Gender-specific association between serum ferritin and neurodevelopment in infants aged 6 to 12 months

Abstract

Early iron deficiency has detrimental consequences on neurodevelopment; whether male and female infants are equally susceptible to the functional outcomes of iron deficiency is unclear. This study aimed to investigate the sex differences in the association between serum ferritin levels and neurodevelopment in infants. Data for this cross-sectional study were drawn from hospital information and early childhood development program service systems at Guangdong Women and Children's Hospital, Guangzhou, China. In total, 4579 infants aged 6-12 months were included from July 2018 to March 2020. Their neurodevelopment was assessed using the Children Neuropsychological and Behavior Scale-Revision 2016. Serum ferritin levels were measured by chemiluminescence assay. The association between serum ferritin levels and neurodevelopmental delay in each domain was estimated using logistic regression models adjusted for potential confounders. The mean concentration of serum ferritin was 35.56 ± 21.57 ng/mL. Serum ferritin levels were significantly higher in female than in male infants (P < 0.001). Iron deficiency (serum ferritin levels < 12 ng/mL) was significantly more prevalent in male than in female infants (P < 0.001). Linear regression revealed a positive association between serum ferritin levels and general quotient, gross motor, fine motor, language, and adaptive behavior in females. Iron deficiency was significantly associated with an increased risk of adaptive behavior delay in females (adjusted odds ratio (OR), 2.22; 95% confidence interval (CI): 1.17-4.20). Iron deficiency anemia was associated with an increased risk of developmental delay for general quotient (adjusted OR, 4.88; 95% CI: 1.74-13.65), fine motor (adjusted OR = 2.58, 95%: CI: 1.13-5.94) and adaptive behavior (adjusted OR, 3.38; 95% CI: 1.51-7.57) among females, but not in males. Associations between serum ferritin levels and neurodevelopment in infants aged 6-12 months were sex-related. Females with iron deficiency, especially those with iron-deficiency anemia, were more susceptible to neurodevelopmental delay than males.