Prenatal and Postnatal Disparities in Very-Preterm Infants in a Study of Infections between 2018-2023 in Southeastern US.

BACKGROUND: The birthrate of Black preterm (BPT) infants is 65% higher than White preterm (WPT) infants with a BPT mortality that is 2.3 times higher. The incidence of culture-positive late-onset sepsis is as high as 41% in very-preterm infants. The main purpose of this study was to examine thermal gradients and the heart rate in relation to the onset of infection. This report presents disparities in very-preterm infection incidence, bacteria, and mortality data amongst BPT and WPT infants. METHODS: 367 preterms born at <32 weeks gestational age (GA) between 2019-2023 in five neonatal intensive care units (NICUs) were enrolled to study the onset of infections and dispositions; REDCap data were analyzed for descriptive statistics. RESULTS: The 362 infants for analyses included 227 BPTs (63.7%) and 107 WPTs (29.6%), with 28 infants of other races/ethnicities (Hispanic, Asian, and other), 50.6% female, mean GA of 27.66 weeks, and 985.24 g birthweight. BPT infants averaged 968.56 g at birth (SD 257.50), and 27.68 (SD 2.07) weeks GA, compared to WPT infants with a mean birthweight of 1006.25 g (SD 257.77, p = 0.2313) and 27.67 (SD 2.00, p = 0.982) weeks GA. Of the 426 episodes of suspected infections evaluated across all the enrolled infants, the incidence of early-onset sepsis (EOS) was 1.9%, with BPT infants having 2.50 times higher odds of EOS than WPT infants (p = 0.4130, OR (odds ratio) = 2.50, p_or = 0.408). The overall incidence of late-onset sepsis (LOS) was 10.8%, with LOS in 11.9% of BPT infants versus 9.3% (p = 0.489, OR = 1.21, p_or = 0.637) of WPT infants. BPT infants made up 69.2% of the 39 infants with Gram-positive infections vs. 25.6% for WPT infants; 16 infants had Gram-negative culture-positive infections, with 81.2% being BPT infants versus 18.8% being WPT infants. Of the 27 urinary tract infections, 78% were in BPTs. The necrotizing enterocolitis incidence was 6.9%; the incidence in BPT infants was 7.5% vs. 6.5% in WPT infants. The overall mortality was 8.3%, with BPTs at 8.4% vs. WPT infants at 9.3%, (p = 0.6715). CONCLUSIONS: BPTs had a higher rate of positive cultures, double the Gram-negative infections, a much higher rate of urinary tract infections, and a higher rate of mortality than their WPT counterparts. This study emphasizes the higher risk of morbidity and mortality for BPTs.

Effect of Early vs Late Inguinal Hernia Repair on Serious Adverse Event Rates in Preterm Infants: A Randomized Clinical Trial.

Importance: Inguinal hernia repair in preterm infants is common and is associated with considerable morbidity. Whether the inguinal hernia should be repaired prior to or after discharge from the neonatal intensive care unit is controversial. Objective: To evaluate the safety of early vs late surgical repair for preterm infants with an inguinal hernia. Design, Setting, and Participants: A multicenter randomized clinical trial including preterm infants with inguinal hernia diagnosed during initial hospitalization was conducted between September 2013 and April 2021 at 39 US hospitals. Follow-up was completed on January 3, 2023. Interventions: In the early repair strategy, infants underwent inguinal hernia repair before neonatal intensive care unit discharge. In the late repair strategy, hernia repair was planned after discharge from the neonatal intensive care unit and when the infants were older than 55 weeks' postmenstrual age. Main Outcomes and Measures: The primary outcome was occurrence of any prespecified serious adverse event during the 10-month observation period (determined by a blinded adjudication committee). The secondary outcomes included the total number of days in the hospital during the 10-month observation period. Results: Among the 338 randomized infants (172 in the early repair group and 166 in the late repair group), 320 underwent operative repair (86% were male; 2% were Asian, 30% were Black, 16% were Hispanic, 59% were White, and race and ethnicity were unknown in 9% and 4%, respectively; the mean gestational age at birth was 26.6 weeks [SD, 2.8 weeks]; the mean postnatal age at enrollment was 12 weeks [SD, 5 weeks]). Among 308 infants (91%) with complete data (159 in the early repair group and 149 in the late repair group), 44 (28%) in the early repair group vs 27 (18%) in the late repair group had at least 1 serious adverse event (risk difference, -7.9% [95% credible interval, -16.9% to 0%]; 97% bayesian posterior probability of benefit with late repair). The median number of days in the hospital during the 10-month observation period was 19.0 days (IQR, 9.8 to 35.0 days) in the early repair group vs 16.0 days (IQR, 7.0 to 38.0 days) in the late repair group (82% posterior probability of benefit with late repair). In the prespecified subgroup analyses, the probability that late repair reduced the number of infants with at least 1 serious adverse event was higher in infants with a gestational age younger than 28 weeks and in those with bronchopulmonary dysplasia (99% probability of benefit in each subgroup). Conclusions and Relevance: Among preterm infants with inguinal hernia, the late repair strategy resulted in fewer infants having at least 1 serious adverse event. These findings support delaying inguinal hernia repair until after initial discharge from the neonatal intensive care unit. Trial Registration: ClinicalTrials.gov Identifier: NCT01678638.

Neurodevelopmental Outcomes of Extremely Preterm Infants Fed Donor Milk or Preterm Infant Formula: A Randomized Clinical Trial.

Importance: Maternal milk feeding of extremely preterm infants during the birth hospitalization has been associated with better neurodevelopmental outcomes compared with preterm formula. For infants receiving no or minimal maternal milk, it is unknown whether donor human milk conveys similar neurodevelopmental advantages vs preterm formula. Objective: To determine if nutrient-fortified, pasteurized donor human milk improves neurodevelopmental outcomes at 22 to 26 months' corrected age compared with preterm infant formula among extremely preterm infants who received minimal maternal milk. Design, Setting, and Participants: Double-blind, randomized clinical trial conducted at 15 US academic medical centers within the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network. Infants younger than 29 weeks 0 days' gestation or with a birth weight of less than 1000 g were enrolled between September 2012 and March 2019. Intervention: Preterm formula or donor human milk feeding from randomization to 120 days of age, death, or hospital discharge. Main Outcomes and Measures: The primary outcome was the Bayley Scales of Infant and Toddler Development (BSID) cognitive score measured at 22 to 26 months' corrected age; a score of 54 (score range, 54-155; a score of ≥85 indicates no neurodevelopmental delay) was assigned to infants who died between randomization and 22 to 26 months' corrected age. The 24 secondary outcomes included BSID language and motor scores, in-hospital growth, necrotizing enterocolitis, and death. Results: Of 1965 eligible infants, 483 were randomized (239 in the donor milk group and 244 in the preterm formula group); the median gestational age was 26 weeks (IQR, 25-27 weeks), the median birth weight was 840 g (IQR, 676-986 g), and 52% were female. The birthing parent's race was self-reported as Black for 52% (247/478), White for 43% (206/478), and other for 5% (25/478). There were 54 infants who died prior to follow-up; 88% (376/429) of survivors were assessed at 22 to 26 months' corrected age. The adjusted mean BSID cognitive score was 80.7 (SD, 17.4) for the donor milk group vs 81.1 (SD, 16.7) for the preterm formula group (adjusted mean difference, -0.77 [95% CI, -3.93 to 2.39], which was not significant); the adjusted mean BSID language and motor scores also did not differ. Mortality (death prior to follow-up) was 13% (29/231) in the donor milk group vs 11% (25/233) in the preterm formula group (adjusted risk difference, -1% [95% CI, -4% to 2%]). Necrotizing enterocolitis occurred in 4.2% of infants (10/239) in the donor milk group vs 9.0% of infants (22/244) in the preterm formula group (adjusted risk difference, -5% [95% CI, -9% to -2%]). Weight gain was slower in the donor milk group (22.3 g/kg/d [95% CI, 21.3 to 23.3 g/kg/d]) compared with the preterm formula group (24.6 g/kg/d [95% CI, 23.6 to 25.6 g/kg/d]). Conclusions and Relevance: Among extremely preterm neonates fed minimal maternal milk, neurodevelopmental outcomes at 22 to 26 months' corrected age did not differ between infants fed donor milk or preterm formula. Trial Registration: ClinicalTrials.gov Identifier: NCT01534481.

Subventricular zone stem cell niche injury is associated with intestinal perforation in preterm infants and predicts future motor impairment.

Brain injury is highly associated with preterm birth. Complications of prematurity, including spontaneous or necrotizing enterocolitis (NEC)-associated intestinal perforations, are linked to lifelong neurologic impairment, yet the mechanisms are poorly understood. Early diagnosis of preterm brain injuries remains a significant challenge. Here, we identified subventricular zone echogenicity (SVE) on cranial ultrasound in preterm infants following intestinal perforations. The development of SVE was significantly associated with motor impairment at 2 years. SVE was replicated in a neonatal mouse model of intestinal perforation. Examination of the murine echogenic subventricular zone (SVZ) revealed NLRP3-inflammasome assembly in multiciliated FoxJ1+ ependymal cells and a loss of the ependymal border in this postnatal stem cell niche. These data suggest a mechanism of preterm brain injury localized to the SVZ that has not been adequately considered. Ultrasound detection of SVE may serve as an early biomarker for neurodevelopmental impairment after inflammatory disease in preterm infants.

Prognostic Discordance Among Parents and Physicians Caring for Infants with Neurologic Conditions.

OBJECTIVE: To determine the frequency, degree, and nature of prognostic discordance between parents and physicians caring for infants with neurologic conditions. STUDY DESIGN: In this observational cohort study, we enrolled parents and physicians caring for infants with neurologic conditions in advance of a family conference. Parent-physician dyads completed a postconference survey targeting expected neurologic outcomes across 3 domains (motor, speech, and cognition) using a 6-point scale. Prognostic discordance was defined as a difference of ≥2 response options and was considered moderate (difference of 2-3 response options) or high (difference of 4-5 response options). Responses were categorized as differences in belief and/or differences in understanding using an existing paradigm. RESULTS: Forty parent-physician dyads of 28 infants completed surveys. Parent-physician discordance about prognosis occurred in ≥1 domain in the majority of dyads (n = 28/40, 70%). Discordance was generally moderate in degree (n = 23/28, 82%) and occurred with similar frequency across all domains. Of parent-physician dyads with discordance, the majority contained a difference in understanding in at least 1 domain (n = 25/28, 89%), while a minority contained a difference of belief (n = 6/28, 21%). When discordance was present, parents were typically more optimistic in their predictions compared with physicians (n = 25/28, 89%). CONCLUSIONS: Differing perceptions about the prognosis of critically ill infants are common and due to differences in both understanding and belief. These findings can be used to develop targeted interventions to improve prognostic communication.

A Pilot Phase I Trial of Allogeneic Umbilical Cord Tissue-Derived Mesenchymal Stromal Cells in Neonates With Hypoxic-Ischemic Encephalopathy.

Hypoxic ischemic encephalopathy (HIE) in neonates causes increased mortality and long-term morbidity in surviving babies. Hypothermia (HT) has improved outcomes, however, mortality remains high with ~half of surviving babies developing neurological impairment in their first years. We previously explored the use of autologous cord blood (CB) to determine if CB cells could lessen long-term damage to the brain. However, the feasibility of CB collection from sick neonates limited the utility of this approach. Allogeneic cord tissue mesenchymal stromal cells (hCT-MSC), cryopreserved and readily available, have been shown to ameliorate brain injury in animal models of HIE. We, therefore, conducted a pilot, phase I, clinical trial to test the safety and describe the preliminary efficacy of hCT-MSC in neonates with HIE. The study treated infants with moderate to severe HIE, treated with HT, with 1 or 2 doses of 2 million cells/kg/dose of hCT-MSC given intravenously. The babies were randomized to receive 1 or 2 doses with the first dose during HT and the second dose 2 months later. Babies were followed for survival and development with scoring of Bayley's at 12 postnatal months. Six neonates with moderate (4) or severe (2) HIE were enrolled. All received 1 dose of hCT-MSC during HT and 2 received a 2nd dose, 2 months later. hCT-MSC infusions were well tolerated although 5/6 babies developed low titer anti-HLA antibodies by 1 year of age. All babies survived, with average to low-average developmental assessment standard scores for ages between 12 and 17 postnatal months. Further study is warranted.

Quality of life burden on United States infants and caregivers due to lower respiratory tract infection and adjusting for selective testing: Pilot prospective observational study.

Background and Aims: Policymakers need data about the burden of respiratory syncytial virus (RSV) lower respiratory tract infections (LRTI) among infants. This study estimates quality of life (QoL) for otherwise healthy term US infants with RSV-LRTI and their caregivers, previously limited to premature and hospitalized infants, and corrects for selective testing. Methods: The study enrolled infants <1 year with a clinically diagnosed LRTI encounter between January and May 2021. Using an established 0-100 scale, the 36 infants' and caregivers' QoL at enrollment and quality-adjusted life year losses per 1000 LRTI episodes (quality-adjusted life years [QALYs]/1000) were validated and analyzed. Regression analyses examined predictors of RSV-testing and RSV-positivity, creating modeled positives. Results: Mean QoL at enrollment in outpatient (n = 11) LRTI-tested infants (66.4) was lower than that in not-tested LRTI infants (79.6, p = 0.096). For outpatient LRTI infants (n = 23), median QALYs/1000 losses were 9.8 and 0.25 for their caregivers. RSV-positive outpatient LRTI infants (n = 6) had significantly milder QALYs/1000 losses (7.0) than other LRTI-tested infants (n = 5)(21.8, p = 0.030). Visits earlier in the year were more likely to be RSV-positive than later visits (p = 0.023). Modeled RSV-positivity (51.9%) was lower than the observed rate (55.0%). Infants' and caregivers' QALYs/1000 loss were positively correlated (rho = 0.34, p = 0.046), indicating that infants perceived as sicker imposed greater burdens on caregivers. Conclusions: The overall median QALYs/1000 losses for LRTI (9.0) and RSV-LRTI (5.6) in US infants are substantial, with additional losses for their caregivers (0.25 and 0.20, respectively). These losses extend equally to outpatient episodes. This study is the first reporting QALY losses for infants with LRTI born at term or presenting in nonhospitalized settings, and their caregivers.

Early pumping frequency and coming to volume for mother's own milk feeding in hospitalized infants.

OBJECTIVE: To identify daily pumping frequencies associated with coming to volume (CTV: producing > 500 milliliters of milk per day by postnatal day 14) for mothers of infants in the neonatal intensive care unit (NICU). STUDY DESIGN: We compared demographics and daily pumping frequencies for mothers who did and did not experience CTV. RESULTS: Of 427 mothers who produced milk, 201 (50.1%) experienced CTV. Race, insurance, delivery type and birthweight were associated with CTV. For mothers who experienced CTV, average pumping episodes increased daily, stabilizing at 5 pumping episodes per day by postnatal day 5 (5 × 5). Women who experienced CTV were also more likely to have pumped between 0100 and 0500 (AM pumping). In multivariable analysis birthweight, 5 × 5 and AM pumping were each independently associated with CTV. CONCLUSION: Supporting mothers of NICU infants to achieve 5 or more daily pumping sessions by postnatal day 5 could improve likelihood of achieving CTV.

Rapid Whole Genome Sequencing in Critically Ill Neonates Enables Precision Medicine Pipeline.

Rapid genome sequencing in critically ill infants is increasingly identified as a crucial test for providing targeted and informed patient care. We report the outcomes of a pilot study wherein eight critically ill neonates received rapid whole genome sequencing with parental samples in an effort to establish a prompt diagnosis. Our pilot study resulted in a 37.5% diagnostic rate by whole genome sequencing alone and an overall 50% diagnostic rate for the cohort. We describe how the diagnoses led to identification of additional affected relatives and a change in management, the limitations of rapid genome sequencing, and some of the challenges with sample collection. Alongside this pilot study, our site simultaneously established a research protocol pipeline that will allow us to conduct research-based genomic testing in the cases for which a diagnosis was not reached by rapid genome sequencing or other available clinical testing. Here we describe the benefits, limitations, challenges, and potential for rapid whole genome sequencing to be incorporated into routine clinical evaluation in the neonatal period.

Respiratory Syncytial Virus During the COVID-19 Pandemic Compared to Historic Levels: A Retrospective Cohort Study of a Health System.

BACKGROUND: Surveillance in 2020-2021 showed that seasonal respiratory illnesses were below levels seen during prior seasons, with the exception of interseasonal respiratory syncytial virus (RSV). METHODS: Electronic health record data of infants aged <1 year visiting the Duke University Health System from 4 October 2015 to 28 March 2020 (pre-COVID-19) and 29 March 2020 to 30 October 2021 (COVID-19) were assessed. International Classification of Diseases-Tenth Revision (ICD-10) codes for RSV (B97.4, J12.1, J20.5, J21.0) and bronchiolitis (RSV codes plus J21.8, J21.9) were used to detail encounters in the inpatient (IP), emergency department (ED), outpatient (OP), urgent care (UC), and telemedicine (TM) settings. RESULTS: Pre-COVID-19, 88% of RSV and 92% of bronchiolitis encounters were seen in ambulatory settings. During COVID-19, 94% and 93%, respectively, occurred in ambulatory settings. Pre-COVID-19, the highest RSV proportion was observed in December-January (up to 38% in ED), while the peaks during COVID-19 were seen in July-September (up to 41% in ED) across all settings. RSV laboratory testing among RSV encounters was low during pre-COVID-19 (IP, 51%; ED, 51%; OP, 41%; UC, 84%) and COVID-19 outside of UC (IP, 33%; ED, 47%; OP, 47%; UC, 87%). Full-term, otherwise healthy infants comprised most RSV encounters (pre-COVID-19, up to 57% in OP; COVID-19, up to 82% in TM). CONCLUSIONS: With the interruption of historical RSV epidemiologic trends and the emergence of interseasonal disease during COVID-19, continued monitoring of RSV is warranted across all settings as the changing RSV epidemiology could affect the distribution of health care resources and public health policy.

Longitudinal medical needs for periviable NICU survivors.

OBJECTIVE: To evaluate the technologies required, medications needed, and early intervention services utilized from discharge to 12 months post-discharge for periviable infants (22 0/7 to 24 6/7 weeks gestational age) followed in a comprehensive NICU follow-up clinic. STUDY DESIGN: Information regarding medication use, technology requirement, and early intervention services was collected prospectively at one, six, and twelve months after discharge. Neurodevelopmental assessment was completed at 12 months corrected age. RESULT: 69 periviable infants were actively treated and survived to discharge during the study period. 54 infants were enrolled and followed in the comprehensive NICU follow-up clinic. Use of technology and prescribed medications decreased with a 46% reduction of infants requiring ≥1 technology device (74.1% vs. 40.4%, p < 0.01) and 64% reduction in infants requiring ≥1 medication (88.9% vs 31.9%, p < 0.01) 12 months post discharge. There was an increase in early intervention services with 83% of infants receiving services by 12 months post discharge. CONCLUSION: Technology and medication requirements were high at discharge but notably decreased in the first year after discharge concurrent with increased enrollment in early interventional services. Many periviable infants survive without severe short-term developmental delays.

A Multicenter Evaluation of a Point-of-Care Blood Glucose Meter System in Critically Ill Patients.

BACKGROUND: Our purpose was to evaluate the performance of the ACCU-CHEK® Inform II blood glucose monitoring system (Roche Diagnostics GmbH) compared with the perchloric acid hexokinase (PCA-HK) comparator method on the cobas® 6000 analyzer (Roche Diagnostics International Ltd) in critically ill patients. METHODS: Overall, 476 arterial (376 pediatric/adult, 100 neonate), 375 venous, and 100 neonatal heel-stick whole-blood samples were collected and evaluated from critical care settings at 10 US hospitals, including the emergency department, medical and surgical intensive care units (ICUs), and neonatal and pediatric ICUs. The ACCU-CHEK Inform II system was evaluated at 2 cutoff boundaries: boundary 1 was ≥95% of results within ±12 mg/dL of the reference (samples with blood glucose <75 mg/dL) or ±12% of the reference (glucose ≥75 mg/dL), and boundary 2 was ≥98% of results within ±15 mg/dL or ±15% of the reference. Clinical performance was assessed by evaluating sample data using Parkes error grid, Monte Carlo simulation, and sensitivity and specificity analyses to estimate clinical accuracy and implications for insulin dosing when using the ACCU-CHEK Inform II system. RESULTS: Proportions of results within evaluation boundaries 1 and 2, respectively, were 96% and 98% for venous samples, 94% and 97% for pediatric and adult arterial samples, 84% and 98% for neonatal arterial samples, and 96% and 100% for neonatal heel-stick samples. Clinical evaluation demonstrated high specificity and sensitivity, with low risk of potential insulin-dosing errors. CONCLUSIONS: The ACCU-CHEK Inform II system demonstrated clinically acceptable performance against the PCA-HK reference method for blood glucose monitoring in a diverse population of critically ill patients in US care settings.

Predicting Infection in Very Preterm Infants: A Study Protocol.

BACKGROUND: Neonatal sepsis causes morbidity and mortality in preterm infants. Clinicians need a predictive tool for the onset of neonatal infection to expedite treatment and prevent morbidity. Abnormal thermal gradients, a central-peripheral temperature difference (CPtd) of >2°C or <0°C, and elevated heart rate characteristic (HRC) scores are associated with infection. OBJECTIVE: This article presents the protocol for the Predictive Analysis Using Temperature and Heart Rate Study. METHODS: This observational trial will enroll 440 very preterm infants to measure abdominal temperature and foot temperature every minute and HRC scores hourly for 28 days to compare infection data. Time with abnormal thermal gradients (Model 1) and elevated HRC scores (Model 2) will be compared to the onset of infections. For data analysis, CPtd (abdominal temperature - foot temperature) will be investigated as two derived variables, high CPtd (number/percentage of minutes with CPtd of >2°C) and low CPtd (number/percentage of minutes with CPtd of <0°C). In the infant-level model, the outcome yi will be an indicator of whether the infant was diagnosed with an infection in the first 28 days of life, and the high CPtd and low CPtd variables will be the average over the entire observation period, logit(yi) = ß0 + xiß1 + ziγ. For the day-level model, the outcome yit will be an indicator of whether the ith infant was diagnosed with an infection on the tth day from t = 4 through t = 28 or the day that infection is diagnosed (25 possible repeated measures), logit(yit) = ß0 + xitß1 + zitγ. It will be determined whether a model with only high CPtd or only low CPtd is superior in predicting infection. Also, the correlation of abnormal HRC scores with high CPtd and low CPtd values will be assessed. DISCUSSION: Study results will inform the design of an interventional study using temperatures and/or heart rate as a predictive tool to alert clinicians of cardiac and autonomic instability present with infection.

Augmented Reality-Assisted Video Laryngoscopy and Simulated Neonatal Intubations: A Pilot Study.

BACKGROUND: For novice providers, achieving competency in neonatal intubation is becoming increasingly difficult, possibly because of fewer intubation opportunities. In the present study, we compared intubation outcomes on manikins using direct laryngoscopy (DL), indirect video laryngoscopy (IVL) using a modified disposable blade, and augmented reality-assisted video laryngoscopy (ARVL), a novel technique using smart glasses to project a magnified video of the airway into the intubator's visual field. METHODS: Neonatal intensive care nurses (n = 45) with minimal simulated intubation experience were randomly assigned (n = 15) to the following 3 groups: DL, IVL, and ARVL. All participants completed 5 intubation attempts on a manikin using their assigned modalities and received verbal coaching by a supervisor, who viewed the video while assisting the IVL and ARVL groups. The outcome and time of each attempt were recorded. RESULTS: The DL group successfully intubated on 32% of attempts compared to 72% in the IVL group and 71% in the ARVL group (P < .001). The DL group intubated the esophagus on 27% of attempts, whereas there were no esophageal intubations in either the IVL or ARVL groups (P < .001). The median (interquartile range) time to intubate in the DL group was 35.6 (22.9-58.0) seconds, compared to 21.6 (13.9-31.9) seconds in the IVL group and 20.7 (13.2-36.5) seconds in the ARVL group (P < .001). CONCLUSIONS: Simulated intubation success of neonatal intensive care nurses was significantly improved by using either IVL or ARVL compared to DL. Future prospective studies are needed to explore the potential benefits of this technology when used in real patients.

Breast Milk and Saliva Lactoferrin Levels and Postnatal Cytomegalovirus Infection.

OBJECTIVE: Very low birth weight preterm infants are at risk for life-threatening infections in the NICU. Breast milk protects against infections but carries the risk of infection by cytomegalovirus (CMV) shed in mother's milk. Lactoferrin is a breast milk and saliva protein with potent neutralizing activity against CMV. STUDY DESIGN: VLBW, maternal breast milk fed infants in the NICU and their lactating mothers were enrolled and followed for 3 months/discharge. Breast milk and infant saliva samples were collected biweekly. Maternal CMV status was determined on breast milk. CMV was measured using quantitative polymerase chain reaction and lactoferrin by enzyme-linked immunosorbent assay. RESULTS: In an in vitro neutralization assay, the IC90 of purified human lactoferrin against CMV was 2.08 ng/mL. Bovine lactoferrins were more potent, IC90s > 10-fold higher. Lactoferrin was detected in all breast milk (median: 3.3 × 106 ng/mL) and saliva (median: 84.4 ng/swab) samples. Median CMV load in breast milk was 893 copies/mL. There was no correlation between breast milk lactoferrin concentration and CMV load. Five infants acquired postnatal CMV. There was no difference in saliva or breast milk lactoferrin concentration for mother-infant pairs and postnatal CMV acquisition. CONCLUSION: Lactoferrin neutralizes CMV in vitro, but concentrations in breast milk and saliva are likely too low for effective neutralization in vivo.

Influence of Early Lactation Assistance on Inpatient Exclusive Breastfeeding Rates.

BACKGROUND: Human milk feeding reduces the incidence and costs of several maternal and childhood illnesses. Initiation and success of human milk feeding are influenced by race, socioeconomic status, and family support. The influence of early in-hospital lactation assistance in breastfeeding success has been not well described. RESEARCH AIMS: We aimed to determine how suspected known factors influencing breastfeeding success influence in-hospital human milk feeding rates. Second, we aimed to examine how timing of lactation assistance is related to success of human milk feeding during the newborn hospitalization for healthy infants. METHODS: We conducted a retrospective cohort study of term infants born between January 1, 2014 and December 31, 2016 at a large tertiary academic hospital. We considered "success" to be 100% human milk feeding during the birth hospitalization, and compared differences in success by demographics, payor, race, and initial feeding preference. Influences of lactation assistance on success were analyzed using multivariable logistic regression. RESULTS: Mean success with exclusive human milk feeding among 7,370 infants was 48.9%, (n = 3,601). Successful participants were more likely to be 39-40 weeks' gestation (64.9%, n = 2,340), non-Hispanic/non-Latino (80.0%, n = 2,882), and using private insurance (69.2%, n = 2,491). Participants who had early feeding assisted by an International Board Certified Lactation Consultant (IBCLC) before being fed any formula were more likely to be successful than participants who had a feeding assisted by a non-IBCLC nurse (80% vs. 40% respectively). CONCLUSIONS: Success for exclusive human milk feeding during newborn hospitalization is strongly associated with several factors. Early intervention with IBCLCs can greatly improve breastfeeding success.

Survival, Morbidities, and Developmental Outcomes among Low Birth Weight Infants with Congenital Heart Defects.

OBJECTIVE: Prematurity and low birth weight (LBW) are risk factors for increased morbidity and mortality in infants with congenital heart defects (CHDs). We sought to describe survival, inhospital morbidities, and 2-year neurodevelopmental follow-up in LBW infants with CHD. STUDY DESIGN: We included infants with birth weight (BW) <2,500 g diagnosed with CHD (except isolated patent ductus arteriosus) admitted January 2013 to March 2016 to a single level-IV academic neonatal intensive care unit. We reported CHD prevalence by BW and gestational age; selected in-hospital morbidities and mortality by infant BW, CHD type, and surgical intervention; and developmental outcomes by Bayley's scales of infant and toddler development, third edition (BSID-III) scores at age 2 years. RESULTS: Among 420 infants with CHD, 28 (7%) underwent cardiac surgery. Median (25th and 75th percentiles) gestational age was 30 (range: 27-33) weeks and BW was 1,258 (range: 870-1,853) g. There were 134 of 420 (32%) extremely LBW (<1,000 g) infants, 82 of 420 (20%) were small for gestational age, and 51 of 420 (12%) multiples. Most common diagnosis: atrial septal defect (260/420, 62%), followed by congenital anomaly of the pulmonary valve (75/420, 18%). Most common surgical procedure: pulmonary artery banding (5/28, 18%), followed by the tetralogy of Fallot corrective repair (4/28, 14%). Survival to discharge was 88% overall and lower among extremely LBW (<1,000 g, 81%) infants and infants undergoing surgery (79%). Comorbidities were common (35%); retinopathy of prematurity and bronchopulmonary dysplasia were most prevalent. BSID-III scores were available on 148 of 176 (84%); any scores <85 were noted in 73 of 148 (49%), with language being most commonly affected. CONCLUSION: Among LBW infants with congenital heart disease, hospital mortality varied by BW and cardiac diagnosis. KEY POINTS: · In low birth weight infants with congenital heart disease, survival varied by birth weight and cardiac diagnosis.. · Overall survival was higher than previously reported.. · There were fewer morbidities than previously reported.. · Bayley's scale-III scores at 2 years of age were <85 for nearly half..

Toto, I've a Feeling We're Not in Kansas Anymore: Navigating the Mid-career Transition to Academic Medicine.

When physicians, nurse practitioners, and physician assistants transition from a community setting to a university-based academic environment during mid-career, it can be challenging. Strategic planning is needed to ensure success. Institutions can assist experienced providers making such a transition, and there are steps the provider can take to self-advocate. As a group of four medical professionals who began their careers in patient care community practices for up to 18 years before transitioning to an academic medical center, we have had to navigate an unfamiliar landscape. We collectively offer our tips for a successful mid-career transition to academic medicine.

Urine gastrin-releasing peptide in the first week correlates with bronchopulmonary dysplasia and post-prematurity respiratory disease.

RATIONALE: Bronchopulmonary dysplasia (BPD) is associated with post-prematurity respiratory disease (PRD) in survivors of extreme preterm birth. Identifying early biomarkers that correlate with later development of BPD and PRD may provide insights for intervention. In a preterm baboon model, elevated gastrin-releasing peptide (GRP) is associated with BPD, and GRP inhibition mitigates BPD occurrence. OBJECTIVE: We performed a prospective cohort study to investigate whether urine GRP levels obtained in the first postnatal week were associated with BPD, PRD, and other urinary biomarkers of oxidative stress. METHODS: Extremely low gestational age infants (23-28 completed weeks) were enrolled in a US multicenter observational study, The Prematurity and Respiratory Outcomes Program (http://clinicaltrials.gov/ct2/show/NCT01435187). We used multivariable logistic regression to examine the association between urine GRP in the first postnatal week and multiple respiratory outcomes: BPD, defined as supplemental oxygen use at 36 + 0 weeks postmenstrual age, and post-PRD, defined by positive quarterly surveys for increased medical utilization over the first year (PRD score). RESULTS: A total of 109 of 257 (42%) infants had BPD, and 120 of 217 (55%) had PRD. On adjusted analysis, GRP level more than 80 was associated with BPD (adjusted odds ratio [aOR], 1.83; 95% confidence interval [CI], 1.03-3.25) and positive PRD score (aOR, 2.46; 95% CI, 1.35-4.48). Urine GRP levels correlated with duration of NICU ventilatory and oxygen support and with biomarkers of oxidative stress: allantoin and 8-hydroxydeoxyguanosine. CONCLUSIONS: Urine GRP in the first postnatal week was associated with concurrent urine biomarkers of oxidative stress and with later diagnoses of BPD and PRD.