Objective Congenital heart block (CHB) may develop in fetuses of women with anti-Ro/SSA autoantibodies, and carries substantial morbidity and mortality. The aim was to evaluate how information on CHB is imparted and identify areas of improvement. Methods A questionnaire was distributed to anti-Ro/SSA antibody-positive women who had either participated in a surveillance programme but whose expected child did not develop CHB ( n = 100, denoted Doppler-Assessed Pregnancies (DAP) group) or given birth to a child with CHB ( n = 88, denoted CHB-Affected Pregnancies (CAP) group). Results The response rate was 83% (157/188). Most women received the information on CHB when they were already pregnant (DAP group 60%, CAP group 83%). However, a majority of them would have wanted the information before pregnancy (DAP group 52%, CAP group 56%), and most stated that it would not have influenced their decision to have a child (DAP group 77%, CAP group 58%). The ability to both understand the information and to perceive the information as sufficient were significantly higher when someone trained in paediatric cardiology gave the information. Conclusions Our findings indicate that information on CHB should be given to women before pregnancy. The data further highlight the importance of having specific knowledge for giving relevant and understandable, yet sufficient information.

Objective: Fetuses exposed to anti-SSA (Sjögren’s) antibodies are at risk of developing irreversible complete atrioventricular block (CAVB), resulting in death or permanent cardiac pacing. Anti-inflammatory treatment during the transition period from normal heart rhythm (fetal heart rhythm (FHR)) to CAVB (emergent CAVB) can restore sinus rhythm, but detection of emergent CAVB is challenging, because it can develop in ⩽24 h. We tested the feasibility of a new technique that relies on home FHR monitoring by the mother, to surveil for emergent CAVB. Study Design: We recruited anti-SSA-positive mothers at 16 to 18 weeks gestation (baseline) from 8 centers and instructed them to monitor FHR two times a day until 26 weeks, using a Doppler device at home. FHR was also surveilled by weekly or every other week fetal echo. If FHR was irregular, the mother underwent additional fetal echo. We compared maternal stress/anxiety before and after monitoring. Postnatally, infants underwent a 12-lead electrocardiogram. Results: Among 133 recruited, 125 (94%) enrolled. Among those enrolled, 96% completed the study. Reasons for withdrawal ( n =5) were as follows: termination of pregnancy, monitoring too time consuming or moved away. During home monitoring, 9 (7.5%) mothers detected irregular FHR diagnosed by fetal echo as normal (false positive, n =2) or benign atrial arrhythmia ( n =7). No CAVB was undetected or developed after monitoring. Questionnaire analysis indicated mothers felt comforted by the experience and would monitor again in future pregnancies. Conclusion: These data suggest ambulatory FHR surveillance of anti-SSA-positive pregnancies is feasible, has a low false positive rate and is empowering to mothers.

Background: Complete fetal heart block (HB) and endocardial fibroelastosis (EFE) are known to be associated with maternal anti-Ro and anti-La antibodies. Complete fetal HB is irreversible.Objectives: We sought to (1) assess die value of the superior vena cava/ascending aorta Doppler approach in the early detection of abnormal delay in the fetal atrioventricular (AV) time of conduction, before appearance of complete fetal HB; and (2) report the effect of prenatal steroid therapy on EFE, HB, or both.Results. The clinical history, echocardiographic, and Doppler investigations of 3 fetuses and children born to mothers positive for anti-Ro and anti-la antibodies are reported. Two fetuses presented with EFE either isolated (29 weeks) or associated with AV block (25 weeks). In this last case, the superior vena cava/ascending aorta approach allowed the identification of a Luciani-Wenckebach phenomenon. in a third fetus, 2:1 AV block was noted at 23 weeks of gestation. Dexamethasone (4 mg/day) was administered to all 3 patients. Complete regression of the EFE and conduction abnormalities was documented in all cases.Conclusion: Early prenatal detection of abnormal delay in fetal AV time conduction is possible with the Doppler superior vena cava/ascending aorta approach. Steroid therapy can cure fetal EFE and AV conduction delays associated with maternal anti-Ro and anti-La antibodies.

Congenital heart block is a passively transferred autoimmune condition, which affects the children of mothers with Ro/SSA autoantibodies. During pregnancy, the antibodies are transported across the placenta and affect the fetus. We have previously demonstrated that antibodies directed to the 200-239 amino acid (aa) stretch of the Ro52 component of the Ro/SSA antigen correlate with the development of congenital heart block. In this report, we investigated the antibody-antigen interaction of this target epitope in detail at a molecular and structural level. Peptides representing aa 200-239 (p200) with structurally derived mutations were synthesized to define the epitopes recognized by two Ro52 human monoclonal antibodies, S3A8 and M4H1, isolated from patient-derived phage display libraries. Analyses by ELISA, circular dichroism and MALDI-TOF-MS demonstrate that the antibody recognition is dependent on a partly alpha-helical fold within the putative leucine zipper of the 200-239 aa stretch and that the two human anti-p200 monoclonal antibodies, M4H1 and S3A8, recognize different epitopic structures within the p200 peptide. In addition, we investigated the representation of each fine specificity within the sera of mothers with children born with congenital heart block, and in such sera, antibodies of the S3A8 idiotype were more commonly detected and at higher levels than M4H1-like antibodies.

Congenital heart block develops in fetuses after placental transfer of Ro/SSA autoantibodies from rheumatic mothers. The condition is often fatal and the majority of live-born children require a pacemaker at an early age. The specific antibody that induces the heart block and the mechanism by which it mediates the pathogenic effect have not been elucidated. In this study, we define the cellular mechanism leading to the disease and show that maternal autoantibodies directed to a specific epitope within the leucine zipper amino acid sequence 200–239 (p200) of the Ro52 protein correlate with prolongation of fetal atrioventricular (AV) time and heart block. This finding was further confirmed experimentally in that pups born to rats immunized with p200 peptide developed AV block. p200-specific autoantibodies cloned from patients bound cultured cardiomyocytes and severely affected Ca2+ oscillations, leading to accumulating levels and overload of intracellular Ca2+ levels with subsequent loss of contractility and ultimately apoptosis. These findings suggest that passive transfer of maternal p200 autoantibodies causes congenital heart block by dysregulating Ca2+ homeostasis and inducing death in affected cells.

AIM:To evaluate foetal left ventricular performance when its preload was increased by banding the pulmonary artery, a study design where a simultaneous change in left ventricular afterload is unlikely. METHODS:Nine ovine foetuses were studied with real-time images and Doppler echocardiography before, 3-4 and 6-8 d after surgery. Seven of these foetuses were also studied during the surgical intervention, immediately before and within 2 min after banding. RESULTS:The immediate effects of a 90-95% reduction of the pulmonary artery cross-sectional area were: a 53 +/- 20% (mean +/- SD) decrease and a 38 +/- 10% increase of right (RvQ) and left ventricular output (LvQ), respectively. Comparing measurements before and 3-4 d after operation, there was a 64 +/- 16% decrease of RvQ and a 64 +/- 25% increase of LvQ. The increase in LvQ was due to an increase in both heart rate (19 +/- 10%) and stroke volume (38 +/- 18%). After an additional 3-4 postoperative days, heart rate remained increased to the same extent, but there was a more pronounced increase of LvQ (93 +/- 19%) and stroke volume (59 +/- 22%). CONCLUSION:The parallel foetal circulation has a capacity to handle a severely increased afterload for the right ventricle by immediately improving and maintaining an increased left ventricular performance. This improvement was in part accomplished by an increase in stroke volume.

At present, fetal electrocardiograms are still hampered by low voltage of the signals obtained from the transmaternal approach; the P waves are hardly visible. The P-QRS interval thus obtained corresponds to the summation of a certain number of heart beats and is therefore unsuitable for individual complex analysis. Magnetocardiography has also been used to evaluate developmental changes in fetal cardiac time intervals.(1) This technique, which requires expensive equipment in a dedicated space rigorously isolated from extramagnetic fields, can hardly be incorporated in routine fetal cardiology practice. Ultrasonography, which is readily available, is the method widely used to indirectly assess the chronology of atrial and ventricular depolarization of fetal cardiomyocytes. Recent experimental(2) and clinical(3) studies have demonstrated the precision superiority of the Doppler approach compared with the M-mode approach to measure fetal atrioventricular (AV) time intervals. To identify fetuses with prolonged AV time intervals, normal values first have to be obtained. A literature search on fetal arrhythmia during the past 10 years found only I report on normal values of fetal AV time intervals with the ultrasonographic approach.(4) This report involved a relatively small number of fetuses (n = 54) investigated by Doppler recordings within the left ventricle. The aim of the present study was to establish reference values for human fetal AV time intervals using 2 different Doppler approaches and assessing the influence of both heart rate and gestational age.

BACKGROUND:No reference values exist concerning the differences between cardio-circulatory variables of normal twin fetuses. The normal data could be useful in the identification of conditions causing opposite hemodynamic effects on each twin. OBJECTIVE:To establish the normal differences among cardio-circulatory parameters of twin fetuses during the second and third trimesters of gestation. MATERIALS AND METHODS:Twenty-seven normal twin pregnancies were used in this longitudinal and prospective study. Doppler-echocardiographic investigations were performed every 2-3 weeks starting at an average of 23.11 +/- 3.13 (mean +/- standard deviation) weeks' gestation. At each visit, the following cardio-circulatory variables were evaluated: the cardio-thoracic ratio, the ventricular wall and septal thicknesses, end-diastolic and systolic diameters, ventricular fractional shortenings, velocity of circumferential fibre shortenings and left and right ventricular outputs. In addition the following measurements were made from Doppler recordings: through both aortic and pulmonary valve the acceleration and ejection times, the peak systolic velocities and the velocity time integrals; and through both mitral and tricuspid valves peak velocities of E and A waves and the E/A ratios. Finally the pulsatility index of the umbilical artery was also evaluated. RESULTS:There was no single variable where the intertwin difference changed with gestational age. No systematic difference between the smaller and larger twin could be demonstrated for any variables except for the cardio-thoracic ratio. CONCLUSION:Reference tables should permit a comparative approach between the two twins in the investigation of life threatening complications such as twin-to-twin transfusion syndrome.

Objective: We sought to investigate whether the reversal of blood flow through the aortic isthmus, as observed during an increase in placental vascular resistance, could be responsible for a significant fall in oxygen delivered to the fetal brain. Study Design: With the appearance of reverse flow in the aortic isthmus, preplacental blood with low oxygen saturation could contaminate the ascending aorta blood destined for the brain. Stepwise compression of the umbilical veins of 8 exteriorized fetal lambs was realized at approximately 140 days of gestation. Four other animals were used as controls. Flows through the aortic isthmus and both carotid and umbilical arteries were measured by Doppler echocardiography in the basal state (hemodynamic class 1) and during moderate (class 2), severe (class 3), and extreme (class 4) increases in resistance to placental flow. Oxygen delivered to the brain was calculated from carotid blood flow and oxygen content. Results: In the control group no change was noted in umbilical and carotid arteries or in the aortic isthmus blood flow. Oxygen delivered to the brain remained stable. In the study group the increase in resistance to placental flow caused a significant fall in umbilical flow and carotid oxygen content, while blood flow in the carotid arteries increased slightly. The values for aortic isthmus flow and oxygen delivered to the brain during the 4 hemodynamic classes were, on average, as follows: class 1, 98.2 and 2.9 mL/(min · kg); class 2, 52.8 and 3.1 mL/(min · kg); class 3, 3.7 and 2.6 mL/(min · kg); and class 4, –29.8 and 0.7 mL/(min · kg), respectively. Conclusion: During an acute increase in placental vascular resistance, delivery of oxygen to the brain is preserved despite a significant drop in arterial oxygen content as long as net flow through the isthmus is anterograde. (Am J Obstet Gynecol 1999;181:1102-7.)

Aim-To verify whether extra uterine changes in total peripheral vascular resistance and cardiac output, caused by raised haematocrit, occur in fetal life and if they can be documented using conventional ultrasound techniques.Methods-An exchange transfusion with packed red cells was performed on five fetal lambs at 140 days of gestation (weight 3.44, SD 0.48 kg);three others were used as controls. The haematocrit was raised from 44 +/- 3 to 64 (SD2)%.Results-Body temperature, blood gas, and pH remained within normal limits. Blood viscosity increased from 5,3 ( 0.3) to 9.6 (1,6) cps. Combined cardiac output fell to 30% of its initial value. The pulsatility index (PI) remained unchanged in the umbilical artery (0.66, SD 0.1) and descending aorta (1.3, SD 0,3). A significant positive correlation was found between haematocrit and PI only in the carotid artery (r=0.67, p<0.01).Conclusion-In the fetus, as in adults, an increase in blood viscosity is associated with a fall in cardiac output. However, the low resistance and the relative inertia of the placental vascular bed blunt the velocimetric changes that could be induced in the lower body vascular system by an increase in resistance. Such changes were observed only in the carotid artery. These results could be of interest in the Doppler monitoring of human fetuses at risk of an abnormal increase in their haematocrit.

This retrospective study (1991-95) presents our experience with sotalol in the treatment of 14 foetuses with supraventricular tachycardia (SVT). SVT was diagnosed in a structurally normal heart at a gestational age of 24-35 (median 28) weeks. In eight foetuses, hydrops was evident at presentation. In all patients pharmacological conversion with digoxin was tried before sotalol treatment was started. Sotalol was given orally to the mothers in a dose of 80-160 mg x 2. Cardioversion was obtained in 10 foetuses. In seven of these patients re-entry tachycardia and in five pre-excitation could be documented after birth. In two foetuses not responding to sotalol a long RP tachycardia was demonstrated; even when using digoxin, sotalol, flecainide and/or propafenone in different combinations after birth complete suppression of the arrhythmia was not obtained. Two severely hydropic foetuses died 1 and 10 d, respectively, after starting with sotalol. The 12 surviving infants were doing well except for one infant, with a cerebral lesion probably related to the arrhythmia. These findings demonstrate that sotalol can be useful in the treatment of foetal SVT.

PURPOSE:In normal pregnancies, as gestation advances, a progressive decrease is observed in the differences between Doppler indices recorded at the 2 extremities of the umbilical cord. The purpose of this study was to determine whether the same pattern is observed in pregnancies complicated by intrauterine growth restriction (IUGR). METHODS:Forty-seven fetuses with sonographic diagnosis of IUGR underwent investigation by Doppler sonography. Blood flow velocities were measured at the abdominal and placental ends of the umbilical cord. The systolic-diastolic ratio, pulsatility index, and resistance index were calculated for each site. The differences in values between the 2 ends of the cord were calculated (abdominal end minus placental end) and then compared with the differences calculated for normal fetuses. RESULTS:In contrast to normal fetuses, IUGR fetuses with abnormal Doppler measurements had significant differences in the pulsatility and resistance indices between the 2 ends of the cord after 28 weeks of gestation. In addition, when compared with normal fetuses, the IUGR fetuses had a significantly greater difference in the values for the 2 ends of the cord for all indices. CONCLUSIONS:These results emphasize the importance of identifying the sampling site for serial Doppler investigations in IUGR-complicated pregnancies.

Objective: The objective of this study was to investigate if Doppler velocimetric indices of the carotid artery could be correlated to physiological variables known to affect cerebral vascular resistance methods. Seven fetal sheep were studied in acute experiments. Carotid artery blood gases and Doppler recordings from the ascending aorta, aortic isthmus, umbilical artery, and carotid artery were obtained at basal state and after three levels of increase in resistance to umbilical blood flow. Results: Due to a decrease in left ventricular output, the left ventricular oxygen delivery started to decrease at the first level of increase in resistance. pCO(2) increased significantly at the second step, Using multiple linear regression it could be demonstrated that the best prediction of carotid artery pulsatility index (r = 0.77, P < 0.0001) was obtained with pCO(2) (P < 0.005) and left ventricular oxygen delivery (P < 0.005) as independent variables. Good correlations between carotid artery pulsatility index and other Doppler variables of the fetoplacental circulation, i.e., the temporal mean velocities of the umbilical artery (r = 0.76, P < 0.0001) and of the aortic isthmus (r = 0.72, P < 0.001), in turn related to left ventricular oxygen delivery and brood flow redistribution could also be demonstrated. Conclusion: These findings provide indirect evidence that Doppler velocimetric indices from arteries supplying the brain can be used as estimates of cerebral vascular resistance.

Experimental studies in animals using Doppler ultrasound suggest that hemodynamic disturbances during fetoplacental circulatory insufficiency will be detected at an earlier and less severe stage in the aortic isthmus compared to the umbilical artery. In cases in which more severe impairment of the placental circulation was achieved, reverse flow was recorded in the aortic isthmus before its appearance in the umbilical artery. The present study was undertaken to investigate whether the same findings could be demonstrated in the aortic isthmus of the human fetus. The video recordings of 100 fetuses with abnormal umbilical artery pulsatility index were reviewed. Qualitative abnormalities of the Doppler waveform, i.e. absence or reversal of end‐diastolic velocities, were more frequently found in the aortic isthmus (absent 28%, reversed 41%) compared to the fetal end of the umbilical artery (absent 20%, reversed 19%; p < 0.0001) and also more frequently found in the fetal end compared to the placental end (absent 13%, reversed 2%; p < 0.0001). This study confirms our previous observations of the aortic isthmus as a site for early detection of fetoplacental hemodynamic disturbances. Reverse diastolic flow in the isthmus could direct poorly oxygenated blood from the descending aorta towards the carotid arteries and the brain. Further prospective studies are needed to establish the clinical value of these findings in terms of perinatal morbidity and, more importantly, of long‐term neurological impairment. Copyright © 1997 International Society of Ultrasound in Obstetrics and Gynecology

We report on two newborn infants with foetal tachycardia and cerebral lesions. Using foetal echocardiography, the diagnosis of supraventricular tachycardia in a structurally normal heart was made at 28 and 37 weeks of gestation, respectively. One infant had a 3 week period of foetal tachycardia and hydrops before successful pharmacological cardioversion. Even several weeks after a term birth he remained hypotonic and needed gavage feeding. A computed tomography (CT) scan demonstrated cerebral lesions indicating a vascular origin. A possible thrombus was found in the heart. The other infant converted to sinus rhythm during birth by Caesarean section on the day after diagnosis. He had convulsions at the second day of life. On CT scan an infarction was found. The observations of this report suggest that cerebrovascular complications to foetal arrhythmias are more common than previously observed and should be considered when managing cases of foetal tachycardia.

Eleven fetal sheep were studied to investigate if Doppler echocardiography could document redistribution of blood flow during maternal oxygen administration. Velocities through the pulmonary valve, aortic valve, common brachiocephalic trunk, aortic arch, descending aorta, umbilical and carotid artery were recorded before, during and after oxygen was delivered to the ewe by face mask. Indices of cardiac performance (shortening fraction, velocity of fiber shortening and systolic time intervals) were also obtained. The aortic arch was the only recording site where significant changes in mean velocity related to oxygen administration and withdrawal were demonstrated ( p < 0.01). Changes in the velocity waveform suggesting an increase in cerebral vascular resistance during oxygen administration were found in the carotid artery. Thus, using Doppler velocimetry, the carotid artery and the aortic arch (equivalent to the human aortic isthmus) appear to be suitable sites to document changes induced by maternal oxygen administration.

ABSTRACT: A fetal lamb model was used to investigate whether the effects of maternal O2 administration on fetal blood gases and hemodynamics were modified when the fetoplacental circulation was compromised by stepwise compression of both umbilical veins. At basal state, O2 administration increased O2 saturation (Sao2) and the pulsatility index (PI) of the carotid artery Doppler wave form (p < 0.01). The first compression decreased left ventricular output (–21 ± 16%, mean ± 1 SD, p < 0.01) and umbilical mean velocity (–22 ± 28%, p < 0.01) but did not modify carotid pH, Sao2, or the PI in any of the arteries studied. At this level of compression, O2 administration increased carotid Sao2 (p < 0.01) but did not affect carotid PI. After a second compression, left ventricular output and umbilical mean velocity were even more reduced [–39 ± 21% (p < 0.01) and –53 ± 23% (p < 0.01), respectively]. With this compression, carotid pH, Sao2, and PI decreased, whereas umbilical and descending aorta PI increased. O2 administration at this level of compression increased carotid Sao2 (p < 0.01) but did not modify carotid PI. Throughout the three stages of the experiment, O2 administration did not affect umbilical PI, descending aorta PI, or umbilical mean velocity. A good linear relationship (r = 0.77, p < 0.001) was demonstrated between left ventricular O2 delivery and carotid PI. Thus, at basal state, O2 administration induced velocity changes compatible with an increase in cerebral vascular resistance. With an increase in umbilical vein resistance, this response was no longer demonstrated, even at a level of vein compression not significantly affecting carotid, umbilical, or descending aorta PI. These results support future use of fetal Doppler velocimetry during maternal hyperoxygenation as a method to evaluate fetal O2 reserve and fetoplacental hemodynamic function.

A range-gated Doppler ultrasound system combined with a real-time imaging system was used to determine arterial blood velocity values from the fetal and placental ends of the umbilical cord in 269 normal pregnancies between 17 and 40 weeks, menstrual age. The systolic-diastolic ratio (S/D), pulsatility index (PI), and resistance index (RI) were higher at the fetal end compared to the placental end of the cord. The individual differences in these Doppler indices, obtained between the fetal and placental recording sites, were inversely related to menstrual age: S/D: r = -0.38, p < 0.001; PI: r = -0.25, p < 0.001; and RI: r = -0.15, p < 0.01. After normalization for the angle of insonation, the peak systolic velocity was higher and the end-diastolic velocity was lower at the fetal than at the placental end of the cord. It is concluded that routine recordings for Doppler velocimetric indices should take into account the recording site on the umbilical cord in order to reduce methodological sources of variance, especially during midgestation. Furthermore, the data presented here in the form of the median and percentile values are proposed as normal reference values to facilitate this procedure.