Rapid infusion of fish oil-based lipid emulsions: Is there a risk of fat overload syndrome? A case report of rapid administration.

WHAT IS KNOWN AND OBJECTIVES: Errors involving the delivery of IVFE containing soybean oil have known significant complications, including fat overload syndrome. However, little is known regarding the risks of fat overload syndrome with other types of lipid emulsions. CASE SUMMARY: We describe a medication administration error that resulted in rapid fish oil-base lipid emulsion (Omegaven) infusion in a five-month-old infant with parenteral nutrition associated liver disease (PNALD). The medication administration error resulted in bolus infusion of Omegaven over 12 min (5 g/kg/h) instead of 12 h (0.083 g/kg/h). WHAT IS NEW AND CONCLUSION: No adverse reactions were notes because of the rapid infusion, supporting conclusion that rapid infusion of fish oil will not result in fat overload syndrome.

Genotypic and phenotypic variability of 22q11.2 microduplications: An institutional experience.

Duplications in the 22q11.2 region can cause 22q11.2 duplication syndrome and encompass a variety of phenotypes including developmental delays, facial abnormalities, cardiovascular defects, central nervous system delays, and other congenital abnormalities. However, the contribution of these contiguous duplicated regions to the clinical phenotypes has not been fully elucidated. In this study, we identified nine patients carrying different 22q11.2 microduplications detected by chromosomal microarray. Of these patients, seven pediatric patients presented with various clinical features including two neonate cases died shortly after birth, and two healthy adults. We examined region specific genotype-phenotype associations and found unpredictability associated with 22q11.2 duplications in these nine patients.

Management of Late Preterm and Term Neonates exposed to maternal Chorioamnionitis.

BACKGROUND: Chorioamnionitis is a significant risk factor for early-onset neonatal sepsis. However, empiric antibiotic treatment is unnecessary for most asymptomatic newborns exposed to maternal chorioamnionitis (MC). The purpose of this study is to report the outcomes of asymptomatic neonates ≥35 weeks gestational age (GA) exposed to MC, who were managed without routine antibiotic administration and were clinically monitored while following complete blood cell counts (CBCs). METHODS: A retrospective chart review was performed on neonates with GA ≥ 35 weeks with MC during calendar year 2013. IT ratio (immature: total neutrophils) was considered suspicious if ≥0.3. The data were analyzed using independent sample T-tests. RESULTS: Among the 275 neonates with MC, 36 received antibiotics for possible sepsis. Twenty-one were treated with antibiotics for > 48 h for clinical signs of infection; only one infant had a positive blood culture. All 21 became symptomatic prior to initiating antibiotics. Six showed worsening of IT ratio. Thus empiric antibiotic administration was safely avoided in 87% of neonates with MC. 81.5% of the neonates had follow-up appointments within a few days and at two weeks of age within the hospital system. There were no readmissions for suspected sepsis. CONCLUSIONS: In our patient population, using CBC indices and clinical observation to predict sepsis in neonates with MC appears safe and avoids the unnecessary use of antibiotics.

Clindamycin Pharmacokinetics and Safety in Preterm and Term Infants.

Clindamycin may be active against methicillin-resistant Staphylococcus aureus, a common pathogen causing sepsis in infants, but optimal dosing in this population is unknown. We performed a multicenter, prospective pharmacokinetic (PK) and safety study of clindamycin in infants. We analyzed the data using a population PK analysis approach and included samples from two additional pediatric trials. Intravenous data were collected from 62 infants (135 plasma PK samples) with postnatal ages of <121 days (median [range] gestational age of 28 weeks [23 to 42] and postnatal age of 17 days [1 to 115]). In addition to body weight, postmenstrual age (PMA) and plasma protein concentrations (albumin and alpha-1 acid glycoprotein) were found to be significantly associated with clearance and volume of distribution, respectively. Clearance reached 50% of the adult value at PMA of 39.5 weeks. Simulated PMA-based intravenous dosing regimens administered every 8 h (≤32 weeks PMA, 5 mg/kg; 32 to 40 weeks PMA, 7 mg/kg; >40 to 60 weeks PMA, 9 mg/kg) resulted in an unbound, steady-state concentration at half the dosing interval greater than a MIC for S. aureus of 0.12 µg/ml in >90% of infants. There were no adverse events related to clindamycin use. (This study has been registered at ClinicalTrials.gov under registration no. NCT01728363.).

Effect of fluconazole prophylaxis on candidiasis and mortality in premature infants: a randomized clinical trial.

IMPORTANCE: Invasive candidiasis in premature infants causes death and neurodevelopmental impairment. Fluconazole prophylaxis reduces candidiasis, but its effect on mortality and the safety of fluconazole are unknown. OBJECTIVE: To evaluate the efficacy and safety of fluconazole in preventing death or invasive candidiasis in extremely low-birth-weight infants. DESIGN, SETTING, AND PATIENTS: This study was a randomized, blinded, placebo-controlled trial of fluconazole in premature infants. Infants weighing less than 750 g at birth (N = 361) from 32 neonatal intensive care units (NICUs) in the United States were randomly assigned to receive either fluconazole or placebo twice weekly for 42 days. Surviving infants were evaluated at 18 to 22 months corrected age for neurodevelopmental outcomes. The study was conducted between November 2008 and February 2013. INTERVENTIONS: Fluconazole (6 mg/kg of body weight) or placebo. MAIN OUTCOMES AND MEASURES: The primary end point was a composite of death or definite or probable invasive candidiasis prior to study day 49 (1 week after completion of study drug). Secondary and safety outcomes included invasive candidiasis, liver function, bacterial infection, length of stay, intracranial hemorrhage, periventricular leukomalacia, chronic lung disease, patent ductus arteriosus requiring surgery, retinopathy of prematurity requiring surgery, necrotizing enterocolitis, spontaneous intestinal perforation, and neurodevelopmental outcomes-defined as a Bayley-III cognition composite score of less than 70, blindness, deafness, or cerebral palsy at 18 to 22 months corrected age. RESULTS: Among infants receiving fluconazole, the composite primary end point of death or invasive candidiasis was 16% (95% CI, 11%-22%) vs 21% in the placebo group (95% CI, 15%-28%; odds ratio, 0.73 [95% CI, 0.43-1.23]; P = .24; treatment difference, -5% [95% CI, -13% to 3%]). Invasive candidiasis occurred less frequently in the fluconazole group (3% [95% CI, 1%-6%]) vs the placebo group (9% [95% CI, 5%-14%]; P = .02; treatment difference, -6% [95% CI, -11% to -1%]). The cumulative incidences of other secondary outcomes were not statistically different between groups. Neurodevelopmental impairment did not differ between the groups (fluconazole, 31% [95% CI, 21%-41%] vs placebo, 27% [95% CI, 18%-37%]; P = .60; treatment difference, 4% [95% CI, -10% to 17%]). CONCLUSIONS AND RELEVANCE: Among infants with a birth weight of less than 750 g, 42 days of fluconazole prophylaxis compared with placebo did not result in a lower incidence of the composite of death or invasive candidiasis. These findings do not support the universal use of prophylactic fluconazole in extremely low-birth-weight infants. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00734539.

Hyperbilirubinemia and transcutaneous bilirubinometry.

BACKGROUND: Neonatal jaundice or hyperbilirubinemia is a common occurrence in newborns. Although most cases of neonatal jaundice have a benign course, severe hyperbilirubinemia can lead to kernicterus, which is preventable if the hyperbilirubinemia is identified early and treated appropriately. CONTENT: This review discusses neonatal jaundice and the use of transcutaneous bilirubin (TcB) measurements for identification of neonates at risk of severe hyperbilirubinemia. Such a practice requires appropriate serial testing and result interpretation according to risk level from a nomogram that provides bilirubin concentrations specific for the age of the neonate in hours. In this context, we have evaluated the potential impact on clinical outcome and limitations of TcB methods in current use. SUMMARY: TcB measurement is a viable option in screening neonates to determine if they are at risk for clinically significant hyperbilirubinemia. Total serum bilirubin should be measured by a clinical laboratory if a newborn is shown to be at higher risk for clinically significant hyperbilirubinemia. In addition, external quality assessment to identify biases and operator training issues should be part of any TcB monitoring program.

Physiologically-Based Pharmacokinetic Modeling of Fluconazole Using Plasma and Cerebrospinal Fluid Samples From Preterm and Term Infants.

Fluconazole is used to treat hematogenous Candida meningoencephalitis in preterm and term infants. To characterize plasma and central nervous system exposure, an adult fluconazole physiologically-based pharmacokinetic (PBPK) model was scaled to infants, accounting for age dependencies in glomerular filtration and metabolism. The model was optimized using 760 plasma samples from 166 infants (median postmenstrual age (range) 28 weeks (24-50)) and 27 cerebrospinal fluid (CSF) samples from 22 infants (postmenstrual age 28 weeks (24-33)). Simulations evaluated achievement of the surrogate efficacy target of area under the unbound concentration-time curve ≥ 400 mg • hour/L over the dosing interval in plasma and CSF using dosing guidelines. Average fold error of predicted concentrations was 0.73 and 1.14 for plasma and CSF, respectively. Target attainment in plasma and CSF was reached faster after incorporating a loading dose of 25 mg/kg. PBPK modeling can be useful in exploring CNS kinetics of drugs in children.

Breastfeeding Education and Support Services Provided to Family Medicine and Obstetrics-Gynecology Residents.

BACKGROUND: Breastfeeding education is known to be insufficient in pediatric (PEDS) training and is, in part, responsible for suboptimal rates of breastfeeding. No recent studies about the level of education provided to family medicine (FM) and obstetrics-gynecology (OB) residency trainees are available. OBJECTIVES: This study was conducted to investigate breastfeeding education and support services provided to FM and OB residents in the United States. The results were compared with a 2011 study of PEDS residents. METHODS: A cross-sectional study was conducted using a web-based survey emailed to program directors (PDs) of FM and OB residency programs in the United States. RESULTS: Eighteen percent of PDs (95 of 515) completed the survey. Of these, 88% answered questions regarding education and support services provided. A median of 23 hours of breastfeeding education is provided to OB residents (4-year program) and 8 hours provided to FM residents (3-year program). In comparison, PEDS programs reported a median of 9 hours. The most commonly used settings included lectures with faculty and lactation consultants, similar to the PEDS study. Approximately 75% of respondents cited barriers to educating residents, with limited resident time being the most common. Eighty-one percent of respondents identified breastfeeding rooms as the service most frequently provided to residents who breastfeed. CONCLUSIONS: FM and PEDS residents are provided similar amounts of breastfeeding education, while OB programs provide more education, but in different settings. Reported barriers to this education are similar in all specialties. Support services are more commonly provided in PEDS programs.

Ebola Virus and Marburg Virus in Human Milk Are Inactivated by Holder Pasteurization.

BACKGROUND: Potential donors of human milk are screened for Ebola virus (EBOV) using standard questions, but testing for EBOV and Marburg virus (MARV) is not part of routine serological testing performed by milk banks. Research aim: This study tested the hypothesis that EBOV would be inactivated in donor human milk (DHM) by standard pasteurization techniques (Holder) used in all North American nonprofit milk banks. METHODS: Milk samples were obtained from a nonprofit milk bank. They were inoculated with EBOV (Zaire strain) and MARV (Angola strain) and processed by standard Holder pasteurization technique. Plaque assays for EBOV and MARV were performed to detect the presence of virus after pasteurization. RESULTS: Neither EBOV nor MARV was detectable by viral plaque assay in DHM or culture media samples, which were pasteurized by the Holder process. CONCLUSION: EBOV and MARV are safely inactivated in human milk by standard Holder pasteurization technique. Screening for EBOV or MARV beyond questionnaire and self-deferral is not needed to ensure safety of DHM for high-risk infants.

High compared with standard gentamicin dosing for chorioamnionitis: a comparison of maternal and fetal serum drug levels.

OBJECTIVE: To compare umbilical cord and maternal serum peak gentamicin concentration, gentamicin elimination, and clinical outcomes between women who received once-daily compared with standard, thrice-daily dosing for clinical chorioamnionitis. METHODS: We randomly assigned 38 laboring women, at least 34 weeks gestation, with clinical chorioamnionitis, into 1 of 2 gentamicin dosing groups: 5.1 mg/kg every 24 hours (once-daily; n = 18), or 120 mg followed by 80 mg every 8 hours (standard; n = 20). We measured maternal serum peak and delivery gentamicin concentrations and cord serum levels at delivery. Polynomial curve fitting was used to summarize gentamicin elimination. We also compared maternal and neonatal outcomes. RESULTS: Demographic characteristics of the 2 groups were similar. Median maternal peak gentamicin levels were higher with once-daily (18.2 microg/mL) compared with standard dosing (7.1 microg/mL) (P < .001). Maternal serum levels decreased below 2 microg/mL by 10 hours in the once-daily group and by 5 hours in the standard dosing group. Extrapolated peak cord serum levels were 6.9 microg/mL in the once-daily and 2.9 microg/mL in the standard dosing arm. Cord levels decreased below 2 microg/mL by 10 hours in the once-daily and by 5 hours in the standard dosing group. We found no differences in maternal or neonatal outcomes. CONCLUSION: Peak maternal serum gentamicin levels ranged from 13 to 25 microg/mL after a dose of 5.1 mg/kg. Single-dose gentamicin resulted in fetal serum peak levels that were closer to optimal neonatal values. Gentamicin clearance in the term fetus was similar to published values for the newborn infant. No adverse effects of high-dose therapy were noted.

Endotoxin protection from oxygen toxicity: effect on pulmonary neutrophils and L-selectin.

The mechanisms by which sublethal doses of endotoxin protect against hyperoxic lung injury are not completely understood. We hypothesized that endotoxin treatment would result in a decreased inflammatory response to hyperoxia and that this would be accompanied by activation of neutrophils (as evidenced by loss of L-selectin) in the peripheral circulation. Adult rats were injected with endotoxin 0.5 mg/kg prior to and 24 hr after onset of exposure to > or = 98% O2. After 56 hr of hyperoxia, pulmonary neutrophils were lower in the O2/endotoxin group compared to O2 controls as measured by myeloperoxidase in lung homogenates and neutrophil counts in bronchoalveolar lavage fluid. Circulating neutrophils were also significantly lower in the O2/endotoxin group compared to O2 controls at 56 hr. Expression of the neutrophil adhesion molecule, L-selectin, was lower at 4 and 24 hr in the endotoxin-treated rats compared to O2 controls. There were no differences at 48 hr. Expression of CD18 rose significantly in the O2/endotoxin group after 4 hr, but thereafter did not differ from O2 controls. In summary, endotoxin protection from O2 toxicity was associated with reduced neutrophils in the lung and a loss of L-selectin from peripheral blood neutrophils.

Intestinal zygomycosis due to Absidia corymbifera mimicking necrotizing enterocolitis in a preterm neonate.

Zygomycosis is a rare fungal disease that occurs in compromised human hosts, including the preterm infant. The three clinical forms of zygomycosis are cellulitis, disseminated, and gastrointestinal, and the last often mimics necrotizing enterocolitis (NEC), complicating the diagnosis. This report details a case of primary gastrointestinal zygomycosis due to Absidia corymbifera, mimicking NEC, in a preterm infant, and emphasizes features that may lead to earlier diagnosis and treatment of future cases.

Association of transcutaneous bilirubin testing in hospital with decreased readmission rate for hyperbilirubinemia.

BACKGROUND: Newborns are being discharged from hospitals within 1-2 days of birth, before hyperbilirubinemia usually becomes clinically evident. We investigated the use of transcutaneous bilirubin (TcB) before discharge to determine whether it affects the use of laboratory bilirubin testing or decreases the number of neonates readmitted for hyperbilirubinemia within 7 days of initial discharge. METHODS: We retrospectively searched a clinical laboratory and hospital database to determine the number of births, newborn readmission rates for hyperbilirubinemia, length of stay, and the number of bilirubin measurements in the clinical laboratory ordered for all babies in the newborn unit at the University of Texas Medical Branch from August 2002 to March 2003 (before TcB testing) and from May 2003 to December 2003 (after TcB). RESULTS: Between August 2002 and December 2003, 8974 newborns (both vaginal and cesarean births) were admitted to the newborn nursery. Babies who did not fit the diagnosis-related group criteria of "normal newborn" were removed, leaving 6933 babies who were included in the study. April was considered a transition month and was not included in the study, leaving 6603 newborns to be included. Of these, 446 (6.8%) required phototherapy for treatment of hyperbilirubinemia before initial discharge. For the 8 months before and 8 months after initiation of TcB testing, the number of laboratory bilirubin measurements ordered per newborn did not change, nor did the mean (SD) length of stay for normal newborns [2.15 (1.1) days vs 2.12 (1.1) days; P = 0.53], nor days of treatment with phototherapy before discharge [2.9 (1.3) days vs 2.9 (1.3) days; P = 0.67]. By contrast, the number of readmissions per 1000 newborns per month for clinically significant hyperbilirubinemia decreased significantly (Wilcoxon rank-sums two-sample test, P = 0.044), from 4.5 (2.4) to 1.8 (1.7) after TcB testing was initiated. CONCLUSION: Access to TcB testing is associated with a reduction in the hospital readmission rate for hyperbilirubinemia within 7 days of the initial discharge.

Early surfactant for neonates with mild to moderate respiratory distress syndrome: a multicenter, randomized trial.

OBJECTIVE: We studied the efficacy and safety of electively providing surfactant to preterm infants with mild to moderate respiratory distress syndrome (RDS) not requiring mechanical ventilation. STUDY DESIGN: A 5-center, randomized clinical trial was performed on 132 infants with RDS, birth weight >or=1250 grams, gestational age or=40% for >or=1 hour, and no immediate need for intubation. Infants were randomly assigned to intubation, surfactant (Survanta, Ross Laboratories, Columbus, Ohio) administration, and expedited extubation (n=65) or expectant management (n=67) with subsequent intubation and surfactant treatment as clinically indicated. The primary outcome was duration of mechanical ventilation. RESULTS: Infants in the surfactant group had a median duration of mechanical ventilation of 2.2 hours compared with 0.0 hours for control infants, since only 29 of 67 control infants required mechanical ventilation (P=.001). Surfactant-treated infants were less likely to require subsequent mechanical ventilation for worsening respiratory disease (26% vs 43%, relative risk=0.60; 95% CI, 0.37, 0.99). There were no differences in secondary outcomes (duration of nasal continuous positive airway pressure, oxygen therapy, hospital stay, or adverse outcomes). CONCLUSIONS: Routine elective intubation for administration of surfactant to preterm infants >or=1250 grams with mild to moderate RDS is not recommended.