Discussion
Accurately and early detecting neurological impairment in young children is challenging due to their limited compliance and the unpredictable nature of traditional neurological tests ( Hobart, 2006 ). Our study finds that a significant 78.65% of children with lead poisoning exhibit neurological damage, thus highlighting the urgency for effective screening methods. Crucially, our study establishes a correlation between increased MCHC*RDW-SD interaction values and neurological damage in children with lead poisoning. The inherent advantages of MCHC and RDW-SD as objective, easily accessible, and reproducible hematological indicators lend them significant potential as reliable biomarkers for screening neurological damage in children affected by lead.

Lead toxicity is known to increase the release of premature erythrocytes into circulation, which have a diminished capacity for oxygen transport ( Kiefer & Snyder, 2000 ; Nishiyama et al., 2016 ). Adequate oxygenation is critical for cerebral metabolism and the repair of neurological damage ( Wang et al., 2020 ). Based on this understanding, we hypothesized that erythrocyte abnormalities might be indicative of neurological damage in children with lead poisoning. Indeed, our results identified a correlation between neurological impairment symptoms in these children and abnormal erythrocyte indicators, notably elevated MCHC*RDW-SD interaction values. This correlation suggests that these indicators, reflecting individual erythrocytes’ hemoglobin concentration, could serve as a more precise measure of cerebral oxygenation, especially considering the oxygen transport mechanism through the blood–brain barrier ( Kornhuber et al., 1987 ; Lee et al., 2017 ).

Numerous studies have established a correlation between abnormal hematological indices and neurological damage in adult patients. For example, elevated mean corpuscular hemoglobin concentration (MCHC) levels have been significantly associated with various neurological and cognitive impairments in adults, as demonstrated in research studies ( Gong et al., 2019 ; Kallianpur et al., 2016 ; Lee et al., 2017 ; Oh et al., 2020 ). Furthermore, abnormalities in red cell distribution width (RDW) have been linked to neurological conditions in adults ( Raymond et al., 2009 ). However, it’s crucial to recognize that children’s hematological profiles are markedly different from those of adults ( Chwalba et al., 2018 ). Raymond et al. (2009) observed that while RDW levels are significantly lower in lead-exposed adults, these levels are noticeably higher in 3- and 4-year-old children exposed to lead, highlighting the differential impact of lead across age groups ( Raymond et al., 2009 ). Given that our study focused on pediatric participants with lead-induced neurological damage, it raises the question of whether MCHC and RDW are as effective in detecting neurological damage in children with lead poisoning as they are in adults.

In our model, the combination of MCHC, RDW-SD, and types of lead exposure was found to be a strong predictor of neurological impairment in lead-poisoned children, with an area under the curve (AUC) of 0.80. However, with the aim of identifying objective hematological indicators, we excluded the variable of lead exposure types and developed a model based solely on the interaction of MCHC and RDW-SD. This model also demonstrated considerable predictive ability for neurological impairment (AUC 0.76). With the cut-off value for the MCHC*RDW-SD interaction set at 1.046094, we observed a significantly higher proportion of neurological damage in children within the high MCHC*RDW-SD interaction group (89.4%) compared to the low interaction group. Furthermore, apart from MCHC and RDW-SD, no other erythrocyte parameters showed more than a weak correlation (less than 0.5) with the MCHC*RDW-SD interaction value, indicating its relative independence as an indicator. These findings suggest that an increased MCHC*RDW-SD interaction value is a reliable marker for the presence of neurological damage in children with lead poisoning.

As the premier children’s hospital in southern Zhejiang, our institution has become the primary destination for consultations and treatment of lead-poisoned children, as well as for routine physical examinations. This position has enabled us to conduct a large case-control study with a substantial sample size. However, there are some limitations to consider. First, our study does not represent a long-term clinical validation; while adjustments and analyses were made for age and gender—factors known to influence hematologic parameters in children ( Bohn et al., 2020 ; Higgins et al., 2020 ; Tahmasebi et al., 2020 )—other potential confounders such as medication and nutritional status were not considered. Second, the out-migration of workshops since 2018 has led to a decrease in the number of new cases of lead-poisoned children, which may affect the contemporaneity of our research data. Despite these limitations, our findings offer valuable insights for the screening of neurological damage in lead-poisoned children, which can be applied in other developing industrial regions.