Neurodevelopmental Abnormality
Conditions
Keywords
Neurodevelopmental outcomes, Disability, Umbilical cord milking, Early cord clamping, Non-vigorous infants, Term infants, Near-Term infants, Developmental screening, Early childhood
Brief summary
A sub-study to evaluate longer-term developmental outcomes in non-vigorous term and near-term newborns who receive umbilical cord milking in comparison to those who undergo early cord clamping at delivery.
Detailed description
This sub-study investigates the potential difference in neurodevelopmental outcomes during early childhood between newborns who undergo umbilical cord milking and those who experience early cord clamping at birth. The developmental progress of participants is evaluated using the Ages and Stages Questionnaire-3 which measures five developmental areas: communication, problem-solving, fine motor skills, gross motor skills, and personal-social behavior. Additionally, the Modified Checklist for Autism in Toddlers is employed as a secondary assessment. The recruitment of participants is conducted through the primary study Umbilical Cord Milking in Nonvigorous Infants trial (NCT03631940) with the method of umbilical cord management for each newborn being dictated by the randomized treatment allocation of the primary study.
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.
PROCEDUREEarly Cord Clamping
The umbilical cord is clamped as soon as possible and within 60 seconds of delivery.
Sponsors
Sharp HealthCare
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
DIAGNOSTIC
Masking
SINGLE (Outcomes Assessor)
Masking description
Neurodevelopmental providers will be blinded to the randomization of the toddler during the examination.
Intervention model description
Randomization assignment was determined at time of enrollment in the primary study (Umbilical Cord Milking in Nonvigorous Infants Study NCT:03631940). The primary study model was a cluster randomized crossover trial.
Eligibility
Sex/Gender
ALL
Age
22 Months to 26 Months
Healthy volunteers
No
Inclusion criteria
* Enrolled in the primary trial NCT:03631940 and parental written consent to participate in developmental follow-up through 2 years of age was obtained. * Enrolled in the primary trial NCT:03631940 and did not survive to 2 years.
Exclusion criteria
\- Enrolled in the primary trial NCT:03631940 but parent/guardian declined consent to developmental follow-up participation.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Total and Domain Scores on the Ages and Stages Questionnaire, Third Edition. | 22 to 26 months | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Score Ranges on the Modified Checklist for Autism in Toddlers Questionnaire | 22-26 months | 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. |
Countries
Canada, Poland, United States
Participant flow
Recruitment details
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.
Pre-assignment details
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.
Participants by arm
| Arm | Count |
|---|---|
| Umbilical Cord Milking Treatment Only- Infant & Maternal Baseline Measures 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. | 502 |
| Early Cord Clamping Treatment Only- Infant & Maternal Baseline Measures 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. | 469 |
| Total | 971 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Crossover Randomized Intervention | Lost to Follow-up | 75 | 45 |
| Crossover Randomized Intervention | Withdrawal by Subject | 0 | 5 |
| First Randomized Intervention | Lost to Follow-up | 51 | 54 |
| First Randomized Intervention | Withdrawal by Subject | 3 | 3 |
Baseline characteristics
| Characteristic | Umbilical Cord Milking Treatment Only- Infant & Maternal Baseline Measures | Total | Early Cord Clamping Treatment Only- Infant & Maternal Baseline Measures |
|---|---|---|---|
| Age, Continuous Infant's gestational age at birth | 39 weeks | 39 weeks | 39 weeks |
| Age, Customized Maternal age at delivery | 31 years, maternal age at delivery STANDARD_DEVIATION 5 | 31 years, maternal age at delivery STANDARD_DEVIATION 6 | 31 years, maternal age at delivery STANDARD_DEVIATION 6 |
| Count of infants born to a mother with a multiple birth pregnancy | 13 infant participants | 31 infant participants | 18 infant participants |
| Count of infants delivered by a mother administered narcotics/CNS depressants before delivery | 51 infant participants | 102 infant participants | 51 infant participants |
| Count of infants delivered by cesarean section | 246 infant participants | 452 infant participants | 206 infant participants |
| Count of newborns delivered by a mother with diabetes | 72 number of infant participants | 135 number of infant participants | 63 number of infant participants |
| Count of newborns delivered by a mother with Group B Streptococcus | 114 infant participants | 202 infant participants | 88 infant participants |
| Count of newborns delivered by a mother with hypertension | 89 number of infant participants | 170 number of infant participants | 81 number of infant participants |
| Count of newborns delivered by a mother with intrauterine inflammation/infection | 54 infant participants | 116 infant participants | 62 infant participants |
| Count of newborns who were administered the correct randomized treatment at delivery | 486 infant participants | 951 infant participants | 465 infant participants |
| Duration of fetal membrane rupture prior to delivery | 6 hours since amnionic sac rupture | 6 hours since amnionic sac rupture | 5 hours since amnionic sac rupture |
| Ethnicity (NIH/OMB) Infant Ethnicity Hispanic or Latino | 100 Participants | 202 Participants | 102 Participants |
| Ethnicity (NIH/OMB) Infant Ethnicity Not Hispanic or Latino | 375 Participants | 677 Participants | 302 Participants |
| Ethnicity (NIH/OMB) Infant Ethnicity Unknown or Not Reported | 27 Participants | 92 Participants | 65 Participants |
| Ethnicity (NIH/OMB) Maternal Ethnicity Hispanic or Latino | 86 Participants | 174 Participants | 88 Participants |
| Ethnicity (NIH/OMB) Maternal Ethnicity Not Hispanic or Latino | 393 Participants | 714 Participants | 321 Participants |
| Ethnicity (NIH/OMB) Maternal Ethnicity Unknown or Not Reported | 23 Participants | 83 Participants | 60 Participants |
| Number of neonates born to a mother with at least some college education | 349 infant participants | 670 infant participants | 321 infant participants |
| Race (NIH/OMB) Infant Race American Indian or Alaska Native | 5 Participants | 7 Participants | 2 Participants |
| Race (NIH/OMB) Infant Race Asian | 31 Participants | 68 Participants | 37 Participants |
| Race (NIH/OMB) Infant Race Black or African American | 29 Participants | 58 Participants | 29 Participants |
| Race (NIH/OMB) Infant Race More than one race | 87 Participants | 173 Participants | 86 Participants |
| Race (NIH/OMB) Infant Race Native Hawaiian or Other Pacific Islander | 2 Participants | 7 Participants | 5 Participants |
| Race (NIH/OMB) Infant Race Unknown or Not Reported | 61 Participants | 111 Participants | 50 Participants |
| Race (NIH/OMB) Infant Race White | 287 Participants | 547 Participants | 260 Participants |
| Race (NIH/OMB) Maternal Race American Indian or Alaska Native | 12 Participants | 17 Participants | 5 Participants |
| Race (NIH/OMB) Maternal Race Asian | 39 Participants | 85 Participants | 46 Participants |
| Race (NIH/OMB) Maternal Race Black or African American | 35 Participants | 71 Participants | 36 Participants |
| Race (NIH/OMB) Maternal Race More than one race | 28 Participants | 58 Participants | 30 Participants |
| Race (NIH/OMB) Maternal Race Native Hawaiian or Other Pacific Islander | 5 Participants | 13 Participants | 8 Participants |
| Race (NIH/OMB) Maternal Race Unknown or Not Reported | 61 Participants | 122 Participants | 61 Participants |
| Race (NIH/OMB) Maternal Race White | 322 Participants | 605 Participants | 283 Participants |
| Region of Enrollment Canada | 159 infant participants | 318 infant participants | 159 infant participants |
| Region of Enrollment Poland | 17 infant participants | 30 infant participants | 13 infant participants |
| Region of Enrollment United States | 326 infant participants | 623 infant participants | 297 infant participants |
| Sex: Female, Male Infant sex Female | 224 Participants | 425 Participants | 201 Participants |
| Sex: Female, Male Infant sex Male | 278 Participants | 546 Participants | 268 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 2 / 502 | 5 / 469 |
| other Total, other adverse events | 0 / 502 | 0 / 469 |
| serious Total, serious adverse events | 0 / 502 | 0 / 469 |
Outcome results
Primary
Total and Domain Scores on the Ages and Stages Questionnaire, Third Edition.
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
Time frame: 22 to 26 months
Population: Children who had Ages and Stages, third edition. Questionnaire scores available at 2 years or died before age 2 years.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Umbilical Cord Milking - Infant | Total and Domain Scores on the Ages and Stages Questionnaire, Third Edition. | Personal-social score | 50 score on a scale |
| Umbilical Cord Milking - Infant | Total and Domain Scores on the Ages and Stages Questionnaire, Third Edition. | Communication score | 55 score on a scale |
| Umbilical Cord Milking - Infant | Total and Domain Scores on the Ages and Stages Questionnaire, Third Edition. | Problem solving score | 50 score on a scale |
| Umbilical Cord Milking - Infant | Total and Domain Scores on the Ages and Stages Questionnaire, Third Edition. | Gross motor score | 60 score on a scale |
| Umbilical Cord Milking - Infant | Total and Domain Scores on the Ages and Stages Questionnaire, Third Edition. | Total Ages and Stages Questionnaire score | 255 score on a scale |
| Umbilical Cord Milking - Infant | Total and Domain Scores on the Ages and Stages Questionnaire, Third Edition. | Fine motor score | 50 score on a scale |
| Early Cord Clamping - Infant | Total and Domain Scores on the Ages and Stages Questionnaire, Third Edition. | Total Ages and Stages Questionnaire score | 255 score on a scale |
| Early Cord Clamping - Infant | Total and Domain Scores on the Ages and Stages Questionnaire, Third Edition. | Problem solving score | 50 score on a scale |
| Early Cord Clamping - Infant | Total and Domain Scores on the Ages and Stages Questionnaire, Third Edition. | Personal-social score | 50 score on a scale |
| Early Cord Clamping - Infant | Total and Domain Scores on the Ages and Stages Questionnaire, Third Edition. | Fine motor score | 50 score on a scale |
| Early Cord Clamping - Infant | Total and Domain Scores on the Ages and Stages Questionnaire, Third Edition. | Communication score | 55 score on a scale |
| Early Cord Clamping - Infant | Total and Domain Scores on the Ages and Stages Questionnaire, Third Edition. | Gross motor score | 60 score on a scale |
Comparison: Total score on the Ages and Stages Questionnaire, 3rd ed.p-value: 0.8795% CI: [-6.36, 5.37]hierarchical generalized linear mixed mo
Secondary
Score Ranges on the Modified Checklist for Autism in Toddlers Questionnaire
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.
Time frame: 22-26 months
Population: Child participants with a total score from the Modified Checklist for Autism in Toddlers or died before the age of 2 years.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Umbilical Cord Milking - Infant | Score Ranges on the Modified Checklist for Autism in Toddlers Questionnaire | Score 0-2 | 441 Participants |
| Umbilical Cord Milking - Infant | Score Ranges on the Modified Checklist for Autism in Toddlers Questionnaire | Score 3-7 | 34 Participants |
| Umbilical Cord Milking - Infant | Score Ranges on the Modified Checklist for Autism in Toddlers Questionnaire | Score 8-20 | 11 Participants |
| Early Cord Clamping - Infant | Score Ranges on the Modified Checklist for Autism in Toddlers Questionnaire | Score 0-2 | 404 Participants |
| Early Cord Clamping - Infant | Score Ranges on the Modified Checklist for Autism in Toddlers Questionnaire | Score 8-20 | 6 Participants |
| Early Cord Clamping - Infant | Score Ranges on the Modified Checklist for Autism in Toddlers Questionnaire | Score 3-7 | 31 Participants |