Relationship Between Maternal Plasma Retinol and Provitamin A Carotenoids with Fetal and Infant Kidney Development: A Comprehensive Analysis.

Objective: Vitamin A (retinol) is essential for fetal organ development, with preclinical studies associating maternal vitamin A deficiency (VAD) with reduced nephron numbers, smaller kidneys, and higher chronic kidney disease (CKD) risk later in life. However, similar findings in humans are limited, and no studies in Nebraska have examined maternal VAD's effect on fetal and infant kidney development, despite 10% of mothers being deficient at delivery. Additionally, the impact of provitamin A compounds (α-carotene, β-carotene, β-cryptoxanthin) on kidney size remains unexplored. This study addresses these gaps by analyzing maternal plasma retinol and provitamin A carotenoids' relationship with fetal and infant kidney sizes.

Design: and Method: An IRB-approved prospective cohort study enrolled 120 pregnant women in Nebraska prior to their anatomy scans (18-20 weeks of gestation). The HPLC and LC-MS/HS evaluated the retinol and provitamin A carotenoid concentrations at 24-28 weeks of gestation (n=79) and at delivery in maternal circulation (n=79) and umbilical cord (n=79). Ultrasounds were used to assess fetal kidney length, volume, and parenchymal thickness at 18-20 weeks and infant kidney measurements within 48-72 hours of birth. Spearman's correlation evaluated the relationship between maternal plasma levels and kidney sizes. Linear regression analysis was performed, adjusting for maternal hypertension, diabetes, and smoking status. A Kruskal-Wallis test was performed to examine kidney size differences across retinol adequate, insufficient, and deficient groups, and a p-value of <0.05 was considered statistically significant.

Results: 10% of mothers (n=8) and 19% of mothers (n=15) had VAD during 24-28 weeks of gestation and at delivery, respectively. Maternal retinol at 24-28 weeks or at delivery was not associated with fetal or infant kidney size, and fetal kidney size did not differ between maternal retinol groups. However, maternal α- and β-carotene at 24-28 gestational weeks were significantly positively associated with fetal kidney lengths (right (R) kidney length with α-carotene: β=0.279, p=0.022, left (L) kidney length with α-carotene: β=0.475, p<0.001, L kidney length with β-carotene: β=0.255, p=0.029). Cord retinol was not associated with infant kidney size, nor did infant kidney size differ between cord retinol groups. In contrast cord α-carotene was significantly positively associated with infant kidney lengths (R kidney length: β=0.178, p=0.029, L kidney length: β=0.168, p=0.040). Lastly, the change in maternal plasma retinol from gestation to delivery was not associated with the change in fetal kidney size from gestation to birth. On the other hand, the changes in maternal α-carotene and β-carotene were significantly positively associated with changes in fetal kidney lengths (change in R kidney length with change in α-carotene: β=0.373, p=0.018, change in L kidney length with change in a-carotene: β=0.505, p=0.001, change in L kidney length with change in β-carotene: β=0.364, p=0.019).

Conclusion: Provitamin A carotenoids during pregnancy may influence fetal kidney development. The impact of maternal retinol deficiency on fetal kidney development remains unclear due to the limited sample size. These findings emphasize the significance of maintaining adequate carotenoid levels during pregnancy to support fetal kidney development. Further studies are needed to determine the mechanism by which provitamin A carotenoids influence kidney size.