Music exposure and maturation of late preterm sleep-wake cycles: a randomised crossover trial.

AIM: To determine the effect of music on sleep-wake cycle (SWC) patterns in late preterm neonates. METHODS: In a masked crossover study, infants between 32 and 36 6/7 weeks gestation were randomised to music exposure either during the first six or last six hours of a 12-hour observation period. SWC characteristics were determined by continuous amplitude-integrated electroencephalography (aEEG) read by two coders masked to exposure sequence. Analysis was performed in paired comparisons. ANOVA was used to assess the effects of music exposure, period and crossover on SWC outcomes: (i) Burdjalov Scores (BS) during active sleep (AS) (ii) per cent and duration of quiet sleep (QS). RESULTS: Thirty infants were studied. A total of 222 QS cycles (median seven per patient; range five to 12) were analysed. Music exposure was associated with higher BS (F = 10.60, p = 0.0019) in AS and decreased interruptions during QS. The advanced postconceptual age (PCA) SWC pattern during AS was equivalent to a one-week mean. Number, duration and ratio of QS cycles did not change with music exposure. CONCLUSION: Music exposure elicits an increasing PCA pattern in AS and fewer interruptions in QS. Music may benefit sleep in late preterm infants.

Multidrug-Resistant Bacterial Infections Among Very Low Birthweight Infants With Late-Onset Sepsis in Johannesburg, South Africa.

Background: An estimated 2.4 million babies died within the first 28 days of life in 2020. The third leading cause of neonatal death continues to be neonatal sepsis. Sepsis-causing bacterial pathogens vary temporally and geographically and, with a rise in multidrug-resistant organisms (MDROs), pose a threat to the neonatal population. Methods: This was a single-center, retrospective study of very low birth weight (VLBW) infants with late-onset sepsis (LOS) admitted to a neonatal unit in South Africa. We aimed to calculate the prevalence of multidrug-resistant (MDR) infections in this population. The data collected included demographic and clinical characteristics, length of hospital stay, risk factors for MDRO and mortality, and microbiology results. Logistic regression was used to assess the association between prespecified risk factors with MDR infections and mortality. Results: Of 2570 VLBW infants admitted, 34% had LOS, of which 33% was caused by MDROs. Infection with Acinetobacter spp., Pseudomonas spp., extended-spectrum beta-lactamase Klebsiella spp., or Escherichia coli was associated with the highest mortality in the LOS cohort. Infants with congenital infections (adjusted odds ratio [aOR], 5.13; 95% CI, 1.19-22.02; P = .028) or a history of necrotizing enterocolitis (aOR, 2.17; 95% CI, 1.05-4.49; P = .037) were at significantly higher risk for MDR infections. Conclusions: More than one-third of LOS cases in VLBW infants were caused by MDROs in this study. MDR infections cause substantial neonatal mortality. Antimicrobial stewardship programs, infection control protocols, and ongoing surveillance are needed to prevent further emergence and spread of MDR infections worldwide.

Necrotizing enterocolitis is associated with ureaplasma colonization in preterm infants.

The study objective was to determine whether Ureaplasma respiratory tract colonization of preterm infants <33 wk gestation is associated with an increased risk for necrotizing enterocolitis (NEC). One or more tracheal or nasopharyngeal aspirates for Ureaplasma culture and PCR were obtained during the first week of life from 368 infants <33 wk gestation enrolled from 1999 to 2003 or from 2007 to 2009. NEC Bell stage ≥ 2 was confirmed by radiological criteria, and pathology, if available. Cord serum samples were analyzed for IL-6 and IL-1ß concentrations, and placentas were reviewed for histological chorioamnionitis in the first cohort. NEC was confirmed in 29 of 368 (7.9%) of the combined cohorts. The incidence of NEC was 2.2-fold higher in Ureaplasma-positive (12.3%) than Ureaplasma-negative (5.5%) infants <33 wk (OR, 2.43; 95% CI, 1.13-5.2; p = 0.023) and 3.3-fold higher in Ureaplasma-positive (14.6%) than Ureaplasma-negative (4.4%) infants ≤ 28 wk (OR, 3.67; 95% CI, 1.36-9.93; p = 0.01). Age of onset, hematologic parameters at onset, and NEC severity were similar between Ureaplasma-positive and negative infants. Cord serum IL-6 and IL-1ß concentrations were significantly higher in Ureaplasma-positive than in Ureaplasma-negative NEC-affected infants. Ureaplasma may be a factor in NEC pathogenesis in preterm infants by contributing to intestinal mucosal injury and/or altering systemic or local immune responses.

Telemedicine: A Reliable Tool to Assess the Severity of Respiratory Distress in Children.

BACKGROUND AND OBJECTIVES: Remote assessment of respiratory distress using telemedicine enabled audio-video conferencing (TM) is of value for medical decision-making. Our goal was to evaluate the interobserver reliability (IOR) of TM compared with face-to-face (FTF) assessment of respiratory distress in children. METHODS: A prospective, cohort study was performed in pediatric emergency department from July 2012 to February 2013. Children (aged 0-18 years) who presented with signs of respiratory distress were included in the study. The respiratory score is a 4-item, 12-point scale (respiratory rate [1-3], retractions [0-3], dyspnea [0-3], and wheezing [0-3]) that assesses the severity of a child's respiratory distress. Each child was evaluated by a pair of observers from a pool of 25 observers. The first observer evaluated the patient FTF, and the second observer simultaneously and independently evaluated remotely via TM. The overall respiratory distress severity is based on the respiratory scale and reported as nonsevere (≤8) and severe (≥9) respiratory distress. The IOR reliability between FTF and TM assessment was measured using a 2-way mixed model, absolute agreement and average measure intraclass correlation coefficient (ICC). RESULTS: Forty-eight patients and 135 paired observations were recorded. IOR between the FTF and TM groups for total respiratory score had an ICC of 0.95 (confidence interval 0.93-0.96) and for subscores, the ICC range was as follows: respiratory rate = 0.92, retractions = 0.85, dyspnea = 0.94, and wheezing = 0.77. CONCLUSIONS: TM is a reliable tool to assess the severity of respiratory distress in children.

Antenatal factors modulate hearing screen failure risk in preterm infants.

OBJECTIVE: The objective of this study was to characterise the effects of antenatal inflammatory factors and maternal therapies on neonatal hearing screen outcomes in very low birthweight infants. METHODS: We conducted a retrospective study of a cohort of infants <33 weeks' gestational age and <1501 g birth weight prospectively enrolled between 1999 and 2003 for whom placental pathology, cord blood interleukin (IL) 6, IL-1ß, tumour necrosis factor-α and neonatal hearing screen results were available. RESULTS: Of 289 infants with documented hearing screen results, 244 (84%) passed and 45 (16%) failed the hearing screen (unilateral, N=25 (56%); bilateral, N=20 (44%)). In the final logistic model, the fetal inflammatory response syndrome defined as the presence of fetal vasculitis and/or cord serum IL-6>18.2 pg/mL was the factor with greatest risk for hearing screen failure (OR 3.62, 95% CI 1.38 to 9.5). A patent ductus arteriosus treated with indomethacin significantly increased the risk (OR 3.3, 95% CI 1.3 to 8.26), while combined maternal steroid and magnesium sulfate exposure (0.37, 95% CI 0.11 to 0.81) reduced the risk for hearing screen failure. CONCLUSIONS: Intrauterine infection with a fetal inflammatory response is a risk factor for neonatal hearing loss while maternal therapies significantly reduced the risk of neonatal hearing loss in very low birthweight infants.

Quantifying uncertainty: physicians' estimates of infection in critically ill neonates and children.

To determine the diagnostic accuracy of physicians' prior probability estimates of serious infection in critically ill neonates and children, we conducted a prospective cohort study in 2 intensive care units. Using available clinical, laboratory, and radiographic information, 27 physicians provided 2567 probability estimates for 347 patients (follow-up rate, 92%). The median probability estimate of infection increased from 0% (i.e., no antibiotic treatment or diagnostic work-up for sepsis), to 2% on the day preceding initiation of antibiotic therapy, to 20% at initiation of antibiotic treatment (P<.001). At initiation of treatment, predictions discriminated well between episodes subsequently classified as proven infection and episodes ultimately judged unlikely to be infection (area under the curve, 0.88). Physicians also showed a good ability to predict blood culture-positive sepsis (area under the curve, 0.77). Treatment and testing thresholds were derived from the provided predictions and treatment rates. Physicians' prognoses regarding the presence of serious infection were remarkably precise. Studies investigating the value of new tests for diagnosis of sepsis should establish that they add incremental value to physicians' judgment.

Hyperglycemia and retinopathy of prematurity in very low birth weight infants.

OBJECTIVE: Retinopathy of prematurity (ROP) remains a leading cause of morbidity in the very low-birth-weight (VLBW) infant. This study investigates a possible association between serum/blood glucose and the development of ROP. METHODS: A retrospective case-control study of all infants born between 1992 and 1997 at the Johns Hopkins Hospital with birth weights less than 1000 g who developed Stage 3 or 4 ROP was conducted. Controls either had Stage 1 ROP or no eye disease and were matched 2:1 with ROP patients for gestational age, birth weight and year of birth. Odds ratios (ORs) of ROP were calculated for multiple exposures over the first month after birth, including oxygen concentration (FiO(2)), blood glucose levels, vitamin E, mean airway pressure and mean blood pressure. RESULTS: In a simple logistic regression analysis, we found an increased ROP risk for: (1) each 10 mg/dl increase of mean glucose (OR 1.96; 95% CI 1.13 to 3.42), (2) each 1% increase of mean FiO(2) (OR 1.06; 95% CI 1.004 to 1.13), (3) history of dopamine infusion (OR 5.4; 95% CI 1.16 to 25.2) and (4) intraventricular hemorrhage Grade 3 or 4 (OR 7.3; 95% CI 1.53 to 34.7). Using a multiple regression model, we found an increased ROP risk for each 10 mg/dl increase of mean glucose (OR 2.7; 95% CI 1.003 to 7.27). Each IU/kg/day of vitamin E supplementation reduced ROP risk (OR 0.37; 95% CI 0.16-0.86). CONCLUSION: In this study, we could demonstrate that glucose levels in the first month of life are associated with the development of ROP. Further studies have to determine if this association is causal or if hyperglycemia is just an expression of severity of illness.

Clonidine clearance matures rapidly during the early postnatal period: a population pharmacokinetic analysis in newborns with neonatal abstinence syndrome.

The population pharmacokinetic (PK) profile of oral clonidine was characterized in newborns with neonatal abstinence syndrome, and significant covariates affecting its PK parameters were identified. Plasma clonidine concentration data were obtained from a clinical trial in which 36 newborns, aged 1 to 25 days (postnatal age, PNA) and weighing 2.1 to 3.9 kg, were enrolled to take multiple oral doses of clonidine. The population PK model of clonidine was developed by NONMEM, and significant covariates were identified, followed by nonparametric bootstraps (2000 replicates) and simulation experiments. A 1-compartment open linear PK model was chosen to describe plasma concentrations of clonidine, and body weight and PNA were significant covariates for apparent clearance (CL/F) as follows: CL/F (L/h) = 15.2 × [body weight (kg)/70](0.75) × [PNA (day)(0.441)/(4.06(0.441) + PNA (day)(0.441))]. Furthermore, CL/F of clonidine increased rapidly with PNA during the first month of life after body weight was adjusted. Any optimal dosage regimen for clonidine in term neonates should be based on infant's age and body weight, and 1.5 µg/kg every 4 hours is proposed starting the second week of life based on the simulation results.

Clonidine as an adjunct therapy to opioids for neonatal abstinence syndrome: a randomized, controlled trial.

OBJECTIVE: To determine if oral clonidine would reduce the duration of opioid detoxification for neonatal abstinence syndrome. METHODS: Infants with intrauterine exposure to methadone or heroin and neonatal abstinence syndrome (2 consecutive modified Finnegan scores of > or =9) were enrolled at 2 hospitals during 2002-2005 and followed until final hospital discharge. All enrolled infants (80) received oral diluted tincture of opium according to a standardized algorithm and were randomly assigned to receive oral clonidine (1 microg/kg every 4 hours) (40 infants) or placebo (40 infants). Primary outcome was duration of opioid therapy. Secondary outcomes included the amount of opium required to control symptoms, number of treatment failures, and differences in blood pressure, heart rate, and oxygen saturation. RESULTS: The median length of therapy was 27% shorter in the clonidine group (11 [95% confidence interval: 8-15 days]) than in the placebo group (15 days [95% confidence interval: 12-17 days]). In the clonidine group, 7 infants required restarting opium after initial discontinuation versus none in the placebo group, with the total length of treatment/observation remaining significantly less in the clonidine group. Higher dosages of opium were required by 40% of the infants in the placebo group versus 20% in the clonidine group. Treatment failures occurred in 12.5% of the infants in the placebo group versus none in the clonidine group. Hypertension, hypotension, bradycardia, or desaturations did not occur in either group. Three infants in the clonidine group died as a result of myocarditis, sudden infant death syndrome, and homicide, all after hospital discharge and before 6 months of age. CONCLUSIONS: In this randomized, double-blind trial, adding clonidine to standard opioid therapy for detoxification from in utero exposure to methadone or heroin reduced the duration of pharmacotherapy for neonatal abstinence without causing short-term adverse cardiovascular outcomes. A larger trial is indicated to determine long-term safety.