Utility of Placental/Umbilical Cord Blood in Early Onset Neonatal Sepsis in Very Low Birth Weight Infants

A Pilot Study to Evaluate the Utility of Placental/Umbilical Cord Blood (PUCB) in Early Onset Neonatal Sepsis (EONS) in Very Low Birth Weight Infants

This study evaluates the utility of placental/umbilical cord blood (PUCB) to perform the baseline workup testing for EONS in Very Low Birth Weight Infants: CBC (Complete Blood Count) with differential, Immature/Total ratio (I/T ratio), and blood culture along with CRP and IL-6 levels. A cohort (63 subjects) of preterm infants will be recruited. All the participants will be evaluated for sepsis using placental/umbilical cord blood (PUCB) and subject blood sample during the first 12 hours of life (after birth).

Study Overview

• Status: Completed
• Conditions: Preterm Infant; Umbilical Cord; Early-Onset Neonatal Sepsis
• Intervention / Treatment: Other: Placental/Umbilical Cord Blood sample

Detailed Description

Early Onset Neonatal Sepsis (EONS) is common in preterm infants, and it is associated with high morbidity and mortality, especially if not diagnosed early. Currently the baseline workup is done using blood samples from the infant to perform Blood culture, CBC, I/T ratio. These tests have shown to have low sensitivity and specificity to diagnosis EONS.

PUCB can be another safe source of blood which is useful, painless and simple to collect. As CBC, I/T ratio and blood culture may not be enough to diagnose EONS we will add IL-6 and CRP which will increase sensitivity and specificity to diagnose EONS in preterm infants without collecting blood from the infants.

This study may be a step to decrease iatrogenic blood loss to diagnose EONS. The primary outcome of the current research will be to find out the utility of PUCB in diagnosing EOS in preterm infants (<30 weeks and <1250 grams birth weight). Using PUCB can increase the accuracy to diagnose Sepsis in Preterm infants, and it will also conserve blood in the extremely premature infants while reducing hemodynamic instability due to acute blood loss.

• Study Type: Interventional
• Enrollment (Actual): 65
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Texas
    • Galveston, Texas, United States, 77550
      • Sergio Mauricio Lerma Narvaez

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 1 day (CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Infants <34 weeks' gestational

Exclusion Criteria:

• Known congenital or chromosomal anomalies
• Congenital heart disease (other than Patent Ductus Arteriosus, Patent Foramen Ovale or Atrial Septum Defect)
• Vaginal bleeding at admission

Study Plan

How is the study designed?

Design Details

• Primary Purpose: DIAGNOSTIC
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

OTHER: Placental/Umbilical Cord Blood sample; Placental/Umbilical Cord Blood sample will be collected after delivery from every participant.

Other: Placental/Umbilical Cord Blood sample; After infant is delivered, placenta along with clamped umbilical cord Blood will be obtained from the ObGyn team. One umbilical clamp will be placed at the umbilical end, and the other clamp will be placed on the placental end of the umbilical cord. Then the umbilical cord will be cut between the clamps. The umbilical cord will be cleaned three times with 2% chlorhexidine, plus 70% isopropyl alcohol under sterile conditions (sterile gloves). Cord blood samples will be collected using vacutainer blood collecting system with a sterile 22-gauge needle. We will collect 3 - 4 ml of blood.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
White Blood Cell Count (WBC) (1)	Normal Range approximately 6,000 - 30,000 cell/mm3.	Completed during the first 30 minutes after birth. This sample is going to be taken from the discarded Placental/umbilical blood cord.
White Blood Cell Count (WBC) (1) INFANT BLOOD	Normal Range: 6.000 - 30.000 cell/mm3.	Completed during the first 6 hours after birth. This sample is going to be taken directly from the participant.
I/T Ratio (Immature/Total Immature Neutrophil).I/T Ratio Was Calculated by Dividing Immature White Cell Count Total White Cell Count	Normal Range of I/T ratio: <0.2.	Completed during the first 30 minutes after birth. This sample is going to be taken from the discarded Placental/umbilical blood cord.
I/T Ratio (Immature/Total Immature Neutrophil Ratio) INFANT BLOOD	Normal Range: <0.2	Completed during the first 12 hours after birth. This sample is going to be taken directly from the participant.
CRP (C-Reactive Protein)(1)	Normal Range: < 10,000 ng/mL	Completed during the first 30 minutes after birth. This sample is going to be taken from the discarded Placental/umbilical blood cord.
CRP (C-Reactive Protein)(2) INFANT BLOOD	Normal Range: <10.000ng/mL	Completed during the first 6 hours after birth. This sample was taken directly from the participant.
IL-6 (1)	Normal Range: 0-10.2 pg/ml	Completed during the first 30 minutes after birth. This sample is going to be taken from the discarded Placental/umbilical blood cord.
IL-6 (Interleukin-6) INFANTS BLOOD	Normal Range: <100 pg/mL	Completed during the first 6hours after birth. This sample is going to be taken directly from the participant.
Procalcitonin PUBC	Blood was taken from PUBC after delivery	Within 30 minutes after delivery
Procalcitonin Level Was Measured in the Blood From Placenta and From the Baby Within 6 Hours After Birth	Procalcitonin levels	Procalcitonin Level was measured in the blood from placenta and in Infant's Blood (within 6 hours)
Number of Participants With Negative Blood Culture From Blood Drawn From Placenta and From Baby Within 6 Hours After Birth	Normal Range: Blood Culture Negative	Blood sample drawn from placenta and from baby within 6 hours after birth.
Presepsin- PUBC	Presepsin level was measured in the blood drawn from placenta and from the baby within 6 hours after birth	First 30 min after birth
Presepsin-Infant's Blood	Levels of presepsin	First 30 min after birth
Number of Participants With a Negative Blood Culture	Blood is taken from infants after birth	first 2 hours after birth

Collaborators and Investigators

• Sponsor: The University of Texas Medical Branch, Galveston
• Investigators: Principal Investigator: sergio M Lerma Narvaez, UTMB, Galveston

Publications and helpful links

General Publications

• Qazi SA, Stoll BJ. Neonatal sepsis: a major global public health challenge. Pediatr Infect Dis J. 2009 Jan;28(1 Suppl):S1-2. doi: 10.1097/INF.0b013e31819587a9. No abstract available.
• Brown DR, Kutler D, Rai B, Chan T, Cohen M. Bacterial concentration and blood volume required for a positive blood culture. J Perinatol. 1995 Mar-Apr;15(2):157-9.
• Hornik CP, Benjamin DK, Becker KC, Benjamin DK Jr, Li J, Clark RH, Cohen-Wolkowiez M, Smith PB. Use of the complete blood cell count in early-onset neonatal sepsis. Pediatr Infect Dis J. 2012 Aug;31(8):799-802. doi: 10.1097/INF.0b013e318256905c.
• Malik A, Hui CP, Pennie RA, Kirpalani H. Beyond the complete blood cell count and C-reactive protein: a systematic review of modern diagnostic tests for neonatal sepsis. Arch Pediatr Adolesc Med. 2003 Jun;157(6):511-6. doi: 10.1001/archpedi.157.6.511.
• Ng PC. Diagnostic markers of infection in neonates. Arch Dis Child Fetal Neonatal Ed. 2004 May;89(3):F229-35. doi: 10.1136/adc.2002.023838.
• Laborada G, Rego M, Jain A, Guliano M, Stavola J, Ballabh P, Krauss AN, Auld PA, Nesin M. Diagnostic value of cytokines and C-reactive protein in the first 24 hours of neonatal sepsis. Am J Perinatol. 2003 Nov;20(8):491-501. doi: 10.1055/s-2003-45382.
• Christensen RD, Lambert DK, Baer VL, Montgomery DP, Barney CK, Coulter DM, Ilstrup S, Bennett ST. Postponing or eliminating red blood cell transfusions of very low birth weight neonates by obtaining all baseline laboratory blood tests from otherwise discarded fetal blood in the placenta. Transfusion. 2011 Feb;51(2):253-8. doi: 10.1111/j.1537-2995.2010.02827.x. Epub 2010 Aug 16.
• Meena J, Charles MV, Ali A, Ramakrishnan S, Gosh S, Seetha KS. Utility of cord blood culture in early onset neonatal sepsis. Australas Med J. 2015 Aug 31;8(8):263-7. doi: 10.4066/AMJ.2015.2460. eCollection 2015.
• Beeram MR, Loughran C, Cipriani C, Govande V. Utilization of umbilical cord blood for the evaluation of group B streptococcal sepsis screening. Clin Pediatr (Phila). 2012 May;51(5):447-53. doi: 10.1177/0009922811431882. Epub 2011 Dec 22.
• Joram N, Boscher C, Denizot S, Loubersac V, Winer N, Roze JC, Gras-Le Guen C. Umbilical cord blood procalcitonin and C reactive protein concentrations as markers for early diagnosis of very early onset neonatal infection. Arch Dis Child Fetal Neonatal Ed. 2006 Jan;91(1):F65-6. doi: 10.1136/adc.2005.074245.
• Baer VL, Lambert DK, Carroll PD, Gerday E, Christensen RD. Using umbilical cord blood for the initial blood tests of VLBW neonates results in higher hemoglobin and fewer RBC transfusions. J Perinatol. 2013 May;33(5):363-5. doi: 10.1038/jp.2012.127. Epub 2012 Oct 4.

Study record dates

Study Major Dates

• Study Start (ACTUAL): June 1, 2019
• Primary Completion (ACTUAL): June 1, 2020
• Study Completion (ACTUAL): August 20, 2020

Study Registration Dates

• First Submitted: September 28, 2018
• First Submitted That Met QC Criteria: October 1, 2018
• First Posted (ACTUAL): October 3, 2018

Study Record Updates

• Last Update Posted (ACTUAL): August 10, 2021
• Last Update Submitted That Met QC Criteria: July 16, 2021
• Last Verified: November 1, 2020

More Information

Terms related to this study

• Keywords: Blood Culture; Placenta; Umbilical Cord; Preterm Infant; Early-Onset Neonatal Sepsis; Complete Cell Count
• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Infant, Newborn, Diseases; Body Weight; Sepsis; Toxemia; Birth Weight; Neonatal Sepsis
• Other Study ID Numbers: 18-0165

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No