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| ID | Type | Description | Link |
|---|---|---|---|
| M01RR016587 | U.S. NIH Grant/Contract | View source | |
| M01RR000030 | U.S. NIH Grant/Contract | View source | |
| M01RR000032 | U.S. NIH Grant/Contract | View source | |
| M01RR000039 | U.S. NIH Grant/Contract | View source | |
| M01RR000044 | U.S. NIH Grant/Contract | View source | |
| M01RR006022 | U.S. NIH Grant/Contract | View source | |
| M01RR000633 | U.S. NIH Grant/Contract | View source | |
| M01RR000070 | U.S. NIH Grant/Contract | View source | |
| M01RR007122 | U.S. NIH Grant/Contract | View source | |
| M01RR000750 | U.S. NIH Grant/Contract | View source | |
| M01RR000080 | U.S. NIH Grant/Contract | View source | |
| M01RR008084 | U.S. NIH Grant/Contract | View source | |
| U01HD036790 | U.S. NIH Grant/Contract | View source | |
| U10HD021364 | U.S. NIH Grant/Contract | View source | |
| U10HD021373 | U.S. NIH Grant/Contract | View source | |
| U10HD021385 | U.S. NIH Grant/Contract | View source | |
| U10HD021397 | U.S. NIH Grant/Contract | View source | |
| U10HD027851 | U.S. NIH Grant/Contract | View source | |
| U10HD027853 | U.S. NIH Grant/Contract | View source | |
| U10HD027856 | U.S. NIH Grant/Contract | View source | |
| U10HD027871 | U.S. NIH Grant/Contract | View source | |
| U10HD027880 | U.S. NIH Grant/Contract | View source | |
| U10HD027904 | U.S. NIH Grant/Contract | View source | |
| U10HD034216 | U.S. NIH Grant/Contract | View source | |
| U10HD040461 | U.S. NIH Grant/Contract | View source | |
| U10HD040492 | U.S. NIH Grant/Contract | View source | |
| U10HD040498 | U.S. NIH Grant/Contract | View source | |
| U10HD040521 | U.S. NIH Grant/Contract | View source | |
| U10HD040689 | U.S. NIH Grant/Contract | View source |
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| Name | Class |
|---|---|
| National Center for Research Resources (NCRR) | NIH |
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This multi-center, randomized clinical trial compared different bilirubin levels as thresholds for timing of phototherapy in extremely low birth weight infants. The primary hypothesis was that there would be no difference in death or neurodevelopmental impairment at 18-22 months corrected age in infants treated by either aggressive or conservative threshold limits. 1,978 infants were enrolled.
In NICHD Neonatal Research Network (NRN) centers in 2002, phototherapy was administered to 94 percent of the extremely low birth weight (ELBW) infants who survive more than 12 hours. Yet, it is unclear what level of bilirubin in the blood is harmful for these very tiny infants -- no data existed from large or recent clinical trials to define the risks, benefits, and appropriate indications for phototherapy in these infants. The largest and most recent trial was the NICHD Collaborative Phototherapy Trial which involved infants treated in 1974-1976 and included only 77 ELBW infants. Data from this study and others suggested that phototherapy could have important hazards as well as benefits for ELBW infants.
This NRN study used two different bilirubin levels as thresholds for timing of phototherapy in 1,978 extremely low birth weight infants, examining the primary hypothesis that there would be no difference in death or neurodevelopmental impairment at 18-22 months corrected age between the aggressively and conservatively treated groups.
Enrolled infants were stratified by birth weight (501-750g and 751-1,000g) and randomized to receive phototherapy regimens based on either an aggressive threshold or a conservative threshold of total serum bilirubin.
In the Aggressive group:
In the Conservative group:
The phototherapy regimens are designed to fall within the range of clinical practice and to assure a sizable difference between groups in total serum bilirubin levels and duration of phototherapy.
The primary outcome was death or neurodevelopmental impairment at 18-22 months corrected age determined at an outpatient clinic visit. Secondary outcomes included death, abnormal neurodevelopmental outcome, severe hearing loss, cerebral palsy, blindness, and important medical outcomes.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Aggressive ELBW | Active Comparator | In Aggressive group 1, infants with birth weights 501-750g. |
|
| Aggressive VLBW | Active Comparator | In the Aggressive group 2, infants with birth weights 751-1000g. |
|
| Conservative ELBW | Active Comparator | In the Conservative group 1, infants with birth weights 501-750g. |
|
| Conservative VLBW | Active Comparator | In the Conservative group 2, infants with birth weights 751-1000g. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Aggressive Phototherapy 501-750g | Procedure | Phototherapy started, stopped, and/or restarted when total serum bilirubin levels reach 5 mg/dl during days of life 1-14. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Death or neurodevelopmental impairment (MDI <70; PDI <70; cerebral palsy; blindness; or severe hearing loss) | 0-22 months corrected age |
| Measure | Description | Time Frame |
|---|---|---|
| Patent ductus arteriosus requiring drug or surgical treatment | 36 weeks post conceptual age | |
| Retinopathy of prematurity | 36 weeks post conceptual age | |
| Bronchopulmonary dysplasia (BPD) |
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Inclusion criteria:
Exclusion criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Abbot R. Laptook, MD | Brown University, Women & Infants Hospital of Rhode Island | Principal Investigator |
| Michele C. Walsh, MD MS | Case Western Reserve University, Rainbow Babies and Children's Hospital | Principal Investigator |
| Ronald N. Goldberg, MD | Duke University | Principal Investigator |
| Brenda B. Poindexter, MD MS | Indiana University | Principal Investigator |
| Abhik Das, PhD | RTI International | Principal Investigator |
| Ronnie Guillet, MD PhD | University of Rochester | Principal Investigator |
| Pablo J. Sanchez, MD | University of Texas, Southwestern Medical Center at Dallas | Principal Investigator |
| Barbara J. Stoll, MD | Emory University | Principal Investigator |
| Krisa P. Van Meurs, MD | Stanford University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Alabama at Birmingham | Birmingham | Alabama | 35233 | United States | ||
| Stanford University |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 18971491 | Result | Morris BH, Oh W, Tyson JE, Stevenson DK, Phelps DL, O'Shea TM, McDavid GE, Perritt RL, Van Meurs KP, Vohr BR, Grisby C, Yao Q, Pedroza C, Das A, Poole WK, Carlo WA, Duara S, Laptook AR, Salhab WA, Shankaran S, Poindexter BB, Fanaroff AA, Walsh MC, Rasmussen MR, Stoll BJ, Cotten CM, Donovan EF, Ehrenkranz RA, Guillet R, Higgins RD; NICHD Neonatal Research Network. Aggressive vs. conservative phototherapy for infants with extremely low birth weight. N Engl J Med. 2008 Oct 30;359(18):1885-96. doi: 10.1056/NEJMoa0803024. | |
| 17069786 |
| Label | URL |
|---|---|
| NICHD Neonatal Research Network | View source |
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| Aggressive Phototherapy 751-1000g | Procedure | Phototherapy started, stopped, and/or restarted when total serum bilirubin levels reach 5 mg/dl during days of life 1-7, and started, stopped, and/or restarted when levels reach 7 mg/dl during days of life 8-14. |
|
| Conservative Phototherapy 501-750g | Procedure | Phototherapy started, stopped, and/or restarted when total serum bilirubin levels reach ≥8.0 mg/dl during days of life 1-14. |
|
| Conservative Phototherapy 751-1000g | Procedure | Phototherapy started, stopped, and/or restarted when total serum bilirubin levels reach ≥10.0 mg/dl during days of life 1-14. |
|
| 36 weeks post conceptual age |
| Ventilator settings and FiO2 at 36 weeks | 36 weeks post conceptual age |
| Necrotizing enterocolitis (NEC) | 120 days old or at discharge |
| Intraventricular hemorrhage (IVH) by grade | 120 days old or at discharge |
| Periventricular leukomalacia | 120 days old or at discharge |
| Sepsis | 120 days old or at discharge |
| Hearing assessments | 120 days old or at discharge |
| Neil N. Finer, MD | University of California, San Diego | Principal Investigator |
| Kurt Schibler, MD | Children's Hospital Medical Center, Cincinnati | Principal Investigator |
| Waldemar A. Carlo, MD | University of Alabama at Birmingham | Principal Investigator |
| Brenda H. Morris, MD | The University of Texas Health Science Center, Houston | Principal Investigator |
| Seetha Shankaran, MD | Wayne State University | Principal Investigator |
| Richard A. Ehrenkranz, MD | Yale University | Principal Investigator |
| Shahnaz Duara, MD | University of Miami | Principal Investigator |
| T. Michael O'Shea, MD MPH | Wake Forest University | Principal Investigator |
| Palo Alto |
| California |
| 94304 |
| United States |
| University of California at San Diego | San Diego | California | 92103-8774 | United States |
| Yale University | New Haven | Connecticut | 06504 | United States |
| University of Miami | Miami | Florida | 33136 | United States |
| Emory University | Atlanta | Georgia | 30303 | United States |
| Indiana University | Indianapolis | Indiana | 46202 | United States |
| Wayne State University | Detroit | Michigan | 48201 | United States |
| University of Rochester | Rochester | New York | 14642 | United States |
| Wake Forest University | Charlotte | North Carolina | 27157 | United States |
| RTI International | Durham | North Carolina | 27705 | United States |
| Duke University | Durham | North Carolina | 27710 | United States |
| Cincinnati Children's Medical Center | Cincinnati | Ohio | 45267 | United States |
| Case Western Reserve University, Rainbow Babies and Children's Hospital | Cleveland | Ohio | 44106 | United States |
| Brown University, Women & Infants Hospital of Rhode Island | Providence | Rhode Island | 02905 | United States |
| University of Texas Southwestern Medical Center at Dallas | Dallas | Texas | 75235 | United States |
| University of Texas Health Science Center at Houston | Houston | Texas | 77030 | United States |
| Result |
| Ahlfors CE, Vreman HJ, Wong RJ, Bender GJ, Oh W, Morris BH, Stevenson DK; Phototherapy Subcommittee; National Institute of Child Health and Development (NICHD) Neonatal Research Network. Effects of sample dilution, peroxidase concentration, and chloride ion on the measurement of unbound bilirubin in premature newborns. Clin Biochem. 2007 Feb;40(3-4):261-7. doi: 10.1016/j.clinbiochem.2006.09.006. Epub 2006 Sep 29. |
| 17974745 | Result | Bender GJ, Cashore WJ, Oh W. Ontogeny of bilirubin-binding capacity and the effect of clinical status in premature infants born at less than 1300 grams. Pediatrics. 2007 Nov;120(5):1067-73. doi: 10.1542/peds.2006-3024. |
| 20105142 | Result | Oh W, Stevenson DK, Tyson JE, Morris BH, Ahlfors CE, Bender GJ, Wong RJ, Perritt R, Vohr BR, Van Meurs KP, Vreman HJ, Das A, Phelps DL, O'Shea TM, Higgins RD; NICHD Neonatal Research Network Bethesda MD. Influence of clinical status on the association between plasma total and unbound bilirubin and death or adverse neurodevelopmental outcomes in extremely low birth weight infants. Acta Paediatr. 2010 May;99(5):673-678. doi: 10.1111/j.1651-2227.2010.01688.x. Epub 2010 Jan 25. |
| ID | Term |
|---|---|
| D051556 | Hyperbilirubinemia, Neonatal |
| D007567 | Jaundice, Neonatal |
| D047928 | Premature Birth |
| ID | Term |
|---|---|
| D007232 | Infant, Newborn, Diseases |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D006932 | Hyperbilirubinemia |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D007752 | Obstetric Labor, Premature |
| D007744 | Obstetric Labor Complications |
| D011248 | Pregnancy Complications |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
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