Browsing by Author "Phelps, Dale L."

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    Blood myo-inositol concentrations in preterm and term infants
    (Springer Nature, 2021-02) Brion, Luc P.; Phelps, Dale L.; Ward, Robert M.; Nolen, Tracy L.; Hallman, N. Mikko K.; Das, Abhik; Zaccaro, Daniel J.; Ball, M. Bethany; Watterberg, Kristi L.; Frantz, Ivan D., III.; Cotten, C. Michael; Poindexter, Brenda B.; Oh, William; Lugo, Ralph A.; Van Meurs, Krisa P.; O’Shea, T. Michael; Zaterka-Baxter, Kristin M.; Higgins, Rosemary D.; Pediatrics, School of Medicine
    Objective: To describe relationship between cord blood (representing fetal) myo-inositol concentrations and gestational age (GA) and to determine trends of blood concentrations in enterally and parenterally fed infants from birth to 70 days of age. Design/methods: Samples were collected in 281 fed or unfed infants born in 2005 and 2006. Myo-inositol concentrations were displayed in scatter plots and analyzed with linear regression models of natural log-transformed values. Results: In 441 samples obtained from 281 infants, myo-inositol concentrations varied from nondetectable to 1494 μmol/L. Cord myo-inositol concentrations decreased an estimated 11.9% per week increase in GA. Postnatal myo-inositol concentrations decreased an estimated 14.3% per week increase in postmenstrual age (PMA) and were higher for enterally fed infants compared to unfed infants (51% increase for fed vs. unfed infants). Conclusions: Fetal myo-inositol concentrations decreased with increasing GA. Postnatal concentrations decreased with increasing PMA and were higher among enterally fed than unfed infants.
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    Emperic Antifungal Therapy and Outcomes in Extremely-Low-Birth-Weight Infants with Invasive Candidiasis
    (Elsevier, 2012) Greenberg, Rachel G.; Benjamin, Daniel K., Jr.; Gantz, Marie G.; Cotten, C. Michael; Stoll, Barbara J.; Walsh, Michele C.; Sánchez, Pablo J.; Shankaran, Seetha; Das, Abhik; Higgins, Rosemary D.; Miller, Nancy A.; Auten, Kathy J.; Walsh, Thomas J.; Laptook, Abbot R.; Carlo, Waldemar A.; Kennedy, Kathleen A.; Finer, Neil N.; Duara, Shahnaz; Schibler, Kurt; Ehrenkranz, Richard A.; Van Meurs, Krisa P.; Frantz, Ivan D., III; Phelps, Dale L.; Poindexter, Brenda B.; Bell, Edward F.; O'Shea, T. Michael; Watterberg, Kristi L.; Goldberg, Ronald N.; Smith, P. Brian; Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network; Pediatrics, School of Medicine
    Objective: To assess the impact of empiric antifungal therapy for invasive candidiasis on subsequent outcomes in premature infants. Study design: This was a cohort study of infants with a birth weight ≤ 1000 g receiving care at Neonatal Research Network sites. All infants had at least one positive culture for Candida. Empiric antifungal therapy was defined as receipt of a systemic antifungal on the day of or the day before the first positive culture for Candida was drawn. We created Cox proportional hazards and logistic regression models stratified on propensity score quartiles to determine the effect of empiric antifungal therapy on survival, time to clearance of infection, retinopathy of prematurity, bronchopulmonary dysplasia, end-organ damage, and neurodevelopmental impairment (NDI). Results: A total of 136 infants developed invasive candidiasis. The incidence of death or NDI was lower in infants who received empiric antifungal therapy (19 of 38; 50%) compared with those who had not (55 of 86; 64%; OR, 0.27; 95% CI, 0.08-0.86). There was no significant difference between the groups for any single outcome or other combined outcomes. Conclusion: Empiric antifungal therapy was associated with increased survival without NDI. A prospective randomized trial of this strategy is warranted.
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    Neurodevelopmental outcome of preterm infants enrolled in myo-inositol randomized controlled trial
    (Springer Nature, 2021) Adams-Chapman, Ira; Watterberg, Kristi L.; Nolen, Tracy L.; Hirsch, Shawn; Cole, Carol A.; Cotten, C. Michael; Oh, William; Poindexter, Brenda B.; Zaterka-Baxter, Kristin M.; Das, Abhik; Backstrom Lacy, Conra; Scorsone, Ann Marie; Duncan, Andrea F.; DeMauro, Sara B.; Goldstein, Ricki F.; Colaizy, Tarah T.; Wilson-Costello, Deanne E.; Purdy, Isabell B.; Hintz, Susan R.; Heyne, Roy J.; Myers, Gary J.; Fuller, Janell; Merhar, Stephanie; Harmon, Heidi M.; Peralta-Carcelen, Myriam; Kilbride, Howard W.; Maitre, Nathalie L.; Vohr, Betty R.; Natarajan, Girija; Mintz-Hittner, Helen; Quinn, Graham E.; Wallace, David K.; Olson, Richard J.; Orge, Faruk H.; Tsui, Irena; Gaynon, Michael; Hutchinson, Amy K.; He, Yu-Guang; Winter, Timothy W.; Yang, Michael B.; Haider, Kathryn M.; Cogen, Martin S.; Hug, Denise; Bremer, Don L.; Donahue, John P.; Lucas, William R.; Phelps, Dale L.; Higgins, Rosemary D.; Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network; Pediatrics, School of Medicine
    Objective: This study evaluates the 24-month follow-up for the NICHD Neonatal Research Network (NRN) Inositol for Retinopathy Trial. Study design: Bayley Scales of Infants Development-III and a standardized neurosensory examination were performed in infants enrolled in the main trial. Moderate/severe NDI was defined as BSID-III Cognitive or Motor composite score <85, moderate or severe cerebral palsy, blindness, or hearing loss that prevents communication despite amplification were assessed. Results: Primary outcome was determined for 605/638 (95%). The mean gestational age was 25.8 ± 1.3 weeks and mean birthweight was 805 ± 192 g. Treatment group did not affect the risk for the composite outcome of death or survival with moderate/severe NDI (60% vs 56%, p = 0.40). Conclusions: Treatment group did not affect the risk of death or survival with moderate/severe NDI. Despite early termination, this study represents the largest RCT of extremely preterm infants treated with myo-inositol with neurodevelopmental outcome data.
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    Pharmacokinetics and safety of a single intravenous dose of myo-inositol in preterm infants of 23-29 wk
    (Springer Nature, 2013) Phelps, Dale L.; Ward, Robert M.; Williams, Rick L.; Watterberg, Kristi L.; Laptook, Abbot R.; Wrage, Lisa A.; Nolen, Tracy L.; Fennell, Timothy R.; Ehrenkranz, Richard A.; Poindexter, Brenda B.; Cotten, C. Michael; Hallman, Mikko K.; Frantz, Ivan D., III; Faix, Roger G.; Zaterka-Baxter, Kristin M.; Das, Abhik; Ball, M. Bethany; O'Shea, T. Michael; Backstrom Lacy, Conra; Walsh, Michele C.; Shankaran, Seetha; Sánchez, Pablo J.; Bell, Edward F.; Higgins, Rosemary D.; Pediatrics, School of Medicine
    Background: Myo-inositol given to preterm infants with respiratory distress has reduced death, increased survival without bronchopulmonary dysplasia, and reduced severe retinopathy of prematurity in two randomized trials. Pharmacokinetic (PK) studies in extremely preterm infants are needed before efficacy trials. Methods: Infants born in 23-29 wk of gestation were randomized to a single intravenous (i.v.) dose of inositol at 60 or 120 mg/kg or placebo. Over 96 h, serum levels (sparse sampling population PK) and urine inositol excretion were determined. Population PK models were fit using a nonlinear mixed-effects approach. Safety outcomes were recorded. Results: A single-compartment model that included factors for endogenous inositol production, allometric size based on weight, gestational age strata, and creatinine clearance fit the data best. The central volume of distribution was 0.5115 l/kg, the clearance was 0.0679 l/kg/h, endogenous production was 2.67 mg/kg/h, and the half-life was 5.22 h when modeled without the covariates. During the first 12 h, renal inositol excretion quadrupled in the 120 mg/kg group, returning to near-baseline value after 48 h. There was no diuretic side effect. No significant differences in adverse events occurred among the three groups (P > 0.05). Conclusion: A single-compartment model accounting for endogenous production satisfactorily described the PK of i.v. inositol.
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    Safety and pharmacokinetics of multiple dose myo-inositol in preterm infants
    (SpringerNature, 2016-08) Phelps, Dale L.; Ward, Robert M.; Williams, Rick L.; Nolen, Tracy L.; Watterberg, Kristi L.; Oh, William; Goedecke, Michael; Ehrenkranz, Richard A.; Fennell, Timothy; Poindexter, Brenda B.; Cotten, C. Michael; Hallman, Mikko; Frantz III, Ivan D.; Faix, Roger G.; Zaterka-Baxter, Kristin M.; Das, Abhik; Ball, M. Bethany; Lacy, Conra Backstrom; Walsh, Michele C.; Carlo, Waldemar A.; Sánchez, Pablo J.; Bell, Edward F.; Shankaran, Seetha; Carlton, David P.; Chess, Patricia R.; Higgins, Rosemary D.; Department of Pediatrics, IU School of Medicine
    BACKGROUND: Preterm infants with respiratory distress syndrome (RDS) given inositol had reduced bronchopulmonary dysplasia (BPD), death and severe retinopathy of prematurity (ROP). We assessed the safety and pharmacokinetics of daily inositol to select a dose providing serum levels previously associated with benefit, and to learn if accumulation occurred when administered throughout the normal period of retinal vascularization. METHODS: Infants ≤ 29 wk GA (n = 122, 14 centers) were randomized and treated with placebo or inositol at 10, 40, or 80 mg/kg/d. Intravenous administration converted to enteral when feedings were established, and continued to the first of 10 wk, 34 wk postmenstrual age (PMA) or discharge. Serum collection employed a sparse sampling population pharmacokinetics design. Inositol urine losses and feeding intakes were measured. Safety was prospectively monitored. RESULTS: At 80 mg/kg/d mean serum levels reached 140 mg/l, similar to Hallman's findings. Levels declined after 2 wk, converging in all groups by 6 wk. Analyses showed a mean volume of distribution 0.657 l/kg, clearance 0.058 l/kg/h, and half-life 7.90 h. Adverse events and comorbidities were fewer in the inositol groups, but not significantly so. CONCLUSION: Multiple dose inositol at 80 mg/kg/d was not associated with increased adverse events, achieves previously effective serum levels, and is appropriate for investigation in a phase III trial.