Early neonatal electrocardiogram changes as an opportunity to detect long-QT syndrome
Y Kato, T Kanagawa, J Yoshimatsu, C Kamiya-Aoki, T AibaAbstract
Background
Electrocardiogram (ECG) changes markedly from day to day in the early neonatal period, and the QT interval frequently overlaps between long-QT syndrome (LQTS) patients and unaffected individuals, complicating diagnosis. Several studies have reported LQTS detection during the neonatal and infant stages; however, the timing of ECG recordings has varied considerably across investigations. We hypothesised that recording at the appropriate time would improve diagnostic accuracy.
Purpose
To determine the optimal timing and cut-off values of neonatal ECG for detecting genotype-positive LQTS.
Methods
We enrolled 36 neonates born to 29 mothers with LQTS (maternal genotypes: 9 LQT1, 8 LQT2, 1 LQT3, and 11 of unknown genotype). Twelve-lead ECGs were recorded daily from day 0 to day 6 of life. We analysed three groups: genotype-positive (carrying the maternal variant), genotype-negative (no variant detected), and unknown-genotype (untested or with a maternal genotype that is unknown). Changes in heart rate and QT interval were compared among those groups.
Results
Genetic testing was performed in 22 cases after infancy. Twelve cases carried the same pathogenic variants as their mothers (genotype-positive) in KCNQ1 (n = 8), KCNH2 (n = 2), and SCN5A (n = 2), while 10 had no pathogenic variant (genotype-negative). The remaining 14 cases were categorised into the unknown-genotype group. In all groups, heart rate decreased on days 1–2 and increased thereafter, while corrected QT interval (QTc) was maximally prolonged on days 1–2 and subsequently tended to shorten. QTc was significantly longer in the genotype-positive group than the genotype-negative group, but the difference was no longer significant by day 6. In the receiver operating characteristic analysis restricted to neonates with genetic confirmation (n=22), the area under the curve on day 2 was 0.88 (95% confidence interval: 0.73–1.00; upper bound truncated at 1.00), demonstrating good discriminative ability. When the QTc cut-off value was set at 443 ms (ROC-derived), the sensitivity was 83.3% and the specificity was 100%.
Conclusion
QTc changes markedly in the early neonatal period, with QT prolongation becoming less apparent by day 6. Although physiological QTc prolongation occurs during this period, electrocardiograms taken on days 1–2 of age—when inter-group QTc differences are most pronounced—are potentially helpful for detecting LQTS.Daily Change in QTc