Two Year Developmental Follow-up for PREMOD2 Trial (Premature Infants Receiving Milking or Delayed Cord Clamping)

Study Overview
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Brief Summary
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An extension of the PREMOD2 trial, the PREMOD2 Follow-Up trial will evaluate the neurodevelopmental outcomes at 22-26 months corrected age of preterm children who received UCM or DCC. This prospective multi-national randomized controlled trial (RCT) is a two-arm parallel non-inferiority design of two alternative approaches of treatment.

Detailed Description
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The PREMOD2 Follow-up trial will examine the difference in early childhood neurodevelopmental outcomes of subjects enrolled in the PREMOD2 umbilical cord milking (UCM) vs. delayed cord clamping (DCC) trial, using standardized neurologic and developmental assessments at 22-26 months corrected age (CA). The corrected age may be extended out to 42 months CA due to Covid-19 pandemic for undetermined period of time.

Official Title
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Two Year Developmental Follow-up for Premature Infants Receiving Milking or Delayed Cord Clamping: PREMOD2

Conditions
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Neurodevelopmental Abnormality

Intervention / Treatment
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* Procedure: Randomized to Umbilical Cord Milking at birth
* Procedure: Randomized to Delayed Cord Clamping at birth


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Children enrolled in the PREMOD2 non-inferiority trial at birth who survive to 2 years corrected age. Exclusion Criteria: Children enrolled in the PREMOD2 non-inferiority trial at birth who did not survive or are lost to follow-up.

Ages Eligible for Study
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Minimum Age: 22 Months
Maximum Age: 42 Months

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Neurodevelopmental assessments will be done at 2 years of corrected age (22-26 months) for subjects who were randomized at birth to receive either delayed cord clamping or umbilical cord milking as part of the PREMOD2 trial. This prospective multi-national randomized controlled trial (RCT) is a two-arm parallel non-inferiority design of two alternative approaches of treatment.
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Randomized to Umbilical Cord Milking at birth<br>Milking the umbilical cord towards the infant at a speed of 20cm/2seconds at birth. | Procedure: Randomized to Umbilical Cord Milking at birth<br>* The subjects in this group were randomized to UCM X4 at birth. This procedure infuses a placental transfusion of blood by milking the umbilical cord towards the infant at birth.<br>* Other names: UCM;|
| Active Comparator: Randomized to Delayed Cord Clamping at birth<br>Delayed clamping of the umbilical cord at birth. | Procedure: Randomized to Delayed Cord Clamping at birth<br>* The subjects in this group were randomized to DCC at birth. At delivery, the obstetrician was instructed to delay clamping of the umbilical cord for 60 seconds.<br>* Other names: DCC;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Developmental Outcome | Bayley Scales of Infant Development (BSID), 3rd or 4th Ed. Composite Score (cognitive 55-145, language 45-155, motor 45-155; higher scores are better) | 22-26 months corrected gestational age (CGA). All assessments may be extended to 42 months CGA due to Covid-19 pandemic. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Moderate/Severe Neurodevelopmental Impairment | Defined having at least one of the following: a cognitive score <70, GMFCS greater or equal 2, blindness (vision <20/200), or hearing impairment interfering with the ability to communicate with amplification. | 22-26 months corrected gestational age | 
| Mild Neurodevelopmental Impairment | Defined having at least one of the following: a cognitive score 70-84, GMFCS =1, unilateral blindness (vision <20/200 in only one eye), or hearing impairment which does not interfere with the ability to communicate. | 22-26 months corrected gestational age | 
| Gross Motor Function Classification System Scale (GMFCS) | The GMFCS is a validated system used to describe the severity of motor dysfunction. Scale measured from Level 0-5 with Level 0 being normal and Level 5 being the worst score. Measures ability to walk, sit, head control, voluntary movements and postures. | 22-26 months corrected gestational age | 
| Cerebral Palsy (CP) | Classified as None, Mild, Moderate or Severe based on GMFCS score; No CP = GMFCS Level 0, Mild CP = GMFCS Level 1, Moderate CP = GMFCS Levels 2-3, Severe CP = GMFCS Levels 4-5 | 22-26 months corrected gestational age | 
| Developmental Outcomes assessed by Ages & Stages Questionnaire, 3rd ed. (ASQ-3) five domains: Communication, Gross motor, Fine motor, Problem solving and Personal-social in infants born between 23-32+6 weeks GA who received UCM or DCC. | Each domain is scored from 0 to 60, the higher score is better. | 22-26 months corrected gestational age | 
| Developmental Outcomes in infants born at 23 -27 and 28-32 weeks GA who received UCM or DCC | BSID Cognitive, Language & Motor composite scores (cognitive 55-145, language 45-155, motor 45-155; higher scores are better) in infants 23-27 weeks GA and 28-32+6 weeks GA. | 22-26 months corrected gestational age | 
| Developmental Outcomes in infants born at 23 -27 and 28-32 weeks GA who received UCM or DCC | ASQ-3 scores (0 to 60, the higher score is better) in infants 23-27 weeks GA and 28-32+6 weeks GA. | 22-26 months corrected gestational age | 
| Compare levels of developmental impairment as assessed by BSID-3 or 4 versus the ASQ-3 screening tool. | Mild, moderate or severe impairment | 22-26 months corrected gestational age | 
| Any grade intraventricular hemorrhage (IVH) in premature newborns 23 - 32+6 weeks GA who received UCM or DCC by mode of delivery (C-Section vs vaginal delivery) | Any IVH grade from 1 to grade 4, higher grade is worse | From birth through hospital discharge, up to 6 months corrected gestational age (CGA) | 
| Death in premature newborns 23 - 32+6 weeks GA who received UCM or DCC by mode of delivery (C-Section vs vaginal delivery) | Death | From birth through hospital discharge, up to 6 months corrected gestational age (CGA) | 
| Compare neurodevelopmental outcomes from BSID assessments in newborns 23-32 weeks GA delivered by C-Section with those born by vaginal delivery receiving UCM or DCC. | BSID Cognitive, Language & Motor composite scores (cognitive 55-145, language 45-155, motor 45-155; higher scores are better) | 22-26 months corrected gestational age | 
| Compare neurodevelopmental outcomes from ASQ assessments in newborns 23-32 weeks GA delivered by C-Section with those born by vaginal delivery receiving UCM or DCC. | ASQ-3 scores (0 to 60, the higher score is better). | 22-26 months corrected gestational age | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Neurodevelopmental impairment, prematurity, Disability, Umbilical cord milking, Delayed cord clamping