Effects of Delayed Cord Clamping During Resuscitation of Newborn Near Term and Term Infants (SAVE)

SAVE (Sustained Cord Circulation Awaiting VEntilation)

This study evaluates resuscitation with an intact umbilical cord compared to resuscitation with the umbilical cord cut. Half of the newborn babies in need of resuscitation will be handled while having an intact umbilical cord and half will have their umbilical cord cut.

Study Overview

• Status: Active, not recruiting
• Conditions: Asphyxia Neonatorum; Resuscitation
• Intervention / Treatment: Procedure: Early (≤ 60 seconds) cord clamping; Procedure: Intact cord (≥ 180 seconds) resuscitation

Detailed Description

The routine procedure when a newborn baby is in need of resuscitation is to cut the umbilical cord and move the baby to a designated area for resuscitation, which can include stimulation, clearing the airways, administration of oxygen and/or positive pressure ventilation by bag and mask och T-piece resuscitator.

It has been suggested, and pilot studies has shown preliminary results, that keeping the umbilical cord intact while performing resuscitation may improve the babies outcome, by continued exchange of oxygen and carbon dioxide be the placenta and facilitating the neonatal pulmonary and circulatory transition.

Because of the limiting length of the umbilical cord, resuscitation with an intact cord must be performed in close proximity to the mother.

• Study Type: Interventional
• Enrollment (Estimated): 600
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Sweden
  • Ystad, Sweden
    • Ystad Hospital
  • Halland
    • Halmstad, Halland, Sweden, 30185
      • Hospital of Halland
  • Skåne
    • Malmö, Skåne, Sweden, 21428
      • Skåne University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 8 months to 9 months (Child)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Pregnancy week ≥35 + 0
• Singletons
• Expected vaginal delivery
• The woman / couple can adequately assimilate information about the study
• Signed informed consent of both prospective parents

Exclusion Criteria:

• Congenital malformation that complicates resuscitation (such as severe malformation of mouth, pharynx, respiratory system) or which causes the child not to be resuscitated due to internal structural malformations (such as more severe heart failure, diaphragm fractures, etc.)
• The child is born via acute caesarean section after inclusion and opening of study envelope
• placenta abruption / or damage to umbilical cord during childbirth (when circulation through an intact umbilical cord cannot be achieved after birth)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Early (≤ 60 seconds) cord clamping; If the infant don't breathe, the umbilical cord is clamped (≤ 60 seconds) and cut and resuscitation will be provided at a resuscitation table Other Name: Immediate clamping	Procedure: Early (≤ 60 seconds) cord clamping; Resuscitation performed at a designated area after umbilical cord is cut
Active Comparator: Intact cord (≥ 180 seconds) resuscitation; If the infant don't breathe, the umbilical cord is not clamped and cut until after 180 seconds. Initial resuscitation will be provided bedside to the mother Other Names: Late cord clamping Deferred cord clamping Optimal cord clamping	Procedure: Intact cord (≥ 180 seconds) resuscitation; Resuscitation performed in near proximity to the mother with umbilical cord uncut

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Apgar score	Assessed by staff, composite of heart rate, breathing effort, skin color, muscle tone and reflexes, each sub scale 0 (absent), 1, 2 (normal). Minimum 0, maximum 10. Less than 4 is a measure for severe asphyxia, less than 7 measure of mild asphyxia.	At 5 minutes after birth

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Presence at one day of age	The place of stay for newborn at one day of age	24 hours
Apgar score	Assessed by staff, composite of heart rate, breathing effort, skin color, muscle tone and reflexes, each sub scale 0 (absent), 1, 2 (normal). Minimum 0, maximum 10. Less than 4 is a measure for severe asphyxia, less than 7 measure of mild asphyxia.	At 1 minute after birth
Apgar score	Assessed by staff, composite of heart rate, breathing effort, skin color, muscle tone and reflexes, each sub scale 0 (absent), 1, 2 (normal). Minimum 0, maximum 10. Less than 4 is a measure for severe asphyxia, less than 7 measure of mild asphyxia.	At 10 minute after birth
Time of first cry or breathing effort	Assessed by staff present	Within 10 minutes after birth
Time of establishing spontaneous breathing	Assessed by staff present	Within 10 minutes after birth
Need of neonatal intensive care	Admission to neonatal intensive care unit	7 days
Score for Neonatal Acute Physiology (SNAP-II)	Assessed by staff at neonatal intensive care unit	7 days
Morbidity Assessment Index for Newborns (MAIN)	Assessed by staff at neonatal intensive care unit	7 days
Blood glucose	Sampled by staff at nursery of neonatal intensive care	4 hours after birth
Breathing difficulties	Respiratory rate > 60, grunting/shallow breathing, nostril flaring, retractions between or under the ribs) Assessed by staff at nursery of neonatal intensive care	1 hours after birth
Breathing difficulties	Respiratory rate > 60, grunting/shallow breathing, nostril flaring, retractions between or under the ribs) Assessed by staff at nursery of neonatal intensive care	6 hours after birth
Mortality	Death after birth	One year
Development	Assessed by Ages and Stages Questionnaire (ASQ). Minimum 0, maximum 300. Consist of 30 questions answered Yes (10), Sometimes (5), Not Yet (0). Five sub scales with six questions each: Communication, Fine motor, Gross motor, Problem solving and Personal-Social. Worse outcome is considered mean minus 2 standard deviations.	12 months
Development	Neurocognitive assessment by Bayley-III (alternative Bayley-IV if available). Derives a developmental quotient (DQ) three main subtests; the Cognitive Scale, the Language Scale, and the Motor Scale. Is assessed by special staff and have standardized interpretations of results.	24 months
Autism	Screening by Modified Checklist for Autism in Toddlers (M-CHAT). 20-question test. Answers "yes" or "no". A total score of 2 and below on the first part of the M-CHAT indicate low autism risk, a total score of 3-7 indicates medium risk and prompts administration of the follow-up form. A total score of 8 or higher indicates high autism risk.	24 months
Development	Neurocognitive assessment by Wechsler Preschool and Primary Scale of Intelligence (WPPSI-IV). 14 subtests. The core subtests are required for the computation of the Verbal, Performance, and Full Scale intelligence quotient (IQ). Also, two other composites Processing Speed Quotient and General Language Composite. Quotient and Composite scores have a mean of 100 and a standard deviation of 15. Subtest scaled scores have a mean of 10 and a standard deviation of 3. For Quotient and Composite score: below 70 is Extremely Low, 70-79 is Borderline, 80-89 is Low Average, 90-109 is Average, 110-119 is High Average, 120-129 is Superior, 130+ is Very Superior.	54 months
Motor development	Assessed by Movement Assessment Battery for Children (ABC). The test contains 8 tasks covering the following 3 areas: Manual Dexterity, Ball Skills, Static and Dynamic Balance. Standard scores for each domain can be compared to normative data and interpreted in terms of percentile equivalents (a) ≤5th percentile reflecting definite motor impairment, (b) ≤15th percentile reflecting borderline motor impairment, or (c) >15th percentile reflecting no motor impairment.	54 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Thompson score	Assessed by staff at neonatal intensive care unit. A scoring system for hypoxic ischaemic encephalopathy in predicting neurodevelopmental outcome. Minimum 0 (normal), maximum 22. A score ≥12 is associated with adverse outcomes.	1 hour after birth
Thompson score	Assessed by staff at neonatal intensive care unit. A scoring system for hypoxic ischaemic encephalopathy in predicting neurodevelopmental outcome. Minimum 0 (normal), maximum 22. A score ≥12 is associated with adverse outcomes.	6 hours after birth
Thompson score	Assessed by staff at neonatal intensive care unit. A scoring system for hypoxic ischaemic encephalopathy in predicting neurodevelopmental outcome. Minimum 0 (normal), maximum 22. A score ≥12 is associated with adverse outcomes.	12 hours after birth
Thompson score	Assessed by staff at neonatal intensive care unit. A scoring system for hypoxic ischaemic encephalopathy in predicting neurodevelopmental outcome. Minimum 0 (normal), maximum 22. A score ≥12 is associated with adverse outcomes.	24 hours after birth
Thompson score	Assessed by staff at neonatal intensive care unit. A scoring system for hypoxic ischaemic encephalopathy in predicting neurodevelopmental outcome. Minimum 0 (normal), maximum 22. A score ≥12 is associated with adverse outcomes.	48 hours after birth

Collaborators and Investigators

• Sponsor: Lund University
• Collaborators: Skane University Hospital
• Investigators: Principal Investigator: Ola Andersson, MD PhD, Lunds University/Skåne University Hospital

Publications and helpful links

General Publications

• Niermeyer S, Velaphi S. Promoting physiologic transition at birth: re-examining resuscitation and the timing of cord clamping. Semin Fetal Neonatal Med. 2013 Dec;18(6):385-92. doi: 10.1016/j.siny.2013.08.008. Epub 2013 Sep 19.
• Katheria AC, Brown MK, Faksh A, Hassen KO, Rich W, Lazarus D, Steen J, Daneshmand SS, Finer NN. Delayed Cord Clamping in Newborns Born at Term at Risk for Resuscitation: A Feasibility Randomized Clinical Trial. J Pediatr. 2017 Aug;187:313-317.e1. doi: 10.1016/j.jpeds.2017.04.033. Epub 2017 May 16.
• Andersson O, Rana N, Ewald U, Malqvist M, Stripple G, Basnet O, Subedi K, Kc A. Intact cord resuscitation versus early cord clamping in the treatment of depressed newborn infants during the first 10 minutes of birth (Nepcord III) - a randomized clinical trial. Matern Health Neonatol Perinatol. 2019 Aug 29;5:15. doi: 10.1186/s40748-019-0110-z. eCollection 2019.
• Ekelof K, Saether E, Santesson A, Wilander M, Patriksson K, Hesselman S, Thies-Lagergren L, Rabe H, Andersson O. A hybrid type I, multi-center randomized controlled trial to study the implementation of a method for Sustained cord circulation And VEntilation (the SAVE-method) of late preterm and term neonates: a study protocol. BMC Pregnancy Childbirth. 2022 Jul 26;22(1):593. doi: 10.1186/s12884-022-04915-5.
• Wilander M, Sandblom J, Thies-Lagergren L, Andersson O, Svedenkrans J. Bilirubin Levels in Neonates >/=35 Weeks of Gestation Receiving Delayed Cord Clamping for an Extended Time-An Observational Study. J Pediatr. 2023 Jun;257:113326. doi: 10.1016/j.jpeds.2023.01.005. Epub 2023 Jan 14.
• Katheria AC. Neonatal Resuscitation with an Intact Cord: Current and Ongoing Trials. Children (Basel). 2019 Apr 22;6(4):60. doi: 10.3390/children6040060. Erratum In: Children (Basel). 2019 May 21;6(5):E71. doi: 10.3390/children6050071.

Helpful Links

• Official homepage

Study record dates

Study Major Dates

• Study Start (Actual): September 30, 2019
• Primary Completion (Actual): November 30, 2024
• Study Completion (Estimated): December 31, 2026

Study Registration Dates

• First Submitted: August 26, 2019
• First Submitted That Met QC Criteria: August 26, 2019
• First Posted (Actual): August 28, 2019

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: March 14, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Keywords: umbilical cord
• Additional Relevant MeSH Terms: Wounds and Injuries; Pathologic Processes; Infant, Newborn, Diseases; Death; Asphyxia; Asphyxia Neonatorum
• Other Study ID Numbers: SAVE1

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Individual participant data that underlie the results reported in publications, after deidentification (text, tables, figures, and appendices).
• IPD Sharing Time Frame: Beginning 9 months and ending 36 months following article publication.
• IPD Sharing Access Criteria: Researchers who provide a methodologically sound proposal, and that most preferably have an approval from an independent review committee.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF

Drug and device information, study documents

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