Fetal ECG: a novel predictor of atrioventricular block in anti-Ro positive pregnancies

Abstract

Objective: Approximately 2.8% of pregnancies are Ro/La antibody positive. 3-15% of fetuses develop complete heart block (CHB). First-degree atrioventricular heart block (1˚AVB) is reported in a third of Ro/La fetuses but as most have a normal postnatal ECG this may reflect inadequacies of Doppler measurement techniques. Methods: Comparison was made between mechanical (mPR) and electrical (ePR) intervals obtained prospectively using Doppler and non-invasive fetal ECG (fECG) in 52 consecutive Ro/La pregnancies in 46 women carrying 54 fetuses in an observational study at a fetal medicine unit. 121 mPR and 37 ePR intervals were recorded in 49 Ro/La fetuses. Five were referred with CHB and excluded. ePR was measured successfully in 35/37 (94%) and mPR was measured in all cases. 1˚AVB was defined as PR .95% CI. Logistic regression predicted abnormal final fetal rhythm from first mPR or ePR.Results: The ePR model gave 66.7% sensitivity (6 of 8 final abnormal fetal rhythm cases were predicted correctly in fetuses .20 weeks) and 96.2% specificity. mPR gave 44.4% sensitivity (4 of 9 cases) and 88.5% specificity. Z scores for ePR (zPR) were calculated from 199 normal fetuses. The area under the receiver operator characteristic (ROC) curve was 0.88 (95% CI, 0.754 to 1.007). A cut-off of 1.65 gave a sensitivity of 87.5% and specificity of 95% for those with prolonged and normal ePR intervals, respectively. Conclusion: zPR is better than mPR at differentiating between normal and prolonged PR intervals, suggesting that fECG is the diagnostic tool of choice to investigate the natural history and therapy of conduction abnormalities in Ro/La pregnancies. A nti-Ro or La antibody positive pregnancies (Ro/La) have been found in about 2.8% of the pregnant population. The most serious consequence of transplacental transfer of these antibodies to the fetus is complete heart block (CHB), which affects 3% of Ro/La pregnancies, with the risk rising to 15% in a subsequent pregnancy. [1][2][3][4] In addition to the morbidity and mortality associated with pacing procedures in young infants, 5 6 progressive myocardial fibrosis has been reported which affects long-term cardiac function and may necessitate transplantation.7-9 The alloimmune process is thought to exert its effect in more than the 3% of fetuses affected by CHB with PR interval prolongation (first-degree atrioventricular heart block or 1˚AVB) described in up to a third of fetuses in studies using Doppler methods of measurement.10 As most babies have a normal outcome, with progression to CHB described in only a small proportion, there is some debate over whether these findings represent a transient biological response to the presence of antibodies or whether they may be due to inadequacies of the existing measurement techniques. 11A simple and robust method of monitoring the PR interval in affected pregnancies is required to enable studies to assess the extent and determinants of progression to CHB in Ro/La pregnancies. Such a tool would also permit the assessment of different trea...

Neonatal Lupus Erythematosus

“…Although there are no formal guidelines for the type or the frequency of testing, performing weekly pulsed Doppler fetal echocardiography from the 18th through the 26th week of pregnancy and then every other week until 32 weeks has been strongly considered. Additional diagnostic modalities include fetal magnetocardiography and electrocardiography [77,78].…”

Early Diagnosis and Treatment of Atrioventricular Block in the Fetus Exposed to Maternal Anti-SSA/Ro-SSB/La Antibodies

“…49 In view of the debatable late effects from prenatal exposure to dexamethasone, our selective therapeutic approach, with treatment reserved for fetuses diagnosed with first-degree AVB, enables selection of a relevant high-risk group while sparing the vast majority of fetuses that are exposed to anti-Ro and/or anti-La antibodies but do not develop AVB. Given of the lack of a prenatal "gold standard" and the few reports of transient AVC time prolongation, 28,29 one may query the justification of treatment with fluorinated steroids; however, we believe, as do others, 31 that the risk for escalation toward high-grade AVB in this high-risk population might outweigh this possibility.…”

“…29 In contrast, the Doppler-based AV interval showed a low sensitivity (44%) and specificity (88%). An important limitation in that study was the lack of fetal ECG data from before 20 weeks of gestation because of poor tracings with wide variability.…”

“…In a recent article, mechanical PR interval has been shown to yield a low sensitivity (44%) and specificity (88%) for diagnosis of first-degree AVB in the fetus. 29 Friedman et al 31 recently showed that left ventricular inflow/outflow Doppler methodology had such a large variability that it required 3 z scores to increase the diagnostic specificity of first-degree AVB. In fact, with this definition of first-degree AVB, Doppler sensitivity dropped because of its failure to diagnose AV prolongation before the appearance of complete AVB.…”

“…Transient AVC prolongation in pregnancies complicated by maternal autoantibodies may occur, 28 although this may be related to a low upper limit of normal AVC time as calculated by the blood-flow Doppler technique. 29,30 We used the novel TVI-based FKCG technique to measure fetal AVC longitudinally from early second trimester (13 weeks) onward. TVI, when stored as scan-line raw data, offers the unique possibility of analyzing activity in any region of the heart and obtaining multiple tissue velocity curves within the same unique temporal domain.…”