Iron Deficiency Anemia, Iron Deficiency Anemia of Pregnancy, Neurodevelopmental Disorder of Foetus, Iron Deficiency Anemia Treatment, Fetal Neurodevelopmental Disorder, Child Development
Conditions
Keywords
India, Neuroimaging, Intravenous iron, MRI, Pediatrics
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.
Interventions
DRUGFerric carboxymaltose
As part of the RAPIDIRON Trial, maternal participants randomized to intervention arm 1 were given a single dose of ferric carboxymaltose between 14 and 17 weeks of pregnancy.
As part of the RAPIDIRON Trial, maternal participants randomized to intervention arm 2 were given a single dose of iron isomaltoside between 14 and 17 weeks of pregnancy.
DRUGFerric Sulfate
As part of the RAPIDIRON Trial, maternal participants randomized to the active comparator arm were given 200 ferrous sulfate tablets immediately after randomization (\ 12 weeks of pregnancy). Participants were instructed to take two tablets a day, with each tablet containing 60mg elemental iron.
Sponsors
Jawaharlal Nehru Medical College
Thomas Jefferson University
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 40 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Fetal hippocampal volume | 32-35 weeks fetal gestational age | Fetal hippocampus volume, measured via fetal MRI |
| Fetal diffusion parameters: mean diffusivity | 32-35 weeks fetal gestational age | Fetal white matter microstructure will be measured via MD at the posterior limb of internal capsule using fetal MRI |
| Fetal diffusion parameters: fractional anisotropy (FA) | 32-35 weeks fetal gestational age | Fetal white matter microstructure will be measured via FA at the posterior limb of internal capsule using fetal MRI |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Fetal white matter microstructure measures | 32-35 weeks fetal gestational age | Additional fetal white matter microstructure measures using fetal MRI, including qualitative T2 MRI measures and NODDI metrics |
| Fetal sub-cortical gray matter structures | 32-35 weeks fetal gestational age | Fetal sub-cortical gray matter structures in the brain using fetal MRI |
| Child hippocampal volume | 4 - 24 months of age | Child hippocampal volume, measured via MRI |
| Child white matter volume | 4 - 24 months of age | Child white matter volume, measured via MRI |
| Child white matter microstructure | 4 - 24 months of age | Child white matter microstructure, including myelination, fiber coherence, and architecture, measured via MRI |
| Child white matter connectivity | 4 - 24 months of age | Child white matter connectivity, measured via MRI |
| Child functional connectivity | 4 - 24 months of age | Child functional connectivity, measured via MRI |
| Child cerebral metabolism | 4 - 24 months of age | Child cerebral metabolism, including perfusion and spectroscopy, measured via MRI |
Other
| Measure | Time frame | Description |
|---|---|---|
| Maternal depression | Measured from 32-35 weeks fetal gestational age - 24 months offspring age | Maternal depression, measured via the Edinburgh Post-Natal Depression Scale |
| Maternal Perceived Stress | Measured from 32-35 weeks fetal gestational age - 24 months offspring age | Maternal Perceived Stress, measured via the Perceived Stress Scale (PSS-10) |
| Maternal Empowerment | Measured from 32-35 weeks fetal gestational age - 24 months offspring age | Maternal empowerment, measured via the SWPER Global Survey |
| Breastmilk micronutrient analysis | 4 months offspring age | Breastmilk micronutrient analysis, measured via maternal breastmilk samples |
| Maternal iron status | 32 - 35 weeks fetal gestational age | Maternal iron status, measured via hemoglobin, ferritin and TSAT |
| Hair cortisol results | Birth | Results from hair cortisol testing |
| Child auditory brain response (ABR) results | Birth - 4 months of age | Results on auditory brain response test |
| Maternal anxiety | Measured from 32-35 weeks fetal gestational age - 24 months offspring age | Maternal anxiety, measured via State-Trait Anxiety Inventory |
Countries
India
Outcome results
None listed