Browsing by Author "Yoder, Bradley A."

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    Definitions of Cardiovascular Insufficiency and Relation to Outcomes in Critically Ill Newborn Infants
    (Thieme, 2015-09) Fernandez, Erika; Watterberg, Kristi L.; Faix, Roger G.; Yoder, Bradley A.; Walsh, Michele C.; Lacy, Conra Backstrom; Osborne, Karen A.; Das, Abhik; Kendrick, Douglas E.; Stoll, Barbara J.; Poindexter, Brenda B.; Laptook, Abbot R.; Kennedy, Kathleen A.; Schibler, Kurt; Bell, Edward F.; Van Meurs, Krisa P.; Frantz, Ivan D. III; Goldberg, Ronald N.; Shankaran, Seetha; Carlo, Waldemar A.; Ehrenkranz, Richard A.; Sánchez, Pablo J.; Higgins, Rosemary D.; Department of Pediatrics, Indiana University School of Medicine
    Background We previously reported on the overall incidence, management, and outcomes in infants with cardiovascular insufficiency (CVI). However, there are limited data on the relationship of the specific different definitions of CVI to short-term outcomes in term and late preterm newborn infants. Objective This study aims to evaluate how four definitions of CVI relate to short-term outcomes and death. Study Design The previously reported study was a multicenter, prospective cohort study of 647 infants ≥ 34 weeks gestation admitted to a Neonatal Research Network (NRN) newborn intensive care unit (NICU) and mechanically ventilated (MV) during their first 72 hours. The relationship of five short-term outcomes at discharge and four different definitions of CVI were further analyzed. Results All the four definitions were associated with greater number of days on MV and days on O2. The definition using a threshold blood pressure (BP) measurement alone was not associated with days of full feeding, days in the NICU or death. The definition based on the treatment of CVI was associated with all the outcomes including death. Conclusions The definition using a threshold BP alone was not consistently associated with adverse short-term outcomes. Using only a threshold BP to determine therapy may not improve outcomes.
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    Early Brain and Abdominal Oxygenation in Extremely Low Birth Weight Infants
    (Springer Nature, 2022) Chock, Valerie Y.; Smith, Emily; Tan, Sylvia; Ball, M. Bethany; Das, Abhik; Hintz, Susan R.; Kirpalani, Haresh; Bell, Edward F.; Chalak, Lina F.; Cotten, C. Michael; Widness, John A.; Kennedy, Kathleen A.; Ohls, Robin K.; Seabrook, Ruth B.; Patel, Ravi M.; Laptook, Abbot R.; Mancini, Toni; Sokol, Gregory M.; Walsh, Michele C.; Yoder, Bradley A.; Poindexter, Brenda B.; Chawla, Sanjay; D’Angio, Carl T.; Higgins, Rosemary D.; Van Meurs, Krisa P.; Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network; Pediatrics, School of Medicine
    Background: Extremely low birth weight (ELBW) infants are at risk for end-organ hypoxia and ischemia. Regional tissue oxygenation of the brain and gut as monitored with near-infrared spectroscopy (NIRS) may change with postnatal age, but normal ranges are not well defined. Methods: A prospective study of ELBW preterm infants utilized NIRS monitoring to assess changes in cerebral and mesenteric saturation (Csat and Msat) over the first week after birth. This secondary study of a multicenter trial comparing hemoglobin transfusion thresholds assessed cerebral and mesenteric fractional tissue oxygen extraction (cFTOE and mFTOE) and relationships with perinatal variables. Results: In 124 infants, both Csat and Msat declined over the first week, with a corresponding increase in oxygen extraction. With lower gestational age, lower birth weight, and 5-min Apgar score ≤5, there was a greater increase in oxygen extraction in the brain compared to the gut. Infants managed with a lower hemoglobin transfusion threshold receiving ≥2 transfusions in the first week had the lowest Csat and highest cFTOE (p < 0.001). Conclusion: Brain oxygen extraction preferentially increased in more immature and anemic preterm infants. NIRS monitoring may enhance understanding of cerebral and mesenteric oxygenation patterns and inform future protective strategies in the preterm ELBW population. Impact: Simultaneous monitoring of cerebral and mesenteric tissue saturation demonstrates the balance of oxygenation between preterm brain and gut and may inform protective strategies. Over the first week, oxygen saturation of the brain and gut declines as oxygen extraction increases. A low hemoglobin transfusion threshold is associated with lower cerebral saturation and higher cerebral oxygen extraction compared to a high hemoglobin transfusion threshold, although this did not translate into clinically relevant differences in the TOP trial primary outcome. Greater oxygen extraction by the brain compared to the gut occurs with lower gestational age, lower birth weight, and 5-min Apgar score ≤5.
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    Early-Onset Neonatal Sepsis 2015 to 2017, the Rise of Escherichia coli, and the Need for Novel Prevention Strategies
    (American Medical Association, 2020-07) Stoll, Barbara J.; Puopolo, Karen M.; Hansen, Nellie I.; Sánchez, Pablo J.; Bell, Edward F.; Carlo, Waldemar A.; Cotten, C. Michael; D’Angio, Carl T.; Kazzi, S. Nadya J.; Poindexter, Brenda B.; Van Meurs, Krisa P.; Hale, Ellen C.; Collins, Monica V.; Das, Abhik; Baker, Carol J.; Wyckoff, Myra H.; Yoder, Bradley A.; Watterberg, Kristi L.; Walsh, Michele C.; Devaskar, Uday; Laptook, Abbot R.; Sokol, Gregory M.; Schrag, Stephanie J.; Higgins, Rosemary D.; Pediatrics, School of Medicine
    Importance: Early-onset sepsis (EOS) remains a potentially fatal newborn condition. Ongoing surveillance is critical to optimize prevention and treatment strategies. Objective: To describe the current incidence, microbiology, morbidity, and mortality of EOS among a cohort of term and preterm infants. Design, setting, and participants: This prospective surveillance study included a cohort of infants born at a gestational age (GA) of at least 22 weeks and birth weight of greater than 400 g from 18 centers of the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network from April 1, 2015, to March 31, 2017. Data were analyzed from June 14, 2019, to January 28, 2020. Main outcomes and measures: Early-onset sepsis defined by isolation of pathogenic species from blood or cerebrospinal fluid culture within 72 hours of birth and antibiotic treatment for at least 5 days or until death. Results: A total of 235 EOS cases (127 male [54.0%]) were identified among 217 480 newborns (1.08 [95% CI, 0.95-1.23] cases per 1000 live births). Incidence varied significantly by GA and was highest among infants with a GA of 22 to 28 weeks (18.47 [95% CI, 14.57-23.38] cases per 1000). No significant differences in EOS incidence were observed by sex, race, or ethnicity. The most frequent pathogens were Escherichia coli (86 [36.6%]) and group B streptococcus (GBS; 71 [30.2%]). E coli disease primarily occurred among preterm infants (68 of 131 [51.9%]); GBS disease primarily occurred among term infants (54 of 104 [51.9%]), with 24 of 45 GBS cases (53.3%) seen in infants born to mothers with negative GBS screening test results. Intrapartum antibiotics were administered to 162 mothers (68.9%; 110 of 131 [84.0%] preterm and 52 of 104 [50.0%] term), most commonly for suspected chorioamnionitis. Neonatal empirical antibiotic treatment most frequently included ampicillin and gentamicin. All GBS isolates were tested, but only 18 of 81 (22.2%) E coli isolates tested were susceptible to ampicillin; 6 of 77 E coli isolates (7.8%) were resistant to both ampicillin and gentamicin. Nearly all newborns with EOS (220 of 235 [93.6%]) displayed signs of illness within 72 hours of birth. Death occurred in 38 of 131 infected infants with GA of less than 37 weeks (29.0%); no term infants died. Compared with earlier surveillance (2006-2009), the rate of E coli infection increased among very low-birth-weight (401-1500 g) infants (8.68 [95% CI, 6.50-11.60] vs 5.07 [95% CI, 3.93-6.53] per 1000 live births; P = .008). Conclusions and relevance: In this study, EOS incidence and associated mortality disproportionately occurred in preterm infants. Contemporary cases have demonstrated the limitations of current GBS prevention strategies. The increase in E coli infections among very low-birth-weight infants warrants continued study. Ampicillin and gentamicin remained effective antibiotics in most cases, but ongoing surveillance should monitor antibiotic susceptibilities of EOS pathogens.
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    Higher or Lower Hemoglobin Transfusion Thresholds for Preterm Infants
    (Massachusetts Medical Society, 2020-12-01) Kirpalani, Haresh; Bell, Edward F.; Hintz, Susan R.; Tan, Sylvia; Schmidt, Barbara; Chaudhary, Aasma S.; Johnson, Karen J.; Crawford, Margaret M.; Newman, Jamie E.; Vohr, Betty R.; Carlo, Waldemar A.; D'Angio, Carl T.; Kennedy, Kathleen A.; Ohls, Robin K.; Poindexter, Brenda B.; Schibler, Kurt; Whyte, Robin K.; Widness, John A.; Zupancic, John A.F.; Wyckoff, Myra H.; Truog, William E.; Walsh, Michele C.; Chock, Valerie Y.; Laptook, Abbot R.; Sokol, Gregory M.; Yoder, Bradley A.; Patel, Ravi M.; Cotten, C. Michael; Carmen, Melissa F.; Devaskar, Uday; Chawla, Sanjay; Seabrook, Ruth; Higgins, Rosemary D.; Das, Abhik; Pediatrics, School of Medicine
    Background: Limited data suggest that higher hemoglobin thresholds for red-cell transfusions may reduce the risk of cognitive delay among extremely-low-birth-weight infants with anemia. Methods: We performed an open, multicenter trial in which infants with a birth weight of 1000 g or less and a gestational age between 22 weeks 0 days and 28 weeks 6 days were randomly assigned within 48 hours after delivery to receive red-cell transfusions at higher or lower hemoglobin thresholds until 36 weeks of postmenstrual age or discharge, whichever occurred first. The primary outcome was a composite of death or neurodevelopmental impairment (cognitive delay, cerebral palsy, or hearing or vision loss) at 22 to 26 months of age, corrected for prematurity. Results: A total of 1824 infants (mean birth weight, 756 g; mean gestational age, 25.9 weeks) underwent randomization. There was a between-group difference of 1.9 g per deciliter (19 g per liter) in the pretransfusion mean hemoglobin levels throughout the treatment period. Primary outcome data were available for 1692 infants (92.8%). Of 845 infants in the higher-threshold group, 423 (50.1%) died or survived with neurodevelopmental impairment, as compared with 422 of 847 infants (49.8%) in the lower-threshold group (relative risk adjusted for birth-weight stratum and center, 1.00; 95% confidence interval [CI], 0.92 to 1.10; P = 0.93). At 2 years, the higher- and lower-threshold groups had similar incidences of death (16.2% and 15.0%, respectively) and neurodevelopmental impairment (39.6% and 40.3%, respectively). At discharge from the hospital, the incidences of survival without severe complications were 28.5% and 30.9%, respectively. Serious adverse events occurred in 22.7% and 21.7%, respectively. Conclusions: In extremely-low-birth-weight infants, a higher hemoglobin threshold for red-cell transfusion did not improve survival without neurodevelopmental impairment at 22 to 26 months of age, corrected for prematurity.
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    Hydrocortisone to Improve Survival without Bronchopulmonary Dysplasia
    (Massachusetts Medical Society, 2022-03-24) Watterberg, Kristi L.; Walsh, Michele C.; Li, Lei; Chawla, Sanjay; D’Angio, Carl T.; Goldberg, Ronald N.; Hintz, Susan R.; Laughon, Matthew M.; Yoder, Bradley A.; Kennedy, Kathleen A.; McDavid, Georgia E.; Backstrom-Lacy, Conra; Das, Abhik; Crawford, Margaret M.; Keszler, Martin; Sokol, Gregory M.; Poindexter, Brenda B.; Ambalavanan, Namasivayam; Hibbs, Anna Maria; Truog, William E.; Schmidt, Barbara; Wyckoff, Myra H.; Khan, Amir M.; Garg, Meena; Chess, Patricia R.; Reynolds, Anne M.; Moallem, Mohannad; Bell, Edward F.; Meyer, Lauritz R.; Patel, Ravi M.; Van Meurs, Krisa P.; Cotten, C. Michael; McGowan, Elisabeth C.; Hines, Abbey C.; Merhar, Stephanie; Peralta-Carcelen, Myriam; Wilson-Costello, Deanne E.; Kilbride, Howard W.; DeMauro, Sara B.; Heyne, Roy J.; Mosquera, Ricardo A.; Natarajan, Girija; Purdy, Isabell B.; Lowe, Jean R.; Maitre, Nathalie L.; Harmon, Heidi M.; Hogden, Laurie A.; Adams-Chapman, Ira; Winter, Sarah; Malcolm, William F.; Higgins, Rosemary D.; Eunice Kennedy Shriver NICHD Neonatal Research Network; Pediatrics, School of Medicine
    BACKGROUND Bronchopulmonary dysplasia is a prevalent complication after extremely preterm birth. Inflammation with mechanical ventilation may contribute to its development. Whether hydrocortisone treatment after the second postnatal week can improve survival without bronchopulmonary dysplasia and without adverse neurodevelopmental effects is unknown. METHODS We conducted a trial involving infants who had a gestational age of less than 30 weeks and who had been intubated for at least 7 days at 14 to 28 days. Infants were randomly assigned to receive either hydrocortisone (4 mg per kilogram of body weight per day tapered over a period of 10 days) or placebo. Mandatory extubation thresholds were specified. The primary efficacy outcome was survival without moderate or severe bronchopulmonary dysplasia at 36 weeks of postmenstrual age, and the primary safety outcome was survival without moderate or severe neurodevelopmental impairment at 22 to 26 months of corrected age. RESULTS We enrolled 800 infants (mean [±SD] birth weight, 715±167 g; mean gestational age, 24.9±1.5 weeks). Survival without moderate or severe bronchopulmonary dysplasia at 36 weeks occurred in 66 of 398 infants (16.6%) in the hydrocortisone group and in 53 of 402 (13.2%) in the placebo group (adjusted rate ratio, 1.27; 95% confidence interval [CI], 0.93 to 1.74). Two-year outcomes were known for 91.0% of the infants. Survival without moderate or severe neurodevelopmental impairment occurred in 132 of 358 infants (36.9%) in the hydrocortisone group and in 134 of 359 (37.3%) in the placebo group (adjusted rate ratio, 0.98; 95% CI, 0.81 to 1.18). Hypertension that was treated with medication occurred more frequently with hydrocortisone than with placebo (4.3% vs. 1.0%). Other adverse events were similar in the two groups. CONCLUSIONS In this trial involving preterm infants, hydrocortisone treatment starting on postnatal day 14 to 28 did not result in substantially higher survival without moderate or severe bronchopulmonary dysplasia than placebo. Survival without moderate or severe neurodevelopmental impairment did not differ substantially between the two groups. (Funded by the National Institutes of Health; ClinicalTrials.gov number, NCT01353313.)
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    Incidence, management, and outcomes of cardiovascular insufficiency in critically ill term and late preterm newborn infants
    (Thieme, 2014-11) Fernandez, Erika; Watterberg, Kristi L.; Faix, Roger G.; Yoder, Bradley A.; Walsh, Michele C.; Backstrom Lacy, Conra; Osborne, Karen A.; Das, Abhik; Kendrick, Douglas E.; Stoll, Barbara J.; Poindexter, Brenda B.; Laptook, Abbot R.; Kennedy, Kathleen A.; Schibler, Kurt; Bell, Edward F.; Van Meurs, Krisa P.; Frantz III, Ivan D.; Goldberg, Ronald N.; Shankaran, Seetha; Carlo, Waldemar A.; Ehrenkranz, Richard A.; Sánchez, Pablo J.; Higgins, Rosemary D.; Department of Pediatrics, IU School of Medicine
    OBJECTIVE: The objective of this study was to characterize the incidence, management, and short-term outcomes of cardiovascular insufficiency (CVI) in mechanically ventilated newborns, evaluating four separate prespecified definitions. STUDY DESIGN: Multicenter, prospective cohort study of infants ≥34 weeks gestational age (GA) and on mechanical ventilation during the first 72 hours. CVI was prospectively defined as either (1) mean arterial pressure (MAP) < GA; (2) MAP < GA + signs of inadequate perfusion; (3) any therapy for CVI; or (4) inotropic therapy. Short-term outcomes included death, days on ventilation, oxygen, and to full feedings and discharge. RESULTS: Of 647 who met inclusion criteria, 419 (65%) met ≥1 definition of CVI. Of these, 98% received fluid boluses, 36% inotropes, and 17% corticosteroids. Of treated infants, 46% did not have CVI as defined by a MAP < GA ± signs of inadequate perfusion. Inotropic therapy was associated with increased mortality (11.1 vs. 1.3%; p < 0.05). CONCLUSION: More than half of the infants met at least one definition of CVI. However, almost half of the treated infants met none of the definitions. Inotropic therapy was associated with increased mortality. These findings can help guide the design of future studies of CVI in newborns
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    Initial Laparotomy Versus Peritoneal Drainage in Extremely Low Birthweight Infants With Surgical Necrotizing Enterocolitis or Isolated Intestinal Perforation: A Multicenter Randomized Clinical Trial
    (Wolters Kluwer, 2021) Blakely, Martin L.; Tyson, Jon E.; Lally, Kevin P.; Hintz, Susan R.; Eggleston, Barry; Stevenson, David K.; Besner, Gail E.; Das, Abhik; Ohls, Robin K.; Truog, William E.; Nelin, Leif D.; Poindexter, Brenda B.; Pedroza, Claudia; Walsh, Michele C.; Stoll, Barbara J.; Geller, Rachel; Kennedy, Kathleen A.; Dimmitt, Reed A.; Carlo, Waldemar A.; Cotten, C. Michael; Laptook, Abbot R.; Van Meurs, Krisa P.; Calkins, Kara L.; Sokol, Gregory M.; Sanchez, Pablo J.; Wyckoff, Myra H.; Patel, Ravi M.; Frantz, Ivan D., III.; Shankaran, Seetha; D'Angio, Carl T.; Yoder, Bradley A.; Bell, Edward F.; Watterberg, Kristi L.; Martin, Colin A.; Harmon, Carroll M.; Rice, Henry; Kurkchubasche, Arlet G.; Sylvester, Karl; Dunn, James C.Y.; Markel, Troy A.; Diesen, Diana L.; Bhatia, Amina M.; Flake, Alan; Chwals, Walter J.; Brown, Rebeccah; Bass, Kathryn D.; St. Peter, Shawn D.; Shanti, Christina M.; Pegoli, Walter, Jr.; Skarda, David; Shilyansky, Joel; Lemon, David G.; Mosquera, Ricardo A.; Peralta-Carcelen, Myriam; Goldstein, Ricki F.; Vohr, Betty R.; Purdy, Isabell B.; Hines, Abbey C.; Maitre, Nathalie L.; Heyne, Roy J.; DeMauro, Sara B.; McGowan, Elisabeth C.; Yolton, Kimberly; Kilbride, Howard W.; Natarajan, Girija; Yost, Kelley; Winter, Sarah; Colaizy, Tarah T.; Laughon, Matthew M.; Lakshminrusimha, Satyanarayana; Higgins, Rosemary D.; Eunice Kennedy Shriver National Institute of Child Health; Human Development Neonatal Research Network; Pediatrics, School of Medicine
    Objective: The aim of this study was to determine which initial surgical treatment results in the lowest rate of death or neurodevelopmental impairment (NDI) in premature infants with necrotizing enterocolitis (NEC) or isolated intestinal perforation (IP). Summary background data: The impact of initial laparotomy versus peritoneal drainage for NEC or IP on the rate of death or NDI in extremely low birth weight infants is unknown. Methods: We conducted the largest feasible randomized trial in 20 US centers, comparing initial laparotomy versus peritoneal drainage. The primary outcome was a composite of death or NDI at 18 to 22 months corrected age, analyzed using prespecified frequentist and Bayesian approaches. Results: Of 992 eligible infants, 310 were randomized and 96% had primary outcome assessed. Death or NDI occurred in 69% of infants in the laparotomy group versus 70% with drainage [adjusted relative risk (aRR) 1.0; 95% confidence interval (CI): 0.87-1.14]. A preplanned analysis identified an interaction between preoperative diagnosis and treatment group (P = 0.03). With a preoperative diagnosis of NEC, death or NDI occurred in 69% after laparotomy versus 85% with drainage (aRR 0.81; 95% CI: 0.64-1.04). The Bayesian posterior probability that laparotomy was beneficial (risk difference <0) for a preoperative diagnosis of NEC was 97%. For preoperative diagnosis of IP, death or NDI occurred in 69% after laparotomy versus 63% with drainage (aRR, 1.11; 95% CI: 0.95-1.31); Bayesian probability of benefit with laparotomy = 18%. Conclusions: There was no overall difference in death or NDI rates at 18 to 22 months corrected age between initial laparotomy versus drainage. However, the preoperative diagnosis of NEC or IP modified the impact of initial treatment.