Prevalence of SARS-CoV-2 in newborns born to SARS-CoV-2-positive mothers at 2 weeks of life.

Introduction: Limited evidence exists on management recommendations for neonates born to SARS-CoV-2-positive mothers. This study looked at transmission risk of neonates presenting for primary care in a large regional health system within New York during the early months of the COVID-19 pandemic. Methods: This was a prospective, observational study of newborns born to SARS-CoV-2-positive mothers presenting at any of the 19 Northwell Health-Cohen Children's Medical Center primary care practices who underwent another oropharyngeal/nasopharyngeal swab for detection of SARS-CoV-2 by day of life (DOL) 14. Results: Among 293 newborns born to SARS-CoV-2-positive mothers who were negative at birth, 222 were retested at DOL 14, corresponding to times with different predominant strains. Of these, seven tested positive but had no symptoms. Conclusion: The overall low transmission rates and absence of symptomatic infection support the safety of direct breastfeeding after hospital discharge with appropriate hand and breast hygiene.

Cefazolin and Carbapenem Combination to Treat Persistent Methicillin-sensitive Staphylococcus aureus Bacteremia in Preterm Infants.

Encouraged by bacteremia clearance using antistaphylococcal beta-lactams plus carbapenem combination in adults with refractory methicillin-sensitive Staphylococcus aureus infection, we present our experience with 2 preterm infants and review 1 previously published case. Noted successful bacteremia clearance in all 3 must be weighed against possible adverse effects associated with carbapenem use.

Does every newborn need an imaging study after a fall? Case series and literature review.

OBJECTIVE: This study examines the clinical and radiographic information from neonates who sustained a newborn fall (NF) to identify risk factors for the NF and the presence of skull fracture and intracranial bleed. In addition, published articles will be reviewed to provide data to assist in the evidence-based management of mothers after delivery and neonates after NF. STUDY DESIGN: This is a retrospective chart review of neonates who sustained a NF in a level 4 NICU between 2016 and 2019. Results of imaging reports, maternal and neonatal clinical information, physical examination after fall, mode of delivery, time of day of fall, time between delivery and fall, feeding regimen, and maternal in hospital opioid use were recorded. Published reports containing imaging results and the incidence of skull fracture after NF were obtained by searching Pub Med from 2000 to 2019. MAIN OUTCOME MEASURES: The main outcome of this study is to determine the presence and location of fractures and intracranial hemorrhage after a NF. Secondary outcome includes identification of clinical factors associated with the NF and presence of fractures. Student's t-test was used for statistical comparisons. RESULTS: Twenty-one neonates sustained a NF and 83% were imaged by cranial CT. Skull fractures were identified by CT in 53% of neonates and ∼1/3 of infants had small intracranial hemorrhage. All infants were clinically stable and no neonate required neurosurgical intervention. Most NFs (73%) occurred between midnight and 8 AM and were associated with maternal sleeping while holding the infant. CONCLUSIONS: Mothers should have increased monitoring and support especially the days after delivery from 11 PM to 9 AM to assess for maternal exhaustion and to prevent NFs regardless of opioid use. When indicated, low-dose rapid sequence CT scan rather than X-ray is preferred for evaluation of the neonate after a fall.

Prolonged outbreak of clonal, mupirocin-resistant methicillin-resistant Staphylococcus aureus in a neonatal intensive care unit: association with personnel and a possible environmental reservoir, analyzed using whole genome sequencing.

BACKGROUND: Outbreaks of MRSA occur in NICUs and may be difficult to control. We describe an outbreak of mupirocin-resistant MRSA, molecular epidemiology of isolates and control. METHODS: Medical record review of personnel contact with infants. MRSA isolates were analyzed by whole genome sequencing (WGS); single nucleotide polymorphisms (SNPs) were identified. RESULTS: A 31-month outbreak of MRSA infection occurred. Weekly colonization surveillance of infants was initiated; initial prevalence was 45%. Isolates exhibited high level mupirocin-resistance. There were 3 periods of increased colonization and new infections despite implementation of multiple infection prevention interventions. During the second period, an analysis identified a frontline staff member associated with newly colonized infants whose nasal culture grew the clonal MRSA. A marked reduction in colonization followed removal from patient contact. WGS of isolates from years 1-3 showed clonality with maximum SNP differences of 33. Importantly, the year 3 isolates were more closely related to the early year 1 isolates (15-20 SNP differences) than to the late year 1 or year 2 isolates (18-33 SNP differences). DISCUSSION/CONCLUSIONS: During a recrudescent MRSA outbreak due to a clonal strain, both contact with a colonized staff member and a putative environmental or personnel reservoir were associated with MRSA acquisition.

Risk factors for nosocomial methicillin resistant Staphylococcus aureus (MRSA) colonization in a neonatal intensive care unit: A Case-control study.

AIM: To determine risk factors for MRSA colonization in a Level IV Neonatal Intensive Care Unit (NICU) independent of length of stay and gestational age in the context of a persistently circulating MRSA clone. DESIGN: Retrospective matched case-control study. SETTING: Level IV NICU PATIENTS: Infants admitted between April 4,2017- March 31,2018. METHODS: Based on weekly surveillance cultures, infants who acquired MRSA were matched 1:1 with MRSA-negative control infants by duration of exposure (length of stay) and gestational age to determine risk factors for acquisition. RESULTS: Fifty case infants were matched with controls. Isolates from 45 of the 50 cases were mupirocin-resistant and related by pulse-field gel electrophoresis. On matched univariable analysis, the following were significantly associated with a risk for MRSA acquisition: 1.Bed location in the acute area(P = 0.03), 2.Requirement of any level of respiratory support during the week prior to MRSA detection(P = 0.04), 3.Higher ATP pass rate (a measure of effectiveness of cleaning) during the week of and week prior(P = 0.01), 4.Higher MRSA colonization pressure during the week of and week prior(P< 0.0001), 5.Not having a hearing test during the time between the previous negative culture and MRSA acquisition(P = 0.01). A multivariable conditional logistic regression model (that excluded ATP pass rate) found that only colonization pressure was associated with acquisition of MRSA colonization. CONCLUSIONS: In an outbreak setting, MRSA colonization pressure is significantly associated with MRSA acquisition in the NICU independent of length of stay and gestational age.

Structured Neonatal Point-of-Care Ultrasound Training Program.

OBJECTIVE: Point-of-care ultrasound (POC US) has been increasingly used by intensive care physicians. Growing use of POC US necessitates defining distinct clinical indications for its application, as well as structured POC US training programs. Homogeneous approach to POC US education combined with rigorous quality assurance should further enable POC US to become standard-of-care clinical tool. This study aimed to present the first, innovative, and structured POC US program in neonatal-perinatal medicine field. In addition, we reviewed the availability of the POC US training programs across different medical specialties. STUDY DESIGN: Available English-language publications on POC US training programs in general and neonatal-perinatal medicine were reviewed in this study. DISCUSSION: Mounting body of evidence suggests improved procedural completion rates, as well as clinical decision making with the use of POC US. However, limited research supported the existence of structured, comprehensive POC US programs. It was recognized that medical institutions need to develop syllabuses, teach, and credential increasing number of health care professionals in the use of POC US. We defined intuitive educational strategy that encompasses POC US clinical indications, educational curriculum, scanning protocols, competence evaluation, and finally credentialing process. In addition, we offered description of the imaging quality assurance, as well as POC US coding, and reimbursement. CONCLUSION: Future efforts need to be dedicated to the ongoing development of neonatal POC US as a clinical instrument. It should allow for eventual paradigm change and improved effectiveness in management of critically ill neonates.

A Quality Improvement Project to Standardize Surfactant Delivery in the Era of Noninvasive Ventilation.

INTRODUCTION: Continuous positive airway pressure (CPAP) and surfactant both improve outcomes for premature infants with respiratory distress syndrome. However, prolonged trials of CPAP, as well as observation periods after intubation, may delay the administration of surfactant. Late surfactant treatment likely increases the incidence of bronchopulmonary dysplasia, which leads to significant morbidity and healthcare utilization. METHODS: We aimed to decrease time from meeting standard criteria (start of a continuous run of FiO2 > 40% or PaCO2 > 65 for >90 min) to intubation, and from intubation to surfactant administration, for infants <1,500 g or younger than 32 weeks gestation. Retrospective data collection from the electronic medical record assessed those process measures as the primary endpoints. Balancing measures were the adverse outcomes of asymmetric lung disease, the inappropriate position of the endotracheal tube, or pneumothorax on the first x-ray (within 24 h) after surfactant. RESULTS: Mean time to intubation for infants 28-32 weeks gestation decreased from 321 to 81 minutes in response to a literature review for physicians and free-text orders for notification. Time to intubation for infants younger than 28 weeks gestation did not change. Administration of surfactant within 1 hour of intubation improved from 78% to 100% after a program for trainees and coordination with radiology. There were no adverse occurrences. CONCLUSIONS: Educational interventions and targeted process change can successfully implement standard criteria for intubation and surfactant administration for premature infants. Determination of an acceptable range of evidence-based practice is essential for the engagement of medical staff. Timely intubation and surfactant may decrease bronchopulmonary dysplasia.

The effect of routine surveillance and decolonization on the rate of Staphylococcus aureus infections in a level IV neonatal intensive care unit.

OBJECTIVE: To evaluate the impact of active surveillance cultures (ASC) for Staphylococcus aureus (SA) and decolonization on the rate of infection in neonates in a neonatal intensive care unit (NICU). STUDY DESIGN: Using a quasi-experimental design with control groups, rates of SA infections before and after implementing weekly ASC and topical mupirocin decolonization in a level IV NICU were compared. Comparators were the rates of gram negative bloodstream infections (BSI) and of SA BSI at an affiliated NICU where the intervention was not implemented. RESULT: There was a 77% (p < 0.010) reduction in rate of NICU-wide methicillin-susceptible SA (MSSA) BSI, but no significant change in rate of methicillin-resistant SA BSI, likely due to a prevalent mupirocin-resistant clone. Rates of gram negative BSI and SA BSI at an affiliated NICU did not change significantly. CONCLUSION: Weekly ASC and decolonization were associated with a unit-wide reduction in MSSA infections in a NICU.

Improving preoperative identification of infants at risk for severe retinopathy of prematurity.

OBJECTIVE: To increase preoperative identification of at-risk infants for severe Retinopathy of prematurity (ROP) to >95% by August 2016, with a secondary aim of reducing the number of infants with 100% intraoperative peripheral oxygen saturation (SpO2) during the same time. STUDY DESIGN: Prospective quality improvement project centered on preterm surgical infants admitted to Primary Children's Hospital (n = 41). Preoperative ROP risk identification rates were analyzed using an annotated run chart, intraoperative SpO2 and laser intervention were compared using un-paired t test. RESULTS: Preoperative identification of ROP risk increased from 60 to 100% and no infant was exposed to 100% SpO2 intraoperatively during the study period. The incidence of laser intervention in this population decreased by 45% from 22 to 12% (p = 0.21). CONCLUSION: Simplifying our preoperative handoff increased our rates of correct identification and communication ROP risk in preterm infants while decreasing exposure to 100% SpO2.

Assessing the Surgical Experience to Identify Risk Factors Associated with Severe Retinopathy of Prematurity and Laser Intervention.

BACKGROUND: Retinopathy of prematurity (ROP) is a known complication of preterm birth and one of the leading causes of blindness. Known risk factors include low gestational age (GA), birth weight, and oxygen exposure. It is unknown if there are surgical risk factors associated with severe ROP. OBJECTIVES: Identify risk factors of a neonatal surgical exposure associated with laser therapy for ROP. METHODS: Institutional review of 76 infants with GA ≤27 weeks or birth weight ≤800 g. Infant demographics and details of surgical experience were collected. Infants who underwent a surgical procedure were analyzed to identify risk factors associated with laser treatment for severe ROP. Surgical and nonsurgical infants were compared to assess if the rate of laser intervention differed among institutions/published data. Data were analyzed using the Mann-Whitney U test, unpaired t test, OR and Fischer's exact test. RESULT: Out of 49 surgical infants, 11 underwent laser intervention. Infants undergoing laser had surgery at an earlier postmenstrual age (PMA; 31.5 [29.3-39.4] weeks vs. 38.1 [31.3-42.5] weeks, p = 0.01), were more likely to have an exploratory laparotomy (adjusted odds ratio 1.3 [1.04-1.64], p = 0.02), and to undergo more surgical procedures (3 vs. 2, p = 0.04). CONCLUSION: At our institution, preterm infants who undergo a surgical procedure prior to 32 weeks PMA and those having ≥3 surgeries were at a higher risk for progressing to laser intervention. Additional studies with larger sample sizes are needed to assess if the risk factors we have identified remain significant and to identify other possible risk factors.

Dietary Docosahexaenoic Acid Improves Cognitive Function, Tissue Sparing, and Magnetic Resonance Imaging Indices of Edema and White Matter Injury in the Immature Rat after Traumatic Brain Injury.

Traumatic brain injury (TBI) is the leading cause of acquired neurologic disability in children. Specific therapies to treat acute TBI are lacking. Cognitive impairment from TBI may be blunted by decreasing inflammation and oxidative damage after injury. Docosahexaenoic acid (DHA) decreases cognitive impairment, oxidative stress, and white matter injury in adult rats after TBI. Effects of DHA on cognitive outcome, oxidative stress, and white matter injury in the developing rat after experimental TBI are unknown. We hypothesized that DHA would decrease early inflammatory markers and oxidative stress, and improve cognitive, imaging and histologic outcomes in rat pups after controlled cortical impact (CCI). CCI or sham surgery was delivered to 17 d old male rat pups exposed to DHA or standard diet for the duration of the experiments. DHA was introduced into the dam diet the day before CCI to allow timely DHA delivery to the pre-weanling pups. Inflammatory cytokines and nitrates/nitrites were measured in the injured brains at post-injury Day (PID) 1 and PID2. Morris water maze (MWM) testing was performed at PID41-PID47. T2-weighted and diffusion tensor imaging studies were obtained at PID12 and PID28. Tissue sparing was calculated histologically at PID3 and PID50. DHA did not adversely affect rat survival or weight gain. DHA acutely decreased oxidative stress and increased anti-inflammatory interleukin 10 in CCI brains. DHA improved MWM performance and lesion volume late after injury. At PID12, DHA decreased T2-imaging measures of cerebral edema and decreased radial diffusivity, an index of white matter injury. DHA improved short- and long-term neurologic outcomes after CCI in the rat pup. Given its favorable safety profile, DHA is a promising candidate therapy for pediatric TBI. Further studies are needed to explore neuroprotective mechanisms of DHA after developmental TBI.

Mid-arm circumference is a reliable method to estimate adiposity in preterm and term infants.

BACKGROUND: Premature birth is associated with increased adipose deposition after birth. Standard anthropometry (body weight, length, and head circumference) may not adequately assess fat deposition. Validated methods to assess adiposity are needed to optimize growth quality in preterm infants. The purpose of this study was to identify covariates of infant body fat. METHODS: Air displacement plethysmography (ADP), standard anthropometry, and body circumferences were measured at hospital discharge in preterm (n = 28; 31-35 wk postmenstrual age (PMA)) and term (n = 28; 38-41 wks PMA) infants. RESULTS: Body weight, length, and head circumference were lower for preterm infants (P < 0.05) at hospital discharge compared with that of term infants. Despite smaller body size and younger PMA, preterm infant percent body fat (%BF) by ADP was 12.33 ± 4.15% vs. 9.64 ± 4.01% in term infants (P = 0.01). Mid-arm circumference (MAC) is a covariate of %BF in both preterm and term infants (adjusted R(2) = 0.49; P < 0.001). In preterm infants alone, MAC accounted for 60.4% of the variability of percent body fat (%BF) by ADP (P < 0.01). CONCLUSIONS: Preterm infants have increased body fat deposition as they approach term-corrected age, and MAC is a reliable, low-cost measure for monitoring infant body fat deposition in preterm and term infants.

Darbepoetin administration to neonates undergoing cooling for encephalopathy: a safety and pharmacokinetic trial.

BACKGROUND: Despite therapeutic hypothermia, neonates with encephalopathy (NE) have high rates of death or disability. Darbepoetin alfa (Darbe) has comparable biological activity to erythropoietin, but has extended circulating half-life (t(1/2)). Our aim was to determine Darbe safety and pharmacokinetics as adjunctive therapy to hypothermia. STUDY DESIGN: Thirty infants (n = 10/arm) ≥36 wk gestation undergoing therapeutic hypothermia for NE were randomized to receive placebo, Darbe low dose (2 µg/kg), or high dose (10 µg/kg) given intravenously within 12 h of birth (first dose/hypothermia condition) and at 7 d (second dose/normothermia condition). Adverse events were documented for 1 mo. Serum samples were obtained to characterize Darbe pharmacokinetics. RESULTS: Adverse events (hypotension, altered liver and renal function, seizures, and death) were similar to placebo and historical controls. Following the first Darbe dose at 2 and 10 µg/kg, t(1/2) was 24 and 32 h, and the area under the curve (AUC(inf)) was 26,555 and 180,886 h*mU/ml*, respectively. In addition, clearance was not significantly different between the doses (0.05 and 0.04 l/h). At 7 d, t(1/2) was 26 and 35 h, and AUC(inf) was 10,790 and 56,233 h*mU/ml*, respectively (*P < 0.01). CONCLUSION: Darbe combined with hypothermia has similar safety profile to placebo with pharmacokinetics sufficient for weekly administration.

Population Pharmacokinetics of Darbepoetin Alfa in Conjunction with Hypothermia for the Treatment of Neonatal Hypoxic-Ischemic Encephalopathy.

AIM: The aim of this study was to determine the population pharmacokinetics of darbepoetin alfa in hypothermic neonates with hypoxic-ischemic encephalopathy treated with hypothermia. METHODS: Neonates ≥36 weeks gestation and <12 h postpartum with moderate to severe hypoxic-ischemic encephalopathy who were undergoing hypothermia treatment were recruited in this randomized, multicenter, investigational, new drug pharmacokinetic study. Two intravenous darbepoetin alfa treatment groups were evaluated: 2 and 10 µg/kg. Serum erythropoietin concentrations were measured using an enzyme-linked immunosorbent assay. Monolix 4.3.1 was used to estimate darbepoetin alfa clearance and volume of distribution. Covariates tested included: birthweight, gestational age, postnatal age, postmenstrual age, sex, Sarnat score, and study site. RESULTS: Darbepoetin alfa pharmacokinetics were well described by a one-compartment model with exponential error. Clearance and the volume of distribution were scaled by birthweight (centered on the mean) a priori. Additionally, gestational age (also centered on the mean) significantly affected darbepoetin alfa clearance. Clearance and volume of distribution were estimated as 0.0465 L/h (95% confidence interval 0.0392-0.0537) and 1.58 L (95% confidence interval 1.29-1.87), respectively. CONCLUSIONS: A one-compartment model successfully described the pharmacokinetics of darbepoetin alfa among hypothermic neonates treated for hypoxic-ischemic encephalopathy. Clearance decreased with increasing gestational age.

Massage improves growth quality by decreasing body fat deposition in male preterm infants.

OBJECTIVES: To assess the effect of massage on weight gain and body fat deposition in preterm infants. STUDY DESIGN: Preterm infants (29-32 weeks) were randomized to the massage group (n = 22, 12 girls, 10 boys) or the control group (n = 22, 12 girls, 10 boys). Treatment was masked with massage or control care administered twice-daily by licensed massage therapists (6 d/wk for 4 weeks). Body weight, length, Ponderal Index (PI), body circumferences, and skinfold thickness (triceps, mid-thigh, and subscapular [SSF]) were measured. Circulating insulin-like growth factor I, leptin, and adiponectin levels were determined by enzyme-linked immunosorbent assay. Daily dietary intake was collected. RESULTS: Energy and protein intake as well as increase in weight, length, and body circumferences were similar. Male infants in the massage group had smaller PI, triceps skinfold thickness, mid-thigh skinfold thickness, and SSF and increases over time compared with control male infants (P < .05). Female infants in the massage group had larger SSF increases than control female infants (P < .05). Circulating adiponectin increased over time in control group male infants (group × time × sex interaction, P < .01) and was correlated to PI (r = 0.39, P < .01). CONCLUSIONS: Twice-daily massage did not promote greater weight gain in preterm infants. Massage did, however, limit body fat deposition in male preterm infants. Massage decreased circulating adiponectin over time in male infants with higher adiponectin concentrations associated with increased body fat. These findings suggest that massage may improve body fat deposition and, in turn, growth quality of preterm infants in a sex-specific manner.

Early and sustained increase in the expression of hippocampal IGF-1, but not EPO, in a developmental rodent model of traumatic brain injury.

Pediatric traumatic brain injury (pTBI) is the leading cause of traumatic death and disability in children in the United States. Impaired learning and memory in these young survivors imposes a heavy toll on society. In adult TBI (aTBI) models, cognitive outcome improved after administration of erythropoietin (EPO) or insulin-like growth factor-1 (IGF-1). Little is known about the production of these agents in the hippocampus, a brain region critical for learning and memory, after pTBI. Our objective was to describe hippocampal expression of EPO and IGF-1, together with their receptors (EPOR and IGF-1R, respectively), over time after pTBI in 17-day-old rats. We used the controlled cortical impact (CCI) model and measured hippocampal mRNA levels of EPO, IGF-1, EPOR, IGF-1R, and markers of caspase-dependent apoptosis (bcl2, bax, and p53) at post-injury days (PID) 1, 2, 3, 7, and 14. CCI rats performed poorly on Morris water maze testing of spatial working memory, a hippocampally-based cognitive function. Apoptotic markers were present early and persisted for the duration of the study. EPO in our pTBI model increased much later (PID7) than in aTBI models (12 h), while EPOR and IGF-1 increased at PID1 and PID2, respectively, similar to data from aTBI models. Our data indicate that EPO expression showed a delayed upregulation post-pTBI, while EPOR increased early. We speculate that administration of EPO in the first 1-2 days after pTBI would increase hippocampal neuronal survival and function.

Neonatal complications following preterm birth.

Improvements in neonatal intensive care during the last 20 years have increased the survival of the most immature newborns at 23 weeks from 0% to 65% at some centres, although rates vary widely among neonatal care centres. University of Utah, USA data show that each week in utero after week 23 raises survival by 6-9%, to 90% by 27-28 weeks and 95% by 33 weeks. Provision of care in specialised centres to provide high-risk obstetric and neonatal intensive care, prenatal treatment with corticosteroids, postnatal treatment with surfactant and nitric oxide, and improvements in respirators and equipment to care for extremely immature infants all contribute to these changes. The increased rate of survival for extremely premature newborns has not been accompanied by an increased rate of severe intraventricular haemorrhage or neurological impairment, such as cerebral palsy. Regardless, intraventricular haemorrhage remains a significant problem, especially if associated with post-haemorrhagic hydrocephalus, leading to long-term neurological impairment and decreased survival. Necrotising enterocolitis (NEC) is more common in premature than in term newborns and is the most frequent cause of short bowel syndrome in infancy. Survival after surgery for NEC has improved during the last two decades, but complications of nutritional support produce many long-term problems. Retinopathy of prematurity (ROP) remains a frequent cause of neurosensory impairment for extremely premature newborns. Laser photocoagulation for advanced ROP is more effective than cryotherapy for preventing retinal detachment and improving visual outcomes. Despite prenatal corticosteroid treatment and postnatal surfactant administration, many extremely premature newborns still develop bronchopulmonary dysplasia. Abnormal pulmonary function may persist into adulthood, but newer ventilators and management schemes appear to be reducing this long-term morbidity. Many changes in neonatal care occur each year, but carefully controlled outcome studies are needed to evaluate the effectiveness of these newer styles of neonatal intensive care.