Fetal cardiovascular function in a late-onset SGA and FGR cohort: CURIOSA study.

Purpose The measurement of fetal cardiovascular function parameters is not yet established in prenatal diagnostics. Now that the research field of fetal programming is becoming increasingly important, this might change. Fetal cardiovascular changes have been described above all in early/severe fetal growth restriction (FGR). The aim of this study was to investigate functional echocardiographic parameters in fetuses with late-onset small for gestational age (SGA)/FGR. Materials and methods A prospective cohort of SGA fetuses (including FGR) and a control group with similar distribution of gestational age were studied. Parameters of systolic, diastolic and global cardiac function, morphometry and measurements of the fetal abdominal aorta were collected. Results A total of 149 SGA fetuses and 143 control fetuses were included from 32 weeks until term. The total SGA group was further divided into SGA 3rd-10th (fetuses between the 3rd and 10th weight percentile) and FGR subgroups. In the total SGA group, relative right and left ventricular wall thickness, left E/A ratio, isovolumetric contraction time and left myocardial performance index were significantly increased compared to controls after adjustment for gestational age. MAPSE, TAPSE, ejection time, left cardiac output and abdominal aortic distensibility were significantly lower. The changes were more pronounced in the FGR subgroup. Conclusion Even in a group of late-onset SGA/FGR situation, echocardiographic parameters are already altered in utero. Zusammenfassung Ziel Die Messung fetaler kardiovaskulärer Funktionsparameter ist in der Pränataldiagnostik noch nicht etabliert. Nachdem das Forschungsgebiet der fetalen Programmierung einen immer höheren Stellenwert hat, könnte sich das bald ändern. Vor allem bei früher fetaler Wachstumsrestriktion (FGR) sind kardiovaskuläre Veränderungen beschrieben. Ziel dieser Studie war es dies bei Feten mit spät einsetzender FGR zu untersuchen. Material und Methode Eine prospektive Kohorte von Feten, die zu klein für das Gestationsalter (SGA) sind (einschließlich FGR) sowie eine Kontrollgruppe ähnlichen Gestionsalters wurden untersucht. Es wurden Parameter der systolischen, diastolischen sowie globalen Herzfunktion, der Morphometrie sowie Messungen der fetalen Aorta abdominalis erhoben. Ergebnisse Insgesamt wurden 149 SGA Feten sowie 143 Kontrollfeten ab 32 Schwangerschaftswochen eingeschlossen. Die Gesamt-SGA Gruppe wurde für eine Subgruppenanalyse weiterhin in eine SGA (SGA 3-10: Feten zwischen der 3. und 10. Gewichtsperzentile) sowie eine FGR Subgruppe unterteilt. In der Gesamt-SGA Gruppe zeigten sich im Vergleich zu den Kontrollen nach Adjustierung an das Gestationsalter die relative rechte sowie linke Ventrikelwanddicke, das linke E/A-Verhältnis, die isovolumetrische Kontraktionszeit und der linke myokardiale Performanceindex signifikant erhöht. MAPSE, TAPSE, die Ejektionszeit, das linke Herzzeitvolumen und die Beweglichkeit der Aorta abdominalis waren signifikant geringer. Die Ergebnisse waren im Subgruppenvergleich in der FGR Subgruppe ausgeprägter. Schlussfolgerung Auch in einer Gruppe spät einsetzender SGA/FGR Situation sind echokardiographische Parameter bereits intrauterin verändert.

Association of European Paediatric and Congenital Cardiology practical recommendations for surveillance and prevention of cardiac disease in childhood cancer survivors: the importance of physical activity and lifestyle changes From the Association of European Paediatric and Congenital Cardiology Working Group Sports Cardiology, Physical Activity and Prevention, Working Group Adult Congenital Heart Disease, Working Group Imaging and Working Group Heart Failure.

BACKGROUND: Childhood cancer survivors are at increased risk of developing cardiovascular diseases, presenting as the main causes of morbidity and mortality within this group. Besides the usual primary and secondary prevention in combination with screening during follow-up, the modifiable lifestyle factors of physical activity, nutrition, and body weight have not yet gained enough attention regarding potential cardiovascular risk reduction. OBJECTIVE: These practical recommendations aim to provide summarised information and practical implications to paediatricians and health professionals treating childhood cancer survivors to reduce the risk of cardiovascular late effects. METHODS: The content derives from either published guidelines or expert opinions from Association of European Paediatric and Congenital Cardiology working groups and is in accordance with current state-of-the-art. RESULTS: All usual methods of prevention and screening regarding the risk, monitoring, and treatment of occurring cardiovascular diseases are summarised. Additionally, modifiable lifestyle factors are explained, and clear practical implications are named. CONCLUSION: Modifiable lifestyle factors should definitely be considered as a cost-effective and complementary approach to already implemented follow-up care programs in cardio-oncology, which can be actively addressed by the survivors themselves. However, treating physicians are strongly encouraged to support survivors to develop and maintain a healthy lifestyle, including physical activity as one of the major influencing factors. This article summarises relevant background information and provides specific practical recommendations on how to advise survivors to increase their level of physical activity.

Effects of cohort, genotype, variant, and maternal ß-blocker treatment on foetal heart rate predictors of inherited long QT syndrome.

AIMS: In long QT syndrome (LQTS), primary prevention improves outcome; thus, early identification is key. The most common LQTS phenotype is a foetal heart rate (FHR) < 3rd percentile for gestational age (GA) but the effects of cohort, genotype, variant, and maternal ß-blocker therapy on FHR are unknown. We assessed the influence of these factors on FHR in pregnancies with familial LQTS and developed a FHR/GA threshold for LQTS. METHODS AND RESULTS: In an international cohort of pregnancies in which one parent had LQTS, LQTS genotype, familial variant, and maternal ß-blocker effects on FHR were assessed. We developed a testing algorithm for LQTS using FHR and GA as continuous predictors. Data included 1966 FHRs at 7-42 weeks' GA from 267 pregnancies/164 LQTS families [220 LQTS type 1 (LQT1), 35 LQTS type 2 (LQT2), and 12 LQTS type 3 (LQT3)]. The FHRs were significantly lower in LQT1 and LQT2 but not LQT3 or LQTS negative. The LQT1 variants with non-nonsense and severe function loss (current density or ß-adrenergic response) had lower FHR. Maternal ß-blockers potentiated bradycardia in LQT1 and LQT2 but did not affect FHR in LQTS negative. A FHR/GA threshold predicted LQT1 and LQT2 with 74.9% accuracy, 71% sensitivity, and 81% specificity. CONCLUSION: Genotype, LQT1 variant, and maternal ß-blocker therapy affect FHR. A predictive threshold of FHR/GA significantly improves the accuracy, sensitivity, and specificity for LQT1 and LQT2, above the infant's a priori 50% probability. We speculate this model may be useful in screening for LQTS in perinatal subjects without a known LQTS family history.

Perinatal Outcome and its Prediction Using Longitudinal Feto-Maternal Doppler Follow-Up in Late Onset Small for Gestational Age Fetuses - A Prospective Cohort Study.

PURPOSE: To describe the perinatal outcome of a prospective cohort of late-onset small-for-gestational-age (SGA) fetuses and to test adverse perinatal outcome (APO) prediction using Doppler measurements. METHODS: Singleton pregnancies from 32 weeks with suspicion of SGA (followed-up each 2 weeks) and randomly selected healthy controls at a university hospital were included. The whole SGA group was divided into the FGR subgroup or SGA percentile 3-10 subgroup. The following Doppler measurements were evaluated prospectively: umbilical artery (UA) pulsatility index (PI), middle cerebral artery (MCA) PI, cerebro-placental ratio (CPR), and mean uterine artery (mUtA) PI. APO was defined as arterial cord blood pH ≤ 7.15 and/or 5-minute Apgar ≤ 7 and/or emergency operative delivery and/or admission to the neonatal unit. Induction of labor was indicated according to a stage-based protocol. RESULTS: A total of 149 SGA and 143 control fetuses were included. The number of operative deliveries was similar between both groups (control: 29 %, SGA: 28 %), especially the cesarean delivery rate after the onset of labor (11 % vs. 10 %). Most SGA cases ended up in induction of labor (61 % vs. 31 %, p < 0.001). The areas under the curve (AUC) for APO prediction were similar using the last UA PI, MCA PI, CPR, and mUtA PI and barely reached 0.60. The AUC was best for the FGR subgroup, using the minimal CPR or maximum mUtA PI z-score of all longitudinal measurements (AUC = 0.63). CONCLUSION: SGA fetuses do not have a higher rate of operative delivery if managed according to a risk stratification protocol. Prediction of APO is best for SGA and FGR using the "worst" CPR or mUtA PI but it remains moderate.

The aorto-left ventricular tunnel from a fetal perspective: Original case series and literature review.

INTRODUCTION: Aorto-left ventricular tunnel (ALVT) accounts for <0.1% of congenital heart defects. Evidence on the prognosis from a fetal perspective is limited. With this retrospective international case series, we provide information on the outcome of fetuses with ALVT. METHODS: All members of the Association for European Pediatric and Congenital Cardiology's (AEPC) fetal working group and fetal medicine units worldwide were invited for participation. We observed antenatal parameters, neonatal outcome and postnatal follow-up. Additionally, a systematic search of the literature was performed. RESULTS: Twenty fetuses with ALVT were identified in 10 participating centers (2001-2019). Fetal echocardiographic characteristics of ALVT included an increased cardiac-thorax ratio (95%), left ventricular end-diastolic diameter (90%) and a dysplastic aortic valve (90%). Extracardiac malformations were rare (5%). Eight fetuses died at a median gestational age (GA) of 21 + 6 weeks (range, 19-24): all showed signs of hydrops prior to 24 weeks or at autopsy. All others (60%, 12/2) were live-born (median GA 38 + 4, range 37-40), underwent surgery and were alive at last follow up (median 3.2 years, range 0.1-17). The literature reported 22 ALVT fetuses with similar outcome. CONCLUSIONS: In the absence of fetal hydrops, ALVT carries a good prognosis. Fetuses who survive to 24 weeks without hydrops are likely to have a good outcome.

Myocardial deformation analysis in late-onset small-for-gestational-age and growth-restricted fetuses using two-dimensional speckle tracking echocardiography: a prospective cohort study.

OBJECTIVES: An association between fetal growth restriction (FGR) and increased predisposition to cardiovascular disease (CVD) is suggested. The aim of this study was to evaluate subclinical signs of fetal cardiac remodeling in late-onset small-for-gestational-age (SGA) and growth-restricted fetuses using two-dimensional speckle tracking echocardiography (2D-STE). METHODS: This is a prospective cohort study, including 117 late-onset (≥32 weeks) SGA (birthweight≤10th centile) fetuses and 102 gestational age matched controls. A subgroup analysis was performed: FGR was defined based on either BW (0.05). Regarding global and segmental LPSS and LSR values of LV/RV, subgroup analysis revealed no significant difference between the FGR (n=81), SGA centile 3-10 (n=36) and control group. CONCLUSIONS: A mild degree of placental dysfunction seems not to influence myocardial deformation properties measured by 2D-STE.

Cardiovascular outcome of former late-onset small-for-gestational-age children at 1 year of age: CURIOSA study.

OBJECTIVE: Late-onset small-for-gestational-age (SGA) fetuses usually show normal uterine artery Doppler and were long considered to have a good peri- and postnatal outcome. Recently, these fetuses were identified to have a risk factor for cardiovascular disease. The aim of our study was to evaluate former SGA children concerning their cardiovascular risk and nutrition behavior at the age of 1 year. METHODS: We performed a prospective longitudinal cohort study at the University Hospital "Klinikum rechts der Isar" of the Technical University of Munich. Singleton pregnancies from 32 weeks with suspicion of SGA and healthy control pregnancies were included. RESULTS: A total of 100 former SGA children and 113 controls with normal weight (AGA) were examined at 1 year of age. Drop-out for 1-year follow-up was 27%. SGA children had significantly higher systolic (92.8 ± 9.8 mmHg vs. 87.5 ± 10.7 mmHg, p = 0.001), diastolic (63.1 ± 8.5 mmHg vs. 60.0 ± 10.3 mmHg, p = 0.028) and mean (73.0 ± 7.8 vs. 69.2 ± 9.7 mmHg, p = 0.004) blood pressure than AGA children. Comparing two breastfeeding periods (0-4 months vs. > 7 months), a downward trend in blood pressure values for longer breastfeeding periods was shown. CONCLUSION: Our study showed that even late-onset small-for-gestational-age fetuses seem to have cardiovascular problems, although they were previously thought to be "healthy". Up to now, blood pressure measurement is not part of indicated health checks in former SGA or even fetal growth-restricted children which should be changed. Further studies are needed to investigate cardiovascular prevention programs in children.

Do children with congenital heart defects meet the vaccination recommendations? Immunisation in children with congenital heart defects.

INTRODUCTION: Congenital heart defects (CHDs) are the most common congenital malformations. Patients with CHD have a higher morbidity and mortality rate and are at greater risk for infectious diseases. The risk might even be higher if complex CHD occurs and if CHD is associated with additional co-morbidities. Therefore, immunisations in these children are essential. MATERIALS AND METHODS: Individuals were recruited at the outpatient centre of the Department of Congenital Heart Defects and Pediatric Cardiology at the German Heart Center Munich in the time between February 2016 and February 2017. Included were children between 23 months and 17 years and a diagnosis of CHD. The vaccination certificate aimed to assess the immunization status. RESULTS: In total, 657 children with CHD were included and analysed. Regarding primary immunisation, only 34 % (n = 221) of the children reached the complete vaccination status within the allowed catch-up time. Among these primary immunisation rates, vaccinations against Hepatitis B, Meningococci, Varicella and Pneumococci were found to have the lowest coverage with all being below 80%. The vaccination rate was partly influenced by the previously performed number of surgeries but not by the diagnosis of specific genetic diseases. At the age of school entry, the immunisation rate in children with CHD was also lower than in the comparable healthy population. CONCLUSION: The vaccination coverage rate in children with CHD is lower than in comparable healthy children, although this is a vulnerable patient group. Further education of parents and treating physicians of children with CHD regarding vaccination is still needed.

Mothers with long QT syndrome are at increased risk for fetal death: findings from a multicenter international study.

BACKGROUND: Most fetal deaths are unexplained. Long QT syndrome is a genetic disorder of cardiac ion channels. Affected individuals, including fetuses, are predisposed to sudden death. We sought to determine the risk of fetal death in familial long QT syndrome, in which the mother or father carries the long QT syndrome genotype. In addition, we assessed whether risk differed if the long QT syndrome genotype was inherited from the mother or father. OBJECTIVE: This was a retrospective review of pregnancies in families with the 3 most common heterozygous pathogenic long QT syndrome genotypes in KCNQ1 (LQT1), KCNH2 (LQT2), or SCN5A (LQT3), which occur in approximately 1 in 2000 individuals. The purpose of our study was to compare pregnancy and birth outcomes in familial long QT syndrome with the normal population and between maternal and paternal carriers of the long QT syndrome genotype. We hypothesized that fetal death before (miscarriage) and after (stillbirths) 20 weeks gestation would be increased in familial long QT syndrome compared with the normal population and that the parent of origin would not affect birth outcomes. STUDY DESIGN: Our study was a multicenter observational case series of 148 pregnancies from 103 families (80 mothers, 23 fathers) with familial long QT syndrome (60 with LQT1, 29 with LQT2, 14 with LQT3) who were recruited from 11 international centers with expertise in hereditary heart rhythm diseases, pediatric and/or adult electrophysiology, and high-risk pregnancies. Clinical databases from these sites were reviewed for long QT syndrome that occurred in men or women of childbearing age (18-40 years). Pregnancy outcomes (livebirth, stillbirth, and miscarriage), birthweights, and gestational age at delivery were compared among long QT syndrome genotypes and between maternal vs paternal long QT syndrome-affected status with the use of logistic regression analysis. RESULTS: Most offspring (80%; 118/148) were liveborn at term; 66% of offspring (73/110) had long QT syndrome. Newborn infants of mothers with long QT syndrome were delivered earlier and, when the data were controlled for gestational age, weighed less than newborn infants of long QT syndrome fathers. Fetal arrhythmias were observed rarely, but stillbirths (fetal death at >20 weeks gestation) were 8 times more frequent in long QT syndrome (4% vs approximately 0.5%); miscarriages (fetal death at ≤20 weeks gestation) were 2 times that of the general population (16% vs 8%). The likelihood of fetal death was significantly greater with maternal vs paternal long QT syndrome (24.4% vs 3.4%; P=.036). Only 10% of all fetal deaths underwent postmortem long QT syndrome testing; 2 of 3 cases were positive for the family long QT syndrome genotype. CONCLUSION: This is the first report to demonstrate that mothers with long QT syndrome are at increased risk of fetal death and to uncover a previously unreported cause of stillbirth. Our results suggest that maternal effects of long QT syndrome channelopathy may cause placental or myometrial dysfunction that confers increased susceptibility to fetal death and growth restriction in newborn survivors, regardless of long QT syndrome status.

Fetal Cardiac Intervention for Pulmonary Atresia with Intact Ventricular Septum: International Fetal Cardiac Intervention Registry.

INTRODUCTION: Invasive fetal cardiac intervention (FCI) for pulmonary atresia with intact ventricular septum (PAIVS) and critical pulmonary stenosis (PS) has been performed with small single-institution series reporting technical and physiological success. We present the first multicenter experience. OBJECTIVES: Describe fetal and maternal characteristics of those being evaluated for FCI, including pregnancy/neonatal outcome data using the International Fetal Cardiac Intervention Registry (IFCIR). METHODS: We queried the IFCIR for PAIVS/PS cases evaluated from January 2001 to April 2018 and reviewed maternal/fetal characteristics, procedural details, pregnancy and neonatal outcomes. Data were analyzed using standard descriptive statistics. RESULTS: Of the 84 maternal/fetal dyads in the registry, 58 underwent pulmonary valvuloplasty at a median gestational age of 26.1 (21.9-31.0) weeks. Characteristics of fetuses undergoing FCI varied in terms of tricuspid valve (TV) size, TV regurgitation, and pulmonary valve patency. There were fetal complications in 55% of cases, including 7 deaths and 2 delayed fetal losses. Among those who underwent successful FCI, the absolute measurement of the TV increased by 0.32 (±0.17) mm/week from intervention to birth. Among 60 liveborn with known outcome, there was a higher percentage having a biventricular circulation following successful FCI (87 vs. 43%). CONCLUSIONS: Our data suggest a possible benefit to fetal therapy for PAIVS/PS, though rates of technically unsuccessful procedures and procedure-related complications, including fetal loss were substantial. FCI criteria are extremely variable, making direct comparison to nonintervention patients challenging and potentially biased. More uniform FCI criteria for fetuses with PAIVS/PS are needed to avoid unnecessary procedures, expose only fetuses most likely to sustain a benefit, and to enable comparisons to be made with nonintervention patients.

Performance of computerized cardiotocography-based short-term variation in late-onset small-for-gestational-age fetuses and reference ranges for the late third trimester.

PURPOSE: Fetal Doppler changes are well characterized in early-onset small-for-gestational-age (SGA) and fetal growth restriction (FGR) but less well characterized where the condition is late-onset. The aim of the study was to evaluate the role of computerized CTG (cCTG)-based short-term variation (STV) in late-onset SGA and FGR as an additional monitoring modality and to establish STV reference ranges in late third trimester healthy pregnancies. METHODS: Of 86 late-onset SGA fetuses diagnosed after 32 weeks, 66 were diagnosed with FGR. 138 healthy pregnancies acted as controls. All underwent umbilical artery pulsatility index (PI), middle cerebral artery PI, cerebroplacental ratio and mean uterine artery PI. cCTG recordings were analyzed by Sonicaid FetalCare software for STV calculation as described by Dawes/Redman. RESULTS: Median interval between inclusion and delivery was 13 (interquantile range = 4-30) days in the FGR group, 22 (12-37) days in the SGA group and 25 (10-40) days in the control group. STV was not different between controls (11.2 ms, 9.7-13.1), late-onset SGA (11.2 ms, 8.1-12.6) and FGR (10.5 ms, 8.5-12.4) fetuses. A greater proportion of late-onset SGA fetuses had STV < 5th percentile (7/86) compared to controls (4/138) (8.1% vs. 2.9%, p = 0.077). In the control group a significant positive correlation was seen between STV, and 1-min (ρ = 0.195, p = 0.026), 5-min (ρ = 0.247, p = 0.004) and 10-min (ρ = 0.211, p = 0.014) Apgar values. CONCLUSIONS: We report no significant difference in STV median values between controls, SGA and FGR pregnancies. However, more SGA fetuses had a low STV compared to controls. Prospective longitudinal studies are needed to investigate if low STV is a useful surveillance method for late-onset FGR.

Application of the INTERGROWTH-21st chart compared to customized growth charts in fetuses with left heart obstruction: late trimester biometry, cerebroplacental hemodynamics and perinatal outcome.

PURPOSE: Birth weight (BW) is crucial for surgical outcome in children with left heart obstruction (LHO). Head circumference (HC) is believed to correlate with the neurocognitive outcome in LHO. Our aim was to investigate the application of international standardized growth charts from the INTERGROWTH-21st project in comparison to customized growth charts in fetal LHO. METHODS: This is a retrospective cohort study consisting of 60 singleton pregnancies complicated by fetal LHO. For the z score calculation of estimated fetal weight (EFW) and biometric parameters, the INTERGROWTH-21st calculator was used as well as algorithms of customized growth charts. Antenatal measurements were compared to newborn biometry and the association with fetal Doppler results (MCA PI: middle cerebral artery pulsatility index and CPR: cerebroplacental ratio) was examined. Furthermore, the ability of each antenatal chart to predict adverse perinatal outcome was evaluated. RESULTS: At a mean gestational age of 37 weeks, all assessment charts showed significantly smaller mean values for antenatal head circumference (HC) z scores. Highest detection rate for restricted HC growth antenatally was achieved with Hadlock charts. MCA PI and CPR were not associated with neonatal HC. A significant association was observed between EFW and 1-year survival, independent of the considered growth chart. CONCLUSIONS: Growth chart independently, antenatal HC did tend to be smaller in LHO fetuses. A significant association was observed between EFW and 1-year survival rate. Prospective investigations in CHD fetuses should be carried out with internationally standardized growth charts to better examine their prognostic value in this high-risk population.

Fetal cardiac time intervals in healthy pregnancies - an observational study by fetal ECG (Monica Healthcare System).

BACKGROUND: Fetal electrocardiogram (fECG) can detect QRS signals in fetuses from as early as 17 weeks' gestation; however, the technique is limited by the minute size of the fetal signal relative to noise ratio. The aim of this study was to evaluate precise fetal cardiac time intervals (fCTIs) with the help of a newly developed fetal ECG device (Monica Healthcare System). METHODS: In a prospective manner we included 15-18 healthy fetuses per gestational week from 32 weeks onwards. The small and wearable Monica AN24 monitoring system uses standard ECG electrodes placed on the maternal abdomen to monitor fECG, maternal ECG and uterine electromyogram (EMG). Fetal CTIs were estimated on 1000 averaged fetal heart beats. Detection was deemed successful if there was a global signal loss of less than 30% and an analysis loss of the Monica AN24 signal separation analysis of less than 50%. Fetal CTIs were determined visually by three independent measurements. RESULTS: A total of 149 fECGs were performed. After applying the requirements 117 fECGs remained for CTI analysis. While the onset and termination of P-wave and QRS-complex could be easily identified in most ECG patterns (97% for P-wave, PQ and PR interval and 100% for QRS-complex), the T-wave was detectable in only 41% of the datasets. The CTI results were comparable to other available methods such as fetal magnetocardiography (fMCG). CONCLUSIONS: Although limited and preclinical in its use, fECG (Monica Healthcare System) could be an additional useful tool to detect precise fCTIs from 32 weeks' gestational age onwards.

Electrophysiologic features of fetal ventricular aneurysms and diverticula.

OBJECTIVE: Congenital ventricular wall defects are very rare and include congenital ventricular aneurysms (CVAs) and diverticula (CVDs). METHOD: We report a series of five fetuses: three with CVAs and two with CVDs referred due to fetal arrhythmia. In addition to routine fetal echocardiography, fetal magnetocardiography (fMCG) was used. The literature in CVA and CVD is reviewed. RESULTS: Incessant premature ventricular contractions (PVC), mainly bigeminy and trigeminy were found in three fetuses with CVAs and in one with CVD, who also had ventricular couplets. The other fetus with CVD, referred because of PVCs, had only sinus tachycardia. ST elevation was noted in two. Fetal movement had a variable impact on PVCs. Postnatal evaluation demonstrated two persistent left ventricular aneurysms and one persistent right CVD; one CVD resolved at 35-week gestation. Two neonates had incessant PVCs. Both arrhythmias resolved spontaneously while being treated with propranolol. CONCLUSION: FMCG is complementary to echocardiographic imaging. In fetuses with left ventricular wall defects, additional electrophysiological diagnosis can be made by fMCG, including the complexity of ventricular ectopy, arrhythmic response to fetal movement, presence of ST-T wave abnormalities, and atrial amplitude increases. Prenatal risk factor assessment using fMCG can additionally support post-natal treatment and follow-up.

Prediction of contrast-induced nephropathy in patients with serum creatinine levels in the upper normal range by cystatin C: a prospective study in 374 patients.

OBJECTIVE: Preexisting renal impairment is a risk factor for contrast-induced nephropathy (CIN). In patients with creatinine in the upper normal level, cystatin C might be a more sensitive predictor of CIN than creatinine. Therefore, in this study, we investigated the usefulness of cystatin C to predict CIN. SUBJECTS AND METHODS: In 400 consecutive patients with creatinine baseline levels between 0.8 and 1.3 mg/dL undergoing coronary angiography (n = 200) or CT (n = 200), baseline values of cystatin C, creatinine, blood urea nitrogen (BUN) and risk factors of CIN were determined. Creatinine was also assessed 24 and 48 hours after contrast administration. RESULTS: Creatinine significantly (p < 0.001) increased after 24 hours and 48 hours compared with baseline (1.06 ± 0.28 and 1.07 ± 0.28 vs 0.99 ± 0.18 mg/dL). Fifty-three of 373 evaluable patients (14.2%) had an increase in creatinine of ≥ 25% or ≥ 0.5 mg/dL within 48 hours. CIN according to this definition was significantly more frequent after intraarterial contrast administration (38/190, 20%) compared with IV contrast administration (15/183, 8.2%; p = 0.001). CIN was predicted by baseline cystatin C (area under the receiver operating characteristic [ROC] curve [AUC], 0.715; p < 0.001), whereas creatinine, creatinine clearance, and BUN were not predictive. The best predictive capabilities were provided by cystatin C/creatinine-ratio (AUC, 0.826; p < 0.001). Multivariate regression analysis showed that intraarterial contrast administration (p = 0.002) and higher baseline cystatin C (p < 0.001) combined with low creatinine (p = 0.044) were independently associated with higher increases in creatinine within 48 hours after contrast administration. CONCLUSION: CIN in patients with creatinine within the upper normal range is significantly more frequent after intraarterial than after IV contrast administration. In these patients, renal impairment after contrast administration is independently predicted by cystatin C and cystatin C/creatinine-ratio, whereas BUN and creatinine were not predictive.

Diagnosis and treatment of fetal arrhythmia.

AIMS: Detection and careful stratification of fetal heart rate (FHR) is extremely important in all pregnancies. The most lethal cardiac rhythm disturbances occur during apparently normal pregnancies where FHR and rhythm are regular and within normal or low-normal ranges. These hidden depolarization and repolarization abnormalities, associated with genetic ion channelopathies cannot be detected by echocardiography, and may be responsible for up to 10% of unexplained fetal demise, prompting a need for newer and better fetal diagnostic techniques. Other manifest fetal arrhythmias such as premature beats, tachycardia, and bradycardia are commonly recognized. METHODS: Heart rhythm diagnosis in obstetrical practice is usually made by M-mode and pulsed Doppler fetal echocardiography, but not all fetal cardiac time intervals are captured by echocardiographic methods. RESULTS AND CONCLUSIONS: This article reviews different types of fetal arrhythmias, their presentation and treatment strategies, and gives an overview of the present and future diagnostic techniques.

Auditory habituation in the fetus and neonate: an fMEG study.

Habituation--the most basic form of learning--is used to evaluate central nervous system (CNS) maturation and to detect abnormalities in fetal brain development. In the current study, habituation, stimulus specificity and dishabituation of auditory evoked responses were measured in fetuses and newborns using fetal magnetoencephalography (fMEG). An auditory habituation paradigm consisting of 100 trains of five 500 Hz tones, one 750 Hz tone (dishabituator) and two more 500 Hz tones, respectively, were presented to 41 fetuses (gestational age 30-39 weeks) and 22 newborns or babies (age 6-89 days). A response decrement between the first and fifth tones (habituation), an increment between the fifth tone and the dishabituator (stimulus specificity) and an increment between the fifth (last tone before the dishabituator) and seventh tones (first tone after the dishabituator) (dishabituation) were expected. Fetuses showed weak responses to the first tone. However, a significant response decrement between the second and fifth tones (habituation) and a significant increment between the fifth tone and the dishabituator (stimulus specificity) were found. No significant difference was found for dishabituation nor was a developmental trend found at the group level. From the neonatal data, significant values for stimulus specificity were found. Sensory fatigue or adaptation was ruled out as a reason for the response decrement due to the strong reactions to the dishabituator. Taken together, the current study used fMEG to directly show fetal habituation and provides evidence of fetal learning in the last trimester of pregnancy.

Development and application of an automated extraction algorithm for fetal magnetocardiography - normal data and arrhythmia detection.

INTRODUCTION: Current standard methods of monitoring fetal heart function are mainly based on echocardiography, which provides indirect information (through mechanical assessment) of the fetal heart rhythm. Fetal magnetocardiography (fMCG) allows a reliable quantification of the temporal structure of fetal heart signals. However, its application in clinical studies is difficult because extracting the fetal heart signal for most current applications requires user intervention. To overcome this limitation, we developed a completely automated extraction algorithm. PATIENTS AND METHODS: The fMCG recordings were acquired using a 156-channel biomagnetic system. To perform an automated analysis, a combination of orthogonal projection and independent component analysis was used. fMCG recordings from 69 healthy uncomplicated singleton pregnancies with normally developing fetuses were included in the study. RESULTS: The normal values achieved by the automated algorithm were comparable to previously published data. The majority of the cardiac time intervals were positively correlated with gestational age (GA). The ST segment, T wave and QT interval did not show any correlation. CONCLUSIONS: The automated detection of fetal heart signals was possible beginning at a GA of 19 weeks. This automated analysis of fMCG recordings might be an objective and easily applicable approach for clinicians to analyze fetal heart signals.

Preventing and Treating Torsades de Pointes in the Mother, Fetus and Newborn in the Highest Risk Pregnancies with Inherited Arrhythmia Syndromes.

The number of women of childbearing age who have been diagnosed in childhood with ion channelopathy and effectively treated using beta blockers, cardiac sympathectomy, and life-saving cardiac pacemakers/defibrillators is increasing. Since many of these diseases are inherited as autosomal dominant, offspring have about a 50% risk of having the disease, though many will be only mildly impacted during fetal life. However, highly complex delivery room preparation is increasingly needed in pregnancies with inherited arrhythmia syndromes (IASs). However, specific Doppler techniques show meanwhile a better understanding of fetal electrophysiology. The advent of fetal magnetocardiography (FMCG) now allows the detection of fetal Torsades de Pointes (TdP) ventricular tachycardia and other LQT-associated arrhythmias (QTc prolongation, functional second AV block, T-wave alternans, sinus bradycardia, late-coupled ventricular ectopy and monomorphic VT) in susceptible fetuses during the second and third trimester. These types of arrhythmias can be due to either de novo or familial Long QT Syndrome (LQTS), Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT), or other IAS. It is imperative that the multiple specialists involved in the antenatal, peripartum, and neonatal care of these women and their fetuses/infants have the optimal knowledge, training and equipment in order to care for these highly specialized pregnancies and deliveries. In this review, we outline the steps to recognize symptomatic LQTS in either the mother, fetus or both, along with suggestions for evaluation and management of the pregnancy, delivery, or post-partum period impacted by LQTS.