These are transient decelerations of the fetal HR which can drop as low as 40 bpm and resolve within one minute, returning to a normal heart rhythm. This type of bradycardia is observed in the second trimester and is considered benign, meaning clinically insignificant. It is believed to be caused by exaggerated vagal tone, which is common during this period. This type of bradycardia does not require treatment (Table 1).

Characterized by a 1:1 AV conduction with a regular fetal HR $>$90 to 100 bpm [1]. This type originates from the sinoatrial node, meaning both atrial and ventricular mechanical events are equally slow [5]. This condition often occurs in situations such as: maternal viral infection, maternal treatment with beta-blockers, sedatives and other drugs, rare fetal metabolic disorders such as Pompe disease, idiopathic sinus bradycardia, neck stretching, or other autonomic causes [5]. In cases of persistent bradycardia, the underlying cause should be investigated. This may include assessment for the presence of maternal anti-Ro autoantibodies and the differential diagnosis of ectopic atrial rhythm must be considered. Furthermore, although rare, LQTS is a diagnosis that should be considered in cases with a family history of sudden death, syncope and congenital deafness. Sinus bradycardia usually does not require specific antiarrhythmic treatment (Table 1).

Unlike sinus bradycardia, low atrial rhythm mechanisms include congenital displacement of atrial activation or absence of the sinoatrial node [5], meaning the electrical stimulus can originate from any focus within the atria. Ectopic atrial rhythm can appear in association with congenital heart defects such as left atrial isomerism or hereditary arrhythmias like LQTS. Low atrial rhythm is characterized by regular low fetal HR ranging from 80 bpm to 110 bpm with 1:1 AV conduction with short AV interval. It does not require antiarrhythmic treatment in utero [1] (Table 1).

LQTS is a very important and currently well-studied condition. It is inherited in an autosomal dominant manner and can present as mild isolated bradycardia, supraventricular extrasystole with 2:1 blocked bigeminy, second-degree atrioventricular block (AVB) [12], Torsades de Pointes (TdP), or ventricular tachycardia (VT) [7]. While TdP and second-degree AV block are generally easily recognized and highly specific, they occur infrequently. It is known that 40% of fetuses with bradycardia have associated LQTS. According to Mitchell et al. [12], this association can reach 44% to 66% between the 26th and 40th weeks of gestation. Previous publications have described fetal HR varying from 100 bpm to 130 bpm in fetuses with LQTS. Other reports indicate that a fetal HR of 110 bpm at any gestational age could exclude potential carriers of this syndrome. Thus, using fetal HR 3rd percentile for gestational age improves the identification of individuals with LQTS from 15% to 85% [12].

When LQTS is suspected, fetal management includes careful observation and a detailed family history of LQTS. Fetal magnetocardiography is an examination used in the diagnosis of such arrhythmias, enabling the detection of fetal repolarization abnormalities, especially in LQTS. In the future, it may become a more accessible diagnostic tool, though it is currently only available in specialized centers [4]. Regardless of family history, a postpartum ECG should be performed with measurement of the corrected QT (QTc) interval. If there is a positive family history or the fetus presents with complex rhythms, first-degree relatives should be screened by ECG, even if they are asymptomatic. First-degree relatives with ECG showing evidence of LQTS may justify genetic testing. If the postnatal genetic test is positive in a fetus suspected of having LQTS without clinical or genetic manifestations in first-degree relatives, parental mosaicism could be a possibility, especially for monitoring future pregnancies [12].

Maternal electrolyte imbalances, such as hypomagnesemia and hypocalcemia, as well as certain drugs and anesthetic agents that can prolong the QT interval, should be avoided [5]. Fetal treatment is not recommended for bradycardia, but tachycardias such as TdP and VT do require intervention. Measuring isovolumetric time intervals derived from spectral Doppler can help distinguish challenging rhythms. In fetuses with blocked bigeminy or antibody-mediated AV block who exhibit an isovolumetric relaxation time (IVRT) $>$70 ms, LQTS should be considered the most likely diagnosis [7, 13]. After birth, $\beta$-blocker treatment should be initiated in all patients with LQTS, including those who are asymptomatic, since the first clinical manifestation of this condition may be sudden death.

Blocked supraventricular extrasystoles present with a 2:1 AV conduction and a ventricular rate that varies from 75 bpm to 110 bpm [1]. Some authors suggest that the fetal HR may vary between 70 bpm and 90 bpm [5] and usually do not require treatment, as their resolution is often spontaneous before delivery [13]. Weekly monitoring is necessary to detect cases that may develop into supraventricular tachycardia (SVT), as approximately 10% to 13% can progress to SVT [1].

Blocked atrial bigeminy (BAB) frequently exhibits a typical atrial rhythm with alternating shorter and longer intervals between atrial contractions (AA interval), while in second-degree AVB, the interatrial frequency is regular (i.e., the AA interval remains consistent). Furthermore, the IVCT is shorter, which can help with the differential diagnosis from 2:1 AVB [5]. Sonesson et al. [13] found IVCT values of 13.6 $\pm$ 5.8 ms in BAB and values of 60.9 $\pm$ 22.6 ms in second-degree AVB, both with IVRT 70 ms (Table 1).

It is important to ensure that this is indeed a BAB, as AV block is a differentiation diagnosis. BAB requires no specific treatment but may progress with spontaneous resolution, whereas second-degree BAB may evolve to complete resolution, which is usually irreversible. It is advisable to follow up BAB with weekly assessment of fetal HR by echocardiogram or sonar.

AV block are electrical conduction disturbances that occur between atrial depolarization and ventricular depolarization. Bradycardia and electromechanical dissociation cause the fetal heart to accommodate a larger stroke volume to maintain adequate cardiac output.

All cardiac impulses are conducted from the atria to the ventricles with a prolonged AV conduction time, marked by a PR interval $>$150 ms. The AV intervals increase during pregnancy and decrease with an increase in HR [14]. The measurement of the PR interval can be done by the measurement of the AV interval using the flow from the mitral valve to the aortic outflow tract (MV-Ao), from the superior vena cava to the aorta (SVC-Ao), or from the pulmonary vein to the pulmonary artery (PV-PA) [14, 15, 16, 17, 18]. These methods using Doppler ultrasound that have been validated in fetuses [19] (Fig. 3).

Fig. 3.

Evaluation of the mechanical PR interval. (A) Doppler of the pulmonary vein and the right pulmonary artery with the mechanical PR interval measured from atrial contraction to the beginning of pulmonary systolic flow. (B) Mitral-aortic Doppler in the five-chamber view, with the PR interval measured between the E and A waves of the mitral flow to the beginning of aortic systolic flow. (C) Tissue Doppler of the left ventricle’s lateral wall, where the PR interval should be measured between the E’ and A’ waves to the start of the S’ wave.

In pregnant women with anti-Ro (anti-SSA) and or anti-La (anti-Sjogren’s-syndrome-related antigen B (anti-SSB)) antibodies such as in Systemic Lupus Erythematosus (SLE) or Sjögren’s Syndrome, without established CAVB, it is recommended to monitor the mechanical PR interval 1 to 2 weekly between 18 and 26 weeks of gestation. After 26 weeks of gestation, it is recommended to continue monitoring until birth, as follows: (1) if the mechanical PR interval remains stable and 150 ms, once a month or (2) if there is progression of the mechanical PR interval or PR $>$150 ms, follow-up may be done every two weeks [1]. It should be noted that anti-Ro/SSA antibodies can also cause endocardial fibroelastosis and dilated cardiomyopathy, even in the absence of AV block [4, 7] (Fig. 4). However, first-degree of AV block may progress to advanced blocks at short intervals, telemedicine with home monitoring of the fetal HR by pregnant women may be a useful tool for detecting the window between incomplete AV block and CAVB [4, 7] (Fig. 4). The use of dexamethasone may be beneficial in cases of progressive prolongation of the AV interval associated with signs of myocardial inflammation (myocardial hyperechogenicity, valve regurgitation, cardiac dysfunction, and pericardial effusion) (Table 1).

Fig. 4.

Newborn of a mother with Sjögren’s Syndrome without congenital complete atrioventricular block, showing signs of fibroelastosis, due to the proliferation of collagen and elastic fibers caused by the transplacental passage of maternal antibodies. (A) Transthoracic echocardiogram, parasternal long-axis view showing thickening of the ventricular endocardium in the septal and left ventricular posterior wall regions (red arrows). (B) Parasternal short-axis view showing endocardial thickening in the septal region (red arrows) with more echogenic points.

There is a regular or not low HR with progressive increase in the PR interval until an atrial electrical impulse is not conducted to the ventricle. The assessment of the IVCT helps differentiate BAB, which usually resolves spontaneously, from second-degree AV block [13].

Ciardulli et al. [20] demonstrated that there was progression to CAVB in 52% of fetuses treated with corticosteroids and 73% of those not treated. Once second-degree AV block is diagnosed, the use of corticosteroids may be benefit to prevent progression to third-degree AV block (until more robust evidence-based studies such meta-analyses are available). Furthermore, it has been suggested that the corticosteroids treatment improves myocardial performance and interferes with the inflammatory process in fetal conduction tissue, in addition to accelerating lung maturity when there is a risk of premature birth.

CAVB is caused by an electrical disorder leading to electromechanical dissociation, with interruption of electrical impulses from the atria to the ventricles (Fig. 5). The incidence of AV block is 1 in every 15,000–20,000 live births. Of these cases, 50% to 55% of the cases are associated with structural congenital heart defects, with 60% associated with left atrial isomerism and about 40% associated with positive maternal SSA/Ro or SSB/La antibodies [21, 22, 23, 24, 25]. Immune-mediated CAVB typically presents with a normal structural heart.

Fig. 5.

Complete atrioventricular block (CAVB) in a case with maternal high anti-SSA and anti-SSB antibody titers. Doppler of mitral and aortic flow recordings showing the A-V dissociation. Note that the atrial HR (number of A waves) higher than ventricular HR (number of V waves). A, atrial contraction; V, ventricular contraction; anti-SSA, anti-Sjogren’s-syndrome-related antigen A; anti-SSB, anti-Sjogren’s-syndrome-related antigen B.

Immune-mediated AV block without cardiac structural anomaly appears to have the best long-term prognosis. Lopes et al. [26] reported that spontaneous regression of AV block in utero is possible in fetuses whose mothers remained seronegative throughout pregnancy. Baruteau and Schleich [27] reported an interim analysis of a multicenter study, showing that 37% of these seronegative fetuses with AV block progressed to third-degree AV block during childhood.

The pathophysiology of immune-mediated AV block is not fully understood in susceptible fetuses. The fetuses of pregnant woman with anti-SSA/Ro and/or anti-SSB/La antibodies are at risk of cardiac damage due to transplacental crossing of these antibodies. The presence of anti-SSA (anti-Ro) and anti-SSB (anti-La) occurs in autoimmune diseases such as Sjögren’s syndrome and systemic lupus erythematosus. The “Ro” autoantigen consists of two proteins (weighing 60 kDa and 50 kDa) which can be detected using separate solid-phase immunoassays. Ribonucleoproteins from the antibodies bind to autoantibodies, which enter the fetal circulation in the middle of the second trimester, being expressed in the cardiomyocytes of the fetal myocardium, particularly: 52 kD Ro/SSA (Ro52), 60 kD Ro/SSA (Ro60), and 48 kD La/SSB (La48) [6]. This immune process results in fetal conduction tissue inflammation of the fetal conduction tissue and myocardium with progressive and irreversible fibrosis [21]. This can lead to functional abnormalities including cardiomegaly, ventricular hypertrophy, impaired ventricular function, and atrioventricular valve regurgitation, contributing to pericardial effusions and, in severe cases, FHF and hydrops fetalis [21]. Furthermore, a study described the presence of ventricular fibroelastosis [24] (Fig. 6).

Fig. 6.

Fetus at 31 weeks of gestation with congenital complete atrioventricular showing signs of fibroelastosis. The fetal echocardiogram, in a four-chamber view, shows thickening of the left ventricular endocardium in the septal and lateral regions, along with left ventricular hypertrabeculation and increased echogenicity.

Fetal congenital immune-mediated CAVB occurs in 2% to 6% of anti-Ro–positive mothers with a recurrence rate of 18% in subsequent pregnancies, and it carries a mortality rate of approximately 30% [4]. The outcome can vary depending on the management and monitoring of these pregnancies [22, 23]. It is known that around 50% of mothers with anti-Ro/SSA antibodies are asymptomatic at the time of delivery or diagnosis [21] (Fig. 7).

Fig. 7.

Fetal heart rate evaluation using M-mode showing right atrial and left ventricular contraction, and spectral Doppler of umbilical artery flow. (A) M-mode with a sample cutting through the right atrium and left ventricle, in an oblique four-chamber view, where arrows indicate atrial contraction (A) and ventricular contraction (V). (B) M-mode demonstrating mechanical movement of atrial contraction with a heart rate of 149 bpm and ventricular contraction with a heart rate of 75 bpm, indicating 2:1 complete atrioventricular block. (C) Spectral Doppler of the umbilical artery showing a ventricular heart rate of 61 bpm.

Several treatments have been attempted for fetal CAVB, but no consistent study has been achieved. Some authors have shown that there is no evidence supporting the use of corticosteroids in already established immune-mediated CAVB due to irreversible fibrosis in the cardiac conduction tissue, as well as the side effects caused in pregnant women [24, 28, 29]. Lopes et al. [26] also demonstrated that in fetuses with a HR 50 bpm or in the presence of hydrops, corticosteroid treatment did not alter the natural history of the condition. However, Yoshida et al. [29] suggested that maternal treatment early in pregnancy, before the onset of CAVB, has been used. This case report revealed that treatment with maternal terbutaline resulted in an increase in fetal ventricular rate and an improvement in cardiac function, ultimately leading to a full-term delivery without complications. Notwithstanding the potential complications of corticosteroids, maternal therapy with dexamethasone (4–8 mg/d) in second-degree AVB, or in first-degree AVB in the event of additional cardiac findings indicative of inflammation (echogenicity, valvular regurgitation, cardiac dysfunction, stroke, etc.), can be considered as a means of preventing progression to CAVB. Cuneo et al. [30] have provided the evidence that the home-monitoring of HR can enhance the chance of therapeutic success through early therapeutic intervention with corticosteroids in cases where CAVB, whereas complete AV block is typically irreversible once stablished. Considering that CAVB can develop in less than 24 hours, telemedicine with home monitoring of fetal HR by pregnant women may facilitate the detection of the window between second-degree AV block and CAVB.

Jaeggi et al. [31] proposed a protocol where: for a fetal HR $>$55 bpm with normal cardiac function, only dexamethasone should be started. The use of dexamethasone is based on the assumption that the cause is inflammatory carditis. Cases of fetal CAVB with HR $>$55 bpm have a good prognosis. Fetal HR 55 bpm is associated with cardiac decompensation and low cardiac output, and the use of $\beta$-sympathomimetics is indicated [1]. Some authors suggest that in addition to HR stimulation, dexamethasone use is also recommended [31]. Fetal HR 50 bpm in immature but viable fetuses, with signs of heart failure and hydrops, have a guarded prognosis. In such cases, the only intervention may be premature delivery and temporary pacemaker implantation. For fetuses with very low HR, hydrops, and extreme immaturity, intrauterine pacemaker implantation can be considered, although it remains technically challenging and is still in experimental studies [1].

Regarding treatment with $\beta$-sympathomimetics, studies have shown mixed results. The use of salbutamol, terbutaline, or isoprenaline are well-tolerated medications, though maternal extrasystole and sinus tachycardia may occur. Groves et al. [32] reported that salbutamol and terbutaline showed better responses in increasing fetal HR compared to isoprenaline. The only contraindication to high-dose salbutamol therapy is placental insufficiency [32]. In another study, terbutaline was administered orally and showed good transplacental passage, with an expected increase in fetal HR [24]. Yoshida et al. [29] reported a study using intravenous terbutaline, with the aim of increasing fetal HR and improving cardiac function, which was achieved, preventing heart failure, especially in fetuses not affected by hydrops or structural heart disease. The use of $\beta$-sympathomimetics increases the fetal HR by approximately 10% to 15% [1, 29]. However, this increase is transient [13], and there are no studies demonstrating that it improves survival in these fetuses.

The follow-up protocol for such cases is not well-established [1, 29]. Weekly or biweekly monitoring of the AV interval is recommended from weeks 18 to 26 weeks of gestation (Table 1). Delivery should be planned in a tertiary center, with either cesarean section or vaginal delivery at 37 weeks of gestation, if the course is satisfactory. In cases of fetal hydrops progression, a cesarean section is recommended, with pacemaker implantation immediately after birth [27].

Although controversial because it does not appear to reverse congenital heart block and may have potential adverse effects on both the developing fetus and the mother, the use of immunoglobulin can improve fetal and postnatal survival in fetuses with systolic cardiac dysfunction and/or signs of endocardial fibroelastosis and/or myocarditis [1]. Dexamethasone may also be used to reduce the prevalence of dilated cardiomyopathy in stablished immune-mediated CAVB with signs of myocardial inflammation, however, it was not classically recommended for CAVB due to the significant side effects that can occur in the mother or fetus. Therefore, the use of this medication should be discontinued if they occur [32, 33, 34]. Histological evidence shows a $\ge$17% risk of dilated cardiomyopathy after birth, associated with heart failure, heart transplantation, or premature death. Treatment with corticosteroids, with or without intravenous immunoglobulin, increases fetal, neonatal, and 1-year survival rates to 95%, and reduces the incidence of dilated cardiomyopathy to 3%. The recommended dose of intravenous immunoglobulin is 1 g/kg, with a maximum of 70 g per dose, administered every 3–4 weeks [4].

Indeed, studies comprehensive studies are currently underway with the objective of evaluating the efficacy of treatment with steroids and intravenous immunoglobulin in the context of immune-mediated incomplete fetal heart block. Additionally, the possibility of restoring the fetal heart rhythm to a normal state or preventing the development of complete heart block is being explored in such trials [Surveillance and Treatment to Prevent Fetal Atrioventricular Block Likely to Occur Quickly; ClinicalTrials.gov: NCT04474223]. These investigations are conducted in a stratified fashion, taking into account the titer of anti-Ro/SSA antibody present in each pregnancy [Slow Heart Registry of Fetal Immune-mediated High Degree Heart Block; ClinicalTrials.gov: NCT04559425].

The maternal use of beta-sympathomimetics (salbutamol 30–40 mg/d or terbutaline5–30 mg/d) is indicated when fetal HR is bellowing 50 bpm to 55 bpm and/or in the presence of ventricular dysfunction. Maternal extrasystoles and sinus tachycardia may occur, but these drugs are generally well tolerated. An increase in fetal heart rate of about 10%–15% of baseline is expected, which may prolong pregnancy to term or near term [1, 24, 29, 32].

Regarding the use of hydroxychloroquine, while it is not a medication for reversing antibody-mediated atrioventricular block, it has been shown to reduce the recurrence rate by more than 50% in future pregnancies [4]. As a result, the prescription of hydroxychloroquine to pregnant women with ant-Ro/SSA antibodies is supported by European League Against Rheumatism (EULAR) since 2016 [35, 36].

The estimated fetal weight is critically important, especially for planning the postnatal management. This is particularly relevant because the permanent pacemaker implantation typically occurs when the infant’s weight exceeds 2800 grams. Additionally, the need for a temporary pacemaker significantly increases the risk of neonatal mortality [33]. Table 1 describes the main characteristics and management of the CAVB and the main types of fetal bradyarrhythmia.