Birth Asphyxia
Conditions
Keywords
Umbilical Cord Milking, Immediate Cord Clamping, Resuscitation
Brief summary
Non-vigorous infants enrolled in the MINVI trial will be approached for consent for ongoing data collection. As part of the data collection, an optional echocardiogram will be performed if the parent consents.
Detailed description
Non-vigorous infants enrolled in the MINVI trial will be approached for consent for ongoing data collection. As part of the data collection, an optional echocardiogram will be performed if the parent consents. The consent will have a check box to indicate if they consent to the additional test. Echocardiographic measurements will be performed on all infants at 12 hours +/- 6 hours of age by our research sonographers who are blinded to infant randomization. Measurements will be taken according to a standard operating procedure to assess systemic blood flow, by superior vena cava (SVC) flow (ml/kg/min), right ventricular output (ml/kg/min), left ventricular output (LVO) (ml/kg/min), measures of left and right ventricular tissue Doppler and strain imaging. These measurements will be performed offline at a later time. Data will be entered into REDCap. If any structural abnormalities are found, the attending pediatrician will be notified of the abnormal echocardiogram. The consent will clearly state that this echo is not for diagnostic purposes. Any additional studies including an official complete echocardiogram and or cardiology consultation will be left to the discretion of the attending pediatrician, as he/she deems necessary
Interventions
PROCEDUREUmbilical Cord Milking
At delivery, the umbilical cord is grasped, and blood is pushed toward the infant 4 times before the cord is clamped. This procedure infuses a placental transfusion of blood into the infant and can be done in 15-20 seconds.
PROCEDUREEarly Cord Clamping
The umbilical cord is clamped within 60 seconds of delivery.
Sponsors
Sharp Mary Birch Hospital for Women & Newborns
Sharp HealthCare
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
DIAGNOSTIC
Masking
SINGLE (Outcomes Assessor)
Masking description
Cardiac research sonographers that obtained study measurements were blinded to the study intervention
Intervention model description
Cluster Randomized Crossover
Eligibility
Sex/Gender
ALL
Age
35 Weeks to 42 Weeks
Healthy volunteers
No
Inclusion criteria
• Non-vigorous newborns born between 35-42 weeks gestation.
Exclusion criteria
* Known major congenital or chromosomal anomalies of newborn. * Known cardiac defects other than small atrial septal defect (ASD), ventricular septal defect (VSD) and patent ductus arteriosus (PDA). * Complete placental abruption/cutting through the placenta at time of delivery. * Monochorionic multiples * Cord anomaly (i.e. cord avulsion or true knot) * Presence of non-reducible nuchal cord * Perinatal providers unaware of the protocol * Incomplete delivery data * Infants born in extremis, for whom additional treatment will not be offered.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Left Ventricular Output | 12 ± 6 hours of life | Left ventricular output measurements taken by cardiac ultrasound. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Neonatal Superior Vena Cava Flow | 12 ± 6 hours of life | superior 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. |
| Neonatal Right Ventricular Output | 12 ± 6 hours of life | Obtained from the modified short axis view of the neonatal echocardiogram performed at 12 hours of life ± 6 hours. |
| Neonatal Peak Systolic Strain | 12 ± 6 hours of life | This 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. |
| Neonatal Peak Systolic Velocity | 12 ± 6 hours of life | Measure of left and right ventricular peak systolic tissue doppler velocity on neonatal echocardiogram performed at 12 hours of life ± 6 hours. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Neonatal Direction of Ductal Shunt | 12 ± 6 hours of life | Direction of ductal shunt in neonate assessed by echocardiogram which was performed at 12 hours of life ± 6 hours. |
| Number of Neonates With a Patent Ductus Arteriosus | 12 ± 6 hours of life | Diagnosis of patent ductus arteriosus in neonate by echocardiogram with diameter measurement and direction of flow. |
| Tricuspid Annular Plane Systolic Excursion Measurement in Neonate | 12 ± 6 hours of life | Assessment of tricuspid annular plane systolic excursion in the neonate by echocardiogram performed at 12 hours of life ± 6 hours |
Countries
United States
Participant flow
Recruitment details
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.
Pre-assignment details
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).
Participants by arm
| Arm | Count |
|---|---|
| Umbilical Cord Milking - Neonate 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. | 106 |
| Early Cord Clamping - Neonate 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. | 121 |
| Total | 227 |
Baseline characteristics
| Characteristic | Total | Umbilical Cord Milking - Neonate | Early Cord Clamping - Neonate |
|---|---|---|---|
| Age, Continuous Maternal Age | 31 years | 31 years | 30 years |
| Age, Continuous Neonatal Birth Gestational Age | 39 weeks | 40 weeks | 39 weeks |
| Arterial Cord Blood Gas Base Excess | -9.29 mEq/L STANDARD_DEVIATION 4.63 | -8.74 mEq/L STANDARD_DEVIATION 3.96 | -9.77 mEq/L STANDARD_DEVIATION 5.11 |
| Arterial Cord Blood Gas pH | 7.148 no units STANDARD_DEVIATION 0.127 | 7.173 no units STANDARD_DEVIATION 0.104 | 7.125 no units STANDARD_DEVIATION 0.14 |
| Delivery of the Neonate via Cesarean Section | 102 Participants | 49 Participants | 53 Participants |
| Ethnicity (NIH/OMB) Maternal Ethnicity Hispanic or Latino | 83 Participants | 39 Participants | 44 Participants |
| Ethnicity (NIH/OMB) Maternal Ethnicity Not Hispanic or Latino | 143 Participants | 66 Participants | 77 Participants |
| Ethnicity (NIH/OMB) Maternal Ethnicity Unknown or Not Reported | 1 Participants | 1 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Neonatal Ethnicity Hispanic or Latino | 97 Participants | 45 Participants | 52 Participants |
| Ethnicity (NIH/OMB) Neonatal Ethnicity Not Hispanic or Latino | 129 Participants | 60 Participants | 69 Participants |
| Ethnicity (NIH/OMB) Neonatal Ethnicity Unknown or Not Reported | 1 Participants | 1 Participants | 0 Participants |
| Maternal Diabetes | 30 Participants | 14 Participants | 16 Participants |
| Maternal General Anesthesia | 9 Participants | 2 Participants | 7 Participants |
| Maternal Group B Streptococcus Positive | 37 Participants | 19 Participants | 18 Participants |
| Maternal Hypertension or Pre-eclampsia | 31 Participants | 14 Participants | 17 Participants |
| Maternal Intrauterine Inflammation/Infection | 46 Participants | 19 Participants | 27 Participants |
| Multiple Gestation | 4 Participants | 1 Participants | 3 Participants |
| Neonatal Weight at Birth | 3413 grams STANDARD_DEVIATION 564 | 3443 grams STANDARD_DEVIATION 543 | 3386 grams STANDARD_DEVIATION 584 |
| Neonates Treated with Cardiac Inotropes | 8 Participants | 3 Participants | 5 Participants |
| Neonates Treated with Therapeutic Hypothermia | 22 Participants | 5 Participants | 17 Participants |
| Neonates Treated with Volume Expanders | 50 Participants | 20 Participants | 30 Participants |
| Neonates with Poor Color at Birth | 223 Participants | 105 Participants | 118 Participants |
| Neonates with Poor Respiratory Effort at Birth | 223 Participants | 103 Participants | 120 Participants |
| Neonates with Poor Tone at Birth | 221 Participants | 104 Participants | 117 Participants |
| Number of hours Membranes were Ruptured Before Delivery | 6 hours | 7 hours | 6 hours |
| Race (NIH/OMB) Maternal Race American Indian or Alaska Native | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Maternal Race Asian | 16 Participants | 5 Participants | 11 Participants |
| Race (NIH/OMB) Maternal Race Black or African American | 10 Participants | 2 Participants | 8 Participants |
| Race (NIH/OMB) Maternal Race More than one race | 29 Participants | 13 Participants | 16 Participants |
| Race (NIH/OMB) Maternal Race Native Hawaiian or Other Pacific Islander | 4 Participants | 0 Participants | 4 Participants |
| Race (NIH/OMB) Maternal Race Unknown or Not Reported | 45 Participants | 21 Participants | 24 Participants |
| Race (NIH/OMB) Maternal Race White | 122 Participants | 64 Participants | 58 Participants |
| Race (NIH/OMB) Neonatal Race American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Neonatal Race Asian | 12 Participants | 5 Participants | 7 Participants |
| Race (NIH/OMB) Neonatal Race Black or African American | 7 Participants | 1 Participants | 6 Participants |
| Race (NIH/OMB) Neonatal Race More than one race | 62 Participants | 28 Participants | 34 Participants |
| Race (NIH/OMB) Neonatal Race Native Hawaiian or Other Pacific Islander | 3 Participants | 0 Participants | 3 Participants |
| Race (NIH/OMB) Neonatal Race Unknown or Not Reported | 41 Participants | 20 Participants | 21 Participants |
| Race (NIH/OMB) Neonatal Race White | 102 Participants | 52 Participants | 50 Participants |
| Sex: Female, Male Neonatal Sex Female | 95 Participants | 45 Participants | 50 Participants |
| Sex: Female, Male Neonatal Sex Male | 132 Participants | 61 Participants | 71 Participants |
| Time of Echocardiogram Exam from Neonate's Time of Birth | 15 hours | 13 hours | 15 hours |
| Venous Cord Blood Gas Base Excess | -6.98 mEq/L STANDARD_DEVIATION 3.75 | -6.60 mEq/L STANDARD_DEVIATION 3.12 | -7.31 mEq/L STANDARD_DEVIATION 4.22 |
| Venous Cord Blood Gas pH | 7.249 no units STANDARD_DEVIATION 0.111 | 7.266 no units STANDARD_DEVIATION 0.095 | 7.234 no units STANDARD_DEVIATION 0.122 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 106 | 0 / 121 |
| other Total, other adverse events | 0 / 106 | 0 / 121 |
| serious Total, serious adverse events | 0 / 106 | 0 / 121 |
Outcome results
Primary
Left Ventricular Output
Left ventricular output measurements taken by cardiac ultrasound.
Time frame: 12 ± 6 hours of life
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Umbilical Cord Milking - Neonate | Left Ventricular Output | 225 mL/kg/min | Standard Deviation 64 |
| Early Cord Clamping - Neonate | Left Ventricular Output | 187 mL/kg/min | Standard Deviation 52 |
p-value: 0.0895% CI: [-29.3, 1.7]Regression, Linear
Secondary
Neonatal Peak Systolic Strain
This 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.
Time frame: 12 ± 6 hours of life
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Umbilical Cord Milking - Neonate | Neonatal Peak Systolic Strain | -17 percent | Standard Deviation 3 |
| Early Cord Clamping - Neonate | Neonatal Peak Systolic Strain | -22 percent | Standard Deviation 3 |
Secondary
Neonatal Peak Systolic Velocity
Measure of left and right ventricular peak systolic tissue doppler velocity on neonatal echocardiogram performed at 12 hours of life ± 6 hours.
Time frame: 12 ± 6 hours of life
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Umbilical Cord Milking - Neonate | Neonatal Peak Systolic Velocity | .06 meters/second | Standard Deviation 0.02 |
| Early Cord Clamping - Neonate | Neonatal Peak Systolic Velocity | .07 meters/second | Standard Deviation 0.02 |
Secondary
Neonatal Right Ventricular Output
Obtained from the modified short axis view of the neonatal echocardiogram performed at 12 hours of life ± 6 hours.
Time frame: 12 ± 6 hours of life
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Umbilical Cord Milking - Neonate | Neonatal Right Ventricular Output | 284 mL/kg/min | Standard Deviation 88 |
| Early Cord Clamping - Neonate | Neonatal Right Ventricular Output | 222 mL/kg/min | Standard Deviation 95 |
Secondary
Neonatal Superior Vena Cava Flow
superior 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.
Time frame: 12 ± 6 hours of life
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Umbilical Cord Milking - Neonate | Neonatal Superior Vena Cava Flow | 100 mL/kg/min | Standard Deviation 36 |
| Early Cord Clamping - Neonate | Neonatal Superior Vena Cava Flow | 86 mL/kg/min | Standard Deviation 40 |
Post Hoc
Diameter of Neonatal Ductus Arteriosus
Diameter of neonatal ductus arteriosus assessed by echocardiogram which was performed at 12 hours of life ± 6 hours
Time frame: 12 ± 6 hours of life
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Umbilical Cord Milking - Neonate | Diameter of Neonatal Ductus Arteriosus | 0.19 cm | Standard Deviation 0.1 |
| Early Cord Clamping - Neonate | Diameter of Neonatal Ductus Arteriosus | 0.20 cm | Standard Deviation 0.1 |
Post Hoc
Mean Neonatal Blood Pressure at Time of Echocardiogram
blood pressure measurement obtained at the time of cardiac ultrasound examination
Time frame: 12 ± 6 hours of life
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Umbilical Cord Milking - Neonate | Mean Neonatal Blood Pressure at Time of Echocardiogram | 45 g/dL | Standard Deviation 7 |
| Early Cord Clamping - Neonate | Mean Neonatal Blood Pressure at Time of Echocardiogram | 46 g/dL | Standard Deviation 7 |
Post Hoc
Median Neonatal Hemoglobin
Single neonatal hemoglobin measurement obtained between 12 and 48 hours of life either as part of standard care or obtained with parental written consent
Time frame: 12 to 48 hours of life
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Umbilical Cord Milking - Neonate | Median Neonatal Hemoglobin | 17.6 g/dL | Standard Deviation 2.1 |
| Early Cord Clamping - Neonate | Median Neonatal Hemoglobin | 16.5 g/dL | Standard Deviation 2.4 |
Other Pre-specified
Neonatal Direction of Ductal Shunt
Direction of ductal shunt in neonate assessed by echocardiogram which was performed at 12 hours of life ± 6 hours.
Time frame: 12 ± 6 hours of life
Population: Direction of shunt assessed only for neonates with a patent ductus arteriosus present.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Umbilical Cord Milking - Neonate | Neonatal Direction of Ductal Shunt | All left to right | 59 Participants |
| Umbilical Cord Milking - Neonate | Neonatal Direction of Ductal Shunt | All right to left | 0 Participants |
| Umbilical Cord Milking - Neonate | Neonatal Direction of Ductal Shunt | Bidirectional | 28 Participants |
| Early Cord Clamping - Neonate | Neonatal Direction of Ductal Shunt | All left to right | 80 Participants |
| Early Cord Clamping - Neonate | Neonatal Direction of Ductal Shunt | All right to left | 1 Participants |
| Early Cord Clamping - Neonate | Neonatal Direction of Ductal Shunt | Bidirectional | 27 Participants |
Post Hoc
Neonatal Peak Pulmonary Artery Pressure
Neonatal peak pulmonary artery pressure as measured by echocardiogram at 12 hours of life ± 6 hours.
Time frame: 12 ± 6 hours of life
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Umbilical Cord Milking - Neonate | Neonatal Peak Pulmonary Artery Pressure | 27 mm Hg | Standard Deviation 15 |
| Early Cord Clamping - Neonate | Neonatal Peak Pulmonary Artery Pressure | 27 mm Hg | Standard Deviation 14 |
Other Pre-specified
Number of Neonates With a Patent Ductus Arteriosus
Diagnosis of patent ductus arteriosus in neonate by echocardiogram with diameter measurement and direction of flow.
Time frame: 12 ± 6 hours of life
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Umbilical Cord Milking - Neonate | Number of Neonates With a Patent Ductus Arteriosus | 88 Participants |
| Early Cord Clamping - Neonate | Number of Neonates With a Patent Ductus Arteriosus | 110 Participants |
Other Pre-specified
Tricuspid Annular Plane Systolic Excursion Measurement in Neonate
Assessment of tricuspid annular plane systolic excursion in the neonate by echocardiogram performed at 12 hours of life ± 6 hours
Time frame: 12 ± 6 hours of life
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Umbilical Cord Milking - Neonate | Tricuspid Annular Plane Systolic Excursion Measurement in Neonate | 9.04 mm | Standard Deviation 2.2 |
| Early Cord Clamping - Neonate | Tricuspid Annular Plane Systolic Excursion Measurement in Neonate | 9.65 mm | Standard Deviation 1.7 |