Packed Red Blood Cell Transfusion and Intestinal Blood Flow in Preterm Neonates

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Aaron Pitzele, MD, St. Louis University
ClinicalTrials.gov Identifier:
NCT01628133
First received: June 1, 2012
Last updated: June 18, 2014
Last verified: June 2014
  Purpose

The purpose of the study is to determine whether packed red blood cell (PRBC) transfusion affects intestinal blood flow of premature infants during feedings and if so, whether return of normal intestinal blood flow pattern occurs within 48 hours of blood transfusion.

Abnormal intestinal responses to the feedings (insufficient postprandial blood flow increase in order to digest given feeding volume or overall decrease of intestinal blood flow) may predispose infants to feeding intolerance and to serious intestinal disease called necrotizing enterocolitis (NEC).

Patent ductus arteriosus (PDA) is a relatively common heart condition found in young preterm infants that can lead to decreased blood flow in different organs, including intestines. Thus, the determination of the presence or absence of PDA is an important part of the study, since it can be a relevant confounding variable.

In this study, the investigators will assess intestinal blood flow by using sonogram to measure velocity through the superior mesenteric artery (SMA), the artery supplying most of the intestine, both pre- and 45 minutes post feeding. The investigators will also use echocardiogram to determine the presence or absence of PDA. Each set of measurements will be done immediately before and after the transfusion, and again 24 and 48 hours after the transfusion.

Specific Hypothesis: The investigators hypothesize that infants will have attenuated postprandial blood flow velocities in immediate posttransfusion state when compared to the pretransfusion values. The investigators further hypothesize that normal, pretransfusion postprandial blood flow velocities will be achieved 48 hrs after the blood transfusion.


Condition Intervention
Intestinal Blood Flow
Procedure: ultrasound

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Official Title: Packed Red Blood Cell Transfusion and Intestinal Blood Flow in Preterm Infants

Resource links provided by NLM:


Further study details as provided by St. Louis University:

Primary Outcome Measures:
  • Assessing intestinal blood flow by comparing superior mesenteric artery velocities in preterm neonates before and after packed red blood cell transfusion using sonogram. [ Time Frame: Measurements are obtained both before and 45 minutes after feeding prior to transfusion; again before and after feeding after transfusion and again at 24 and 48 hours after the transfusion. ] [ Designated as safety issue: No ]
    Prospective investigation of pre- and post-prandial (45 minutes after feeding completion) SMA BVF in preterm neonates before and after blood transfusion. The pretransfusion SMA BFV measurements (pre- and post-prandial) are done during the last feeding before the transfusion; the postransfusion SMA BFV (pre- and post-prandial) measurements are done during the first feeding immediately following the blood transfusion and again during the feedings 24 and 48 hrs after the transfusion (Total of 8 SMA BFV assessments).


Secondary Outcome Measures:
  • To determine whether packed red blood cell transfusion affects patent ductus arteriosus status of the subjects using Echocardiogram to determine the presence or absence of PDA. [ Time Frame: Each set of measurements will be done immediately before and after the transfusion, and again 24 and 48 hours after the transfusion. ] [ Designated as safety issue: No ]
    Before each SMA BFV measurement prior to feeding, the investigators will determine the presence or absence of PDA, since the presence of PDA can affect SMA BFV (total of 4 PDA studies for each enrolled subject).


Enrollment: 25
Study Start Date: December 2011
Study Completion Date: January 2014
Primary Completion Date: August 2013 (Final data collection date for primary outcome measure)
Groups/Cohorts Assigned Interventions
blood transfusion group Procedure: ultrasound
sonographic evaluation of intestinal blood flow

Detailed Description:

Necrotizing enterocolitis (NEC) is the death of intestinal tissue. It most often affects premature or sick babies. NEC occurs when the lining of the intestinal wall dies and the tissue falls off. NEC is a known complication of prematurity with high morbidity and mortality. About 7 to 13% of all very low birth weight infants admitted to Neonatal Intensive Care Units (NICU) develop NEC, with mortality ranging from 10 to 44% (1,2,3).

NEC is considered a multifactorial disorder converging on a common final clinical presentation associated with several etiologic mechanisms, including ischemia (eg reperfusion), infection (eg, gut colonization), mechanical injury (eg, viscosity, embolic), iatrogenic factors (eg catheters, excessive enteral feeding), and immunological barrier dysfunction (1,13,4,5) To date, there is no single, unifying consensus on causation (6).

Newly, the association between NEC and Packed Red Blood Cell (PRBC)transfusion has been a subject of recent debate. Several retrospective studies report increased incidence of NEC 22 hrs (7) or 48-72 hrs after PRBC transfusion (8) and increased odds of NEC development within 48 hrs posttransfusion (9). Singh, measuring the strength of association between the NEC and PRBC transfusion describes the association as strong < 24hrs, less strong < 48 hrs and absent at 96 hrs (10). Importantly, the majority of the infants in these studies were stable premature neonates on full enteral feeds, who decompensated and developed NEC after being transfused.

Based on poor or no evidence, many NICUs are implementing policy not to feed premature infants during the blood transfusion (11). A small recent prospective trial (8) reported decreased incidence of NEC (from 5.3 to 1.3%) when feeds are withheld during the transfusion. Similarly, the limited investigation of the superior mesenteric artery (blood vessel that supplies the greatest volume of blood to the intestinal tract) blood flow velocities (SMA BFV) revealed that the expected post-prandial increase in SMA BFV disappeared following the PRBC, placing the fed neonates receiving blood transfusion at higher risk for NEC (12).

This initial study had several major limitations, such as enrolling larger and more mature preterm neonates at lesser risk for PRBC transfusion related NEC, excluding infants with patent ductus arteriosus (PDA), common clinical condition in preterm neonates, losing 11 out of 22 patients for follow up studies (hence "normalization" of post-prandial blood flow velocities and finding potentially safe time point for feeds reintroduction could not be suggested by the study results) and using relatively less commonly transfused PRBC volumes over longer period of time.

In this study, the investigators intend to further their understanding of the hemodynamic consequences of PRBC transfusion in very low birth weight (VLBW) neonates by evaluating pre-and post-prandial SMA BFV in neonates who are not fed during the transfusion at different time points and correlate those with relevant clinical outcome measures. The investigators anticipate that the results from this study will be used by clinicians to help guide them in making decisions regarding the safety of administering PRBC transfusion in VLBW neonates.

  Eligibility

Ages Eligible for Study:   up to 3 Months
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population

Preterm neonates (≤1500 grams of birth weight) of singleton and multiple births who are admitted to the NICU at Cardinal Glennon Children's Hospital and who are tolerating ≥ 20 ml/kg/day of feeding volume run over 30 minutes or less; both males and females of all ethnic groups.

Very Low Birth Weight (VLBW) neonates will be studied since morbidities such as transfusion related acute gastrointestinal injury and/or necrotizing enterocolitis, PDA and feeding intolerance most frequently occur in this group.

Because the need to ensure parental comprehension prior to consent documentation, parents who, in the judgement of the attending physician and/or research team members, do not have an adequate command of the English language will not be invited to participate in the study.

Criteria

Inclusion Criteria:

  • birth weight ≤ 1500 gm
  • singleton and multiple gestation
  • small and appropriate birth weight for gestational age
  • tolerance of ≥ 20 ml/kg/day of feeding volumes over 30 minutes or less
  • at least 14 days of age and ≤ 35 6/7 weeks corrected gestational age at time of transfusion.
  • Expected age range of 0-3 months is based on expected age of extremely low birth weight infants at limit (35 6/7 weeks) of corrected gestational age.

Only those infants who receive transfusion at < or equal to 35 weeks will undergo the PDA/SMA and BFV procedures and have data included in analysis.

Exclusion Criteria:

  • major congenital or chromosomal anomalies
  • presence of congenital heart disease (minus patent ductus arteriosus
  • presence of shock
  • presence of vasopressor use
  • presence of severe lung disease
  • concurrent treatment with antibiotics for sepsis
  • history of NEC Bell stage 2 or greater
  • Infants experiencing changes in vital signs or oxygen level drop needing intervention (such as oxygen increase or stimulation) will have studies discontinued and will be excluded from further analysis.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01628133

Locations
United States, Missouri
Cardinal Glennon Children's Hospital / Saint Louis University
St Louis, Missouri, United States, 63104
Sponsors and Collaborators
St. Louis University
Investigators
Study Director: Thomas Havranek, MD Saint Louis University, Cardinal Glennon Children's Hospital
Principal Investigator: Aaron Pitzele, MD Saint Louis University, Cardinal Glennon Children's Medical Center
  More Information

Publications:
El-Dib M, Narang S, Lee E, Massaro AN, Aly H. Red blood cell transfusion, feeding and nerotizing enterocolitis in preterm infants. J Perinatol 2011; 31: 183-187
Singh R, Visintainer PF, Frantz ID, Shah BL, Meyer KM, Favila SA, Thomas MS, Kent DM. Association of necrotizing enterocolitis with anemia and packed red blood cell transfusions in preterm infants. J perinatol 2011; 31:176-182

Responsible Party: Aaron Pitzele, MD, Associte Professor of Pediatrics, St. Louis University
ClinicalTrials.gov Identifier: NCT01628133     History of Changes
Other Study ID Numbers: `20969
Study First Received: June 1, 2012
Last Updated: June 18, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by St. Louis University:
Transfusion
Neonate
Infant, Very Low Birth Weight
Patent Ductus Arteriosus
Packed Red Blood Cell

ClinicalTrials.gov processed this record on September 22, 2014