Iron DeficiencyNCT02619006
Infant Brain Study Follow-Up at 3 and 4 Years of Age
An observational study of Iron Deficiency and Child Development, run by University of Rhode Island.
Trial 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… Read more about this study
- Who is it for?
- Ages 30 to 48 months
- Conditions the study is for
- Iron Deficiency, Child Development
- What is being tested?
- Delayed Cord Clamping or Cord Milking
- How many people
- 10 participants
- Where
- No sites listed yet
- Study dates
- Nov 2015to Jan 2017
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 30 to 48 months
- All sexes
- No healthy volunteers
- Child
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.
Who may be able to join
- Children who previously participated in the Infant Brain Study
Who cannot join
None listed.
About this study
Official title: 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?
Read the 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.
- Conditions
- Iron Deficiency, Child Development
- Being tested
- Delayed Cord Clamping or Cord Milking
- Keywords
- Anemia, Iron-Deficiency, Myelination, Ferritin, Umbilical cord clamping, Umbilical Cord Milking, Placental Transfusion, Brain Development
- Medical subject headings
- Iron Deficiencies, Anemia, Iron-Deficiency, Fetofetal Transfusion
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Delayed Cord Clamping or Cord MilkingOther
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Other: Delayed Cord Clamping or Cord Milking |
What is being measured
The primary outcome is the main question the study is designed to answer.
Brain myelination trajectory
Using MRI (McDespot technique) to map the myelin water volume fraction in brain
Measured: 48 months of age
Secondary outcomes (1)
Composite 48 Months of Age Neurodevelopmental Assessment
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]
Measured: 48 months of age
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Dec 2015 (estimated)
- Study startNov 2015
- Primary completionDec 2016
- Study completionJan 2017
Why it stopped: Lack of Funding
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for Iron DeficiencyStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 10 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Rhode Island
- Sponsor type
- University, hospital or other
- Collaborators
- Women and Infants Hospital of Rhode Island, Brown University
- Responsible party
- Principal investigator, Judith S Mercer, University of Rhode Island
- Investigators
- Judith S Mercer, PhD, Principal investigator, University of Rhode Island, Women and Infants Hospital of Rhode IslandDebra A Erickson-Owens, PhD, Principal investigator, University of Rhode Island, Women and Infants Hospital of Rhode IslandSean Deoni, PhD, Principal investigator, Brown University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02619006
- Sponsor's protocol ID
- HU1112-086
- Status last verified
- Sep 2018
- First submitted
- 23 Nov 2015
- Last updated
- 15 Oct 2018
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Mercer JS, Erickson-Owens DA. Rethinking placental transfusion and cord clamping issues. J Perinat Neonatal Nurs. 2012 Jul-Sep;26(3):202-17; quiz 218-9. doi: 10.1097/JPN.0b013e31825d2d9a.
PubMed 22843002Erickson-Owens DA, Mercer JS, Oh W. Umbilical cord milking in term infants delivered by cesarean section: a randomized controlled trial. J Perinatol. 2012 Aug;32(8):580-4. doi: 10.1038/jp.2011.159. Epub 2011 Nov 17.
PubMed 22094494Deoni SC, Dean DC 3rd, Piryatinsky I, O'Muircheartaigh J, Waskiewicz N, Lehman K, Han M, Dirks H. Breastfeeding and early white matter development: A cross-sectional study. Neuroimage. 2013 Nov 15;82:77-86. doi: 10.1016/j.neuroimage.2013.05.090. Epub 2013 May 28.
PubMed 23721722Mercer JS, Erickson-Owens DA, Collins J, Barcelos MO, Parker AB, Padbury JF. Effects of delayed cord clamping on residual placental blood volume, hemoglobin and bilirubin levels in term infants: a randomized controlled trial. J Perinatol. 2017 Mar;37(3):260-264. doi: 10.1038/jp.2016.222. Epub 2016 Dec 8.
PubMed 27929530Mercer JS, Erickson-Owens DA, Deoni SCL, Dean DC 3rd, Collins J, Parker AB, Wang M, Joelson S, Mercer EN, Padbury JF. Effects of Delayed Cord Clamping on 4-Month Ferritin Levels, Brain Myelin Content, and Neurodevelopment: A Randomized Controlled Trial. J Pediatr. 2018 Dec;203:266-272.e2. doi: 10.1016/j.jpeds.2018.06.006. Epub 2018 Jul 6.
PubMed 30473033
Study at a glance
From the registry record, last updated by the sponsor on 15 Oct 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effects of Placental Transfusion on Early Brain Development in Infants Born at Term: Follow-Up at 3 & 4 Years of Age
- ClinicalTrials.gov ID
- NCT02619006
- Acronym / sponsor ID
- HU1112-086
- Conditions
- Iron Deficiency, Child Development
- Keywords
- Anemia, Iron-Deficiency, Myelination, Ferritin, Umbilical cord clamping, Umbilical Cord Milking, Placental Transfusion, Brain Development
- Study type
- Observational
- Recruitment status
- TerminatedReason stopped: Lack of Funding
- Enrolment
- 10 participants (actual)
- Lead sponsor
- University of Rhode IslandUniversity, hospital or other
- Collaborators
- Women and Infants Hospital of Rhode Island, Brown University
- Study start
- Nov 2015
- Primary completion
- Dec 2016 (actual)
- Study completion
- Jan 2017 (actual)
- First posted
- 2 Dec 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 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 | – | Other: Delayed Cord Clamping or Cord MilkingHealthy 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. |
Who may qualify
- Ages
- 30 to 48 months
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
- 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.
Key inclusion criteria (1 listed)
- Children who previously participated in the Infant Brain Study
Key exclusion criteria (0 listed)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Delayed Cord Clamping or Cord MilkingHealthy 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 |
Primary outcome
Brain myelination trajectory
Time frame: 48 months of age
Using MRI (McDespot technique) to map the myelin water volume fraction in brain
1 secondary outcome
Composite 48 Months of Age Neurodevelopmental Assessment
Time frame: 48 months of age
Results and safety
The study was stopped early (reason given: Lack of Funding). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Oct 2018.
- Background: PubMed 22843002Mercer JS, Erickson-Owens DA. Rethinking placental transfusion and cord clamping issues. J Perinat Neonatal Nurs. 2012 Jul-Sep;26(3):202-17; quiz 218-9. doi: 10.1097/JPN.0b013e31825d2d9a.
- Background: PubMed 22094494Erickson-Owens DA, Mercer JS, Oh W. Umbilical cord milking in term infants delivered by cesarean section: a randomized controlled trial. J Perinatol. 2012 Aug;32(8):580-4. doi: 10.1038/jp.2011.159. Epub 2011 Nov 17.
- Background: PubMed 23721722Deoni SC, Dean DC 3rd, Piryatinsky I, O'Muircheartaigh J, Waskiewicz N, Lehman K, Han M, Dirks H. Breastfeeding and early white matter development: A cross-sectional study. Neuroimage. 2013 Nov 15;82:77-86. doi: 10.1016/j.neuroimage.2013.05.090. Epub 2013 May 28.
- Results publication: PubMed 27929530Mercer JS, Erickson-Owens DA, Collins J, Barcelos MO, Parker AB, Padbury JF. Effects of delayed cord clamping on residual placental blood volume, hemoglobin and bilirubin levels in term infants: a randomized controlled trial. J Perinatol. 2017 Mar;37(3):260-264. doi: 10.1038/jp.2016.222. Epub 2016 Dec 8.
- Results publication: PubMed 30473033Mercer JS, Erickson-Owens DA, Deoni SCL, Dean DC 3rd, Collins J, Parker AB, Wang M, Joelson S, Mercer EN, Padbury JF. Effects of Delayed Cord Clamping on 4-Month Ferritin Levels, Brain Myelin Content, and Neurodevelopment: A Randomized Controlled Trial. J Pediatr. 2018 Dec;203:266-272.e2. doi: 10.1016/j.jpeds.2018.06.006. Epub 2018 Jul 6.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Judith S Mercer, PhD principal investigator
University of Rhode Island, Women and Infants Hospital of Rhode Island
Debra A Erickson-Owens, PhD principal investigator
University of Rhode Island, Women and Infants Hospital of Rhode Island
Sean Deoni, PhD principal investigator
Brown University
Questions about this trial
What is this clinical trial studying?
An observational study of Iron Deficiency and Child Development, run by University of Rhode Island.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 0 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 15 Oct 2018. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study was stopped early (reason given: Lack of Funding). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Brain myelination trajectory (time frame: 48 months of age). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02619006, which also lists 5 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Oct 2018.