The natural history of fetal long QT syndrome.

INTRODUCTION: Fetal magnetocardiography (fMCG), the magnetic analog of ECG, has provided invaluable insight into the mechanisms of fetal arrhythmias. In the past 15years, we have evaluated over 300 fetuses with arrhythmia by fMCG. We review the unique characteristics and natural history of the long QT syndrome (LQTS) rhythms. METHODS: We reviewed the fMCGs of subjects referred with suspected LQTS based on either a positive family history or echo diagnosis of the LQTS rhythms (sinus bradycardia, ventricular tachycardia, or 2:1 AV conduction) to the Biomagnetism laboratory in the Department of Medical Physics, UW-Madison. We recorded fMCGs using a 37-channel (Magnes, 4D Neuroimaging, Inc., San Diego, CA) superconducting quantum interference device (SQUID) biomagnetometer, housed in a magnetically-shielded room for 1200-6000s. Signal processing was used to remove maternal interference. Cardiac intervals (R-R, p, QRS, QT) were measured and compared to published normals. We correlated fetal heart rate (FHR) patterns and effects of fetal movement on FHR and rhythm using actocardiography. RESULTS: Thirty-nine fetuses were studied at a mean of 28 (19-38) weeks of gestation. All had structurally normal hearts. One was on amiodarone for suspected supraventricular tachycardia and hydrops. Five had serial fMCGs. Isolated sinus bradycardia with a QTc >490ms was found in 35: 33 had a KCNQ1 mutation There was one false positive and one false negative LQTS diagnosis. Four fetuses had torsades de pointes (TdP) and 3 had periods of 2:1 conduction and either KCNH2 or SCN5A mutations. TdP was rarely initiated with a preceding long-short pattern and did not degenerate into ventricular fibrillation. One fetus with TdP died in utero, 2 with fetal TdP had postnatal cardiac arrest. CONCLUSION: Fetal LQTS is diagnosed by an fMCG QTc >490ms with an 89% sensitivity and specificity. TdP are seen with uncharacterized, KCNH2 or SCN5A R1623q mutations. Fetal TdP occurs when QTc ≥620ms. Identifying fetal LQTS and defining its rhythms by fMCG risk stratifies postnatal management.

Diagnosis and treatment of fetal cardiac disease: a scientific statement from the American Heart Association.

BACKGROUND: The goal of this statement is to review available literature and to put forth a scientific statement on the current practice of fetal cardiac medicine, including the diagnosis and management of fetal cardiovascular disease. METHODS AND RESULTS: A writing group appointed by the American Heart Association reviewed the available literature pertaining to topics relevant to fetal cardiac medicine, including the diagnosis of congenital heart disease and arrhythmias, assessment of cardiac function and the cardiovascular system, and available treatment options. The American College of Cardiology/American Heart Association classification of recommendations and level of evidence for practice guidelines were applied to the current practice of fetal cardiac medicine. Recommendations relating to the specifics of fetal diagnosis, including the timing of referral for study, indications for referral, and experience suggested for performance and interpretation of studies, are presented. The components of a fetal echocardiogram are described in detail, including descriptions of the assessment of cardiac anatomy, cardiac function, and rhythm. Complementary modalities for fetal cardiac assessment are reviewed, including the use of advanced ultrasound techniques, fetal magnetic resonance imaging, and fetal magnetocardiography and electrocardiography for rhythm assessment. Models for parental counseling and a discussion of parental stress and depression assessments are reviewed. Available fetal therapies, including medical management for arrhythmias or heart failure and closed or open intervention for diseases affecting the cardiovascular system such as twin-twin transfusion syndrome, lung masses, and vascular tumors, are highlighted. Catheter-based intervention strategies to prevent the progression of disease in utero are also discussed. Recommendations for delivery planning strategies for fetuses with congenital heart disease including models based on classification of disease severity and delivery room treatment will be highlighted. Outcome assessment is reviewed to show the benefit of prenatal diagnosis and management as they affect outcome for babies with congenital heart disease. CONCLUSIONS: Fetal cardiac medicine has evolved considerably over the past 2 decades, predominantly in response to advances in imaging technology and innovations in therapies. The diagnosis of cardiac disease in the fetus is mostly made with ultrasound; however, new technologies, including 3- and 4-dimensional echocardiography, magnetic resonance imaging, and fetal electrocardiography and magnetocardiography, are available. Medical and interventional treatments for select diseases and strategies for delivery room care enable stabilization of high-risk fetuses and contribute to improved outcomes. This statement highlights what is currently known and recommended on the basis of evidence and experience in the rapidly advancing and highly specialized field of fetal cardiac care.

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.

In utero diagnosis of long QT syndrome by magnetocardiography.

BACKGROUND: The electrophysiology of long QT syndrome (LQTS) in utero is virtually unstudied. Our goal here was to evaluate the efficacy of fetal magnetocardiography (fMCG) for diagnosis and prognosis of fetuses at risk of LQTS. METHODS AND RESULTS: We reviewed the pre/postnatal medical records of 30 fetuses referred for fMCG because of a family history of LQTS (n=17); neonatal/childhood sudden cardiac death (n=3), or presentation of prenatal LQTS rhythms (n=12): 2° atrioventricular block, ventricular tachycardia, heart rate < 3(rd) percentile. We evaluated heart rate and reactivity, cardiac time intervals, T-wave characteristics, and initiation/termination of Torsade de Pointes, and compared these with neonatal ECG findings. After birth, subjects were tested for LQTS mutations. Based on accepted clinical criteria, 21 subjects (70%; 9 KCNQ1, 5 KCNH2, 2 SCN5A, 2 other, 3 untested) had LQTS. Using a threshold of corrected QT= 490 ms, fMCG accurately identified LQTS fetuses with 89% (24/27) sensitivity and 89% (8/9) specificity in 36 sessions. Four fetuses (2 KCNH2 and 2 SCN5A), all with corrected QT ≥ 620 ms, had frequent episodes of Torsade de Pointes, which were present 22-79% of the time. Although some episodes initiated with a long-short sequence, most initiations showed QRS aberrancy and a notable lack of pause dependency. T-wave alternans was strongly associated with severe LQTS phenotype. CONCLUSIONS: Corrected QT prolongation (≥490 ms) assessed by fMCG accurately identified LQTS in utero; extreme corrected QT prolongation (≥620 ms) predicted Torsade de Pointes. FMCG can play a critical role in the diagnosis and management of fetuses at risk of LQTS.

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.

Diagnosis and Management of Fetal Arrhythmias in the Current Era.

Diagnosis and management of fetal arrhythmias have changed over the past 40-50 years since propranolol was first used to treat fetal tachycardia in 1975 and when first attempts were made at in utero pacing for complete heart block in 1986. Ongoing clinical trials, including the FAST therapy trial for fetal tachycardia and the STOP-BLOQ trial for anti-Ro-mediated fetal heart block, are working to improve diagnosis and management of fetal arrhythmias for both mother and fetus. We are also learning more about how "silent arrhythmias", like long QT syndrome and other inherited channelopathies, may be identified by recognizing "subtle" abnormalities in fetal heart rate, and while echocardiography yet remains the primary tool for diagnosing fetal arrhythmias, research efforts continue to advance the clinical envelope for fetal electrocardiography and fetal magnetocardiography. Pharmacologic management of fetal arrhythmias remains one of the most successful achievements of fetal intervention. Patience, vigilance, and multidisciplinary collaboration are key to successful diagnosis and treatment.

Low Baseline Fetal Heart Rate Leads to Diagnosis of Long QT Syndrome Type 1.

A low baseline fetal heart rate at 20 weeks' gestation was detected in a fetus without cardiac structural anomalies. Fetal echocardiography and magnetocardiography were used to diagnose congenital long QT syndrome. It was confirmed in the neonate, and the same pathogenic variant in KCNQ1 was subsequently identified in the mother.

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.

2023 HRS expert consensus statement on the management of arrhythmias during pregnancy.

This international multidisciplinary expert consensus statement is intended to provide comprehensive guidance that can be referenced at the point of care to cardiac electrophysiologists, cardiologists, and other health care professionals, on the management of cardiac arrhythmias in pregnant patients and in fetuses. This document covers general concepts related to arrhythmias, including both brady- and tachyarrhythmias, in both the patient and the fetus during pregnancy. Recommendations are provided for optimal approaches to diagnosis and evaluation of arrhythmias; selection of invasive and noninvasive options for treatment of arrhythmias; and disease- and patient-specific considerations when risk stratifying, diagnosing, and treating arrhythmias in pregnant patients and fetuses. Gaps in knowledge and new directions for future research are also identified.

Contribution of Fetal Magnetocardiography to Diagnosis, Risk Assessment, and Treatment of Fetal Arrhythmia.

Background Fetal echocardiography has been the mainstay of fetal arrhythmia diagnosis; however, fetal magnetocardiography (fMCG) has recently become clinically available. We sought to determine to what extent fMCG contributed to the precision and accuracy of fetal arrhythmia diagnosis and risk assessment, and in turn, how this altered pregnancy management. Methods and Results We reviewed fMCG tracings and medical records of 215 pregnancies referred to the Biomagnetism Laboratory, UW-Madison, over the last 10 years, because of fetal arrhythmia or risk of arrhythmia. We compared referral diagnosis and treatment with fMCG diagnosis using a rating scale and restricted our review to the 144 subjects from the tachycardia, bradycardia/AV block, and familial long QT syndrome categories. Additional fMCG findings beyond those of the referring echocardiogram, or an alternative diagnosis were seen in 117/144 (81%), and 81 (56%) were critical changes. Eight (5.5%) had resolution of arrhythmia before fMCG. At least moderate changes in management were seen in 109/144 (76%) fetuses, of which 35/144 (24%) were major. The most diverse fMCG presentation was long QT syndrome, present in all 3 referral categories. Four of 5 stillbirths were seen with long QT syndrome. Nine fetuses showed torsades de pointes ventricular tachycardia, of which only 2 were recognized before fMCG. Conclusions FMCG has a significant impact on prenatal diagnosis and management of arrhythmias or familial arrhythmia risk, which cannot be fully met by existing technology. The combination of fMCG and fetal echocardiography in fetal care centers will be needed in the future to optimize care.

Fetal Arrhythmia Diagnosis and Pharmacologic Management.

One of the most successful achievements of fetal intervention is the pharmacologic management of fetal arrhythmias. This management usually takes place during the second or third trimester. While most arrhythmias in the fetus are benign, both tachy- and bradyarrhythmias can lead to fetal hydrops or cardiac dysfunction and require treatment under certain conditions. This review will highlight precise diagnosis by fetal echocardiography and magnetocardiography, the 2 primary means of diagnosing fetuses with arrhythmia. Additionally, transient or hidden arrhythmias such as bundle branch block, QT prolongation, and torsades de pointes, which can lead to cardiomyopathy and sudden unexplained death in the fetus, may also need pharmacologic treatment. The review will address the types of drug therapies; current knowledge of drug usage, efficacy, and precautions; and the transition to neonatal treatments when indicated. Finally, we will highlight new assessments, including the role of the nurse in the care of fetal arrhythmias. The prognosis for the human fetus with arrhythmias continues to improve as we expand our ability to provide intensive care unit-like monitoring, to better understand drug treatments, to optimize subsequent pregnancy monitoring, to effectively predict timing for delivery, and to follow up these conditions into the neonatal period and into childhood. Coordinated initiatives that facilitate clinical fetal research are needed to address gaps in knowledge and to facilitate fetal drug and device development.

Assessment of left ventricular pre-ejection period in the fetus using simultaneous magnetocardiography and echocardiography.

INTRODUCTION: Fetal magnetocardiography (fMCG) is a promising new technique for assessing fetal rhythm; however, no prior studies have utilized fMCG to evaluate human fetal electromechanical physiology. Pre-ejection period (PEP) is an important measure of the electromechanical activation of the heart, and is altered by disease states and arrhythmias. MATERIALS AND METHODS: A novel technique was used to assess fetal PEP and its relationship to other fetal systolic time intervals, RR interval, and gestational age (GA). 25 normal human fetuses between 19 and 38 weeks' gestation were studied using simultaneous pulsed Doppler ultrasound and fMCG. Correlations among PEP, ejection time, QRS width and RR interval were assessed using linear regression. RESULTS: Across all subjects, PEP was found to correlate with GA (R = 0.57, p < 0.0001), QRS width (R = 0.35, p = 0.026), and RR interval (R = 0.37, p = 0.018). In individual sessions, PEP negatively correlated beat-to-beat with the preceding RR interval. CONCLUSION: PEP exhibits developmental trends that provide a better understanding of the normal development of the human fetal heart.

Repolarization Predictors of Fetal Long QT Syndrome.

BACKGROUND: Diagnosis of fetal long QT syndrome (LQTS) using fetal magnetocardiography (fMCG) is straightforward in cases of overt QTc prolongation accompanied by LQTS rhythms; however, cases of isolated QTc prolongation can be challenging. OBJECTIVE: To characterize repolarization in normal and phenotype-positive LQTS fetuses with the goal of utilizing additional parameters of repolarization to improve the accuracy of fMCG diagnosis of LQTS. METHODS: FMCG recordings were taken from 37 phenotype-positive fetuses with confirmed LQTS and 132 normal controls. The normal fetuses were grouped into those with T-and U-waves and those with only T-waves. We compared the repolarization characteristics of normal fetuses with only T-waves with those of LQTS fetuses. We also compared the repolarization characteristics of normal fetuses with T-and U-waves with those of LQTS fetuses with two-component T-waves. RESULTS: Late-peaking T-waves were strongly associated (35/37= 95%) with LQTS. No normal fetuses showed both QTc prolongation (QTc> 500 ms) and a late-peaking T-wave. U-waves were seen in 11 normal fetuses (8%) and resulted in waveforms that often mimicked those of the 19 LQTS fetuses with two-component T-waves; however, in normal fetuses the polarities of the T-and U-waves were the same, whereas in LQTS fetuses with two-component T-waves the polarity of the components was usually opposite. CONCLUSION: A late-peaking T-wave in association with QTc prolongation is a distinctive, reliable indicator of fetal LQTS. U-waves confound assessment of QTc; however, normal U-waves can usually be distinguished from LQTS T-waves based on polarity.

Complex and Novel Arrhythmias Precede Stillbirth in Fetuses With De Novo Long QT Syndrome.

BACKGROUND: Long QT syndrome (LQTS) is a leading cause of sudden cardiac death in early life and has been implicated in ≈10% of sudden infant deaths and unexplained stillbirths. The purpose of our study was to use fetal magnetocardiography to characterize the electrophysiology and rhythm phenotypes of fetuses with de novo and inherited LQTS variants and identify risk factors for sudden death before birth. METHODS: We reviewed the fetal magnetocardiography database from the University of Wisconsin Biomagnetism Laboratory for fetuses with confirmed LQTS. We assessed waveform intervals, heart rate, and rhythm, including the signature LQTS rhythms: functional 2° atrioventricular block, T-wave alternans, and torsade de pointes (TdP). RESULTS: Thirty-nine fetuses had pathogenic variants in LQTS genes: 27 carried the family variant, 11 had de novo variants, and 1 was indeterminate. De novo variants, especially de novo SCN5A variants, were strongly associated with a severe rhythm phenotype and perinatal death: 9 (82%) showed signature LQTS rhythms, 6 (55%) showed TdP, 5 (45%) were stillborn, and 1 (9%) died in infancy. Those that died exhibited novel fetal rhythms, including atrioventricular block with 3:1 conduction ratio, QRS alternans in 2:1 atrioventricular block, long-cycle length TdP, and slow monomorphic ventricular tachycardia. Premature ventricular contractions were also strongly associated with TdP and perinatal death. Fetuses with familial variants showed a lower incidence of signature LQTS rhythm (6/27=22%), including TdP (3/27=11%). All were live born. CONCLUSIONS: The malignancy of de novo LQTS variants was remarkably high and demonstrate that these mutations are a significant cause of stillbirth. Their ability to manifest rhythms not known to be associated with LQTS increases the difficulty of echocardiographic diagnosis and decreases the likelihood that a resultant fetal loss is attributed to LQTS. Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT03047161.

Dynamics of the use of magnetocardiography in the study of the cardiac conduction system of the chick embryo.

INTRODUCTION: Human fetal magnetocardiography (fMCG) has been done for several decades to evaluate fetal arrhythmias using a superconducting quantum interference device (SQUID) magnetometer, but there is little work in embryonic/fetal animal models. This study uses an optically-pumped magnetometer (OPM) to obtain an fMCG in the chick embryo. METHODS: White Leghorn chick embryos were examined from incubation Day #10-19. Different examination chambers were tested to optimize embryonic thermal stability and magnetic signal acquisition. All examinations were done with magnetic shielding. The OPM sensors were placed next to the egg shell. The embryo's position was localized by transilluminating the intact egg or ultrasound imaging the egg with an open air cell to optimize sensor placement. The raw data for each embryo was postprocessed to obtain a fMCG composite waveform. RESULTS: fMCG's were obtained in embryos from Day #12 to 19. The best success with intact eggs was obtained using five sensors; one at the bottom and four around the lower perimeter of the egg at 90° intervals with the egg oriented vertically and the air cell up. Using ultrasound imaging with the air cell open only two sensors were necessary, one at the bottom and one laterally next to the embryo. fMCGs were analyzed for heart rate and rhythm, each portion of the PQRST waveform, and the PR interval, QRS complex, RR interval, and QT interval. CONCLUSIONS: This study validates the chick embryo as an animal model to study in a longitudinal and noninvasive fashion the fetal cardiac conduction system by using OPM magnetocardiography.

Genotype Predicts Outcomes in Fetuses and Neonates With Severe Congenital Long QT Syndrome.

OBJECTIVES: This study sought to determine the relationship between long QT syndrome (LQTS) subtype (LTQ1, LTQ2, LTQ3) and postnatal cardiac events (CEs). BACKGROUND: LQTS presenting with 2:1 atrioventricular block or torsades de pointes in the fetus and/or neonate has been associated with risk for major CEs, but overall outcomes and predictors remain unknown. METHODS: A retrospective study involving 25 international centers evaluated the course of fetuses/newborns diagnosed with congenital LQTS and either 2:1 atrioventricular block or torsades de pointes. The primary outcomes were age at first CE after dismissal from the newborn hospitalization and death and/or cardiac transplantation during follow-up. CE was defined as aborted cardiac arrest, appropriate shock from implantable cardioverter-defibrillator, or sudden cardiac death. RESULTS: A total of 84 fetuses and/or neonates were identified with LQTS (12 as LQT1, 35 as LQT2, 37 as LQT3). Median gestational age at delivery was 37 weeks (interquartile range: 35 to 39 weeks) and age at hospital discharge was 3 weeks (interquartile range: 2 to 5 weeks). Fetal demise occurred in 2 and pre-discharge death in 1. Over a median of 5.2 years, there were 1 LQT1, 3 LQT2, and 23 LQT3 CEs (13 aborted cardiac arrests, 5 sudden cardiac deaths, and 9 appropriate shocks). One patient with LQT1 and 11 patients with LQT3 died or received cardiac transplant during follow-up. The only multivariate predictor of post-discharge CEs was LQT3 status (LQT3 vs. LQT2: hazard ratio: 8.4; 95% confidence interval: 2.6 to 38.9; p < 0.001), and LQT3, relative to LQT2, genotype predicted death and/or cardiac transplant (p < 0.001). CONCLUSIONS: In this large multicenter study, fetuses and/or neonates with LQT3 but not those with LQT1 or LQT2 presenting with severe arrhythmias were at high risk of not only frequent, but lethal CEs.

Meeting the research infrastructure needs of micropolitan and rural communities.

In the 1800s, this country chose to establish land-grant colleges to see that the working class could attain higher education, and that the research needs of the agricultural and manufacturing segments of this country could be met. It seems contrary to our origins to see so little support at present for research infrastructure going to the very communities that need such research to sustain their populations, grow their economies, to attract physicians, to provide adequate health care, and to educate, retain, and employ their youth. Cities are viewed as sources for high-paying jobs, yet many of these same jobs could be translated to rural and micropolitan areas, provided that the resources are established to support it. One of the fastest growing economic periods in this country's history was during World War II, when even the smallest and most remote towns contributed substantially to the innovations, manufacture, and production of goods benefiting our nation as a whole. Rural areas have always lagged somewhat behind metropolitan areas in acquisition of new technology. Rural electricity and rural phone access are examples from the past. Testing our universities' abilities to grow distributive research networks beyond their campuses will create a competitive edge regionally, against global workplace, educational, and research competition, and will lay the groundwork for efficiency in research and for new innovation.

Fetal magnetocardiogram waveform characteristics.

BACKGROUND: Fetal magnetocardiography (fMCG) is the most direct and precise method of assessing fetal rhythm and conduction. Although the utility of fMCG for evaluation of fetuses with serious arrhythmia is generally acknowledged, many aspects of fetal rhythm and conduction are relatively unstudied. OBJECTIVE: To record fMCG in a large group of normal fetuses in order to provide a more comprehensive evaluation of fMCG waveform characteristics, including waveform intervals, amplitudes, and morphology. METHODS: The subjects were 132 healthy women with uncomplicated singleton pregnancies, studied at 15.7-39.9 (mean 28.9) weeks' gestation in 259 sessions. The P, PR, QRS, QT, QTc, and RR intervals and the P/QRS and T/QRS amplitude ratios were measured. MAIN RESULTS: The P, PR, QRS, and RR intervals increased with gestational age, but QT and QTc did not. U-waves were seen in 11% of fetuses. The T-waves were often flat with low T/QRS amplitude ratios. Equiphasic QRS complexes were associated with tall P-waves. The PR, QRS, and QT intervals showed a power law dependence on RR interval with power law exponents 0.445, 0.363, and 0.381, respectively. SIGNIFICANCE: The data establish prediction intervals for fMCG waveform intervals and amplitudes in normal fetuses. This is critical for identification of fetuses with abnormal rhythm. Our study is the first to document the incidence of U-waves and flat T-waves in the fetus, both of which are uncommon postnatally. The association of tall P-waves with equiphasic QRS complexes provides a useful means of improving the resolution of fetal P-waves.