The American Journal of Human Genetics 85 (2009) 537-537. doi:10.1016/j.ajhg.2009.08.013Received by publisher: 0000-01-01Harvest Date: 2016-01-04 12:18:59DOI: 10.1016/j.ajhg.2009.08.013Page Range: 537-53

Background-Fetal atrioventricular (AV) block is an uncommon lesion with significant mortality. Because of the rarity of this disorder, the natural course, extensive evaluation of untreated fetuses, and late follow-up remain unclear. Methods and Results-Of the 116 consecutive cases of fetal AV block studied from 1988 to 2006, only 1 was terminated, and 75% were live births. Fifty-nine cases of AV block were associated with major structural heart disease, mainly left atrial isomerism (nϭ40), with only 26% of neonatal survivors. Of the 57 fetuses with normal cardiac anatomy, 41 (72%) were positive for maternal antinuclear antibodies, and 32 of these seropositive mothers did not receive any treatment. This untreated group had live-birth and 1-year infant survival rates of 93% and 90%, respectively. Five fetuses from seronegative mothers showed regression to sinus rhythm during pregnancy. The presence of major structural heart disease, hydrops, an atrial rate Յ120 bpm, and a ventricular rate Յ55 bpm were identified as risk factors for mortality. Logistic regression analysis of the whole group showed that the presence of structural heart disease was the only independent predictor of death (PϽ0.001). Conclusions-This long-term study confirms that fetal AV block has a poor outcome when associated with structural heart disease and that spontaneous regression of AV block is possible in seronegative forms. The survival rate of Ͼ90% of our untreated patients with isolated forms of AV block raises concerns about any decision to intervene with immunosuppressive agents. (Circulation. 2008;118:1268-1275.)

We wish to thank Marijon for his comments on our recent article. 1 We were also surprised with our results, which showed that in fetuses with normal cardiac anatomy, fetal, neonatal, and late death were not related to the presence or absence of anti-RO (SS-A) antibodies (29 positive anti-RO and 9 negative anti-RO of 38 surviving; PϾ0.05). Although our data showed no significant differences between the 2 groups in terms of fetal, neonatal, or late deaths, we agree that the finding of maternal autoantibodies is of great importance not only because they are mainly related to the genesis of the heart block (72% in our series) but also because they are related to the late outcome of maternal autoimmune diseases and dilated cardiomyopathy (DCM). Of course, these 2 entities differ completely in terms of pathophysiology and may also do so in terms of prognosis. Moreover, we do not have a ready explanation for the great differences in the incidence of DCM between our series and the series described by Villain et al. 2 Although the title of this long-term study was "Perinatal Outcome of Fetal Av Block," we have not focused only on this period and all patients were carefully followed up using the classically accepted diagnostic criteria for DCM 3 and by physicians with expertise in pediatric cardiology. Our incidence of DCM was 6% (2/32 neonatal survivors of seropositive mothers), similar to those of other studies, 4,5 and we are therefore sure that there has not been any kind of underestimation of DCM in this series.We also wish to thank Jaeggi et al for their comments about our recent article. 1 Of course, not all forms of isolated atrioventricular (AV) block have the same risks or outcome, and we think this article supports this idea, seeing that it presents many different aspects of this complex disorder:First, we included all cases of AV block diagnosed by the first fetal echocardiogram, not to "improve survival estimates by 7%," but because our intention was to show the natural history of this disease by not having any interruption in the isolated group. Even excluding cases that showed spontaneous regression of the AV block (all seronegative), page 1272 still showed that the 32 seropositive untreated fetuses had live birth and 1-year survival rates of 93% (95% confidence interval, 85 to 100) and 90% (95% confidence interval, 80 to 100), respectively. Moreover, after Ͼ20 years working with fetal echocardiography, we can affirm that minimal differences in the interatrial interval could occur in 2:1 AV block, and we should not celebrate when this aspect is present and immediately counsel the parents that everything will work itself out. When we perform the first fetal echocardiogram, we know neither the antibody status of the mother nor the "functional nature" of the heart block, and it is necessary to exercise caution before predicting a happy ending. We agree that Figure 3B shows some shadows that resemble atrial wall movement differing in time, but Figure 3A clearly shows that the intervals between atrial contractio...

The proteins SMA, calponin, CD29, S100 and p63, which are present from the earliest stages of salivary gland maturation, are valuable myoepithelial markers but, although very specific, are not exclusive markers for this cell type.

Objective To determine the accuracy and practicality of fetal echocardiography in the identification of structural and functional cardiac abnormalities prior to 16 weeks' gestation in fetuses with increased nuchal translucency thickness (NT). Methods

Conjoined twin pregnancies should be referred to tertiary centers for detailed fetal anomaly and echocardiographic assessment to evaluate prognosis and determine the possibility of postnatal surgical separation.

No abstract

Depth of trophoblastic penetration into the tubal wall of the ampullary region of Fallopian tube is correlated with beta-hCG concentration and the type of ultrasonographic image; serum beta-hCG is the best predictor of the depth of penetration.