.gov: NCT03232931.

Cerebral perfusion and neurological examination characterise neonatal opioid withdrawal syndrome: a prospective cohort study.

OBJECTIVE: To test the hypothesis that cerebral blood flow (CBF) assessed with arterial spin labelling (ASL) MRI is increased and standardised neurological examination is altered in infants with neonatal opioid withdrawal syndrome (NOWS) compared with those without. DESIGN: Prospective cohort study. SETTING: Level IV neonatal intensive care unit and outpatient primary care centre. PARTICIPANTS: Infants with NOWS receiving pharmacological treatment and unexposed controls matched for gestational age at birth and post-menstrual age at MRI. MAIN OUTCOMES: CBF assessed by ASL on non-sedated 3-Tesla MRI and standardised Hammersmith Neonatal Neurological Examination (HNNE) within 14 days of birth. RESULTS: Thirty infants with NOWS and 31 control infants were enrolled and included in the final analysis. Global CBF across the brain was higher in the NOWS group compared with controls (14.2 mL/100 g/min±5.5 vs 10.7 mL/100 g/min±4.3, mean±SD, Cohen's d=0.72). HNNE total optimality score was lower in the NOWS group compared with controls (25.9±3.6 vs 28.4±2.4, mean±SD, Cohen's d=0.81). A penalised logistic regression model including both CBF and HNNE items discriminated best between the two groups. CONCLUSIONS: Increased cerebral perfusion and neurological examination abnormalities characterise infants with NOWS compared with those without intrauterine drug exposure and suggest prenatal substance exposure affects fetal brain development. Identifying neurological and neuroimaging characteristics of infants with NOWS can contribute to understanding mechanisms underlying later outcomes and to designing potential new treatments.

Randomized controlled trial of the "WISER" intervention to reduce healthcare worker burnout.

OBJECTIVE: Test web-based implementation for the science of enhancing resilience (WISER) intervention efficacy in reducing healthcare worker (HCW) burnout. DESIGN: RCT using two cohorts of HCWs of four NICUs each, to improve HCW well-being (primary outcome: burnout). Cohort 1 received WISER while Cohort 2 acted as a waitlist control. RESULTS: Cohorts were similar, mostly female (83%) and nurses (62%). In Cohorts 1 and 2 respectively, 182 and 299 initiated WISER, 100 and 176 completed 1-month follow-up, and 78 and 146 completed 6-month follow-up. Relative to control, WISER decreased burnout (-5.27 (95% CI: -10.44, -0.10), p = 0.046). Combined adjusted cohort results at 1-month showed that the percentage of HCWs reporting concerning outcomes was significantly decreased for burnout (-6.3% (95%CI: -11.6%, -1.0%); p = 0.008), and secondary outcomes depression (-5.2% (95%CI: -10.8, -0.4); p = 0.022) and work-life integration (-11.8% (95%CI: -17.9, -6.1); p < 0.001). Improvements endured at 6 months. CONCLUSION: WISER appears to durably improve HCW well-being. CLINICAL TRIALS NUMBER: NCT02603133; https://clinicaltrials.gov/ct2/show/NCT02603133.

Changes in Use of Respiratory Support for Preterm Infants in the US, 2008-2018.

Importance: In preterm infants, mechanical ventilation (MV) is associated with adverse pulmonary and neurodevelopmental outcomes. Multiple randomized clinical trials over the past 2 decades have shown the effectiveness of early noninvasive ventilation (NIV) in decreasing the use of MV in preterm infants. The epidemiologic factors associated with respiratory support in US preterm infants and any temporal changes after these trials is unknown. Objective: To evaluate temporal changes in MV and noninvasive respiratory support in US preterm infants. Design, Setting, and Participants: In a cohort design, 2 large national data sets (Pediatrix Clinical Data Warehouse for the clinical cohort and National Inpatient Sample for the national cohort) were used to collect data on preterm infants (<35 weeks' gestation) without congenital anomalies who received active intensive care and were discharged home or died in the birth hospital from January 1, 2008, to December 31, 2018. Data analysis was conducted from December 10, 2019, to December 16, 2020. Exposure: Discharge year. Main Outcome and Measures: In the clinical cohort, detailed respiratory support data were generated, including days of MV and NIV modalities, and temporal trends were evaluated using multivariable modified Poisson or negative binomial regression models with discharge year as a continuous variable. In the national cohort, observed and expected national MV use were calculated. Results: Among 259 311 infants (47.2% female) in 359 neonatal intensive care units in the clinical cohort, decreases were noted in the use (from 29.4% of infants in 2008 to 18.5% in 2018, relative risk for annual change, 0.96; 95% CI, 0.95-0.96) and duration (mean days, from 10.3 in 2008 to 9.7 in 2018; rate ratio for annual change, 0.98; 95% CI, 0.97-0.98) of MV. Noninvasive ventilation use increased from 57.9% of infants in 2008 to 67.4% in 2018 (adjusted relative risk for annual change, 1.02; 95% CI, 1.02-1.03), and mean NIV duration increased by 3.2 days (95% CI, 2.9-3.6 days). With increased use of continuous positive airway pressure and nasal intermittent positive-pressure ventilation as the main factors in the increase, the mean duration of respiratory support increased from 13.8 to 15.4 days (adjusted rate ratio for annual change, 1.03; 95% CI, 1.02-1.04) from 2008 to 2018. Among 1 169 441 infants in the national cohort, MV use decreased from 22.0% in 2008 to 18.5% in 2018, with an estimated 29 700 fewer ventilated infants and 142 000 fewer days of MV than expected during this period. Conclusions and Relevance: These findings suggest that preterm respiratory support changed significantly from 2008 to 2018, with decreased use and duration of MV, increased use and duration of NIV, and an overall increase in respiratory support duration.

Increasing Volume-Targeted Ventilation Use in the NICU.

BACKGROUND: In preterm infants who require mechanical ventilation (MV), volume-targeted ventilation (VTV) modes are associated with lower rates of bronchopulmonary dysplasia compared with pressure-limited ventilation. Bronchopulmonary dysplasia rates in our NICU were higher than desired, prompting quality improvement initiatives to improve MV by increasing the use of VTV. METHODS: We implemented and tested interventions over a 3-year period. Primary outcomes were the percentage of conventional MV hours when any-VTV mode was used and the percentage of conventional MV hours when an exclusively VTV mode was used. Exclusively VTV modes were modes in which all breaths were volume targeted. We evaluated outcomes during 3 project periods: baseline (May 2016-December 2016); epoch 1 (December 2016-October 2018), increasing the use of any-VTV mode; and epoch 2 (October 2018-November 2019), increasing the use of exclusively VTV modes. RESULTS: Use of any-VTV mode increased from 18 694 of 22 387 (83%) MV hours during baseline to 72 846 of 77 264 (94%) and 58 174 of 60 605 (96%) MV hours during epochs 1 and 2, respectively (P < .001). Use of exclusively VTV increased from 5967 of 22 387 (27%) during baseline to 47 364 of 77 264 (61%) and 46 091 of 60 605 (76%) of all conventional MV hours during epochs 1 and 2, respectively (P < .001). In statistical process control analyses, multiple interventions were associated with improvements in primary outcomes. Measured clinical outcomes were unchanged. CONCLUSIONS: Quality improvement interventions were associated with improved use of VTV but no change in measured clinical outcomes.

Prenatal Exposures Are Associated With Worse Neurodevelopmental Outcomes in Infants With Neonatal Opioid Withdrawal Syndrome.

Aim: To define a developmental trajectory in infants with neonatal opioid withdrawal syndrome (NOWS) and determine whether the impacted developmental domain varies with the type of antenatal exposure. Methods: We performed a retrospective cohort study of infants treated pharmacologically for NOWS and assessed using a standardized schedule for follow-up visits. We compared outcomes of the study population to published norms using one-sample t-tests. Multivariable models examined associations with exposures in addition to opioids. Results: In our cohort of 285 infants with 9-12-months testing, 164 (55.7%) were seen at 3-4 months, and 125 (44%), at 15-18 months. The majority (58%) had intrauterine drug exposures in addition to opioids. Neurodevelopmental scores of infants with NOWS at 3-4 and 9-12 months were not different from published norms. Cognitive and language scores at 15-18 months were worse than published norms. Male sex, older maternal age, and additional barbiturate or alcohol exposure were associated with worse outcomes. Conclusion: Infants with pharmacologically treated NOWS had development similar to unexposed infants during the 1st year but worse cognitive and language scores during the 2nd year. These data support the need for a prospective follow-up of large cohorts of infants with NOWS, with systematic assessments and an evaluation of contributing factors.

Glucose concentrations in enterally fed preterm infants.

OBJECTIVES: Determine the prevalence of glucose concentrations below the Pediatric Endocrine Society (PES) term and late preterm-focused guideline target for mean glucose concentrations (≥70 mg/dL) among preterm NICU infants on full enteral nutrition and assess the impact on monitoring practices. STUDY DESIGN: Retrospective cohort study. RESULTS: We analyzed 1717 infants who were at least 2 days old and 48 hours after parenteral fluids were discontinued. Glucose concentrations were ≥70, 60-69, 50-59, and <50 mg/dL in 76.6, 16.2, 5.9, and 1.3% of measurements, respectively. In multivariate models, concentrations <60 mg/dL were common among male infants at lower postnatal age, small-for-gestational age, and born to women with hypertension (p < 0.05). After PES guideline, infants were more likely to have >3 glucose measurements (p < 0.05). CONCLUSIONS: Glucose concentrations <70 mg/dL are not uncommon among preterm infants receiving full enteral nutrition. Monitoring increased after guideline publication. Applying PES threshold to well-appearing preterm infants may promote increased monitoring and intervention without clear long-term benefit.

Outcomes, Resource Use, and Financial Costs of Unplanned Extubations in Preterm Infants.

OBJECTIVES: Unplanned extubations (UEs) in adult and pediatric populations are associated with poor clinical outcomes and increased costs. In-hospital outcomes and costs of UE in the NICU are not reported. Our objective was to determine the association of UE with clinical outcomes and costs in very-low-birth-weight infants. METHODS: We performed a retrospective matched cohort study in our level 4 NICU from 2014 to 2016. Very-low-birth-weight infants without congenital anomalies admitted by 72 hours of age, who received mechanical ventilation (MV), were included. Cases (+UE) were matched 1:1 with controls (-UE) on the basis of having an equivalent MV duration at the time of UE in the case, gestational age, and Clinical Risk Index for Babies score. We compared MV days after UE in cases or the equivalent date in controls (postmatching MV), in-hospital morbidities, and hospital costs between the matched pairs using raw and adjusted analyses. RESULTS: Of 345 infants who met inclusion criteria, 58 had ≥1 UE, and 56 out of 58 (97%) were matched with appropriate controls. Postmatching MV was longer in cases than controls (median: 12.5 days; interquartile range [IQR]: 7 to 25.8 vs median 6 days; IQR: 2 to 12.3; adjusted odds ratio: 4.3; 95% confidence interval: 1.9-9.5). Inflation-adjusted total hospital costs were higher in cases (median difference: $49 587; IQR: -15 063 to 119 826; adjusted odds ratio: 3.8; 95% confidence interval: 1.6-8.9). CONCLUSIONS: UEs in preterm infants are associated with worse outcomes and increased hospital costs. Improvements in UE rates in NICUs may improve clinical outcomes and lower hospital costs.

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.

Building the Driver Diagram: A Mixed-Methods Approach to Identify Causes of Unplanned Extubations in a Large Neonatal ICU.

BACKGROUND: The key driver diagram (KDD) is an important tool used by improvement teams to guide and frame their work. Methods to build a KDD when little relevant literature or reliable local data exist are poorly described. This article describes the process used in our neonatal ICU (NICU) to build a KDD to decrease unplanned extubations (UE) in chronically ventilated infants. METHODS: Twenty-seven factors hypothesized to be associated with UE in our NICU were identified. An expert panel of 33 staff members completed three rounds of a modified Delphi process administered through an online interface. After the third round, panel members provided suggestions for interventions to target all factors meeting criteria for consensus. These qualitative data were analyzed by inductive thematic analysis. A follow-up survey to all panel members was used to assess the feasibility of this process for future use. RESULTS: After three Delphi rounds, 14 factors met consensus and eight main interventions were identified through thematic analysis. These data were used to build a KDD for testing. All participants who completed the follow-up survey (20/20) stated willingness to participate in this process in the future and 18/20 (90%) stated they would be "more willing" or "much more willing" to support interventions developed using this process. CONCLUSION: A novel mixed-methods approach was used to generate a KDD combining a Delphi process with thematic analysis. This approach provides improvement teams a rigorous and reproducible method to understand local context, generate consensus KDDs, and improve local buy-in for improvement interventions.

Neonatal abstinence syndrome: an update.

PURPOSE OF REVIEW: The current review provides an update focused on the evolving epidemiology of neonatal abstinence syndrome (NAS), factors influencing disease expression, advances in clinical assessment of withdrawal, novel approaches to NAS treatment, and the emerging role of quality improvement in assessment and management of NAS. RECENT FINDINGS: The rise in the incidence of NAS disproportionately occurred in rural and suburban areas. Polysubstance exposure and genetic polymorphisms have been shown to modify NAS expression and severity. New bedside assessments using a limited number of factors to identify infants with NAS result in fewer infants receiving pharmacotherapy. In addition, buprenorphine may be a promising therapeutic alternative to morphine to treat NAS. Lastly, local, state, and national quality improvement initiatives have emerged as an effective mechanism to advance the care of infants with NAS. SUMMARY: NAS remains a critical public health issue associated with significant medical, economic, and personal burdens. Emerging data on associated risk factors, assessment of and treatment for NAS provide clinicians and hospitals with new knowledge and an urgency to promote standardization of care for infants with NAS.

Cry presence and amplitude do not reflect cortical processing of painful stimuli in newborns with distinct responses to touch or cold.

OBJECTIVE: Newborns requiring hospitalisation frequently undergo painful procedures. Prevention of pain in infants is of prime concern because of adverse associations with physiological and neurological development. However, pain mitigation is currently guided by behavioural observation assessments that have not been validated against direct evidence of pain processing in the brain. The aim of this study was to determine whether cry presence or amplitude is a valid indicator of pain processing in newborns. DESIGN: Prospective observational cohort. SETTING: Newborn nursery. PATIENTS: Healthy infants born at >37 weeks and <42 weeks gestation. INTERVENTIONS: We prospectively studied newborn cortical responses to light touch, cold and heel stick, and the amplitude of associated infant vocalisations using our previously published paradigms of time-locked electroencephalogram (EEG) with simultaneous audio recordings. RESULTS: Latencies of cortical peak responses to each of the three stimuli type were significantly different from each other. Of 54 infants, 13 (24%), 19 (35%) and 35 (65%) had cries in response to light touch, cold and heel stick, respectively. Cry in response to non-painful stimuli did not predict cry in response to heel stick. All infants with EEG data had measurable pain responses to heel stick, whether they cried or not. There was no association between presence or amplitude of cries and cortical nociceptive amplitudes. CONCLUSIONS: In newborns with distinct brain responses to light touch, cold and pain, cry presence or amplitude characteristics do not provide adequate behavioural markers of pain signalling in the brain. New bedside assessments of newborn pain may need to be developed using brain-based methodologies as benchmarks in order to provide optimal pain mitigation.

Interventions to Improve Patient Safety During Intubation in the Neonatal Intensive Care Unit.

OBJECTIVE: To improve patient safety in our NICU by decreasing the incidence of intubation-associated adverse events (AEs). METHODS: We sequentially implemented and tested 3 interventions: standardized checklist for intubation, premedication algorithm, and computerized provider order entry set for intubation. We compared baseline data collected over 10 months (period 1) with data collected over a 10-month intervention and sustainment period (period 2). Outcomes were the percentage of intubations containing any prospectively defined AE and intubations with bradycardia or hypoxemia. We followed process measures for each intervention. We used risk ratios (RRs) and statistical process control methods in a times series design to assess differences between the 2 periods. RESULTS: AEs occurred in 126/273 (46%) intubations during period 1 and 85/236 (36%) intubations during period 2 (RR = 0.78; 95% confidence interval [CI], 0.63-0.97). Significantly fewer intubations with bradycardia (24.2% vs 9.3%, RR = 0.39; 95% CI, 0.25-0.61) and hypoxemia (44.3% vs 33.1%, RR = 0.75, 95% CI 0.6-0.93) occurred during period 2. Using statistical process control methods, we identified 2 cases of special cause variation with a sustained decrease in AEs and bradycardia after implementation of our checklist. All process measures increased reflecting sustained improvement throughout data collection. CONCLUSIONS: Our interventions resulted in a 10% absolute reduction in AEs that was sustained. Implementation of a standardized checklist for intubation made the greatest impact, with reductions in both AEs and bradycardia.