Infant Brain Study Follow-Up at 3 and 4 Years of Age

Terminated

• Conditions: Iron Deficiency; Child Development
• Interventions: Other: Delayed Cord Clamping or Cord Milking

• Registration Number: NCT02619006
• Lead Sponsor: University of Rhode Island

Brief Summary

When immediate clamping of the umbilical cord (ICC) occurs at birth, 20 to 30% of the fetal-placental blood volume is left behind in the placenta. Preliminary results from our current study comparing effects of ICC versus placental transfusion from delayed cord clamping (DCC) show that infants who have DCC have higher ferritin levels at 4 months of age and more myelin in important regions of the brain. Our objective for this follow-up study is to see if the effects of placental transfusion persist to three and four years of age. The investigators plan to enroll only children who participated in the previous trial (Infant Brain Study/NCT01620008) at birth for assessments at three and four years of age. Assessments include MRIs and neurodevelopmental testing to examine cognitive, motor, visual, and behavioral outcomes.

The proposed research addresses two central questions regarding the potential benefits of DCC on brain myelin development in children who were born healthy at term: 1. Does DCC result in increased brain myelin deposition at three and four years of age? and 2) Are DCC, iron stores, and brain myelin content in infancy associated with improved cognitive, motor, and socio-behavioral outcomes at three and four years of age?

Detailed Description

The current obstetrical practice at birth in the United States is to cut and clamp umbilical cord of the infant immediately after birth. When immediate clamping occurs, 20 to 30% of the fetal-placental blood volume is left behind in the placenta. This blood contains enough iron-rich red blood cells to meet the infant's iron needs for the first 4 to 6 months of life. Delaying cord clamping has been shown to increase early iron stores without contributing to adverse outcomes. The investigators hypothesize that iron sufficiency is essential for long-term neurologic health. Iron deficiency in infancy adversely affects cognitive, motor, socio-emotional, and behavioral development. Human and animal studies have shown that inadequate iron stores in early infancy have an irreversible negative impact on the developing brain with deficits persisting even after iron levels have been restored by iron supplementation. Iron is an essential component of myelination which is critical for normal brain development and function. Myelination, which peaks during the first year of life, establishes and maintains efficient communication between the discrete regions of the brain.

The gap is that the effect of increased iron stores from delayed cord clamping on myelination and long-term neurodevelopment during childhood is unknown. Our hypothesis is that placental transfusion affects myelination and early childhood neurodevelopment in the following ways: 1) placental transfusion (delayed cord clamping or cord milking) leads to increased blood volume (BV) and red blood cell volume (RBCV) at birth; 2) increased RBCV results in more available iron for early body iron stores; 3) increased body iron stores provide essential iron supply for optimal brain myelination; 4) optimal myelination results in improved cognitive, behavioral and socio-emotional performance.

The main objective of this study is to conduct a prospective cohort study following the children enrolled in a previous randomized controlled trial (birth to 24 months) known as the Infant Brain Study. The purpose is to measure the effects of cord clamping time on the structure and function of the developing brain at three and four years of age. The investigators will use a non-invasive neuroimaging technique to measure myelin acquisition over time and conduct neurodevelopmental assessments and correlate the findings with early iron stores and long-term developmental outcomes.

Study Timeline

• Study Start: 2015-11
• Study First Submitted: 2015-11-23
• Study First Submitted QC: 2015-11-27
• Study First Posted: 2015-12-02
• Primary Completion: 2016-12
• Study Completion: 2017-01
• Status Verified: 2018-09
• Last Update Submitted: 2018-10-10
• Last Update Posted: 2018-10-15

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 10

Inclusion Criteria

• Children who previously participated in the Infant Brain Study

Exclusion Criteria

Not provided

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Delayed Cord Clamping or Cord Milking	Delayed Cord Clamping or Cord Milking	Healthy term infants who were previously randomized or assigned at birth to the intervention group known as delayed cord clamping. The cord was clamped and cut at or beyond 300 seconds (5 mins). Cord milking (cord milked x 5) was used as a proxy for delayed cord clamping when there was a clinical situation of concern.

Primary Outcome Measures

Name	Time	Method
Brain myelination trajectory	48 months of age	Using MRI (McDespot technique) to map the myelin water volume fraction in brain

Secondary Outcome Measures

Name	Time	Method
Composite 48 Months of Age Neurodevelopmental Assessment	48 months of age	At 48 months of age using a composite of neurodevelopmental testing (i.e. Mullens Scales of Early Learning) and parent assessment questionaires (i.e. Child Behavior Checklist \[CBCL\]