Electrocardiographic QT Intervals in Infants Exposed to Hydroxychloroquine Throughout Gestation

Abstract

Background - Based on inhibition of viral replication and limited reports on clinical efficacy, hydroxychloroquine (HCQ) is being considered as prophylaxis and treatment of COVID-19. Although HCQ is generally considered safe during pregnancy based on studies in patients with systemic lupus erythematous and other rheumatic conditions, there may still be reluctance to institute this antimalarial during pregnancy for the sole purpose of antiviral therapy. Methods - To provide data regarding any potential fetal/neonatal cardiotoxicity, we leveraged a unique opportunity in which neonatal electrocardiograms (ECGs) and HCQ blood levels were available in a recently completed study evaluating the efficacy of HCQ 400mg daily to prevent the recurrence of congenital heart block associated with anti-SSA/Ro antibodies. Results - Forty-five ECGs were available for QTc measurement, and levels of HCQ were assessed during each trimester of pregnancy and in the cord blood, providing unambiguous assurance of drug exposure. Overall, there was no correlation between cord blood levels of HCQ and the neonatal QTc (R = 0.02, P = 0.86) or the mean of HCQ values obtained throughout each individual pregnancy and the QTc (R = 0.04, P = 0.80). In total 5 (11%; 95% CI: 4% - 24%) neonates had prolongation of the QTc > 2SD above historical healthy controls (2 markedly and 3 marginally) but ECGs were otherwise normal. Conclusions - In aggregate, these data provide reassurances that the maternal use of HCQ is associated with a low incidence of infant QTc prolongation. However, if included in clinical COVID-19 studies, early postnatal ECGs should be considered.

Anti-Ro/SSA Antibodies and the Autoimmune Long-QT Syndrome

“…Then, Jaeggi et al ( 60 ) reported that in a Canadian cohort 116 anti-Ro/SSA-positive newborns/infants without aCHB, transient QTc prolongation was rather frequent, it being present in 15% of cases ( 60 ). Consistent data were more recently obtained by Friedman et al ( 62 ) who analyzed the ECGs of 45 infants without aCHB born from anti-Ro/SSA-positive mothers and found that QTc prolongation > 2 standard deviations above historical healthy controls was present in 11% of subjects. Moreover, AlTwajery et al ( 61 ) demonstrated that among 41 children affected with SLE, anti-Ro/SSA-positivity was associated with a higher prevalence of ECG abnormalities, particularly QTc prolongation > 450 ms.…”

Recurrent Congenital Heart Block Due to Maternal Anti-Ro Antibodies: Successful Prevention of Poor Pregnancy Outcome with Hydroxychloroquine and Added Dexamethasone

“…Friedman et al show no correlation between cord blood levels of HCQ and neonatal corrected QT interval (QTc) after analyzing 45 neonatal ECGs (R = 0.02, p = 0.86). Only 5 neonates in Friedman's study, 11% of the population had prolonged QTc above 2 SD when compared with historical healthy controls but ECGs were otherwise unremarkable [17].…”

Narrative Review: Risk-Benefit Hydroxychloroquine and Chloroquine in COVID-19

“…Prolonged QTc was also reported in an open-label single-arm study in 5/45 (11%) infants from the gestation of pregnant mothers taking HCQ. Still, they were asymptomatic, and there was no correlation with maternal or cord HCQ levels (Friedman et al, 2020). In contrast, two observational studies using the hospital database in the New York region showed that the used of HCQ, azithromycin, or both, compared with no treatment, was not significantly differences in in-hospital mortality, and none of patients was found to have an abnormal electrocardiogram.…”