Clinical trial NCT05545527: Neuroimaging Ancillary Study
Official title: Neuroimaging Ancillary Study of the IV Iron RAPIDIRON Trial
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Iron Deficiency Anemia
Iron Deficiency Anemia of Pregnancy
Neurodevelopmental Disorder of Foetus
Iron Deficiency Anemia Treatment
Fetal Neurodevelopmental Disorder
Child Development
Keywords: India
Neuroimaging
Intravenous iron
MRI
Pediatrics
Lead sponsor: Thomas Jefferson University
Sponsor class: OTHER
Collaborators: name: Jawaharlal Nehru Medical College
First posted: 2022-09-19
Enrollment: 184
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 40
Standard ages: ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: For this ancillary study, only infants of randomized RAPIDIRON Trial (NCT05358509) participants recruited in Karnataka State will be eligible for participation.

Brief summary: As a follow-up to the RAPIDIRON Trial (NCT05358509), and in combination with the RAPIDIRON-KIDS Study (NCT05504863), this study will involve infants of RAPIDIRON Trial participants recruited at one site in Karnataka and is designed to implement a magnetic resonance imaging (MRI) protocol and incorporate neuroimaging measures. Implementation of this study will promote an understanding of the effects on fetal and neonatal brain development, including iron deposition in brain tissues, when a woman is treated for iron deficiency anemia (IDA) by either (a) providing her oral iron tablets and instructions for use; or (b) administering a single-dose IV iron infusion for the treatment of IDA during pregnancy.

Detailed description: The hypothesis of this study is as follows:

* Reduced iron availability through fetal development impacts fundamental early neurodevelopmental processes, including neurogenesis of the hippocampus, amygdala, and other 'core' deep brain basal ganglia regions (e.g., globus pallidus); and myelination of the brain's white matter connecting these deep brain structures and higher-order cortical regions involved in motor, memory, and executive functioning.

The specific aims of this Neuroimaging Ancillary Study are:

* To determine impact of the IV iron intervention compared to oral iron on specific markers of brain development; and
* As a secondary analysis, to explore whether infant sex acts as a moderator of treatment on these specific brain development markers.

This study will recruit pregnant mothers currently participating in the parent RAPIDIRON Trial, who will be approached to give consent for themselves and their offspring for participation in this Neuroimaging Ancillary Study. Participation in this Ancillary Study will involve assessments at 32-35 weeks fetal gestational age, birth, 4 months, 12 months, and 24 months post-delivery. This will involve a fetal MRI and three post-birth MRIs conducted with the offspring to collect the main neuroimaging measures. In addition, we will collect various secondary offspring and maternal measures including child auditory brain response; maternal depression, anxiety, perceived stress, and empowerment; hair cortisol; and breastmilk micronutrient analysis.

Please see the protocol for additional details.

Eligibility criteria: Inclusion Criteria:

* For the maternal participant in the parent RAPIDIRON Trial - a pregnancy that has not gone beyond the period for obtaining a fetal MRI (by scanning the mother at 32-35 weeks fetal gestational age)
* An indication of the pregnant woman's intent to deliver in the study area and to reside there so as to be available not only to complete RAPIDIRON participation but also to allow her and her offspring to participate in ancillary study visits;
* Informed consent of the pregnant RAPIDIRON participant for her participation and that of her offspring in this ancillary trial; and
* Concurrent participation in the RAPIDIRON-KIDS follow-up study (NCT05504863).

Exclusion Criteria:

* If a fetal brain anomaly is found when the maternal participant undergoes an MRI at 32-35 weeks fetal gestational age, the dyad would be excluded from the ancillary study;
* If any of the following occur, this would result in dyad ineligibility for participation or continued participation in this ancillary study: maternal blood transfusion after enrollment, a pregnancy ending in stillbirth, neonatal death, diagnosis in the offspring of moderate to severe hypoxic-ischemic encephalopathy (or HIE), and/or blood transfusion to the offspring.

Primary outcomes:
measure: Fetal hippocampal volume
timeFrame: 32-35 weeks fetal gestational age
measure: Fetal diffusion parameters: fractional anisotropy (FA)
timeFrame: 32-35 weeks fetal gestational age
measure: Fetal diffusion parameters: mean diffusivity
timeFrame: 32-35 weeks fetal gestational age
Secondary outcomes:
measure: Fetal sub-cortical gray matter structures
timeFrame: 32-35 weeks fetal gestational age
measure: Fetal white matter microstructure measures
timeFrame: 32-35 weeks fetal gestational age
measure: Child hippocampal volume
timeFrame: 4 - 24 months of age
measure: Child white matter volume
timeFrame: 4 - 24 months of age
measure: Child white matter microstructure
timeFrame: 4 - 24 months of age
measure: Child white matter connectivity
timeFrame: 4 - 24 months of age
measure: Child functional connectivity
timeFrame: 4 - 24 months of age
measure: Child cerebral metabolism
timeFrame: 4 - 24 months of age
Other outcomes:
measure: Child auditory brain response (ABR) results
timeFrame: Birth - 4 months of age
measure: Hair cortisol results
timeFrame: Birth
measure: Maternal depression
timeFrame: Measured from 32-35 weeks fetal gestational age - 24 months offspring age
measure: Maternal anxiety
timeFrame: Measured from 32-35 weeks fetal gestational age - 24 months offspring age
measure: Maternal Perceived Stress
timeFrame: Measured from 32-35 weeks fetal gestational age - 24 months offspring age
measure: Maternal Empowerment
timeFrame: Measured from 32-35 weeks fetal gestational age - 24 months offspring age
measure: Breastmilk micronutrient analysis
timeFrame: 4 months offspring age
measure: Maternal iron status
timeFrame: 32 - 35 weeks fetal gestational age
Locations:
city: Belgaum
country: India
facility: Jawaharlal Nehru Medical College
state: Karnataka
Study officials:
affiliation: Thomas Jefferson University
name: Richard Derman, MD, MPH
role: PRINCIPAL_INVESTIGATOR
References: