Extrauterine Placental Transfusion In Neonatal Resuscitation Of Very Low Birth Weight Infants (EXPLAIN)

Extrauterine Placental Transfusion In Neonatal Resuscitation (EXPLAIN) of Very Low Birth Weight Infants (VLBW): A Randomized Clinical Trial

To investigate the effect of extrauterine placental transfusion (EPT) compared to delayed cord clamping (DCC) on the mean hematokrit on the first day of life in very low birth weight infants (VLBW) born by caesarian section. The investigators hypothesize that EPT provides higher blood volume during neonatal transition and improves neonatal outcome of VLBW infants.

Study Overview

• Status: Completed
• Conditions: Anemia; Very Low Birth Weight Infant; Placental Transfusion
• Intervention / Treatment: Procedure: Extrauterine placental transfusion (Intervention group); Procedure: Delayed cord clamping (Control group)

Detailed Description

This prospective randomized controlled study will be conducted among 2 groups, all of them are preterm infants with birth weight less than 1500 g ("very low birth weight" (VLBW)) who are delivered by caesarean section, in the first interventional group an extrauterine placental transfusion (EPT) will be done during neonatal resuscitation with respiratory pressure support. There will be a delayed cord clamping (DCC) of at least 30 - 60 seconds in the control group, before starting neonatal resuscitation with respiratory support.

In EPT approach preterm born infants are delivered by caesarean section with the placenta still attached to the infant via the umbilical cord. Then, placental transfusion is performed up to several minutes by holding the placenta ~40-50cm above the babies' heart level while respiratory support by mask continuous-positive-airway-pressure (CPAP) is initiated simultaneously.

Extrauterine placental transfusion may give more blood in babies delivered by cesarean section and may improve perfusion during the fetal-to-neonatal transition with impact on neonatal outcome.

• Study Type: Interventional
• Enrollment (Actual): 60
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Germany
  • Cologne, Germany
    • University Hospital of Cologne, Department of pediatrics

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 5 months and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Birth weight < 1500 gram ("very low birth weight infant")
• Delivery by caesarean section
• Gestational age > 23+6 weeks

Exclusion Criteria:

• Vaginal delivery
• Fetal or maternal risk (i.e. compromise, emergency c-section)
• Congenital anomalies and/or major cardiac defects
• Placental abruption or previa with hemorrhage
• Placenta accreta or increta
• Monochorionic multiples (i.e. Di/Mo or Mo/Mo twins)
• Parents declined study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Extrauterine Placental Transfusion EPT; Intervention group	Procedure: Extrauterine placental transfusion (Intervention group); At delivery by caesarean section, the infant is born with the placenta still attached via the umbilical cord and placental transfusion is performed at least 1 minute but not more than 10 minutes by holding the placenta ~40-50cm above the babies' heart level while respiratory support by mask continuous-positive-airway-pressure (CPAP) is initiated simultaneously.
Active Comparator: Delayed cord clamping DCC; Control group	Procedure: Delayed cord clamping (Control group); At delivery by caesarean section, delayed cord clamping will be performed by having the delivering obstetrician delay clamping of the umbilical cord for at least 30 seconds with initiation of respiratory support by mask CPAP after cord clamping.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hematocrit	Mean Hematocrit in the first 24 hours of life	0 - 24 hours of life

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cerebral tissue oxygen saturation	Transcutaneous measured cerebral tissue oxygen saturation given in percent (%) during neonatal resuscitation	During first hour of life
Mean airway pressure	Mean airway pressure given in cmH2O during neonatal resuscitation	During first hour of life
Mean tidal volume	Mean tidal volume given in milliliter (ml) during neonatal resuscitation	During first hour of life
Heart rate	Heart rate given in beats-per-minute (bpm) during neonatal resuscitation	During first hour of life
Blood oxygen saturation	Transcutaneous measured blood oxygen saturation given in percent (%) during neonatal resuscitation	During first hour of life
Admission temperature	Mean temperature at admission	Admission to ward is up to 120 minutes of age
All Grade Intraventricular Hemorrhage (IVH)	Incidence of any intraventricular hemorrhage (grades 1-4)	Up to 28 days of life
All Grade BPD	Incidence of Bronchopulmonary Disease (BPD) (all grades)	At the corrected age of 36 weeks
Spontaneous Pneumothorax/Pneumoperitoneum	Early incidence of spontaneous pneumothorax and/or pneumoperitoneum	During the first 7 days of life
Spontaneous Pneumothorax/Pneumoperitoneum	Late incidence of spontaneous pneumothorax and/or pneumoperitoneum	Between day 7 and day 28 of life
NEC/SIP with surgery	Incidence of necrotizing enterocolitis (NEC) and/or spontaneous intestinal perforation (SIP) with need for surgery	During the first 28 days of life
Retinopathy of Prematurity (ROP), higher grades	Incidence of retinopathy of prematurity with treatment (drugs and/or surgery)	At the corrected age of 40 weeks
Death	Incidence of death in studied infants	Until corrected age of 40 weeks
Number of participants who received red blood cell (RBC) transfusion	Amount of RBC Transfusion [cumulative ml/kg over the first 7 days] in those participants who received RBC transfusion	During the first 7 days of life
Hyperbilirubinemia	Peak bilirubin concentration	During the first 14 days of life
Blood Exchange Transfusion	Incidence of blood exchange transfusion due to critical hyperbilirubinemia of the neonate.	During the first 14 days of life
Intubation and Mechanical Ventilation	Incidence of intubation and time duration of mechanical ventilation	During the first 72 hours of life
Intubation and Mechanical Ventilation	Incidence of intubation and time duration of mechanical ventilation	During hospitalization
Neurodevelopmental Outcome	Bayley Scales of Infant and Toddler Development - Third Edition (Bayley-III) composite score (motor, cognitive, language)	22-26 month corrected gestational age

Collaborators and Investigators

• Sponsor: Universitätsklinikum Köln
• Investigators: Principal Investigator: André Oberthuer, MD, University Hospital of Cologne, Department of pediatrics

Publications and helpful links

General Publications

• Kuehne B, Kirchgaessner C, Becker I, Kuckelkorn M, Valter M, Kribs A, Oberthuer A. Mask Continuous Positive Airway Pressure Therapy with Simultaneous Extrauterine Placental Transfusion for Resuscitation of Preterm Infants - A Preliminary Study. Biomed Hub. 2018 Jun 26;3(2):1-10. doi: 10.1159/000488926. eCollection 2018 May-Aug.
• Kuehne B, Gruttner B, Hellmich M, Hero B, Kribs A, Oberthuer A. Extrauterine Placental Perfusion and Oxygenation in Infants With Very Low Birth Weight: A Randomized Clinical Trial. JAMA Netw Open. 2023 Nov 1;6(11):e2340597. doi: 10.1001/jamanetworkopen.2023.40597.

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2019
• Primary Completion (Actual): December 5, 2021
• Study Completion (Actual): October 24, 2023

Study Registration Dates

• First Submitted: April 5, 2019
• First Submitted That Met QC Criteria: April 12, 2019
• First Posted (Actual): April 16, 2019

Study Record Updates

• Last Update Posted (Estimated): November 8, 2023
• Last Update Submitted That Met QC Criteria: November 6, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Keywords: delayed cord clamping; neonatal resuscitation; extrauterine placental transfusion
• Additional Relevant MeSH Terms: Body Weight; Birth Weight
• Other Study ID Numbers: 18-232; DRKS00017041 (Registry Identifier: German Clinical Trials Register)

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