Prenatal Exposure to Toxic Metals and Early Neurodevelopmental Outcomes in Infants Following Intrauterine Blood Transfusion: A Prospective Cohort Study

Abstract

Fetal exposure to toxic metals is a major public health concern, yet the contribution of intrauterine blood transfusion (IUBT) to this exposure remains unclear. This prospective cohort study assessed mercury, cadmium, lead, and arsenic levels in maternal blood, cord blood, and residual IUBT red blood cell (RBC) units from 90 pregnant women enrolled at King Faisal Specialist Hospital & Research Centre. Metals were detected in nearly all maternal and cord blood samples and in every transfusion bag, with several measurements exceeding established benchmark values. Higher maternal mercury and combined mercury-arsenic levels were suggestively associated with small reductions in personal-social scores (approximately -3% to -5%). Elevated cord mercury, arsenic, and combined mercury-arsenic-cadmium levels were associated with modest decreases in problem-solving performance. Increased mercury and mercury-arsenic concentrations in transfused RBCs were linked to lower gross motor scores. Overall, these patterns indicate a potential contribution of IUBT-related metals to fetal exposure, although effect sizes were small. These preliminary findings highlight the importance of monitoring metal content in transfusion materials and reinforce the need for larger studies to clarify their clinical relevance.

Keywords: arsenic; cadmium; fetal exposure; intrauterine blood transfusion; lead; mercury; neurodevelopment.

Figure 1

Neurodevelopmental assessment using the Ages & Stages Questionnaire, Third Edition (ASQ-3), at a corrected age of 2 months (n = 30). (a) displays the distribution of infant scores across the five ASQ-3 developmental domains (communication, gross motor, fine motor, problem-solving, and personal–social) relative to established ASQ-3 cutoff values. (b) shows the proportion of infants scoring one standard deviation below the mean, indicating areas of potential developmental concern. All domain labels and thresholds are highlighted in red for clarity.

Figure 1

Neurodevelopmental assessment using the Ages & Stages Questionnaire, Third Edition (ASQ-3), at a corrected age of 2 months (n = 30). (a) displays the distribution of infant scores across the five ASQ-3 developmental domains (communication, gross motor, fine motor, problem-solving, and personal–social) relative to established ASQ-3 cutoff values. (b) shows the proportion of infants scoring one standard deviation below the mean, indicating areas of potential developmental concern. All domain labels and thresholds are highlighted in red for clarity.

Figure 2

Rotated principal component loading plots illustrating metal co-exposure patterns based on principal component analysis (PCA). Panels depict loading vectors for metals measured in (a) maternal blood, (b) cord blood, (c) combined maternal + cord blood datasets, (d) intrauterine transfused red blood cells (RBCs), and (e) the combined dataset of maternal, cord, and RBC metals. Red vectors represent Principal Component 1 (PC1), and blue vectors represent Principal Component 2 (PC2). Only metals with factor loadings ≥ 0.50 are displayed, indicating strong contributions to the corresponding component. These loading patterns reflect exploratory co-exposure structures rather than definitive latent components.

Figure 2

Rotated principal component loading plots illustrating metal co-exposure patterns based on principal component analysis (PCA). Panels depict loading vectors for metals measured in (a) maternal blood, (b) cord blood, (c) combined maternal + cord blood datasets, (d) intrauterine transfused red blood cells (RBCs), and (e) the combined dataset of maternal, cord, and RBC metals. Red vectors represent Principal Component 1 (PC1), and blue vectors represent Principal Component 2 (PC2). Only metals with factor loadings ≥ 0.50 are displayed, indicating strong contributions to the corresponding component. These loading patterns reflect exploratory co-exposure structures rather than definitive latent components.