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Effects of Transplacental Dexamethasone Therapy on Fetal Immune-Mediated Complete Heart Block
Mika Saito1, Earl Silverman2, Fraser Golding1
1Department of Pediatrics, Fetal Cardiac Program, Labatt Family Heart Centre, The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada.
Insights
Transplacental dexamethasone may transiently restore fetal atrioventricular conduction in some cases of antibody-mediated complete heart block. This treatment was associated with reduced need for postnatal pacing in responders.
Area of Science:
- Cardiology
- Immunology
- Neonatology
Background:
- Antibody-mediated complete atrioventricular block (CAVB) in fetuses is typically irreversible.
- Transplacental steroid administration is being investigated for its potential effects on fetal cardiac conduction.
Purpose of the Study:
- To examine the effects of transplacental steroids, specifically dexamethasone, on fetal atrioventricular (AV) conduction in cases of CAVB.
- To assess if early and high-dose dexamethasone improves treatment response and outcomes.
Main Methods:
- Retrospective review of 59 fetuses diagnosed with CAVB between 1996 and 2018.
- Analysis of routine dexamethasone administration protocols, focusing on timing and dosage.
- Classification of AV conduction restoration as an "unexpected" treatment response.
Main Results:
- CAVB resolved in 17% of fetuses treated early (≤24 weeks gestation) with 8 mg/day dexamethasone, compared to 0% with later treatment or lower doses (4 mg/day).
- Treatment response was linked to a faster ventricular rate at diagnosis (80 bpm vs. 58 bpm).
- Responders required less frequent postnatal pacing (40% vs. 92%) compared to non-responders, despite transient restoration of AV conduction.
Conclusions:
- Dexamethasone can transiently restore AV conduction in a subgroup of fetuses with CAVB.
- Early and higher-dose dexamethasone appears more effective in achieving this response.
- While transient, this restoration is associated with a decreased need for postnatal pacing.
Introduction:
Antibody-mediated complete atrioventricular block (CAVB) is considered irreversible. We sought to examine the effects of transplacental steroids on fetal AV conduction.
Methods:
Fifty-nine fetuses diagnosed with CAVB at our center from 1996 to 2018 were reviewed. Routine dexamethasone administration to birth was used to limit cardiac inflammatory damage. Restoration of fetal AV conduction was classified as "unexpected" treatment response.
Results:
CAVB resolved in 5/29 (17%) fetuses first treated ≤24-week gestation with 8 mg/day of dexamethasone, when compared with 0/30 (0%) when treatment was initiated later and/or at a starting dose of 4 mg/day (odds ratio 13.69; 95% confidence interval 0.72-260.13; p = 0.024). Treatment response was also associated with a faster ventricular rate at diagnosis (median [range]: 80 [60-97] beats per minute [bpm] vs. 58 [38-92] bpm; p = 0.0036). CAVB reappeared in all 5 responders either prenatally (n = 1) or postnatally before (n = 3) or after (n = 1) the first year of life. When compared with infants with treatment-resistant CAVB (median follow-up 10.3 years), responders (median follow-up 12.3 years) required postnatal pacing less frequent (2/5 [40%] vs. 45/49 [92%]; p = 0.013).
Conclusions:
In a subgroup of CAVB fetuses, dexamethasone transiently restored AV conduction. This was associated with a lower rate of postnatal pacing when compared with nonresponders.
