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

October 10, 2018 updated by: Judith S Mercer, University of Rhode Island

Effects of Placental Transfusion on Early Brain Development in Infants Born at Term: Follow-Up at 3 & 4 Years of Age

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?

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

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 Type

Observational

Enrollment (Actual)

10

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

2 years to 4 years (Child)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

The eligible population includes 106 children who randomized in the controlled trial known as the "Effects of Placental Transfusion on Early Brain Development" (Infant Brain Study) (NCT01620008). The children were randomized to either immediate cord clamping or delayed cord clamping (or cord milking as a proxy for delayed clamping). The study population also includes a parallel preference group that self-selected cord clamping timing.

Description

Inclusion Criteria:

  • Children who previously participated in the Infant Brain Study

Exclusion Criteria:

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Cohort
  • Time Perspectives: Prospective

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
Immediate Cord Clamping
Healthy term infants who were previously randomized or assigned at birth to the control group known as immediate cord clamping. The cord was clamped and cut within10 seconds after birth.
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.
Other: 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Brain myelination trajectory
Time Frame: 48 months of age
Using MRI (McDespot technique) to map the myelin water volume fraction in brain
48 months of age

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Composite 48 Months of Age Neurodevelopmental Assessment
Time Frame: 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]
48 months of age

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Rhode Island

Collaborators

Brown University
Women and Infants Hospital of Rhode Island

Investigators

  • Principal Investigator: Judith S Mercer, PhD, University of Rhode Island, Women and Infants Hospital of Rhode Island
  • Principal Investigator: Debra A Erickson-Owens, PhD, University of Rhode Island, Women and Infants Hospital of Rhode Island
  • Principal Investigator: Sean Deoni, PhD, Brown University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

November 1, 2015

Primary Completion (Actual)

December 1, 2016

Study Completion (Actual)

January 1, 2017

Study Registration Dates

First Submitted

November 23, 2015

First Submitted That Met QC Criteria

November 27, 2015

First Posted (Estimate)

December 2, 2015

Study Record Updates

Last Update Posted (Actual)

October 15, 2018

Last Update Submitted That Met QC Criteria

October 10, 2018

Last Verified

September 1, 2018

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • HU1112-086

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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