681 - Intravenous Iron Supplementation During Pregnancy: Effects on Fetal Brain Development Assessed by Structural MRI

Publication Number: 2664.681

Douglas Dean, University of Wisconsin–Madison, Madison, WI, United States; Virupaxi V. Hattiholi, KAHER University Jawaharlal Nehru Medical College, Belagavi, Karnataka, India; Mahesh Kamate, J N Medical College, Belagavi, Karnataka, India; Moriah E. Thomason, Hassenfeld Children's Hospital at NYU Langone, New York, NY, United States; Kiran S. Talekar, Sidney Kimmel Medical College at Thomas Jefferson University, Media, PA, United States; Anmol Patted, Thomas Jefferson University, Philadelphia, PA, United States; Simal Thind, Sidney Kimmel Medical College at Thomas Jefferson University, Philadelphia, PA, United States; Jesse Bradford-Rogers, Thomas Jefferson University, Philadelphia, PA, United States; Danielle DeSantis, Sidney Kimmel Medical College at Thomas Jefferson University, Point Pleasant Boro, NJ, United States; Umesh s. Charantimath, J N Medical College, KAHER, Belagavi, Karnataka, India; Manjunath S. Somannavar, J N Medical College, KLE Academy of Higher Education and Research Belagavi, Belagavi, Karnataka, India; S Yogeshkumar, Jawaharlal Nehru Medical College, KLE Academy of Higher Education and Research (Deemed-to-be-University)), Belagavi, Karnataka, India; Rebecca Hartman, Sidney Kimmel Medical College at Thomas Jefferson University, Philadelphia, PA, United States; Benjamin E. Leiby, Thomas Jefferson University, Philadelphia, PA, United States; Roopa M. Bellad, Jawaharal Nehru Medical college,KL E Academy of Higher Education & Reserach ,Belagavi, Belagavi, Karnataka, India; Zubair Aghai, Nemours Children's Hospital, Philadelphia, PA, United States; Michael K. Georgieff, University of Minnesota, Saint Paul, MN, United States; Shivaprasad S. Goudar, J N Medical College, KLE Academy of Higher Education and Research (Deemed-to-be-University) Belgaum, Belgaum, Karnataka, India; Mrutyunjaya B. Bellad, KAHER's J N medical College Belagavi, Belagavi, Karnataka, India; Richard Derman, Sidney Kimmel Medical College at Thomas Jefferson University, Greenville, DE, United States

Background: Iron deficiency (ID) and ID anemia are significant public health challenges. Anemia in pregnancy increases the risk of adverse health outcomes for mothers and their offspring. The developing fetal brain is vulnerable to inadequate iron availability, as iron serves as an essential nutrient that supports early brain development. However, few studies have investigated the effect of maternal ID on fetal brain structure.

Objective: We utilize fetal neuroimaging data from the Neuroimaging Ancillary Study of the IV Iron RAPIDIRON Trial to investigate the impact of the single-dose IV iron intervention, compared to standard oral iron, on volumetric measures of fetal brain structure.

Design/Methods: Participants were recruited from the RAPIDIRON and RAPIDIRON-KIDS trials. Fetal MRI scans were performed using a 3T Siemens Magnetom Spectra scanner. Structural T2-weighted imaging were acquired in multiple planes (axial, coronal, sagittal), reconstructed to a 3D fetal brain volume, and segmented using an automated pipeline. Fetal brain volumes were compared across three treatment groups (two IV iron formulations and oral iron) using a non-parametric Kruskal-Wallis test. Post-hoc pairwise comparisons were performed when significant overall differences were observed.

Results: Forty-nine fetal MRI exams were performed at 30-37 weeks gestational age (mean=31.2±1.5 weeks). Representative fetal brain volumes are shown in Fig. 1, and illustrative brain parcellation in Fig. 2. Significant differences in left (p=0.012) and right (p=0.03) thalamus volumes across the three iron supplementation groups were observed. Post-hoc analyses revealed one IV iron supplementation group had significantly higher left and right thalamus volumes than the other IV iron supplementation group (left: p=0.011, right: p=0.022) and oral iron group (left: p=0.0072; right: 0.019).

Conclusion(s): Our findings demonstrate that iron supplementation is associated with differential fetal thalamic development, with one IV iron formulation yielding larger bilateral thalamic volumes compared to the alternative IV formulation and oral iron. These findings suggest that route of administration and potentially the pharmacokinetics of different iron formulations may influence iron delivery to the fetal brain. The specificity to the thalamus may reflect regional variations in iron demand, timing of developmental trajectories, or sensitivity to maternal iron status during the third trimester. Understanding iron supplementation strategies to support fetal brain development has important prenatal care implications in populations with high rates of iron deficiency.

Figure 1: Representative slice to volume reconstructed 3D fetal brain volumes.
High resolution fetal brain volumes are reconstructed from stacks of 2D MRI slices acquired in axial, coronal, and sagittal orientations using the SVRTK pipeline.

Figure 2: Representative fetal brain parcellation computed via BOUNTI
Fetal regional brain volumes were subsequently measured from regional segmentation.

Figure 3: Comparison of left and right thalamus volume across iron supplementation groups.
A significant difference across the groups was observed such that the IV-A group had overall larger thalamus volume compared to the oral and IV-B arms.