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ObjectiveTo 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.DesignProspective cohort study.SettingLevel IV neonatal intensive care unit and outpatient primary care centre.ParticipantsInfants with NOWS receiving pharmacological treatment and unexposed controls matched for gestational age at birth and post-menstrual age at MRI.Main outcomesCBF assessed by ASL on non-sedated 3-Tesla MRI and standardised Hammersmith Neonatal Neurological Examination (HNNE) within 14 days of birth.ResultsThirty 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.ConclusionsIncreased 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.

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 Conclusion WISER appears to durably improve HCW well-being. Clinical Trials Number NCT02603133; https://clinicaltrials.gov/ct2/show/NCT02603133

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 1,717 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 3 glucose measurements (p

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.

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.

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.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.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.Contingent infant-directed foreign language exposure increased speech sound differentiation specific to the intervention language and did not decrease differentiation in response to English.ClinicalTrials.gov: NCT03232931.

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.

Surgical procedures are performed in the United States in a wide variety of clinical settings and with variation in clinical outcomes. In May 2012, the Task Force for Children’s Surgical Care, an ad hoc multidisciplinary group comprising physicians representing specialties relevant to pediatric perioperative care, was convened to generate recommendations to optimize the delivery of children’s surgical care. This group generated a white paper detailing the consensus opinions of the involved experts. Following these initial recommendations, the American College of Surgeons (ACS), Children’s Hospital Association, and Task Force for Children’s Surgical Care, with input from all related perioperative specialties, developed and published specific and detailed resource and quality standards designed to improve children’s surgical care (https://www.facs.org/quality-programs/childrens-surgery/childrens-surgery-verification). In 2015, with the endorsement of the American Academy of Pediatrics (https://pediatrics.aappublications.org/content/135/6/e1538), the ACS established a pilot verification program. In January 2017, after completion of the pilot program, the ACS Children’s Surgery Verification Quality Improvement Program was officially launched. Verified sites are listed on the program Web site at https://www.facs.org/quality-programs/childrens-surgery/childrens-surgery-verification/centers, and more than 150 are interested in verification. This report provides an update on the ACS Children’s Surgery Verification Quality Improvement Program as it continues to evolve.

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 (

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 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.

Objective To quantify the daily risk of unplanned extubation (UE) in newborns based on developmental and anatomical factors. Methods Prospective cohort of ventilated newborns over an 18-month period in a level IV neonatal intensive care unit (NICU). We captured UEs through four data streams. We generated multivariable logistic regression models to assess the association of UE with chronological age, birth weight, and postmenstrual age. Results During the study, 718 infants were ventilated for 5,611 patient days with 117 UEs in 81 infants. The daily risk of UE had a significant, nonlinear relationship (p 28 days, OR: 1.06, 95% CI: 1.0–1.14). Birth weight and postmenstrual age were not associated with UE. Adverse events occurred in 83/117 (71%) UE events. Iatrogenic causes of UE were more common in younger, smaller infants, whereas older, larger infants were more likely to self-extubate. Conclusion The daily risk and causes of UE change over the course of an infant's NICU hospitalization. These data can be used to identify infants at the highest risk of UE for whom targeted proactive interventions can be developed.

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.

This study examined the association between increased early oxidative stress, measured by F2-isoprostanes (IsoPs), and respiratory morbidity at term equivalent age and neurological impairment at 12 months of corrected age (CA). Plasma samples were collected from 136 premature infants on days 14 and 28 after birth. All participants were infants born at ⩽28 weeks of gestational age enrolled into the Prematurity and Respiratory Outcomes Program (PROP) study. Respiratory morbidity was determined at 40 weeks of postmenstrual age (PMA) by the Respiratory Severity Index (RSI), a composite measure of oxygen and pressure support. Neurodevelopmental assessment was performed using the Developmental Assessment of Young Children (DAYC) at 12 months of CA. Multivariable logistic regression models estimated associations between IsoP change, RSI and DAYC scores. Mediation analysis was performed to determine the relationship between IsoPs and later outcomes. Developmental data were available for 121 patients (90% of enrolled) at 12 months. For each 50-unit increase in IsoPs, regression modeling predicted decreases in cognitive, communication and motor scores of −1.9, −1.2 and −2.4 points, respectively (P

Anemia is an uncommon problem in the newborn nursery and may have serious consequences when it occurs. Using a case-based method and clinical questions that confront the practitioner, common presentations of hemolytic disease, intracranial hemorrhage, acute blood loss, and infectious causes of anemia are reviewed. The chapter includes reference ranges for red cell indices in newborns, a diagnostic algorithm, recommendations for initial laboratory assessment, and indications for red blood cell transfusion. Case examples highlight recommendations for observation, evaluation, treatment, and referral.

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.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.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.

BACKGROUND/GOAL: We sought to evaluate published evidence in aggregate regarding the impact of parenting style on the cognitive and behavioral outcomes of former preterm infants. METHODS: We searched five databases using germane MeSH terms. We defined parenting style as any descriptor of parenting using ≥2 dimensions on published parenting axes. We evaluated studies for quality of evidence and strength of recommendations using standardized tools and categorized summative recommendations by parenting axis and child outcome. RESULTS: Twenty-seven articles met our inclusion criteria. Parental responsivity is the only parenting axis strongly associated with both improved child cognition and behavior. Parental demandingness is associated only with improved child cognition, and parental warmth and rejection are associated only with child behavior. Parental coercion is not associated with subsequent child outcomes. CONCLUSIONS: Parental responsivity may be essential to optimizing neurodevelopment in former preterm infants. More targeted studies are needed to inform this relationship and identify opportunities for intervention.

Children have often been underrepresented in clinical research studies, in part, because many issues make translational research in children both different from and sometimes more difficult than research in adults. Considerations that must be taken into account when performing translational and clinical research in children include pediatric-specific disease processes, developmental differences in physiology and metabolism, practical limitations related to physical size, small numbers of subjects available for inclusion in studies, and the need for long-term follow-up to determine study outcomes. In addition, specific regulatory and ethical issues must be considered when performing clinical research in children.

Background Sensory experience is the basis for learning in infancy. In older children, abnormal sensory reactivity is associated with behavioural and developmental disorders. We hypothesised that in preterm infants, abnormal sensory reactivity during infancy would be associated with perinatal characteristics and correlate with 2-year neurodevelopmental outcomes. Methods We conducted a prospective observational study of infants with birth weight ≤1500 g using the Test of Sensory Function in Infants (TSFI) in the first year. Infants with gestational age ≤30 weeks were tested with the Bayley Scales of Infant and Toddler Development III (BSID III) at 24 months. Results Of the 72 participants evaluated at 4–12 months corrected age (median 8 months), 59 (82%) had a least one TSFI score concerning for abnormal sensory reactivity. Lower gestational age was associated with abnormal reactivity to deep pressure and vestibular stimulation (p

Caffeine, standard treatment for apnea of prematurity, improves brainstem auditory processing. We hypothesized that caffeine also improves cortical differentiation of complex speech sounds. We used event-related potential methodology to measure responses to speech-sound contrasts in 45 intensive care neonates, stratified by cumulative exposure as no-, low-, and high-caffeine groups. Sound differentiation in the low-caffeine group and near-term no-caffeine infants was similar with repeated measures analysis of variance controlling for gestational and postnatal age. However, a generalized estimating equation approach demonstrated that, at equivalent postnatal age, differentiation was reduced in the high-caffeine (gestational age 25 weeks) compared to the low-caffeine group (gestational age 28 weeks), reflecting the importance of maturity at birth (Z = 2.77, P < .006). We conclude that caffeine improves measures of auditory processing associated with improved neurodevelopmental outcomes in preterm infants. However, current usage of caffeine for apnea of prematurity cannot fully compensate for the effects of brain immaturity on speech sound processing.

OBJECTIVES: We conducted a randomized trial to test the hypothesis that mother’s voice played through a pacifier-activated music player (PAM) during nonnutritive sucking would improve the development of sucking ability and promote more effective oral feeding in preterm infants. METHODS: Preterm infants between 34 0/7 and 35 6/7 weeks’ postmenstrual age, including those with brain injury, who were taking at least half their feedings enterally and less than half orally, were randomly assigned to receive 5 daily 15-minute sessions of either PAM with mother’s recorded voice or no PAM, along with routine nonnutritive sucking and maternal care in both groups. Assignment was masked to the clinical team. RESULTS: Ninety-four infants (46 and 48 in the PAM intervention and control groups, respectively) completed the study. The intervention group had significantly increased oral feeding rate (2.0 vs 0.9 mL/min, P < .001), oral volume intake (91.1 vs 48.1 mL/kg/d, P = .001), oral feeds/day (6.5 vs 4.0, P < .001), and faster time-to-full oral feedings (31 vs 38 d, P = .04) compared with controls. Weight gain and cortisol levels during the 5-day protocol were not different between groups. Average hospital stays were 20% shorter in the PAM group, but the difference was not significant (P = .07). CONCLUSIONS: A PAM using mother’s voice improves oral feeding skills in preterm infants without adverse effects on hormonal stress or growth.

Feeding difficulties common in preterm infants often delay their initial discharge to home (1). Neonatal intensive care unit (NICU) graduates are then at high risk for rehospitalisation during the first year of life, and feeding problems such as aspiration contribute significantly to this morbidity. Gastrointestinal and respiratory diagnoses, primarily aspiration and feeding disorders, account for one-quarter of all readmissions and are among the most expensive readmissions (2). One possible aetiology for these problems is that feeding skills of preterm infants continue to mature to the level of term infants well after discharge from the NICU (3). The acquisition of optimal basic feeding skills in preterm infants before discharge to home can establish a solid basis for later learning of more complex skills and prevention of serious complications. Effective non-nutritive sucking (NNS) is the basis for more complex oral feeding skills and the focus of multiple feeding interventions (4,5). In a trial of a pacifier-activated music (PAM) player with mother's voice, preterm infants treated between 34 and 36 weeks postmenstrual age showed an improvement of NNS and feeding outcomes with five intervention sessions (6). The intervention, based on operant conditioning of suck with positive reinforcement using mother's voice, improved suck strength and shortened time to oral feeding. Currently, there are no published follow-up studies with patients who received this intervention. In addition, concerns were raised that infants would later not feed orally unless they heard their mother singing or that this technique may create later oral feeding problems (6). We designed a follow-up study using parental report and medical chart audit to test the hypothesis that infants in the PAM intervention group, given their earlier establishment of a basic feeding skill, would have no worse acquisition of developmental feeding milestones than infants in the control group in the first year after discharge to home. As an additional safety measure, we reviewed the medical charts for severe feeding-related morbidities. Institutional Review Board Approval was obtained to contact parents of previously enrolled infants, to review the infants' medical records and administer by phone a follow-up questionnaire modified (to ensure English was at the level of six years of school) from the Pediatric Feeding History and Clinical Assessment Form (six months and older) section `C6: Current Nutritional Status/Feeding History/Responses to Food/Current Skills' created by American Speech-Language-Hearing Association (7). Parents of participants, mean age of 17 months CA, were contacted by phone every day, no more than twice a day, and if not available after one month, were labelled `unreachable'. Required responses were numeric, multiple choice, and yes/no, with opportunities for elaborating on responses as needed. Medical record review identified number of hospitalisations related to feeding problems, documentation of feeding therapy services, aspiration events, result of most recent swallow study, and any new feeding diagnoses. Analyses of group differences were conducted using ANOVA with correction for multiple comparisons for continuous variables and Fisher's exact test for logistic variables. Of the initial 94 infants in the study, two were deceased, 18 were unreachable, and 72 consented to the study (78.3%). Characteristics of the entire cohort can be found in the original report (6). There were no measurable differences in between infants in the intervention and control groups, or between those lost to follow-up and those who participated (Table 1). All questionnaires were complete. No parent, including those in the intervention group, reported a need for contingent singing in order for their infants to feed at any time between discharge and follow-up. There were no differences between the groups in reflux diagnoses, difficulties with transition to pureed foods or solid foods, drinking from a cup, frequency of mealtimes greater than 30 minutes, nor parental mealtime stress perception. All infants in the intervention group were introduced to pureed food prior to 10 months corrected age, while two of 37 control infants were introduced to pureed food after 10 months, with one reporting difficulties introducing solids as well. Parents of three control group infants reported that their children received feeds via nasogastric or gastrostomy tube after discharge and up to 12 months, confirmed in the medical records. There were no reports or medical record instances of enteral feeds in the PAM group. Parents of two control group infants and no PAM infants reported severe sensory-oral aversions. On medical chart review, infants assigned to the PAM intervention had fewer hospitalisations due to feeding difficulties in the first year of life (p < 0.001) and fewer aspiration events requiring intervention during the first three months after discharge (p = 0.05). Table 1 Characteristics of follow-up cohort Our study shows that use of PAM with mother's voice to optimise the acquisition of NNS in preterm infants during NICU hospitalisation does not result in worse developmental progression of feeding milestones or increase the risk of documented feeding-related medical morbidities during the first year of life (Table 2). Infants in the intervention group fed without contingent singing as these behaviours extinguished when the initial reinforcement (singing) was replaced with a stronger reinforcement (food) (8). The developmental progression of feeding skills was not adversely altered by early acquisition of NNS, and there was no increase in feeding aversions as hypothesised in a critique of the original study. Furthermore, all intervention group infants had successful introduction to textured food by 10 months of age, decreasing their likelihood of consuming inadequate food volumes or refusing solids (9). Although it is unlikely that NNS training directly resulted in oromotor and orosensory improvements by 10 months of age, it is possible that a successful and safe early experience with liquid foods resulted in positive reinforcement of early oral feeding behaviours. Table 2 Feeding behaviours and medical morbidities in the first year of life We can only speculate on the links between NNS training and decreased aspiration events and feeding-related hospitalisations. Aspiration occurs during the pharyngeal stage of swallowing when airway protective reflexes fail and allow a bolus to enter the lower airway below the vocal folds (10–12). This can lead to permanent damage to the lungs, hypoxic events, and interruptions to normal development (11,12). Chronic aspiration can cause inflammation and increase a child's risk for recurrent pneumonia, interstitial lung disease, bronchiolitis, and apnoea and eventually cause severe impairment of lung function (11,13). Silent aspiration, present in 90–100% of children with documented aspiration, increases the risk of growth failure, malnutrition, and developmental delays (13) and is associated with mealtime behaviour disturbances or oral aversions (12). PAM training increases amplitude and rate of swallowing (6), and NNS training improves the rhythmicity of sucking patterns (9). These gains may in turn benefit the suck–swallow–breathe relationship, acknowledging that reduced aspiration is most likely related to improved swallow–respiration coordination (14,15). Aspiration in early childhood affects preterm more than term infants and contributes to morbidity and mortality (11,13). This follow-up study suggests that these infants may have fewer rehospitalisations due to feeding problems in the first year of life, possibly associated with more mature feeding skills, resulting in fewer adverse events. PAM's potential effect on oral feeding skills may therefore have economic consequences on postdischarge care of preterm infants. In the United States, the average hospital costs per readmission due to gastrointestinal and chronic respiratory diagnoses are $4153 and $9049 respectively (2). Although neither the initial trial nor the current study was powered to analyse cost-effectiveness, the potential gains from a decrease in length of stay during the initial hospitalisation and fewer subsequent readmissions suggest the need for further studies designed to address these questions (6). This study suffered from the limitations inherent to questionnaires and chart reviews, such as potential recall bias or incomplete medical record documentation. A questionnaire may also lack the sensitivity to detect feeding difficulties not related to acquisition of developmental processes. Future studies using prospective, quantitative assessment of feeding skills (feeding volumes/rates/patterns, oropharyngeal assessment of deglutition or orosensory responses) and long-term neurodevelopmental outcomes would strengthen the widespread use of NNS training. In conclusion, we have previously shown that PAM using mother's voice as positive reinforcement is an effective oromotor intervention to improve oral feeding skills in the NICU. Our follow-up study shows that a brief exposure to PAM in the NICU is not associated with a slower developmental progression of feeding skills in the first year of life and may be associated with fewer aspiration events and fewer rehospitalisations with feeding-related diagnoses. Further studies are needed to examine these potential long-term benefits.

Objective Compare neurodevelopment after levetiracetam (LEV) and phenobarbital (PB) for neonatal seizures. Study design Retrospective study of infants who received antiepileptic drugs (AEDs) for neonatal seizures. Effect of cumulative exposure to LEV and PB on outcomes of death, cerebral palsy (CP), and Bayley Scales of Infant Development (BSID) scores were evaluated at 24 months corrected age. Analyses were adjusted for number of electrographic seizures and gestational age. Results In 280 infants with comparable seizure etiology and cranial imaging results, increased exposure to PB was associated with worse BSID cognitive and motor scores (8.1- and 9-point decrease per 100 mg/kg; p=0.01). The effect was less with LEV (2.2- and 2.6-point decrease per 300 mg/kg LEV (p=0.01). CP probability increased by 2.3-fold per 100 mg/kg PB and was not associated with increasing LEV. Conclusion Increased exposure to PB is associated with worse neurodevelopmental outcomes than LEV. Prospective studies of outcomes of neonatal exposure to AEDs are essential.

Of the 500 000 premature babies born each year in the United States, nearly 75%—or 375 000—of them are born at 34 0/7 through 36 6/7 weeks of gestational age (GA). These infants are referred to as ‘late preterm infants' (LPI) by many who publish research and commentaries about their care, including the consensus panel at the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD).1 Late preterm infants are physiologically and metabolically immature at the time of birth, often lacking the self-regulatory ability to respond appropriately to the extra-uterine environment. Despite their appearance as small but ‘normal' babies, LPIs have higher rates of morbidity and mortality than their term counterparts, not only during birth hospitalization, but also throughout the first year after birth and beyond.2 In some hospitals, LPIs account for up to 20% of admissions to the NICU, and LPIs are more likely to be re-hospitalized within the first 2 weeks of discharge.3, 4, 5 The morbidity rate approximately doubles for every week below 38 weeks gestational age that a baby is born (38 weeks: 3.3% 37 weeks: 5.9% 36 weeks: 12.4% 35 weeks: 25% 34 weeks: 51.2%).6 Because of these inherent risks, LPIs require increased surveillance and monitoring of the mother–infant dyad to direct their healthcare needs. The level and intensity of care provided should be based on ongoing assessment of the infant's physiological status and availability of services and personnel within the birthing facility, so that any needed interventions can occur quickly to prevent permanent consequences. With appropriate awareness of potential risks, the care of many LPIs can be managed in the postpartum setting, and the Multidisciplinary Guidelines for the Care of Late Preterm Infants are focused on these infants. However, some infants may require transfer to a higher level of care for suitable management and monitoring. A multidisciplinary approach to caring for the LPI is recommended. Care should be implemented and coordinated by clinicians within their scope of practice and should be family-centered, developmentally supportive, and within the context of the family's culture and preferences. Communication should occur and education should be provided in ways that are appropriate for individual family needs, including families with limited or no English proficiency or health literacy. Care standards should always be of the highest quality but may require different methods of implementation.

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.

Bronchopulmonary dysplasia (BPD), also known as chronic lung disease of prematurity, and typically defined as the need for supplemental oxygen at 36 weeks' postmenstrual age, affects approximately 10% and 40% of very low birth weight and extremely low birth weight infants, respectively. Contributing factors include infection, oxygen exposure and ventilator induced lung injury, which can lead to impaired lung function. Several preventative and therapeutic strategies have been used in BPD, including lung protective ventilator strategies, and pharmacologic interventions. While many infants with BPD are treated with a wide variety of medications, little evidence for the efficacy of these treatments exist. This article will review current practice in the prevention and management of this complication of prematurity.

The purpose of this study was to describe variation among states in designations of hospital neonatal services levels. We systematically searched all 50 states and District of Columbia governmental web sites and extracted definitions and levels terminology, functional and utilization criteria, regulatory compliance and funding measures, and citation of American Academy of Pediatrics (AAP) documents on levels of neonatal care. Thirty-three states designate multiple graduated levels of neonatal services. Two to six levels were designated by numbers, titles, or both. Regulatory sources include hospital licensure, Certificate of Need or State Health Plan (CON/SHP), State Health Department, or an affiliated non-governmental entity (SHD/affiliate). Twenty-four states have a single source and nine have two or more. Functional criteria include population characteristics, respiratory care capabilities, and neonatal and cardiac surgery in 25 states. Utilization criteria include capacity, volume, occupancy, or case mix. Compliance mechanisms include license renewal, CON/SHP approval, and/or SHD/affiliate certification. Thirteen states link funding for the highest level of care through Medicaid, Maternal Child Health Title V funds or regional programs. AAP documents are cited or incorporated by reference in 22 states. All states regulate health care services and facilities. Definitions, criteria, compliance mechanisms, and regulatory source and status of neonatal levels of service vary widely. A consistent national approach would facilitate comparisons in neonatal outcomes and resource use and be informative to parents, providers, and policy makers. AAP documents could serve as a mechanism to foster such consistency.

The neonatal intensive care unit (NICU) depends heavily on advanced biomedical devices for monitoring, diagnosis, and treatment. Developing safe and effective devices for use in the NICU requires collaborative research and testing efforts between the bioengineering and biomedical disciplines. However, no mechanism exists to match the needs of the clinical community and the efforts of the bioengineering community. To address this issue, in February 2009, the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) of the National Institutes of Health (NIH) invited a team of experts from diverse fields of biomedicine and bioengineering to participate in a workshop. The team reviewed and summarized bioinstrumentation needs and proposed a research agenda to develop safe and effective devices and instruments. The discussants addressed topics in cardiopulmonary, cerebrovascular, metabolic, and infectious conditions of the neonate. The authors provide a summary of the workshop discussions in this paper.

Providing safe and effective care requires coordination among the multiple levels of the health care system. These levels comprise the newborn (patient, family and community), nursery or primary care practice (microsystem), hospital or managed care organization (macro-organization) and policy, payment or regulatory issues (environmental context). Contemporary care practices associated with childbirth and early newborn care often reflect disruptions in coordination of these processes and place newborns at risk for poor outcomes. For example, with routine early postpartum discharge, often at less than 48 h after vaginal birth, the peak of serum bilirubin at 3 to 5 days of age typically occurs at home, rather than observed by clinicians in a newborn nursery. In addition, lactation is rarely well established by early discharge and support is often inadequate, increasing the risk of hyperbilirubinemia and discontinuation of breastfeeding. Also, late preterm infants are frequently cared for in the newborn nursery, although they often have difficulty establishing oral feeding and are at substantially higher risk for severe hyperbilirubinemia than infants born at term. Finally, pediatric follow-up is often delayed beyond the first week, after the optimal time for continued assessment of jaundice and lactation. The American Academy of Pediatrics Safe and Healthy Beginnings Initiative, a pilot quality improvement project, will target newborn nurseries, primary care practices and coordination between these sites using a systems-based approach to facilitate implementation of the 2004 guideline for management of hyperbilirubinemia.

With increasing numbers of extremely premature infants surviving, the outcome for these infants has generated much interest and controversy. This article reviews recent progress in the management and outcomes of some of the most common conditions affecting infants with very low birth weight (1500 g or less) and extremely low birth weight (1000 g or less).

Current evidence does not favour use of corticosteroids as neurological side effects may outweigh the benefits of treatment, except perhaps in critically ill infants with respiratory failure

Background Bloodstream infection (BSI) among neonatal intensive care unit (NICU) infants is a frequent problem associated with poor outcomes. Monitoring for abnormal heart rate characteristics (HRCs) may decrease infant mortality by alerting clinicians to sepsis before it becomes clinically apparent. Methods HRC scores were acquired using the HRC (HeRO) monitor system from Medical Predictive Science Corporation and entered into the electronic medical record by bedside staff. We retrospectively analysed HRC scores recorded twice daily in the medical record during a 30-month period (1 January 2010 through 30 June 2012) for infants in the NICU at the Monroe Carell Jr. Children9s Hospital at Vanderbilt. We identified infants that met Centers for Disease Control criteria for late-onset BSI (>3 days of life) during the study period. Results During the study period, we recorded 127 673 HRC scores from 2384 infants. We identified 46 infants with BSI. Although 8% (9701/127 673) of the HRC scores were ≥2 and 1% (1387/127 673) were ≥5, BSI (at any time) was observed in just 5% of patients with HRC scores ≥2, and 9% of patients with HRC scores ≥5. Of infants with BSI, 5/46 (11%) had at least one HRC score ≥5 and 17/46 (37%) had at least one score ≥2 recorded in the 48 h period prior to the evaluation that resulted in the first positive blood culture of the episode. Conclusions In our single-centre retrospective study, elevated HRC scores had limited ability to detect BSI. BSI was infrequent at any time during hospitalisation in infants with significantly elevated HRC scores.

Objective To determine the rate of adverse events associated with endotracheal intubation in newborns and modifiable factors contributing to these events. Study design We conducted a prospective, observational study in a 100-bed, academic, level IV neonatal intensive care unit from September 2013 through June 2014. We collected data on intubations using standardized data collection instruments with validation by medical record review. Intubations in the delivery or operating rooms were excluded. The primary outcome was an intubation with any adverse event. Adverse events were defined and tracked prospectively as nonsevere or severe. We measured clinical variables including number of attempts to successful intubation and intubation urgency (elective, urgent, or emergent). We used logistic regression models to estimate the association of these variables with adverse events. Results During the study period, 304 intubations occurred in 178 infants. Data were available for 273 intubations (90%) in 162 patients. Adverse events occurred in 107 (39%) intubations with nonsevere and severe events in 96 (35%) and 24 (8.8%) intubations, respectively. Increasing number of intubation attempts (OR 2.1, 95% CI, 1.6-2.6) and emergent intubations (OR 4.7, 95% CI, 1.7-13) were predictors of adverse events. The primary cause of emergent intubations was unplanned extubation (62%). Conclusions Adverse events are common in the neonatal intensive care unit, occurring in 4 of 10 intubations. The odds of an adverse event doubled with increasing number of attempts and quadrupled in the emergent setting. Quality improvement efforts to address these factors are needed to improve patient safety.

In 2003, 12.3% of births in the United States were preterm (

Summary Chronic lung disease (CLD) of the premature, also known as bronchopulmonary dysplasia (BPD), is a disease of multifactorial aetiology that primarily affects premature infants. The management of these infants requires a multidisciplinary approach, and is largely supportive. The focal points in the care of these infants are the optimisation of respiratory care and nutritional status. This review presents management strategies for CLD and the supporting evidence. Although significant progress has been made in caring for infants with CLD, further research is required to fully understand and prevent the disease, or at least minimise its severity.

Kernicterus, thought to be due to severe hyperbilirubinemia, is an uncommon disorder with tragic consequences, especially when it affects healthy term and near-term infants. Early identification, prevention and treatment of severe hyperbilirubinemia should make kernicterus a preventable disease. However, national epidemiologic data are needed to monitor any preventive strategies. Recommendations are provided to obtain prospective data on the prevalence and incidence of severe hyperbilirubinemia and associate mortality and neurologic injury using standardized definitions, explore the clinical characteristics and root causes of kernicterus in children identified in the Kernicterus Pilot Registry, identify and test an indicator for population surveillance, validating systems-based approaches to the management of newborn jaundice, and explore the feasibility of using biologic or genetic markers to identify infants at risk for hyperbilirubinemia. Increased knowledge about the incidence and consequences of severe hyperbilirubinemia is essential to the planning, implementation and assessment of interventions to ensure that infants discharged as healthy from their birth hospitals have a safer transition to home, avoiding morbidity due to hyperbilirubinemia and other disorders. At a recent NIHCD-sponsored conference, key questions were raised about kernicterus and the need for additional strategies for its prevention. These questions and an approach to their answers form the basis of this report.

To determine whether minimal ventilation decreases death or bronchopulmonary dysplasia (BPD).Infants with birth weight 501 g to 1000 g and mechanically ventilated before 12 hours were randomly assigned to minimal ventilation (partial pressure of carbon dioxide [PCO(2)] target52 mm Hg) or routine ventilation (PCO(2) target48 mm Hg) and a tapered dexamethasone course or saline placebo for 10 days, using a 2 x 2 factorial design. The primary outcome was death or BPD at 36 weeks' postmenstrual age.After enrollment of 220 patients, the trial was halted because of unanticipated nonrespiratory adverse events related to dexamethasone therapy. The relative risk for death or BPD at 36 weeks in the minimal versus routine ventilation groups was 0.93 (95% CI, 0.77-1.12; P =.43). Ventilator support at 36 weeks was 1% in the minimal versus 16% in the routine group (P.01). Major morbidities and long-term outcome were comparable in both treatment groups.With the sample size studied, minimal ventilation did not reduce the incidence of death or BPD. The reduced ventilator support at 36 weeks in the minimal ventilation group warrants further study of this intervention.

Objective. Late-onset sepsis (occurring after 3 days of age) is an important problem in very low birth weight (VLBW) infants. To determine the current incidence of late-onset sepsis, risk factors for disease, and the impact of late-onset sepsis on subsequent hospital course, we evaluated a cohort of 6956 VLBW (401–1500 g) neonates admitted to the clinical centers of the National Institute of Child Health and Human Development Neonatal Research Network over a 2-year period (1998–2000).Methods. The National Institute of Child Health and Human Development Neonatal Research Network maintains a prospective registry of all VLBW neonates admitted to participating centers within 14 days of birth. Expanded infection surveillance was added in 1998.Results. Of 6215 infants who survived beyond 3 days, 1313 (21%) had 1 or more episodes of blood culture-proven late-onset sepsis. The vast majority of infections (70%) were caused by Gram-positive organisms, with coagulase-negative staphylococci accounting for 48% of infections. Rate of infection was inversely related to birth weight and gestational age. Complications of prematurity associated with an increased rate of late-onset sepsis included patent ductus arteriosus, prolonged ventilation, prolonged intravascular access, bronchopulmonary dysplasia, and necrotizing enterocolitis. Infants who developed late-onset sepsis had a significantly prolonged hospital stay (mean length of stay: 79 vs 60 days). They were significantly more likely to die than those who were uninfected (18% vs 7%), especially if they were infected with Gram-negative organisms (36%) or fungi (32%).Conclusions. Late-onset sepsis remains an important risk factor for death among VLBW preterm infants and for prolonged hospital stay among VLBW survivors. Strategies to reduce late-onset sepsis and its medical, social, and economic toll need to be addressed urgently.

It is uncertain whether the rates and causes of early-onset sepsis (that occurring within 72 hours after birth) among very-low-birth-weight infants have changed in recent years, since antibiotics have begun to be used more widely during labor and delivery.We studied 5447 very-low-birth-weight infants (those weighing between 401 and 1500 g) born at centers of the Neonatal Research Network of the National Institute of Child Health and Human Development between 1998 and 2000 who had at least one blood culture in the first three days of life and compared them with 7606 very-low-birth-weight infants born at centers in the network between 1991 and 1993.Early-onset sepsis (as confirmed by positive blood cultures) was present in 84 infants in the more recent birth cohort (1.5 percent). As compared with the earlier birth cohort, there was a marked reduction in group B streptococcal sepsis (from 5.9 to 1.7 per 1000 live births of infants weighing 401 to 1500 g, P0.001) and an increase in Escherichia coli sepsis (from 3.2 to 6.8 per 1000 live births, P=0.004); the overall rate of early-onset sepsis was not significantly changed. Most E. coli isolates from the recent birth cohort (85 percent) were resistant to ampicillin, and mothers of infants with ampicillin-resistant E. coli infections were more likely to have received intrapartum ampicillin than were those with ampicillin-sensitive strains (26 of 28 with sensitivity data vs. 1 of 5, P=0.01). Infants with early-onset sepsis were more likely to die than uninfected infants (37 percent vs. 13 percent, P0.001), especially if they were infected with gram-negative organisms.Early-onset sepsis remains an uncommon but potentially lethal problem among very-low-birth-weight infants. The change in pathogens over time from predominantly gram-positive to predominantly gram-negative requires confirmation by ongoing surveillance.