Trial Outcomes & Findings for Umbilical Cord Milking in Non-Vigorous Infants Developmental Followup (MINVIFU) (NCT NCT03621943)
NCT ID: NCT03621943
Last Updated: 2025-03-27
Results Overview
Neurodevelopmental Outcome at 2 Years of Age defined as overall and domain scores on the Ages and Stages, third edition. Questionnaire. Minimum score of 0 and maximum score of 60 per domain. Scores from 5 subscales are summed to obtain a total score. 5 domains assessed include communication, gross motor, fine motor, problem solving, personal social with a total minimum score of 0 and maximum score of 300. Higher scores indicate a lower risk of developmental delays or conditions
Recruitment status
COMPLETED
Study phase
NA
Target enrollment
1207 participants
Primary outcome timeframe
22 to 26 months
Results posted on
2025-03-27
Participant Flow
Study design: cluster crossover randomization of 10 maternity hospitals to perform cord milking or early cord clamping. Participants were recruited among non-vigorous newborn born during the initial study period: January 2019 - January 2020 and crossover period: February 2020 - March 2021.
Hospital sites were informed of their randomization status two months before initiation of recruitment to permit time for physician and staff education on the assigned intervention. Prior to the start of recruitment in the crossover study period a 1 to 2-month washout period for each hospital site was specified by the protocol for the purpose of site hospital staff education on the change in assigned intervention and to assess adherence prior to recruitment initiation in the second study period.
Unit of analysis: Hospital
Participant milestones
| Measure |
Umbilical Cord Milking Then Early Cord Clamping Site Randomization - Infant
In the first study period infants assessed as non-vigorous at delivery had the umbilical cord is grasped by the obstetric provider, and blood was pushed toward the infant 4 times before the cord is clamped.
In the second study period infants assessed as non-vigorous at delivery had the umbilical cord clamped by 60 seconds of life.
|
Early Cord Clamping Then Umbilical Cord Milking Site Randomization - Infant
In the first study period infants assessed as non-vigorous at delivery had the umbilical cord clamped as soon as possible and within 60 seconds of delivery. In the second study period umbilical cord was grasped by the obstetric provider, and blood was pushed toward the infant 4 times before the cord is clamped.
|
|---|---|---|
|
First Randomized Intervention
STARTED
|
284 5
|
321 5
|
|
First Randomized Intervention
COMPLETED
|
230 5
|
264 5
|
|
First Randomized Intervention
NOT COMPLETED
|
54 0
|
57 0
|
|
Crossover Randomized Intervention
STARTED
|
280 5
|
322 5
|
|
Crossover Randomized Intervention
COMPLETED
|
205 5
|
272 5
|
|
Crossover Randomized Intervention
NOT COMPLETED
|
75 0
|
50 0
|
Reasons for withdrawal
| Measure |
Umbilical Cord Milking Then Early Cord Clamping Site Randomization - Infant
In the first study period infants assessed as non-vigorous at delivery had the umbilical cord is grasped by the obstetric provider, and blood was pushed toward the infant 4 times before the cord is clamped.
In the second study period infants assessed as non-vigorous at delivery had the umbilical cord clamped by 60 seconds of life.
|
Early Cord Clamping Then Umbilical Cord Milking Site Randomization - Infant
In the first study period infants assessed as non-vigorous at delivery had the umbilical cord clamped as soon as possible and within 60 seconds of delivery. In the second study period umbilical cord was grasped by the obstetric provider, and blood was pushed toward the infant 4 times before the cord is clamped.
|
|---|---|---|
|
First Randomized Intervention
Lost to Follow-up
|
51
|
54
|
|
First Randomized Intervention
Withdrawal by Subject
|
3
|
3
|
|
Crossover Randomized Intervention
Lost to Follow-up
|
75
|
45
|
|
Crossover Randomized Intervention
Withdrawal by Subject
|
0
|
5
|
Baseline Characteristics
Maternal level of education was not collected for infant-mother dyads who refused to self-disclose birth mother's highest level of education at time of consent to long-term follow-up. All participants represented are unique with no duplicate participants
Baseline characteristics by cohort
| Measure |
Umbilical Cord Milking Treatment Only- Infant & Maternal Baseline Measures
n=502 Participants
Baseline measures presented by randomized treatment assignment. Includes all infants who were assigned to umbilical cord milking (umbilical cord is grasped, and blood is pushed toward the infant 4 times before the cord is clamped) treatment based on hospital randomization. Maternal data is presented for all participating mothers. Only unique participants are presented.
|
Early Cord Clamping Treatment Only- Infant & Maternal Baseline Measures
n=469 Participants
Baseline measures presented by randomized treatment assignment. Includes all infants who were assigned to the early cord clamping (The umbilical cord is clamped as soon as possible and within 60 seconds of delivery) treatment at delivery based on hospital randomization. Maternal data is presented for all participating mothers. Only unique participants are presented.
|
Total
n=971 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
Infant's gestational age at birth
|
39 weeks
n=502 Participants
|
39 weeks
n=469 Participants
|
39 weeks
n=971 Participants
|
|
Age, Customized
Maternal age at delivery
|
31 years, maternal age at delivery
STANDARD_DEVIATION 5 • n=502 Participants
|
31 years, maternal age at delivery
STANDARD_DEVIATION 6 • n=469 Participants
|
31 years, maternal age at delivery
STANDARD_DEVIATION 6 • n=971 Participants
|
|
Sex: Female, Male
Infant sex · Female
|
224 Participants
n=502 Participants
|
201 Participants
n=469 Participants
|
425 Participants
n=971 Participants
|
|
Sex: Female, Male
Infant sex · Male
|
278 Participants
n=502 Participants
|
268 Participants
n=469 Participants
|
546 Participants
n=971 Participants
|
|
Ethnicity (NIH/OMB)
Infant Ethnicity · Hispanic or Latino
|
100 Participants
n=502 Participants
|
102 Participants
n=469 Participants
|
202 Participants
n=971 Participants
|
|
Ethnicity (NIH/OMB)
Infant Ethnicity · Not Hispanic or Latino
|
375 Participants
n=502 Participants
|
302 Participants
n=469 Participants
|
677 Participants
n=971 Participants
|
|
Ethnicity (NIH/OMB)
Infant Ethnicity · Unknown or Not Reported
|
27 Participants
n=502 Participants
|
65 Participants
n=469 Participants
|
92 Participants
n=971 Participants
|
|
Ethnicity (NIH/OMB)
Maternal Ethnicity · Hispanic or Latino
|
86 Participants
n=502 Participants
|
88 Participants
n=469 Participants
|
174 Participants
n=971 Participants
|
|
Ethnicity (NIH/OMB)
Maternal Ethnicity · Not Hispanic or Latino
|
393 Participants
n=502 Participants
|
321 Participants
n=469 Participants
|
714 Participants
n=971 Participants
|
|
Ethnicity (NIH/OMB)
Maternal Ethnicity · Unknown or Not Reported
|
23 Participants
n=502 Participants
|
60 Participants
n=469 Participants
|
83 Participants
n=971 Participants
|
|
Race (NIH/OMB)
Infant Race · American Indian or Alaska Native
|
5 Participants
n=502 Participants
|
2 Participants
n=469 Participants
|
7 Participants
n=971 Participants
|
|
Race (NIH/OMB)
Infant Race · Asian
|
31 Participants
n=502 Participants
|
37 Participants
n=469 Participants
|
68 Participants
n=971 Participants
|
|
Race (NIH/OMB)
Infant Race · Native Hawaiian or Other Pacific Islander
|
2 Participants
n=502 Participants
|
5 Participants
n=469 Participants
|
7 Participants
n=971 Participants
|
|
Race (NIH/OMB)
Infant Race · Black or African American
|
29 Participants
n=502 Participants
|
29 Participants
n=469 Participants
|
58 Participants
n=971 Participants
|
|
Race (NIH/OMB)
Infant Race · White
|
287 Participants
n=502 Participants
|
260 Participants
n=469 Participants
|
547 Participants
n=971 Participants
|
|
Race (NIH/OMB)
Infant Race · More than one race
|
87 Participants
n=502 Participants
|
86 Participants
n=469 Participants
|
173 Participants
n=971 Participants
|
|
Race (NIH/OMB)
Infant Race · Unknown or Not Reported
|
61 Participants
n=502 Participants
|
50 Participants
n=469 Participants
|
111 Participants
n=971 Participants
|
|
Race (NIH/OMB)
Maternal Race · American Indian or Alaska Native
|
12 Participants
n=502 Participants
|
5 Participants
n=469 Participants
|
17 Participants
n=971 Participants
|
|
Race (NIH/OMB)
Maternal Race · Asian
|
39 Participants
n=502 Participants
|
46 Participants
n=469 Participants
|
85 Participants
n=971 Participants
|
|
Race (NIH/OMB)
Maternal Race · Native Hawaiian or Other Pacific Islander
|
5 Participants
n=502 Participants
|
8 Participants
n=469 Participants
|
13 Participants
n=971 Participants
|
|
Race (NIH/OMB)
Maternal Race · Black or African American
|
35 Participants
n=502 Participants
|
36 Participants
n=469 Participants
|
71 Participants
n=971 Participants
|
|
Race (NIH/OMB)
Maternal Race · White
|
322 Participants
n=502 Participants
|
283 Participants
n=469 Participants
|
605 Participants
n=971 Participants
|
|
Race (NIH/OMB)
Maternal Race · More than one race
|
28 Participants
n=502 Participants
|
30 Participants
n=469 Participants
|
58 Participants
n=971 Participants
|
|
Race (NIH/OMB)
Maternal Race · Unknown or Not Reported
|
61 Participants
n=502 Participants
|
61 Participants
n=469 Participants
|
122 Participants
n=971 Participants
|
|
Region of Enrollment
Canada
|
159 infant participants
n=502 Participants
|
159 infant participants
n=469 Participants
|
318 infant participants
n=971 Participants
|
|
Region of Enrollment
United States
|
326 infant participants
n=502 Participants
|
297 infant participants
n=469 Participants
|
623 infant participants
n=971 Participants
|
|
Region of Enrollment
Poland
|
17 infant participants
n=502 Participants
|
13 infant participants
n=469 Participants
|
30 infant participants
n=971 Participants
|
|
Number of neonates born to a mother with at least some college education
|
349 infant participants
n=446 Participants • Maternal level of education was not collected for infant-mother dyads who refused to self-disclose birth mother's highest level of education at time of consent to long-term follow-up. All participants represented are unique with no duplicate participants
|
321 infant participants
n=406 Participants • Maternal level of education was not collected for infant-mother dyads who refused to self-disclose birth mother's highest level of education at time of consent to long-term follow-up. All participants represented are unique with no duplicate participants
|
670 infant participants
n=852 Participants • Maternal level of education was not collected for infant-mother dyads who refused to self-disclose birth mother's highest level of education at time of consent to long-term follow-up. All participants represented are unique with no duplicate participants
|
|
Count of newborns delivered by a mother with diabetes
|
72 number of infant participants
n=502 Participants
|
63 number of infant participants
n=469 Participants
|
135 number of infant participants
n=971 Participants
|
|
Count of newborns delivered by a mother with hypertension
|
89 number of infant participants
n=502 Participants
|
81 number of infant participants
n=469 Participants
|
170 number of infant participants
n=971 Participants
|
|
Count of newborns delivered by a mother with intrauterine inflammation/infection
|
54 infant participants
n=502 Participants
|
62 infant participants
n=469 Participants
|
116 infant participants
n=971 Participants
|
|
Count of newborns delivered by a mother with Group B Streptococcus
|
114 infant participants
n=501 Participants • One neonate-mother dyad in the umbilical cord clamping group has unknown screening status for Group B Streptococcus.
|
88 infant participants
n=469 Participants • One neonate-mother dyad in the umbilical cord clamping group has unknown screening status for Group B Streptococcus.
|
202 infant participants
n=970 Participants • One neonate-mother dyad in the umbilical cord clamping group has unknown screening status for Group B Streptococcus.
|
|
Duration of fetal membrane rupture prior to delivery
|
6 hours since amnionic sac rupture
n=502 Participants
|
5 hours since amnionic sac rupture
n=469 Participants
|
6 hours since amnionic sac rupture
n=971 Participants
|
|
Count of infants delivered by a mother administered narcotics/CNS depressants before delivery
|
51 infant participants
n=502 Participants
|
51 infant participants
n=469 Participants
|
102 infant participants
n=971 Participants
|
|
Count of infants delivered by cesarean section
|
246 infant participants
n=502 Participants
|
206 infant participants
n=469 Participants
|
452 infant participants
n=971 Participants
|
|
Count of infants born to a mother with a multiple birth pregnancy
|
13 infant participants
n=501 Participants • Reported for all infant participants with maternal multiple gestation status collected.
|
18 infant participants
n=467 Participants • Reported for all infant participants with maternal multiple gestation status collected.
|
31 infant participants
n=968 Participants • Reported for all infant participants with maternal multiple gestation status collected.
|
|
Count of newborns who were administered the correct randomized treatment at delivery
|
486 infant participants
n=502 Participants
|
465 infant participants
n=469 Participants
|
951 infant participants
n=971 Participants
|
PRIMARY outcome
Timeframe: 22 to 26 monthsPopulation: Children who had Ages and Stages, third edition. Questionnaire scores available at 2 years or died before age 2 years.
Neurodevelopmental Outcome at 2 Years of Age defined as overall and domain scores on the Ages and Stages, third edition. Questionnaire. Minimum score of 0 and maximum score of 60 per domain. Scores from 5 subscales are summed to obtain a total score. 5 domains assessed include communication, gross motor, fine motor, problem solving, personal social with a total minimum score of 0 and maximum score of 300. Higher scores indicate a lower risk of developmental delays or conditions
Outcome measures
| Measure |
Umbilical Cord Milking - Infant
n=502 Participants
At delivery, the umbilical cord is grasped, and blood is pushed toward the infant 4 times before the cord is clamped.
|
Early Cord Clamping - Infant
n=469 Participants
The umbilical cord is clamped as soon as possible and within 60 seconds of delivery.
|
|---|---|---|
|
Total and Domain Scores on the Ages and Stages Questionnaire, Third Edition.
Communication score
|
55 score on a scale
Interval 40.0 to 60.0
|
55 score on a scale
Interval 40.0 to 60.0
|
|
Total and Domain Scores on the Ages and Stages Questionnaire, Third Edition.
Gross motor score
|
60 score on a scale
Interval 50.0 to 60.0
|
60 score on a scale
Interval 50.0 to 60.0
|
|
Total and Domain Scores on the Ages and Stages Questionnaire, Third Edition.
Fine motor score
|
50 score on a scale
Interval 45.0 to 60.0
|
50 score on a scale
Interval 45.0 to 60.0
|
|
Total and Domain Scores on the Ages and Stages Questionnaire, Third Edition.
Problem solving score
|
50 score on a scale
Interval 40.0 to 55.0
|
50 score on a scale
Interval 40.0 to 60.0
|
|
Total and Domain Scores on the Ages and Stages Questionnaire, Third Edition.
Personal-social score
|
50 score on a scale
Interval 40.0 to 55.0
|
50 score on a scale
Interval 45.0 to 55.0
|
|
Total and Domain Scores on the Ages and Stages Questionnaire, Third Edition.
Total Ages and Stages Questionnaire score
|
255 score on a scale
Interval 225.0 to 280.0
|
255 score on a scale
Interval 230.0 to 280.0
|
SECONDARY outcome
Timeframe: 22-26 monthsPopulation: Child participants with a total score from the Modified Checklist for Autism in Toddlers or died before the age of 2 years.
Modified Checklist for Autism in Toddlers. Minimum score of 0 and maximum score of 20. Higher scores indicate higher risk for autism spectrum disorder. Total scores of 0 to 2 indicates a low risk of autism spectrum disorder. Total scores of 3 to 7 indicates a moderate risk of autism spectrum disorder. Total scores of 8 to 20 indicate high risk of autism spectrum disorder.
Outcome measures
| Measure |
Umbilical Cord Milking - Infant
n=486 Participants
At delivery, the umbilical cord is grasped, and blood is pushed toward the infant 4 times before the cord is clamped.
|
Early Cord Clamping - Infant
n=441 Participants
The umbilical cord is clamped as soon as possible and within 60 seconds of delivery.
|
|---|---|---|
|
Score Ranges on the Modified Checklist for Autism in Toddlers Questionnaire
Score 0-2
|
441 Participants
|
404 Participants
|
|
Score Ranges on the Modified Checklist for Autism in Toddlers Questionnaire
Score 3-7
|
34 Participants
|
31 Participants
|
|
Score Ranges on the Modified Checklist for Autism in Toddlers Questionnaire
Score 8-20
|
11 Participants
|
6 Participants
|
Adverse Events
Umbilical Cord Milking - Infant
Serious events: 0 serious events
Other events: 0 other events
Deaths: 2 deaths
Early Cord Clamping - Infant
Serious events: 0 serious events
Other events: 0 other events
Deaths: 5 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
Adverse event data not reported
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place