substantial morbidity and mortality of fetuses in patients with anti - ssa / ro antibodies in pregnancy are associated with the development of congenital heart block [ 14 ] . fetal av block in ssa / ro pregnancies is generally not seen before 18-week gestation and onset is rare after 28-week gestation . if complete congenital heart block in these fetuses occurs , it is believed to be irreversible . nevertheless , intrauterine therapy might be possible , although it is empiric at the moment . the rationale for treatment strategies is to identify the heart block as early as possible and to diminish the inflammatory insult to the heart by lowering the maternal antibodies . immune - mediated av block may benefit from in utero treatment with fluorinated steroids , ivig , or both . although no clear consensus exists , most clinicians use dexamethasone 48  mg / day to treat not only second - degree av block and recent onset av block but also severe cardiac dysfunction and hydrops . several investigators have reported a transient prolongation of av conduction time by echocardiography during midtrimester , which was still present on postnatal electrocardiograms ( ecg ) in 50% of the subjects . the long - term prognosis in these studies was reported as being excellent [ 10 , 11 ] . these findings might indicate a time frame , where reversal of incomplete block without treatment can be seen . the methods used are mainly doppler techniques which measure the mechanical rather than the electrophysiological events to obtain av intervals . this innovative method is more precise in detecting fetal conduction and arrhythmias [ 1214 ] . however , fmcg generally captures each of the cardiac time intervals ( p wave , qrs complex , and t waves , rr- , pr- , and qt intervals ) in fetuses over 24-week gestation ; in fetuses below 24-week gestation , which is the most important time frame in the development of av conduction delay , only qrs and rr intervals can be reliably measured in most fetuses [ 15 , 16 ] . in consequence we have previously reported pr segment prolongation , relative to controls , in sixteen 3rd trimester fetuses , however , analysis of fmcg intervals at younger gestations was difficult until a new method of signal extraction based on a combination of orthogonal projection and independent component analysis was developed . with the help of this new method , the aim of this study was to investigate precise electrophysiological fetal cardiac time intervals in these high - risk fetuses from 18-week gestation onwards by fmcg . baseline characteristics of all 80 patients for this observational study were evaluated with regard to medical history , previous pregnancy outcomes , and medication intake . 21 fetuses of pregnant women with collagen vascular diseases such as systemic lupus erythematosus or sjogren 's syndrome were included in the study group . at study entry , all patients of the study group fulfilled the following inclusion criteria : presence of anti - ssa / ro and/or anti - ssb / la antibodies tested by an enzyme linked immunosorbent assay ( elisa ) and/or an immunofluorescence test , an immunodiffusion test , and dot blots by a commercial laboratory . rheumatologic disease was diagnosed by a rheumatologist according to defined criteria [ 18 , 19 ] . pregnancies over 18-week of gestation with a normal heart beat and a structural normal heart were included . . data of the study group were compared to already established norm values of healthy women with uncomplicated pregnancies and normally developing fetuses . neonatal outcomes defined as normal av conduction by physical exam and established normative cardiac time intervals for age were assessed by a paediatrician by clinical routine examination , fetal heart rate monitoring , and neonatal ecg . informed written consent was obtained from each subject . at the beginning of the study , conventional echocardiography was performed in the study group to evaluate structural cardiac abnormalities , myocardial function , and fetal heart rate , in addition to regular ultrasound examinations . prior to the beginning of each fmcg measurement , ultrasound was performed in all patients to check the fetal position and to localize the fetal heart . furthermore , cardiotocography was performed over a 20-minute period to obtain complete information about the health of the fetus . the fmcg recordings were acquired using a 156-channel biomagnetic system with channels arranged in a curved array that matched the shape of the gravid abdomen ( sara system , vsm med tech ltd . , all of the measurements were recorded with a sampling rate of 1220.7  hz in a magnetically shielded room ( vakuumschmelze , hanau , germany ) . data collection was performed between 18 and 38 weeks gestation , focusing primarily on second trimester . the analysis of the fetal heart signals was performed according to our previously published work . an automated algorithm using orthogonal projection and independent component analysis was applied to reconstruct the fetal heart signal [ 2023 ] . fcti evaluation was performed using a custom - made matlab program ( r2008b , mathworks , natick , ma , usa ) . the time points identified were used to calculate the duration of the cti as follows . p  wave = pend  ponset , qrs  complex = qrsend  qrsonset . the pr interval was determined as p wave  +  pr segment , whereas pr segment was defined as pend to qrsonset . the pr segment may more accurately reflect the av conduction as the pr interval , because it eliminates any intra - atrial conduction delay reflected by the p wave duration measurement . all fmcg recordings were reviewed by at least one physician who has extended experience in pediatric cardiology . ancova was used for data analysis and the influence of age , gender , and birth weight was tested . 21 mothers were included in the study group . the median age of the mothers with systemic lupus erythematosus ( n = 15 patients ) or sjogren 's syndrome ( n = 6 patients ) was 31 years ( range 2146 years ) ( table 1 ) . the maternal suppressive therapies in these 21 patients were low - dose prednisolone ( n = 13 ) , high - dose prednisolone ( n = 1 ) , hydroxychloroquine ( n = 12 ) , cyclosporine ( n = 1 ) , and azathioprine ( n = 6 ) . 21 fetuses were measured with a median gestational age of 28 weeks ( range 1838 weeks ) . chronic diseases were found in the following patients : thalassaemia minor ( two patients ) , crohn 's disease ( one patient ) , and factor v leiden mutation ( one patient ) . twelve women had a previous history of hypothyroidism but were euthyroid at time of measurement . 59 fetuses were measured with a median gestational age of 32 weeks ( range 1938 weeks ) . four fetuses were born prematurely ( > 32 and < 37 weeks of gestation ) . one newborn was small for gestational age whereas three newborns were large for gestational age . altogether 36 measurements in 21 patients were included in the study group and 63 measurements in 59 subjects were included in the control group . table 2 focuses on second trimester ( 1826 weeks of gestation ) , whereas table 3 has its impact on late gestational ages ( 2738 weeks of gestation ) . as the mean birth weight ( shown in table 1 ) was significantly smaller ( p = 0.013 ) in the study group compared to the control group , p values were adjusted for this parameter . in addition , p values were adjusted for age and gender . the pr segment ( isoelectric segment between the end of the p wave and the start of the qrs complex ) was significantly prolonged in both trimesters within the study group ( p < 0.036 2nd trimester , p < 0.023 3rd trimester ) . available postnatal ecgs in the study group did not show first- , second- or third - degree av block . the main finding in this study was that the pr segment ( pr  interval  p  wave ) , measured by fmcg , was significantly prolonged in the study group not only in the third but also in the second trimester when compared to controls . four of the study subjects and only one of the control subjects had pr segment measurements equal to or exceeding 75  ms . in fetuses less than 23-week gestational age , a nearly complete separation was found , where a pr segment of 60  ms or greater completely excluded control fetuses ( see figure 1 ) . all other fctis did not differ significantly and none of the fetuses progressed to second- or third - degree heart block . these findings support the concept that mild av conduction delays may not progress . in a large multicenter study , first - degree av block did not predict development of advanced av block , whereas tricuspid regurgitation of moderate or severe degree , and endocardial fibroelastosis , was associated with subsequent onset of 2nd or 3rd degree av block . van leeuwen and colleagues and stinstra and colleagues , both , have reported dependency of fctis ( also the pr segment duration ) on gestational age and gender [ 16 , 24 , 25 ] . additionally , subjects in the study group had a lower weight at birth than those of the control group . however , significant pr segment prolongation was found in the study group , relative to the control group , even after adjusting for all these possible confounding factors . the new analyzing method improved signal detection and reconstruction in early gestational ages . in consequence , a total of 99 measurements ( in 80 patients ) could be achieved , 18 under 24-week gestational age . in this study , pr segment prolongation was additionally found in the second trimester ( from 18-week gestation onwards ) by fmcg . the prolongation of the pr segment duration might indicate antibody effects already present in the second trimester of pregnancy . jaeggi and colleagues reported similar findings by echocardiography from 15 untreated fetuses either with av prolongation between 2 and 6 z - scores or with type one second - degree block . in addition sonesson and colleagues reported eight of 24 fetuses who had signs of first - degree block in their study . one of these fetuses had progression to complete block , another showed recovery from second - degree to first - degree block with treatment . the lack of progression of first - degree av block to more severe block makes treatment on the basis of first - degree av block unnecessary , except perhaps in the most severe prolongation . rein and colleagues have reported treating patients with dexamethasone for first - degree av block and attributed the lack of progression as a sign that steroids were effective . mechanical measurements by doppler echocardiography and electrophysiological measurements by fmcg , both , show av prolongation . therefore serial fetal doppler echocardiography and additional fmcg measurements of av time intervals are proposed as a useful method to measure early and precise av conduction time to achieve best surveillance of these high - risk pregnancies . in summary , antibody in pregnancy patients might have an effect on the fetal atrioventricular conduction already from early second trimester onwards . but this effect can be reversible and does not consecutively lead to congenital heart block . to develop new management strategies , fmcg measurements in addition to doppler echocardiography might be helpful . however , a higher number of these high - risk patients in multicenter studies of this rare condition are probably necessary .
introduction . fetal av block in ssa / ro pregnancies 
 is generally not seen before 18-week gestation and onset is rare after 28-week gestation . 
 if complete av block appears , it is believed to be irreversible . 
 the purpose of the study was to evaluate precise electrophysiological av conduction from 18-week gestation onwards . 
 patients and methods . 
 21 fetuses of pregnant women with collagen vascular diseases were included in the study group and 59 healthy fetuses served as controls . 
 in addition to fetal echocardiography , fetal magnetocardiography ( fmcg ) was used to investigate precise electrophysiological fetal cardiac time intervals ( fctis ) 
 . results . the pr segment ( isoelectric segment between the end of the p wave and the start of the qrs complex ) was significantly prolonged ( p < 
 0.036 2nd trimester , p < 0.023 3rd trimester ) in both trimesters within the study group . in fetuses less than 23-week gestational age , a nearly complete separation was found , where a pr segment of 60  ms or greater completely excluded control fetuses . 
 all other fctis did not differ significantly . 
 none of the fetuses progressed to a more advanced heart block . 
 conclusion . 
 slight antibody effects in pregnancy , leading to pr segment prolongation , can already be seen from 18-week gestation onwards by fmcg . 
 serial fetal doppler echocardiography and additional fmcg can be useful methods to measure early and precise av conduction time , to achieve best surveillance for these high - risk pregnancies .