Neuroimaging Ancillary Study

Thomas Jefferson University184 enrolled

Overview

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.

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.

Study Type

OBSERVATIONAL

Enrollment

184

Interventions

Ferric carboxymaltoseDRUG

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.

Iron isomaltosideDRUG

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.

Ferric SulfateDRUG

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.

Eligibility

Sex: FEMALEMin age: 18 YearsMax age: 40 Years

Medical Language ↔ Plain English

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.

Outcomes

Primary Outcomes

Fetal hippocampal volume

Fetal hippocampus volume, measured via fetal MRI

Time frame: 32-35 weeks fetal gestational age

Fetal diffusion parameters: fractional anisotropy (FA)

Fetal white matter microstructure will be measured via FA at the posterior limb of internal capsule using fetal MRI

Time frame: 32-35 weeks fetal gestational age

Fetal diffusion parameters: mean diffusivity

Fetal white matter microstructure will be measured via MD at the posterior limb of internal capsule using fetal MRI

Time frame: 32-35 weeks fetal gestational age

Secondary Outcomes

Fetal sub-cortical gray matter structures

Fetal sub-cortical gray matter structures in the brain using fetal MRI

Time frame: 32-35 weeks fetal gestational age

Fetal white matter microstructure measures

Additional fetal white matter microstructure measures using fetal MRI, including qualitative T2 MRI measures and NODDI metrics

Time frame: 32-35 weeks fetal gestational age

Child hippocampal volume

Child hippocampal volume, measured via MRI