Michael R. Stenger

Variation in the Use of Diuretic Therapy for Infants With Bronchopulmonary Dysplasia

OBJECTIVES: To determine (1) between-hospital variation in diuretic use for infants with bronchopulmonary dysplasia (BPD), including hospital-specific treatment frequency, treatment duration, and percentage of infants receiving short (≤5 consecutive days) versus longer (>5 days) courses, and to determine (2) demographic and clinical variables associated with diuretic administration. METHODS: A retrospective cohort study was conducted with the use of the Pediatric Health Information System to determine between-hospital variation in diuretic utilization patterns (primary outcome) and variables associated with diuretic use among <29-week-gestation infants with evolving BPD at age 28 days who were discharged between January 2007 and June 2011. RESULTS: During the 54-month study period, 1429 infants within 35 hospitals met the inclusion criteria for BPD at age 28 days, with 1222 (86%) receiving diuretic therapy for a median of 9 days (25th–75th percentile: 2–33 days). Short courses were administered to 1203 (83%) infants, and 570 (40%) infants received treatment for >5 consecutive days. Furosemide was the most widely prescribed diuretic (1218 infants; 85%), although chlorothiazide had the longest median duration of use (21 days; 25th–75th percentile: 8–46 days). The range of infants receiving a diuretic course of >5 days duration varied by hospital from 4% to 86%, with wide between-hospital variation even after adjustment for confounding variables. CONCLUSIONS: The frequency of diuretic administration to infants with BPD at US children’s hospitals, as well as the specific diuretic regimen used, varies markedly by institution. Safety and effectiveness research of long-term diuretic therapy for BPD patients is needed to develop evidence-based recommendations.

Probiotics and Prebiotics for the Prevention of Necrotizing Enterocolitis

Necrotizing enterocolitis (NEC) continues to be a major cause of morbidity and mortality in premature infants. Although the pathogenesis of NEC remains unclear, abnormal bacterial colonization has been postulated as playing a central role. Various factors impact bacterial colonization following delivery. Compared to term infants, the bacterial colonization pattern in prematurely born infants is markedly different, with a greater predilection for colonization with pathogenic bacteria. Probiotic and prebiotic administration offers the opportunity to manipulate the intestinal bacterial environment, favoring the growth of commensal bacteria. Experimental data from animal studies and data from human trials suggest that probiotics decrease the incidence of NEC. These preliminary studies support the need for a large, randomized, controlled trial to further investigate the role of probiotics in the prevention of NEC.

Utilization of Inhaled Corticosteroids for Infants with Bronchopulmonary Dysplasia

Objective To determine demographic and clinical variables associated with inhaled corticosteroid administration and to evaluate between-hospital variation in inhaled steroid use for infants with bronchopulmonary dysplasia (BPD). Design Retrospective Cohort Study. Setting Neonatal units of 35 US childrens hospitals; as recorded in the Pediatric Health Information System (PHIS) database. Patients 1429 infants with evolving BPD at 28 days who were born at <29 weeks gestation with birth weight <1500 grams, admitted within the first 7 postnatal days, and discharged between January 2007–June 2011. Results Inhaled steroids were prescribed to 25% (n = 352) of the cohort with use steadily increasing during the first two months of hospitalization. The most frequently prescribed steroid was beclomethasone (n = 194, 14%), followed by budesonide (n = 125, 9%), and then fluticasone (n = 90, 6%). Birth gestation <24 weeks, birth weight 500–999 grams, and prolonged ventilation all increased the adjusted odds of ever receiving inhaled corticosteroids (p<0.05). Wide variations between hospitals in the frequency of infants ever receiving inhaled steroids (range: 0–60%) and the specific drug prescribed were noted. This variation persisted, even after controlling for observed confounders. Conclusions Inhaled corticosteroid administration to infants with BPD is common in neonatal units within U.S. Childrens hospitals. However, its utilization varies markedly between centers from no treatment at some institutions to the majority of infants with BPD being treated at others. This supports the need for further research to identify the benefits and potential risks of inhaled steroid usage in infants with BPD.

The contrast sensitivity of the newborn human infant.

PURPOSE To measure the binocular contrast sensitivity (CS) of newborn infants using a fixation-and-following card procedure. METHODS The CS of 119 healthy newborn infants was measured using stimuli printed on cards under the descending method of limits (93 infants) and randomized/masked designs (26 infants). One experienced and one novice adult observer tested the infants using vertical square-wave gratings (0.06 and 0.10 cyc/deg; 20/10,000 and 20/6000 nominal Snellen equivalent); the experienced observer also tested using horizontal gratings (0.10 cyc/deg) and using the Method of Constant Stimuli while being kept unaware of the stimulus values. RESULTS The CS of the newborn infant was 2.0 (contrast threshold = 0.497; 95% confidence interval: 0.475-0.524) for vertically oriented gratings and 1.74 (threshold = 0.575; 95% confidence interval: 0.523-0.633) for horizontally oriented gratings (P < 0.0006). The standard deviation of infant CS was comparable to that obtained by others on adults using the Pelli-Robson chart. The two observers showed similar practice effects. Randomization of stimulus order and masking of the adult observer had no effect on CS. CONCLUSIONS The CS of individual newborn human infants can be measured using a fixation-and-following card procedure.

Role of Oxidative Stress in Necrotizing Enterocolitis: Advances and Possibilities for Future Therapy

During normal fetal development, a balance between the production of oxidants and the antioxidant defense systems is critical for proper growth and development. Studies have shown that an imbalance between oxidant production and antioxidant defense mechanisms may lead to preterm birth, fetal growth restriction, and related morbidities. Premature infants are highly susceptible to oxidant-induced damage due to immature antioxidant defense systems or deficiency of antioxidants. As a result there is an increased risk for the development of oxidant-induced diseases of the newborn, such as bronchopulmonary dysplasia, retinopathy of prematurity, and periventricular leukomalacia.

Necrotizing Enterocolitis and Oxidative Stress

Necrotizing enterocolitis (NEC) is one of the most common gastrointestinal conditions affecting newborn infants. Despite vigorous research the pathogenesis of NEC remains unclear. Oxidative stress has been shown to contribute to the development of other diseases involving premature infants such as bronchopulmonary dysplasia (BPD) and retinopathy of prematurity (ROP). More recently, oxidative stress has implicated in the pathogenesis of NEC. This chapter will briefly review the clinical presentation and management of NEC, discuss the potential role of oxidative stress in the pathogenesis of NEC, and finally review possible therapeutic targets in the hope of preventing NEC in high-risk infants.