Electrocardiographic QT Intervals in Infants Exposed to Hydroxychloroquine Throughout Gestation.
BACKGROUND
Based on inhibition of viral replication and limited reports on clinical efficacy, hydroxychloroquine is being considered as prophylaxis and treatment of coronavirus disease-19 (COVID-19). Although hydroxychloroquine is generally considered safe during pregnancy based on studies in patients with systemic lupus erythematosus 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 ECGs and hydroxychloroquine blood levels were available in a recently completed study evaluating the efficacy of hydroxychloroquine 400 mg daily to prevent the recurrence of congenital heart block associated with anti-SSA/Ro (anti-Sjögren's Syndrome A/Ro) antibodies.


RESULTS
Forty-five ECGs were available for corrected QT interval (QTc) measurement, and levels of hydroxychloroquine 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 hydroxychloroquine and the neonatal QTc (R=0.02, P=0.86) or the mean of hydroxychloroquine 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 >2 SD 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 hydroxychloroquine is associated with a low incidence of infant QTc prolongation. However, if included in clinical COVID-19 studies, early postnatal ECGs should be considered. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01379573.
['Friedman|Deborah M|DM|', 'Kim|Mimi|M|', 'Costedoat-Chalumeau|Nathalie|N|', 'Clancy|Robert|R|', 'Copel|Joshua|J|', 'Phoon|Colin K|CK|', 'Cuneo|Bettina F|BF|', 'Cohen|Rebecca|R|', 'Masson|Mala|M|', 'Wainwright|Benjamin J|BJ|', 'Zahr|Noel|N|', 'Saxena|Amit|A|', 'Izmirly|Peter M|PM|', 'Buyon|Jill P|JP|']
D000998:Antiviral Agents D066126:Cardiotoxicity D004334:Drug Administration Schedule D016903:Drug Monitoring D004562:Electrocardiography D005260:Female D005312:Fetal Blood D005318:Fetal Heart D005865:Gestational Age D006327:Heart Block D006339:Heart Rate D006801:Humans D006886:Hydroxychloroquine D007223:Infant D007231:Infant, Newborn D008297:Male D011237:Predictive Value of Tests D011247:Pregnancy D018570:Risk Assessment D012307:Risk Factors D013997:Time Factors D016896:Treatment Outcome
hydroxychloroquine COVID-19 pregnancy heart block incidence