Iron Deficiency in Young Children Beyond Anemia: Clinical Features, Maternal Factors, and the Predictor for Neuropsychomotor Development Delay
Authors: Cheng Mei-Mei , Hsiao Ching-Heng , Liu Yen-Lin , Chang Hsi , Lee Ya-Lin , Tsai Min-Lan , Ho Wan-Ling , Tseng Sung-Hui , Weng Tefu , Chang Chia-Yau 
Published: December 2023

Introduction: Iron deficiency (ID) is the most common micronutrient deficiency in children and is prevalent in young children, especially in those with long-term exclusive breastfeeding (BF). Iron deficiency anemia (IDA), the most common type of pediatric anemia, while it is not the only clinical manifestation of ID. In Taiwan, prevalence of IDA was up to 23% in child-bearing women. It was reported that the iron levels in the breast milk of IDA mothers were markedly lower than that of non-IDA mothers. ID alone in young children can cause neurocognitive development symptoms, including inattention, psychomotor delay, cognition impairment, pica, etc, in children. However, clinical reports on ID, not IDA, are relatively few. We aimed to investigate the clinical features and influencing factors of ID in young children.

Methods and Materials: There were 33 young children diagnosed as ID at outpatient department at Taipei Medical University Hospital from 2017 to 2019. The charts were retrospectively reviewed and clinical data were collected, including diagnostic age, initial symptoms, periods of breast-feeding (BF), hemoglobin (Hb), mean corpuscular volume (MCV), serum ferritin (SF), serum iron, total iron binding capacity (TIBC), zinc levels, thalassemia survey, duration of iron supplement, and laboratory improvement after iron supplement. Whether there were neuropsychomotor (NPMD) delay depended on the chart record of doctors of pediatric rehabilitation.

Results: The median age of ID diagnosis was 2.5 years (range: 5 month－7.17 years). There were 31 (94%) of ID children initially presented with either koilonychias, picky eating, or poor appetite. 24 (72.7%) were found to have koilonychias, and among them, 18 (54.5%) had flat nails and 6 (18.2%) had spoon nails. 17 (51.5%) were picky eaters, 16 (48.5%) had poor appetite, 7 (21.2%) had pale nails, and 3 (9.1%) had pica. 11 (33.3%) had NPMD delay. The median duration of BF was 10.8 months (range: 0 to 36). There were 12 (36.4%) children whose mother had IDA. The median Hb was 11.2 g/dL (IQR: 10－12.65), median MCV was 76.45 fL, median SF level was 25 ng/mL (IQR: 13.25－45.5), and median transferrin saturation was 9.25% (IQR: 7－12.88). The median serum zinc level at diagnosis of ID was 66.4 μg/dL. In addition, 21 (63.6%) has concurrent zinc deficiency, 10 (30.3%) had pediatric IDA, and 2 (6.3%) had combined thalassemia trait. The median (IQR) duration of iron supplement is 3 (3-6) months. After treatment, patients' data revealed a significant increase in median Hb of 12.6 mg/dL, median MCV of 78.7 fL, median SF of 47 ng/mL, and median transferrin saturation of 15.35%. By correlation analysis, breastfeeding duration was also moderately correlated to SF level (Pearson rank=-0.5224). Maternal IDA history also had a negative correlation to SF level in ID children (Pearson rank=-0.4053). By multivariate linear regression (MVLR) analysis, breastfeeding duration and maternal IDA history were identified as significantly inverse predictors for SF levels in ID children. ID children with NPMD delay had significantly higher rate of concurrent zinc deficiency. By MVLR analysis, serum zinc level was identified as a significant inverse predictor for NPMD delay among ID children (Odd's ratio: 0.89, 95%CI: 0.799-0.991, p-value=0.0336*).

Conclusion: Our results highlighted the clinical features of ID in infants and children. A high proportion of ID children had maternal IDA history (36.4%) and NPMD delay (33.3%). Iron supplementary was effective to improve ID. Breastfeeding duration and maternal IDA history can negatively impact SF level in ID children. Good levels of serum zinc in ID children can predict lower risk of NPMD delay.

Disclosures : No relevant conflicts of interest to declare.