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This study evaluates the relationship between anemia and stool microbiota in premature infants. It also evaluates the relationship between blood transfusion and stool microbiota.
Necrotizing enterocolitis (NEC) is a leading cause of death in preterm infants, yet the disease mechanism is not well understood. Among the factors that have been studied are the change in stool microbiota (dysbiosis), severe anemia, and transfusion. Studies suggest that dysbiosis occurs in neonates with NEC. Large studies and meta-analyses have shown a predominance of Gammaproteobacteria, a decrease in Firmicutes, and decreased bacterial diversity in stool from infants with NEC. Studies do not support a relationship between transfusions and NEC since there are conflicting findings on this topic. There is a suggestion, however, that severe anemia may be associated with NEC though this requires further study.
No studies have been done evaluating the relationship between anemia and change in stool microbiota, or blood transfusion and change in stool microbiota. This study aims to primarily evaluate the relationship between anemia and stool microbiota, and secondarily evaluate the relationship between transfusion and stool microbiota.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Anemia | Stool samples from infants with anemia. Severe anemia defined as hematocrit less than 25%. Anemia defined as hematocrit greater than or equal to 25% and less than 30%. | ||
| No Anemia | Stool samples from infants without anemia. No anemia defined as hematocrit equal to or greater than 30%. |
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| Measure | Description | Time Frame |
|---|---|---|
| qRT-PCR (polymerase chain reaction) quantitative stool analysis | Quantify major bacterial groups, including Proteobacteria, Firmicutes, and Bacteroides in stool samples | qRT-PCR will be analyzed for infant stool samples from enrollment until infants are 38 weeks corrected, or until they are discharged from the hospital. This time frame will be an average of 10 weeks per infant. |
| Measure | Description | Time Frame |
|---|---|---|
| Alpha diversity | Use next generation sequencing to assess changes in alpha diversity of bacteria between non-anemic and anemic stool samples | Infant stool samples will be analyzed from enrollment until infants are 38 weeks corrected, or until they are discharged from the hospital. This time frame will be an average of 10 weeks per infant. |
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Inclusion Criteria:
Exclusion Criteria:
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The study will enroll preterm infants that are less than 32 weeks gestational age at birth. At time of enrollment, these infants must be between 7 days of age up to (and including) 30 days of age. They must also be on enteral feeds of at least 100mL/kg/day. The investigators will exclude infants who have developed NEC prior to enrollment, who have had surgery prior to enrollment, who have major congenital anomalies, or who are requiring FiO2 >50% at time of enrollment.
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| Name | Affiliation | Role |
|---|---|---|
| Julie Mirpuri Hathiramani, MD | University of Texas Southwestern Medical Center | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Parkland Health & Hospital System | Dallas | Texas | 75235 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 25798435 | Background | Gritz EC, Bhandari V. The human neonatal gut microbiome: a brief review. Front Pediatr. 2015 Mar 5;3:17. doi: 10.3389/fped.2015.00017. eCollection 2015. | |
| 25992911 | Background | Patel RM, Denning PW. Intestinal microbiota and its relationship with necrotizing enterocolitis. Pediatr Res. 2015 Sep;78(3):232-8. doi: 10.1038/pr.2015.97. Epub 2015 May 20. |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Nov 22, 2017 | May 23, 2018 | Prot_000.pdf |
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| ID | Term |
|---|---|
| D000751 | Anemia, Neonatal |
| D020345 | Enterocolitis, Necrotizing |
| D064806 | Dysbiosis |
| D047928 | Premature Birth |
| ID | Term |
|---|---|
| D000740 | Anemia |
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D007232 | Infant, Newborn, Diseases |
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Stool
| 27343151 | Background | Warner BB, Tarr PI. Necrotizing enterocolitis and preterm infant gut bacteria. Semin Fetal Neonatal Med. 2016 Dec;21(6):394-399. doi: 10.1016/j.siny.2016.06.001. Epub 2016 Jun 22. |
| 26969089 | Background | Warner BB, Deych E, Zhou Y, Hall-Moore C, Weinstock GM, Sodergren E, Shaikh N, Hoffmann JA, Linneman LA, Hamvas A, Khanna G, Rouggly-Nickless LC, Ndao IM, Shands BA, Escobedo M, Sullivan JE, Radmacher PG, Shannon WD, Tarr PI. Gut bacteria dysbiosis and necrotising enterocolitis in very low birthweight infants: a prospective case-control study. Lancet. 2016 May 7;387(10031):1928-36. doi: 10.1016/S0140-6736(16)00081-7. Epub 2016 Mar 9. |
| 25741698 | Background | Zhou Y, Shan G, Sodergren E, Weinstock G, Walker WA, Gregory KE. Longitudinal analysis of the premature infant intestinal microbiome prior to necrotizing enterocolitis: a case-control study. PLoS One. 2015 Mar 5;10(3):e0118632. doi: 10.1371/journal.pone.0118632. eCollection 2015. |
| 28274256 | Background | Pammi M, Cope J, Tarr PI, Warner BB, Morrow AL, Mai V, Gregory KE, Kroll JS, McMurtry V, Ferris MJ, Engstrand L, Lilja HE, Hollister EB, Versalovic J, Neu J. Intestinal dysbiosis in preterm infants preceding necrotizing enterocolitis: a systematic review and meta-analysis. Microbiome. 2017 Mar 9;5(1):31. doi: 10.1186/s40168-017-0248-8. |
| 26934258 | Background | Patel RM, Knezevic A, Shenvi N, Hinkes M, Keene S, Roback JD, Easley KA, Josephson CD. Association of Red Blood Cell Transfusion, Anemia, and Necrotizing Enterocolitis in Very Low-Birth-Weight Infants. JAMA. 2016 Mar 1;315(9):889-97. doi: 10.1001/jama.2016.1204. |
| 27866662 | Background | Hay S, Zupancic JA, Flannery DD, Kirpalani H, Dukhovny D. Should we believe in transfusion-associated enterocolitis? Applying a GRADE to the literature. Semin Perinatol. 2017 Feb;41(1):80-91. doi: 10.1053/j.semperi.2016.09.021. Epub 2016 Nov 17. |
| D009358 |
| Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D004760 | Enterocolitis |
| D005759 | Gastroenteritis |
| D005767 | Gastrointestinal Diseases |
| D004066 | Digestive System Diseases |
| D007410 | Intestinal Diseases |
| 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 |