Children with hyperhomocysteinemia showed significantly increased P-wave dispersion compared with controls, with plasma homocysteine levels demonstrating a moderate positive correlation with P-wave dispersion (ρ = 0.441, p < 0.001), suggesting an association between elevated homocysteine levels and altered atrial conduction parameters in children.
Key Findings
Results
P-wave dispersion and maximum P-wave duration were significantly higher in children with hyperhomocysteinemia compared with healthy controls.
P-wave dispersion was 48.96 ms (range 19.48–100.0) in the hyperhomocysteinemia group versus 38.57 ms (range 10.57–71.19) in controls (p < 0.001).
The study included 47 children with hyperhomocysteinemia (plasma total homocysteine ≥ 15 µmol/L) and 43 age- and sex-matched controls.
Both P-wave dispersion and maximum P-wave duration were reported as significantly elevated in the patient group.
This was a multicenter retrospective case-control study conducted across four tertiary pediatric metabolism centers between January 2023 and December 2025.
Results
Plasma homocysteine levels showed a moderate positive correlation with P-wave dispersion.
Spearman's correlation coefficient was ρ = 0.441 (p < 0.001).
This correlation was identified across all 90 participants included in the study.
The correlation was described as 'moderate positive,' indicating that higher homocysteine levels were associated with greater P-wave dispersion.
Results
The differences in P-wave dispersion between groups were more pronounced in children with higher homocysteine levels and in younger age groups.
More pronounced differences were observed in children younger than 2 years and in the 2–14 years age group.
Children with higher homocysteine levels showed more marked increases in P-wave dispersion.
This age-related pattern suggests younger children may be particularly susceptible to homocysteine-related atrial conduction changes.
Results
PR interval and QTc interval did not differ significantly between the hyperhomocysteinemia group and controls.
PR interval comparison yielded p = 0.790, indicating no statistically significant difference.
QTc interval comparison yielded p = 0.183, also not statistically significant.
These findings suggest that hyperhomocysteinemia in children specifically affects atrial conduction parameters rather than atrioventricular conduction or ventricular repolarization.
Results
Vitamin B12 levels were significantly lower in children with hyperhomocysteinemia, while folate levels were comparable between groups.
Vitamin B12 levels differed significantly between groups (p = 0.013).
Folate levels were comparable between the hyperhomocysteinemia group and controls (p = 0.974).
Lower vitamin B12 is a known contributor to elevated homocysteine levels through impaired remethylation pathways.
Results
Sodium, potassium, and magnesium levels differed significantly between groups, but all values remained within normal physiological ranges.
Statistically significant differences were observed in sodium, potassium, and magnesium levels between the two groups.
Despite statistical significance, all electrolyte values were reported to be within normal physiological ranges.
This finding suggests the electrolyte differences are unlikely to account for the observed electrocardiographic differences.
What This Means
This research suggests that children with elevated homocysteine levels in their blood—a condition called hyperhomocysteinemia—show measurable changes in how electrical signals travel through the upper chambers of their hearts (the atria). The study measured a specific electrocardiogram (ECG) marker called P-wave dispersion, which reflects variability in how electrical impulses spread across the atria and is linked to risk of irregular heart rhythms. Children with high homocysteine had notably higher P-wave dispersion values than healthy children of similar age and sex, and the higher a child's homocysteine level, the greater their P-wave dispersion tended to be.
The effects were especially notable in younger children (under 2 years and between 2–14 years), raising the possibility that the developing heart may be particularly sensitive to the effects of elevated homocysteine. Importantly, other ECG measurements—including the PR interval and QTc interval, which reflect different aspects of heart electrical activity—were not significantly different between the groups, suggesting the effect of high homocysteine appears to be relatively specific to atrial conduction in this pediatric population. Children with hyperhomocysteinemia also had lower vitamin B12 levels, which is a known cause of elevated homocysteine.
This research matters because it extends findings previously seen in adults—linking high homocysteine to heart rhythm risk—to a pediatric population, where such data were previously limited. Hyperhomocysteinemia in children can result from inherited metabolic disorders, nutritional deficiencies, or other causes, and these findings suggest it may warrant attention not just for long-term vascular health but potentially for cardiac electrical function as well. The authors note that further prospective studies are needed to confirm whether these ECG changes translate into clinically meaningful heart rhythm problems in children.
Kulu B, Taşçı O, Olgun H, Mintaş N, Uyar S, Gülten Z, et al.. (2026). Association between plasma homocysteine levels and P-wave dispersion in pediatric patients with hyperhomocysteinemia.. European journal of pediatrics. https://doi.org/10.1007/s00431-026-07389-1