Background: In the fetus, the signature rhythms of torsade de pointes and 2° atrioventricular block are usually due to de novo long QT syndrome (LQTS), while the fetus with inherited LQTS causative variants manifests asymptomatic bradycardia (fetal heart rate (FHR) less than 3^rd % for gestational age (GA)). Fetal bradycardia is often attributed to the mother’s beta-adrenergic blocker (BB) treatment.
Objective: To assess effects of maternal BB therapy on FHR in inherited LQTS.
Methods: We reviewed data from pregnancies collected in the International Fetal LQTS Registry and the Swedish Fetal LQTS Database. Parental data included parent of origin, genotype, and BB therapy during pregnancy. Offspring data included, FHR across GA, LQTS status and neonatal (first week of life) HR. Both descriptive and categorical measures were included to assess effect of maternal BB on FHR. We incorporated a linear regression mixed effects model to assess multiple FHR in each pregnancy and multiple pregnancies in the same family using GA as a continuous predictor.
Results: We evaluated 282 pregnancies (225 LQT1, 42 LQT2 and 15 LQT3). The origin of the LQTS variant was maternal in 68% and paternal in 32%. BB were administered to 48% of LQTS positive (+) mothers. HRs of LQTS-negative (-) fetuses were unaffected by maternal BB therapy when comparing FHRs from LQTS+ mothers on and off BB (p=0.1) or comparing FHRs of LQTS- mothers and LQTS+ fathers (neither on BB) (p=0.13). However, HRs of LQTS+ fetuses were lower by 7.6 (95% CI: 5.7-9.4) beats per minute (bpm) if the mother was LQTS+ and not receiving BB, and lowest by 10 (95% CI: 7.6-12.3) bpm if the mother was LQTS+ and receiving BB (both, p= 0.001). Similar differences based on parent of origin, fetal LQTS status and BB treatment were seen in neonatal HR. FHR was not different between LQT1 and LQT2 (p=0.6) but 7.1 (95% CI: 3.3-10.9) bpm higher in LQT3, when compared to LQT1 (p=) and0.001 6.4 (95% CI: 2-10.9 bpm) higher compared to LQT2 (p= 0.005).
Conclusion: Fetal bradycardia is a marker for LQTS and cannot be attributed solely to maternal BB therapy. Maternal BBs are additive to inherent bradycardia in LQTS+ fetuses but do not affect FHR of LQTS- fetuses. FHR may be useful in identifying fetuses who inherit the maternal/paternal LQTS-causative variant.