Maternal iron deficiency anemia is associated with reduced fetal thymic size in the early second trimester

Aims: To evaluate the association between maternal iron-deficiency anemia (IDA) and fetal thymic size in the early second trimester using standardized ultrasonographic measurements. Methods: This prospective observational study included 78 pregnant women with IDA and 78 healthy controls with singleton pregnancies between 20+0 and 24+6 weeks of gestation. A priori power analysis indicated that at least 126 participants (63 per group) were required to provide 80% power. Standardized fetal thoracic and thymic ultrasonography was performed in all participants. Thoracic and thymus anteroposterior (AP) diameters were measured, and the thymic-thoracic ratio (TTR) was calculated. Thymus volume, surface area, and gestational age-adjusted Z-scores were obtained from orthogonal measurements and reference charts. Intraobserver reliability was assessed using the intraclass correlation coefficient (ICC). Because the main ultrasound variables were not normally distributed, group comparisons were performed using the Mann-Whitney U test, and effect sizes were expressed as r. Adjusted linear regression analyses evaluated maternal IDA as the exposure and fetal thymic measurements as outcomes. Results: A total of 189 women were screened, 33 were excluded, and 156 were included in the final analysis. Intraobserver reliability was excellent (ICC=0.91). Maternal age, gestational age at examination, gravidity, and parity were similar between groups, whereas body-mass index was lower in the IDA group (p=0.006, r=0.219). Thoracic AP diameter did not differ significantly between groups (p=0.241). In contrast, fetuses of mothers with IDA had smaller thymus AP diameter (8.0 vs. 8.7 mm, p<0.001), lower TTR (0.38 vs. 0.40, p=0.001), lower thymus volume (6.8 vs. 7.5 cm³, p<0.001), smaller thymus surface area (148 vs. 161 mm², p=0.001), and lower gestational age-adjusted thymus Z-scores (-0.43 vs. -0.05, p<0.001). A graded reduction in fetal thymic measurements was observed from controls to mild and moderate IDA. In adjusted linear regression analyses, maternal IDA remained independently associated with lower fetal thymic measurements, whereas thoracic AP diameter was not significantly associated with IDA. Conclusion: Maternal IDA was associated with smaller fetal thymic measurements during the early second trimester despite preserved thoracic size. These findings support an association between maternal iron status and fetal thymic morphometry. Longitudinal studies incorporating postnatal immune outcomes are needed to determine the clinical significance of these findings.