Background Although peanut oral immunotherapy (OIT) has been conclusively shown to cause desensitization, it is currently unknown whether clinical protection persists after stopping therapy. ...Objective Our primary objective was to determine whether peanut OIT can induce sustained unresponsiveness after withdrawal of OIT. Methods We conducted a pilot clinical trial of peanut OIT at 2 US centers. Subjects age 1 to 16 years were recruited and treated for up to 5 years with peanut OIT. The protocol was modified over time to permit dose increases to a maximum of 4000 mg/d peanut protein. Blood was collected at multiple time points. Clinical end points were measured with 5000-mg double-blinded, placebo-controlled food challenges once specific criteria were met. Results Of the 39 subjects originally enrolled, 24 completed the protocol and had evaluable outcomes. Twelve (50%) of 24 successfully passed a challenge 1 month after stopping OIT and achieved sustained unresponsiveness. Peanut was added to the diet. At baseline and the time of challenge, such subjects had smaller skin test results, as well as lower IgE levels specific for peanut, Ara h 1, and Ara h 2 and lower ratios of peanut-specific IgE/total IgE compared with subjects not passing. There were no differences in peanut IgG4 levels or functional activity at the end of the study. Conclusions This is the first demonstration of sustained unresponsiveness after peanut OIT, occurring in half of subjects treated for up to 5 years. OIT favorably modified the peanut-specific immune response in all subjects completing the protocol. Smaller skin test results and lower allergen-specific IgE levels were predictive of successful outcome.
Objective To characterize administration of sedatives, analgesics, and paralytics in a large cohort of mechanically ventilated premature infants. Study design Retrospective cohort study including all ...infants <1500 g birth weight and <32 weeks gestational age (GA) mechanically ventilated at 348 Pediatrix Medical Group neonatal intensive care units from 1997 to 2012. The primary outcome is the proportion of mechanically ventilated days in which infants were administered drugs of interest. Multivariable logistic regression was used to evaluate the predictors of administration of drugs of interest. Results We identified 85 911 mechanically ventilated infants. Infants received a drug of interest (opioids, benzodiazepines, other sedatives, and paralytics) on 433 587/1 305 413 (33%) of mechanically ventilated infant days. The administration of opioids increased during the study period from 5% of infant days in 1997 to 32% in 2012. The administration of benzodiazepines increased during the study period from 5% of infant days in 1997 to 24% in 2012. Use of paralytics and other drugs remained ≤1% throughout the study period. Predictors of drug administration included younger GA, small for GA status, male sex, presence of a major congenital anomaly, older postnatal age at intubation, exposure to high-frequency ventilation, exposure to inotropes, more recent year of discharge, and neonatal intensive care unit site. Conclusions Administration of opioids and benzodiazepines in mechanically ventilated premature infants increased over time. Because infant characteristics were unchanged, site-specific differences in practice likely explain our observations. Increased administration over time is concerning given limited evidence of benefit and potential for harm.
Objective To examine the effect of early initiation of caffeine therapy on neonatal outcomes and characterize the use of caffeine therapy in very low birth weight (VLBW) infants. Study design We ...analyzed a cohort of 62 056 VLBW infants discharged between 1997 and 2010 who received caffeine therapy. We compared outcomes in infants receiving early caffeine therapy (initial dose before 3 days of life) and those receiving late caffeine therapy (initial dose at or after 3 days of life) through propensity scoring using baseline and early clinical variables. The primary outcome was the association between the timing of caffeine initiation and the incidence of bronchopulmonary dysplasia (BPD) or death. Results We propensity score–matched 29 070 VLBW infants at a 1:1. Of infants receiving early caffeine therapy, 3681 (27.6%) died or developed BPD, compared with 4591 infants (34.0%) receiving late caffeine therapy (OR, 0.74; 99% CI, 0.69-0.80). Infants receiving early caffeine had a lower incidence of BPD (23.1% vs 30.7%; OR, 0.68; 95% CI, 0.63-0.73) and a higher incidence of death (4.5% vs 3.7%; OR, 1.23; 95% CI, 1.05-1.43). Infants receiving early caffeine therapy had less treatment of patent ductus arteriosus (OR, 0.60; 95% CI, 0.55-0.65) and a shorter duration of mechanical ventilation (mean difference, 6 days; P < .001). Conclusion Early caffeine initiation is associated with a decreased incidence of BPD. Randomized trials are needed to determine the efficacy and safety of early caffeine prophylaxis in VLBW infants.
Objective To compare effectiveness of 3 surfactant preparations (beractant, calfactant, and poractant alfa) in premature infants for preventing 3 outcomes: (1) air leak syndromes; (2) death; and (3) ...bronchopulmonary dysplasia (BPD) or death (composite outcome). Study design We conducted a comparative effectiveness study of premature infants admitted to 322 neonatal intensive care units in the US from 2005-2010 who were treated with beractant, calfactant, or poractant alfa. We compared the incidence of air leak syndromes, death, and BPD or death, adjusting for gestational age (GA), antenatal steroids, discharge year, and small for GA status. Results A total of 51 282 infants received surfactant; 40% received beractant, 30% calfactant, and 30% poractant alfa. Median birth weight was 1435 g (IQR 966-2065); median GA was 30 weeks (27-33). On adjusted analysis, we observed a similar risk of air leak syndromes (calfactant vs beractant OR = 1.17 95% CI: 0.95, 1.43; calfactant vs poractant OR = 1.23 0.98, 1.56; beractant vs poractant OR = 1.06 0.87, 1.29), death (calfactant vs beractant OR = 1.14 0.93, 1.39; calfactant vs poractant OR = 0.98 0.78, 1.23; beractant vs poractant OR = 0.86 0.72, 1.04), and BPD or death (calfactant vs beractant OR = 1.08 0.93, 1.26; calfactant vs poractant OR = 1.19 1.00, 1.41; beractant vs poractant OR = 1.10 0.96, 1.27). Conclusions Beractant, calfactant, and poractant alfa demonstrated similar effectiveness in prevention of air leak syndromes, death, and BPD or death in premature infants when adjusted for site. Previously described differences in mortality between surfactants likely do not represent true differences in effectiveness but may relate to site variation in outcomes.
Gabapentin was used for the treatment of term and preterm infants with suspected visceral hyperalgesia caused by a variety of neurologic and gastrointestinal morbidities. Improved feeding tolerance ...and decreased irritability were seen, as well as decreased usage of opioids and benzodiazepines. Adverse events occurred with abrupt discontinuation of this medication.
Objective To describe the epidemiology, risk factors, and in-hospital outcomes of tracheostomy in infants in the neonatal intensive care unit. Study design We analyzed electronic medical records from ...348 neonatal intensive care units for the period 1997 to 2012, and evaluated the associations among infant demographics, diagnoses, and pretracheostomy cardiopulmonary support with in-hospital mortality. We also determined the trends in use of infant tracheostomy over time. Results We identified 885 of 887 910 infants (0.1%) who underwent tracheostomy at a median postnatal age of 72 days (IQR, 27-119 days) and a median postmenstrual age of 42 weeks (IQR, 39-46 weeks). The most common diagnoses associated with tracheostomy were bronchopulmonary dysplasia (396 of 885; 45%), other upper airway anomalies (202 of 885; 23%), and laryngeal anomalies (115 of 885; 13%). In-hospital mortality after tracheostomy was 14% (125 of 885). On adjusted analysis, near-term gestational age (GA), small for GA status, pulmonary diagnoses, number of days of forced fraction of inspired oxygen >0.4, and inotropic support before tracheostomy were associated with increased in-hospital mortality. The proportion of infants requiring tracheostomy increased from 0.01% in 1997 to 0.1% in 2005 ( P < .001), but has remained stable since. Conclusion Tracheostomy is not commonly performed in hospitalized infants, but the associated mortality is high. Risk factors for increased in-hospital mortality after tracheostomy include near-term GA, small for GA status, and pulmonary diagnoses.
Objective To assess the effect of enteral feeding with human milk on the time from initiation of feeds to discharge after gastroschisis repair through review of a multi-institutional database. Study ...design Infants who underwent gastroschisis repair between 1997 and 2012 with data recorded in the Pediatrix Medical Group Clinical Data Warehouse were categorized into 4 groups based on the percentage of days fed human milk out of the number of days fed enterally. Cox proportional hazards regression modeling was performed to determine the adjusted effect of human milk on the time from initiation of feeds to discharge. Results Among 3082 infants, 659 (21%) were fed human milk on 0% of enteral feeding days, 766 (25%) were fed human milk on 1%-50% of enteral feeding days, 725 (24%) were fed human milk on 51%-99% of enteral feeding days, and 932 (30%) were fed human milk on 100% of enteral feeding days. Following adjustment, being fed human milk on 0% of enteral feeding days was associated with a significantly increased time to discharge compared with being fed human milk on 100% of enteral feeding days (hazard ratio HR for discharge per day, 0.46; 95% CI, 0.40-0.52). The same was found for infants fed human milk on 1%-50% of enteral feeding days (HR, 0.37; 95% CI, 0.32-0.41) and for infants fed human milk on 51%-99% of enteral feeding days (HR, 0.51; 95% CI, 0.46-0.57). Conclusion The use of human milk for enteral feeding of infants following repair of gastroschisis significantly reduces the time to discharge from initiation of feeds.
Invasive candidiasis is a leading infectious cause of morbidity and mortality in premature infants. Improved recognition of modifiable risk factors and antifungal prophylaxis has contributed to the ...recent decline in the incidence of this infection among infants. Invasive candidiasis typically occurs in the first 6 weeks of life and presents with nonspecific signs of sepsis. Definitive diagnosis relies on the growth of Candida in blood culture or cultures from other normally sterile sites, but this may identify fewer than half of cases. Improved diagnostics are needed to guide the initiation of antifungal therapy in premature infants.
Objective To evaluate the relationship between ampicillin dosing, exposure, and seizures. Study design This was a retrospective observational cohort study of electronic health record (EHR) data ...combined with pharmacokinetic model derived drug exposure predictions. We used the EHR from 348 Pediatrix Medical Group neonatal intensive care units from 1997 to 2012. We included all infants 24-41 weeks gestational age, 500-5400 g birth weight, first exposed to ampicillin prior to 25 days postnatal age. Using a 1-compartment pharmacokinetic model and EHR data, we simulated maximum ampicillin concentration at steady state (Cmaxss, µg/mL) and area under the concentration time curve from 0 to 24 hours (AUC24, µg*h/dL). Using multivariable logistic regression, we evaluated association between ampicillin dosing, exposure, and seizures as documented in the EHR. Results We identified 131 723 infants receiving 134 041 courses of ampicillin for 653 506 infant-days of exposure. The median daily dose was 200 mg/kg/d (25th, 75th percentile; 100, 200). Median Cmaxss and AUC24 were 256.6 µg/mL (164.3, 291.5) and 2593 µg*h/dL (1917, 3334). On multivariable analysis, dosing was not associated with seizures. However increasing Cmaxss (OR = 1.10, 95% CI 1.03, 1.17) and AUC24 (OR 1.11, 95% CI 1.05, 1.18) were associated with increased odds of seizures. Conclusions In this cohort of hospitalized infants, higher ampicillin exposure was associated with seizures as documented in the EHR.
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