Trial Outcomes & Findings for Echocardiography Sub-Study of the Umbilical Cord Milking in Non-Vigorous Infants Trial (MINVI) (NCT NCT03798093)
NCT ID: NCT03798093
Last Updated: 2025-03-25
Results Overview
Left ventricular output measurements taken by cardiac ultrasound.
Recruitment status
COMPLETED
Study phase
NA
Target enrollment
227 participants
Primary outcome timeframe
12 ± 6 hours of life
Results posted on
2025-03-25
Participant Flow
Recruitment took place at two maternity hospitals involved in a cluster crossover randomization trial of non-vigorous infants at birth randomized to perform umbilical cord milking in the initial period (January 2019-January 2020) and early cord clamping in the crossover period (February 2020- March 2021). Participants were enrolled in this study upon parental consent for a neonatal echocardiogram in the first 12 hours of life. Participants enrolled in periods 1 \& 2 are unique participants.
The two hospitals who participated in the echocardiography sub-study and were both randomized to implement umbilical cord milking in the initial period (Period 1) and randomized to implement early cord clamping in the cross over period (Period 2).
Unit of analysis: Hospital
Participant milestones
| Measure |
Umbilical Cord Milking Then Early Cord Clamping Site Randomization - Neonate
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 - Neonate
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.
|
|---|---|---|
|
Initial Randomized Intervention
STARTED
|
106 2
|
0 0
|
|
Initial Randomized Intervention
COMPLETED
|
106 2
|
0 0
|
|
Initial Randomized Intervention
NOT COMPLETED
|
0 0
|
0 0
|
|
Crossover Randomized Intervention
STARTED
|
121 2
|
0 0
|
|
Crossover Randomized Intervention
COMPLETED
|
121 2
|
0 0
|
|
Crossover Randomized Intervention
NOT COMPLETED
|
0 0
|
0 0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Venous cord gas values reported for all neonates with results available for venous cord blood pH results.
Baseline characteristics by cohort
| Measure |
Umbilical Cord Milking - Neonate
n=106 Participants
At delivery, the umbilical cord is grasped, and blood is pushed toward the infant 4 times before the cord is clamped. Both participating hospitals were randomized to perform umbilical cord milking as the first intervention in the primary trial. Maternal data is presented for all participating mothers. Only unique participants are presented.
|
Early Cord Clamping - Neonate
n=121 Participants
The umbilical cord is clamped as early as possible and within 60 seconds of delivery. Both participating hospitals were randomized to perform early cord clamping as the second intervention in the primary trial. Maternal data is presented for all participating mothers. Only unique participants are presented.
|
Total
n=227 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
Neonatal Birth Gestational Age
|
40 weeks
n=106 Participants
|
39 weeks
n=121 Participants
|
39 weeks
n=227 Participants
|
|
Age, Continuous
Maternal Age
|
31 years
n=106 Participants
|
30 years
n=121 Participants
|
31 years
n=227 Participants
|
|
Sex: Female, Male
Neonatal Sex · Female
|
45 Participants
n=106 Participants
|
50 Participants
n=121 Participants
|
95 Participants
n=227 Participants
|
|
Sex: Female, Male
Neonatal Sex · Male
|
61 Participants
n=106 Participants
|
71 Participants
n=121 Participants
|
132 Participants
n=227 Participants
|
|
Ethnicity (NIH/OMB)
Neonatal Ethnicity · Hispanic or Latino
|
45 Participants
n=106 Participants
|
52 Participants
n=121 Participants
|
97 Participants
n=227 Participants
|
|
Ethnicity (NIH/OMB)
Neonatal Ethnicity · Not Hispanic or Latino
|
60 Participants
n=106 Participants
|
69 Participants
n=121 Participants
|
129 Participants
n=227 Participants
|
|
Ethnicity (NIH/OMB)
Neonatal Ethnicity · Unknown or Not Reported
|
1 Participants
n=106 Participants
|
0 Participants
n=121 Participants
|
1 Participants
n=227 Participants
|
|
Ethnicity (NIH/OMB)
Maternal Ethnicity · Hispanic or Latino
|
39 Participants
n=106 Participants
|
44 Participants
n=121 Participants
|
83 Participants
n=227 Participants
|
|
Ethnicity (NIH/OMB)
Maternal Ethnicity · Not Hispanic or Latino
|
66 Participants
n=106 Participants
|
77 Participants
n=121 Participants
|
143 Participants
n=227 Participants
|
|
Ethnicity (NIH/OMB)
Maternal Ethnicity · Unknown or Not Reported
|
1 Participants
n=106 Participants
|
0 Participants
n=121 Participants
|
1 Participants
n=227 Participants
|
|
Race (NIH/OMB)
Neonatal Race · American Indian or Alaska Native
|
0 Participants
n=106 Participants
|
0 Participants
n=121 Participants
|
0 Participants
n=227 Participants
|
|
Race (NIH/OMB)
Neonatal Race · Asian
|
5 Participants
n=106 Participants
|
7 Participants
n=121 Participants
|
12 Participants
n=227 Participants
|
|
Race (NIH/OMB)
Neonatal Race · Native Hawaiian or Other Pacific Islander
|
0 Participants
n=106 Participants
|
3 Participants
n=121 Participants
|
3 Participants
n=227 Participants
|
|
Race (NIH/OMB)
Neonatal Race · Black or African American
|
1 Participants
n=106 Participants
|
6 Participants
n=121 Participants
|
7 Participants
n=227 Participants
|
|
Race (NIH/OMB)
Neonatal Race · White
|
52 Participants
n=106 Participants
|
50 Participants
n=121 Participants
|
102 Participants
n=227 Participants
|
|
Race (NIH/OMB)
Neonatal Race · More than one race
|
28 Participants
n=106 Participants
|
34 Participants
n=121 Participants
|
62 Participants
n=227 Participants
|
|
Race (NIH/OMB)
Neonatal Race · Unknown or Not Reported
|
20 Participants
n=106 Participants
|
21 Participants
n=121 Participants
|
41 Participants
n=227 Participants
|
|
Race (NIH/OMB)
Maternal Race · American Indian or Alaska Native
|
1 Participants
n=106 Participants
|
0 Participants
n=121 Participants
|
1 Participants
n=227 Participants
|
|
Race (NIH/OMB)
Maternal Race · Asian
|
5 Participants
n=106 Participants
|
11 Participants
n=121 Participants
|
16 Participants
n=227 Participants
|
|
Race (NIH/OMB)
Maternal Race · Native Hawaiian or Other Pacific Islander
|
0 Participants
n=106 Participants
|
4 Participants
n=121 Participants
|
4 Participants
n=227 Participants
|
|
Race (NIH/OMB)
Maternal Race · Black or African American
|
2 Participants
n=106 Participants
|
8 Participants
n=121 Participants
|
10 Participants
n=227 Participants
|
|
Race (NIH/OMB)
Maternal Race · White
|
64 Participants
n=106 Participants
|
58 Participants
n=121 Participants
|
122 Participants
n=227 Participants
|
|
Race (NIH/OMB)
Maternal Race · More than one race
|
13 Participants
n=106 Participants
|
16 Participants
n=121 Participants
|
29 Participants
n=227 Participants
|
|
Race (NIH/OMB)
Maternal Race · Unknown or Not Reported
|
21 Participants
n=106 Participants
|
24 Participants
n=121 Participants
|
45 Participants
n=227 Participants
|
|
Maternal Diabetes
|
14 Participants
n=106 Participants
|
16 Participants
n=121 Participants
|
30 Participants
n=227 Participants
|
|
Maternal Hypertension or Pre-eclampsia
|
14 Participants
n=106 Participants
|
17 Participants
n=121 Participants
|
31 Participants
n=227 Participants
|
|
Maternal Intrauterine Inflammation/Infection
|
19 Participants
n=106 Participants
|
27 Participants
n=121 Participants
|
46 Participants
n=227 Participants
|
|
Maternal Group B Streptococcus Positive
|
19 Participants
n=106 Participants
|
18 Participants
n=121 Participants
|
37 Participants
n=227 Participants
|
|
Maternal General Anesthesia
|
2 Participants
n=106 Participants
|
7 Participants
n=121 Participants
|
9 Participants
n=227 Participants
|
|
Multiple Gestation
|
1 Participants
n=106 Participants
|
3 Participants
n=121 Participants
|
4 Participants
n=227 Participants
|
|
Delivery of the Neonate via Cesarean Section
|
49 Participants
n=106 Participants
|
53 Participants
n=121 Participants
|
102 Participants
n=227 Participants
|
|
Number of hours Membranes were Ruptured Before Delivery
|
7 hours
n=106 Participants
|
6 hours
n=121 Participants
|
6 hours
n=227 Participants
|
|
Neonatal Weight at Birth
|
3443 grams
STANDARD_DEVIATION 543 • n=106 Participants
|
3386 grams
STANDARD_DEVIATION 584 • n=121 Participants
|
3413 grams
STANDARD_DEVIATION 564 • n=227 Participants
|
|
Neonates with Poor Color at Birth
|
105 Participants
n=106 Participants
|
118 Participants
n=121 Participants
|
223 Participants
n=227 Participants
|
|
Neonates with Poor Tone at Birth
|
104 Participants
n=106 Participants
|
117 Participants
n=121 Participants
|
221 Participants
n=227 Participants
|
|
Neonates with Poor Respiratory Effort at Birth
|
103 Participants
n=106 Participants
|
120 Participants
n=121 Participants
|
223 Participants
n=227 Participants
|
|
Neonates Treated with Therapeutic Hypothermia
|
5 Participants
n=106 Participants
|
17 Participants
n=121 Participants
|
22 Participants
n=227 Participants
|
|
Neonates Treated with Cardiac Inotropes
|
3 Participants
n=106 Participants
|
5 Participants
n=121 Participants
|
8 Participants
n=227 Participants
|
|
Neonates Treated with Volume Expanders
|
20 Participants
n=106 Participants
|
30 Participants
n=121 Participants
|
50 Participants
n=227 Participants
|
|
Time of Echocardiogram Exam from Neonate's Time of Birth
|
13 hours
n=106 Participants
|
15 hours
n=121 Participants
|
15 hours
n=227 Participants
|
|
Venous Cord Blood Gas pH
|
7.266 no units
STANDARD_DEVIATION .095 • n=84 Participants • Venous cord gas values reported for all neonates with results available for venous cord blood pH results.
|
7.234 no units
STANDARD_DEVIATION .122 • n=96 Participants • Venous cord gas values reported for all neonates with results available for venous cord blood pH results.
|
7.249 no units
STANDARD_DEVIATION .111 • n=180 Participants • Venous cord gas values reported for all neonates with results available for venous cord blood pH results.
|
|
Venous Cord Blood Gas Base Excess
|
-6.60 mEq/L
STANDARD_DEVIATION 3.12 • n=84 Participants • Venous cord gas values reported for all neonates with results available for venous cord blood base excess results.
|
-7.31 mEq/L
STANDARD_DEVIATION 4.22 • n=96 Participants • Venous cord gas values reported for all neonates with results available for venous cord blood base excess results.
|
-6.98 mEq/L
STANDARD_DEVIATION 3.75 • n=180 Participants • Venous cord gas values reported for all neonates with results available for venous cord blood base excess results.
|
|
Arterial Cord Blood Gas pH
|
7.173 no units
STANDARD_DEVIATION .104 • n=70 Participants • Arterial cord gas values reported for all neonates with results available arterial cord blood pH results.
|
7.125 no units
STANDARD_DEVIATION .140 • n=80 Participants • Arterial cord gas values reported for all neonates with results available arterial cord blood pH results.
|
7.148 no units
STANDARD_DEVIATION .127 • n=150 Participants • Arterial cord gas values reported for all neonates with results available arterial cord blood pH results.
|
|
Arterial Cord Blood Gas Base Excess
|
-8.74 mEq/L
STANDARD_DEVIATION 3.96 • n=70 Participants • Venous cord gas values reported for all neonates with results available for arterial cord blood base excess results.
|
-9.77 mEq/L
STANDARD_DEVIATION 5.11 • n=80 Participants • Venous cord gas values reported for all neonates with results available for arterial cord blood base excess results.
|
-9.29 mEq/L
STANDARD_DEVIATION 4.63 • n=150 Participants • Venous cord gas values reported for all neonates with results available for arterial cord blood base excess results.
|
PRIMARY outcome
Timeframe: 12 ± 6 hours of lifeLeft ventricular output measurements taken by cardiac ultrasound.
Outcome measures
| Measure |
Umbilical Cord Milking - Neonate
n=106 Participants
At delivery, the umbilical cord is grasped, and blood is pushed toward the infant 4 times before the cord is clamped. Both participating hospitals were randomized to perform umbilical cord milking as the first intervention in the primary trial.
|
Early Cord Clamping - Neonate
n=121 Participants
The umbilical cord is clamped as early as possible and within 60 seconds of delivery. Both participating hospitals were randomized to perform early cord clamping as the second intervention in the primary trial.
|
|---|---|---|
|
Left Ventricular Output
|
225 mL/kg/min
Standard Deviation 64
|
187 mL/kg/min
Standard Deviation 52
|
SECONDARY outcome
Timeframe: 12 ± 6 hours of lifeObtained from the modified short axis view of the neonatal echocardiogram performed at 12 hours of life ± 6 hours.
Outcome measures
| Measure |
Umbilical Cord Milking - Neonate
n=106 Participants
At delivery, the umbilical cord is grasped, and blood is pushed toward the infant 4 times before the cord is clamped. Both participating hospitals were randomized to perform umbilical cord milking as the first intervention in the primary trial.
|
Early Cord Clamping - Neonate
n=121 Participants
The umbilical cord is clamped as early as possible and within 60 seconds of delivery. Both participating hospitals were randomized to perform early cord clamping as the second intervention in the primary trial.
|
|---|---|---|
|
Neonatal Right Ventricular Output
|
284 mL/kg/min
Standard Deviation 88
|
222 mL/kg/min
Standard Deviation 95
|
SECONDARY outcome
Timeframe: 12 ± 6 hours of lifesuperior vena cava (SVC) flow (Diameter obtained from the infraclavicular view (hybrid view) and doppler assessment from the subcostal view of the neonatal echocardiogram exam performed at 12 hours of life ± 6 hours.
Outcome measures
| Measure |
Umbilical Cord Milking - Neonate
n=106 Participants
At delivery, the umbilical cord is grasped, and blood is pushed toward the infant 4 times before the cord is clamped. Both participating hospitals were randomized to perform umbilical cord milking as the first intervention in the primary trial.
|
Early Cord Clamping - Neonate
n=121 Participants
The umbilical cord is clamped as early as possible and within 60 seconds of delivery. Both participating hospitals were randomized to perform early cord clamping as the second intervention in the primary trial.
|
|---|---|---|
|
Neonatal Superior Vena Cava Flow
|
100 mL/kg/min
Standard Deviation 36
|
86 mL/kg/min
Standard Deviation 40
|
SECONDARY outcome
Timeframe: 12 ± 6 hours of lifeThis measurement reflects the deformation (strain) of the heart muscle during systole (the phase of the heartbeat when the heart contracts) relative to its original length. More negative values indicate better myocardial function while values closer to 0 suggest impaired myocardial function.
Outcome measures
| Measure |
Umbilical Cord Milking - Neonate
n=106 Participants
At delivery, the umbilical cord is grasped, and blood is pushed toward the infant 4 times before the cord is clamped. Both participating hospitals were randomized to perform umbilical cord milking as the first intervention in the primary trial.
|
Early Cord Clamping - Neonate
n=121 Participants
The umbilical cord is clamped as early as possible and within 60 seconds of delivery. Both participating hospitals were randomized to perform early cord clamping as the second intervention in the primary trial.
|
|---|---|---|
|
Neonatal Peak Systolic Strain
|
-17 percent
Standard Deviation 3
|
-22 percent
Standard Deviation 3
|
SECONDARY outcome
Timeframe: 12 ± 6 hours of lifeMeasure of left and right ventricular peak systolic tissue doppler velocity on neonatal echocardiogram performed at 12 hours of life ± 6 hours.
Outcome measures
| Measure |
Umbilical Cord Milking - Neonate
n=106 Participants
At delivery, the umbilical cord is grasped, and blood is pushed toward the infant 4 times before the cord is clamped. Both participating hospitals were randomized to perform umbilical cord milking as the first intervention in the primary trial.
|
Early Cord Clamping - Neonate
n=121 Participants
The umbilical cord is clamped as early as possible and within 60 seconds of delivery. Both participating hospitals were randomized to perform early cord clamping as the second intervention in the primary trial.
|
|---|---|---|
|
Neonatal Peak Systolic Velocity
|
.06 meters/second
Standard Deviation .02
|
.07 meters/second
Standard Deviation .02
|
OTHER_PRE_SPECIFIED outcome
Timeframe: 12 ± 6 hours of lifeAssessment of tricuspid annular plane systolic excursion in the neonate by echocardiogram performed at 12 hours of life ± 6 hours
Outcome measures
| Measure |
Umbilical Cord Milking - Neonate
n=106 Participants
At delivery, the umbilical cord is grasped, and blood is pushed toward the infant 4 times before the cord is clamped. Both participating hospitals were randomized to perform umbilical cord milking as the first intervention in the primary trial.
|
Early Cord Clamping - Neonate
n=121 Participants
The umbilical cord is clamped as early as possible and within 60 seconds of delivery. Both participating hospitals were randomized to perform early cord clamping as the second intervention in the primary trial.
|
|---|---|---|
|
Tricuspid Annular Plane Systolic Excursion Measurement in Neonate
|
9.04 mm
Standard Deviation 2.2
|
9.65 mm
Standard Deviation 1.7
|
OTHER_PRE_SPECIFIED outcome
Timeframe: 12 ± 6 hours of lifeDiagnosis of patent ductus arteriosus in neonate by echocardiogram with diameter measurement and direction of flow.
Outcome measures
| Measure |
Umbilical Cord Milking - Neonate
n=106 Participants
At delivery, the umbilical cord is grasped, and blood is pushed toward the infant 4 times before the cord is clamped. Both participating hospitals were randomized to perform umbilical cord milking as the first intervention in the primary trial.
|
Early Cord Clamping - Neonate
n=121 Participants
The umbilical cord is clamped as early as possible and within 60 seconds of delivery. Both participating hospitals were randomized to perform early cord clamping as the second intervention in the primary trial.
|
|---|---|---|
|
Number of Neonates With a Patent Ductus Arteriosus
|
88 Participants
|
110 Participants
|
OTHER_PRE_SPECIFIED outcome
Timeframe: 12 ± 6 hours of lifePopulation: Direction of shunt assessed only for neonates with a patent ductus arteriosus present.
Direction of ductal shunt in neonate assessed by echocardiogram which was performed at 12 hours of life ± 6 hours.
Outcome measures
| Measure |
Umbilical Cord Milking - Neonate
n=87 Participants
At delivery, the umbilical cord is grasped, and blood is pushed toward the infant 4 times before the cord is clamped. Both participating hospitals were randomized to perform umbilical cord milking as the first intervention in the primary trial.
|
Early Cord Clamping - Neonate
n=108 Participants
The umbilical cord is clamped as early as possible and within 60 seconds of delivery. Both participating hospitals were randomized to perform early cord clamping as the second intervention in the primary trial.
|
|---|---|---|
|
Neonatal Direction of Ductal Shunt
All left to right
|
59 Participants
|
80 Participants
|
|
Neonatal Direction of Ductal Shunt
All right to left
|
0 Participants
|
1 Participants
|
|
Neonatal Direction of Ductal Shunt
Bidirectional
|
28 Participants
|
27 Participants
|
POST_HOC outcome
Timeframe: 12 ± 6 hours of lifeDiameter of neonatal ductus arteriosus assessed by echocardiogram which was performed at 12 hours of life ± 6 hours
Outcome measures
| Measure |
Umbilical Cord Milking - Neonate
n=106 Participants
At delivery, the umbilical cord is grasped, and blood is pushed toward the infant 4 times before the cord is clamped. Both participating hospitals were randomized to perform umbilical cord milking as the first intervention in the primary trial.
|
Early Cord Clamping - Neonate
n=121 Participants
The umbilical cord is clamped as early as possible and within 60 seconds of delivery. Both participating hospitals were randomized to perform early cord clamping as the second intervention in the primary trial.
|
|---|---|---|
|
Diameter of Neonatal Ductus Arteriosus
|
0.19 cm
Standard Deviation 0.10
|
0.20 cm
Standard Deviation 0.10
|
POST_HOC outcome
Timeframe: 12 ± 6 hours of lifeNeonatal peak pulmonary artery pressure as measured by echocardiogram at 12 hours of life ± 6 hours.
Outcome measures
| Measure |
Umbilical Cord Milking - Neonate
n=106 Participants
At delivery, the umbilical cord is grasped, and blood is pushed toward the infant 4 times before the cord is clamped. Both participating hospitals were randomized to perform umbilical cord milking as the first intervention in the primary trial.
|
Early Cord Clamping - Neonate
n=121 Participants
The umbilical cord is clamped as early as possible and within 60 seconds of delivery. Both participating hospitals were randomized to perform early cord clamping as the second intervention in the primary trial.
|
|---|---|---|
|
Neonatal Peak Pulmonary Artery Pressure
|
27 mm Hg
Standard Deviation 15
|
27 mm Hg
Standard Deviation 14
|
POST_HOC outcome
Timeframe: 12 ± 6 hours of lifeblood pressure measurement obtained at the time of cardiac ultrasound examination
Outcome measures
| Measure |
Umbilical Cord Milking - Neonate
n=106 Participants
At delivery, the umbilical cord is grasped, and blood is pushed toward the infant 4 times before the cord is clamped. Both participating hospitals were randomized to perform umbilical cord milking as the first intervention in the primary trial.
|
Early Cord Clamping - Neonate
n=121 Participants
The umbilical cord is clamped as early as possible and within 60 seconds of delivery. Both participating hospitals were randomized to perform early cord clamping as the second intervention in the primary trial.
|
|---|---|---|
|
Mean Neonatal Blood Pressure at Time of Echocardiogram
|
45 g/dL
Standard Deviation 7
|
46 g/dL
Standard Deviation 7
|
POST_HOC outcome
Timeframe: 12 to 48 hours of lifeSingle neonatal hemoglobin measurement obtained between 12 and 48 hours of life either as part of standard care or obtained with parental written consent
Outcome measures
| Measure |
Umbilical Cord Milking - Neonate
n=106 Participants
At delivery, the umbilical cord is grasped, and blood is pushed toward the infant 4 times before the cord is clamped. Both participating hospitals were randomized to perform umbilical cord milking as the first intervention in the primary trial.
|
Early Cord Clamping - Neonate
n=121 Participants
The umbilical cord is clamped as early as possible and within 60 seconds of delivery. Both participating hospitals were randomized to perform early cord clamping as the second intervention in the primary trial.
|
|---|---|---|
|
Median Neonatal Hemoglobin
|
17.6 g/dL
Standard Deviation 2.1
|
16.5 g/dL
Standard Deviation 2.4
|
Adverse Events
Umbilical Cord Milking - Neonate
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Early Cord Clamping - Neonate
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 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