Fetal Complete Congenital Heart Block

4 chamber with colour to visualize the inflow, as well as output via the LVOT and RVOT. 

These clips outline the contractions of the atriums at a faster rate than the ventricular contraction. The M-Mode (Ventricular-Atrial) will help characterize further the entity. 

M-mode outlining that the atrial rate is 161 bpm and the ventricular rate is 52 bpm. 

Dopplers outlining the underlying ventricular rate

Views outlining the low ventricular rate. One may perceive the faster atrial contraction on the B-Mode. This will be better exemplified by the M-Mode (better temporal resolution), allowing for evaluation of atrial and ventricular rates and relationship. 

M-Mode outlining that the ventricular rate is 66 bpm, while the atrial rate is 140. There is no clear relationship between the atrial and ventricular rates. 

Doppler in the arch may be used to estimate the ventricular rate. 

Normal atrivoentricular (AV) time interval (mitral-aortic) at 107 msec, (superior vena cava (SVC)-aorta) at 97 msec

Case of complete heart block with hydrops in fetal life provided by Dr Wadi Mawad, Pediatric Cardiologist at the Montreal Children's Hospital

Presentation on Congenital Heart Block

Elements to consider in the care of fetuses with complete immune-mediated CHB (not exhaustive)

The management of these fetuses is still controversial. There are variations in practice due to the lack of trial-informed studies. These are elements to consider and adapt based on the practice at your institution and in consultation with your local experts. Ambulatory monitoring with Dopplers being performed by the pregnant patient may be considered, although the data does not seem to be convincing regarding the detection of first and second-degree heart block by the pregnant individual. A multi-centric study (STOP-BLOQ) is ongoing.

Prenatal:

1. Continue vigilant monitoring of fetal cardiac function and signs of hydrops. Adjust delivery timing based on maternal or fetal alterations in well-being.

2. Fetal cardiology to evaluate positive Anti-Ro or Anti-La pregnancy starting 16 weeks and up to 24 weeks with screening for fetal heart block 

3. Review recent ultrasounds and fetal echocardiography conducted before the delivery.

4. Evaluate for presence of fetal heart block (quantification of mechanical AV interval), fetal cardiac performance, fetal endocardial fibroelastosis, hydrops, polyhydramnios, growth restriction, fetal umbilical and cerebral Dopplers, and presence/severity of atrio-ventricular valvular insufficiency. These are all factors of prognosis.

5. Consider prenatal treatment with maternal dexamethasone to reduce the risk of postnatal neonatal cardiomyopathy with those having fetal heart block. IVIG are reserved under certain circumstances (worsening CHB, signs of fetal cardiomyopathy). Please review section on fetal cardiac function.

6. Pregnant individuals with SSa (Anti-Ro) or SSb (Anti-La) circulating antibodies should be followed by rheumatology and maternal fetal medicine (and possibly obstetrical medicine). A titre value of the corresponding circulating antibody should be considered during pregnancy.

7. "The use of β-sympathomimetics such as terbutaline, salbutamol, and isoprenaline to augment fetal ventricular rates when <55 bpm has been reported. β-Sympathomimetics are reasonable to use in fetuses with heart rates <55 bpm or in fetuses with higher heart rates if there is underlying severe CHD or symptoms of fetal heart failure or hydrops. Terbutaline appears to be well tolerated, although maternal resting heart rates of 100 to 120 bpm and benign ectopy are commonly encountered. Unfortunately, although terbutaline may increase fetal rates and prolong pregnancy, no studies have shown survival benefit. Although there is merit to the notion, because of significant technical limitations, fetal pacing has not been shown to be successful in improving survival or prolonging gestation and therefore at present is experimental and not recommended as part of usual care." Reference.

8. After delivery - collaborate with pharmacy (adult) to devise a dexamethasone tapering strategy post-delivery in the mother exposed to prolonged dexamethasone therapy.

Delivery Room Management:

1. Plan a daytime and weekday C-section due to fetal bradycardia (inability to monitor fetal wellbeing during labour).

2. Ensure NICU and Cardiology team aware of delivery. NICU team presence at delivery and prompt notification when the mother arrives at the birthing center.

3. Evaluate the possibility of delayed cord clamping (DCC) at the discretion of the neonatologist and obstetrician, with immediate clamping if the baby lacks vigor and respiratory efforts.

4.  Prepare for potential neonatal bradycardia, with readiness for respiratory support, intubation, line placement, and chest compression if needed.

5. The baby may be born with a heart rate lower than 60 (often ventricular rate can hover around 55-60 bpm during fetal echocardiography). Heart rate typically increases during the postnatal transition (adrenergic stimulation from delivery and transitional process increasing background ventricular rate) but it may be that the newborn will have a heart rate below 60 bpm with appropriate output to sustain transition without the need of significant resuscitation. These newborns will have had some adaptation in-utero to the low ventricular rate, if their cardiac performance was not impacted by myocardial inflammation (myocarditis) and if the AV valve have appropriate coaptation. 

6. It could also be that these newborns experience significant need for support – respiratory support, and chest compression if significantly hypoperfused and dropping heart rate. Heart rate may not be an adequate indicator of efficiency of resuscitation measures. As such, the team should be ready to provide respiratory assistance and intubation, line placement and chest compression. The advancement to chest compression should only be after airway securement and adequate oxygenation/ventilation and if significant instability with no reactivity, poor perfusion (long refill, pale/blue, limp, weak pulses, mottled), poor pulses. Saturometer will often have a poor or no tracing due to the low perfusional status.  

7. In the delivery room, a team member should be ready to install an umbilical venous line. 

8. Isoproterenol should be prepared for an infusion and be available in the delivery room on a pump. The medication range is: 0.01 - 0.5 microgram/kg/minute (Maximum dose: 2 microgram/kg/ minute). This medication should be considered for initiation at 0.01 mcg/kg/min and up titration to effect (higher dosages such as 0.1 mcg/kg/min can be fairly pro-arrhythmic and vasodilating). It should only be started for hemodynamically instability rather than purely based on a heart rate value. Typically, it is initiated in babies with significant bradycardia hovering less than 50 bpm and with concomitant hemodynamics instability. This medication is used to accelerate the ventricular rhythm (not to increase atrio-ventricular conduction, since the AV node is often fibrosed in infants with complete congenital heart block). It may be titrated up if the response is not adequate (usually fast acting and titration can occur after 5-10 minutes of initiation or change in dose).

9. Transcutaneous pacing should be a last resort and may lead to significant skin burns. Ideally, it should be initiated only in consultation with cardiology, unless there is an extremely urgent situation and cardiology not available in the delivery room or at bedside. Skin needs to be dried and pads should not be touching each other (one pad on front and one pad on the back). Output should be initiated at 20 mA and rate at 90 bpm. Output may be increased by increment of 5 mA until there is QRS capture. The pacer machine should be set on “fixed” mode in the delivery room, and only be transitioned to “demand” mode once there is the possibility of connecting the ECG leads to the pacer machine. 

10. Cardiac surgery and cardiology need to be aware of these cases in advance, in case there is a need for urgent pacemaker or epicardial pacemaker (if premature newborn / small weight).

Neonatal admission:

1. Newborn should be admitted to the NICU and UVL/UAL should be installed for administration of medication and monitoring. A double-lumen UVL should be placed for medications. In the case of pacing, analgesia may be required. Sedation/Analgesia may also be required to decrease cardiac work if the baby is unstable and with signs of heart failure. 

2. Document liver edge on exam (presence of hepatomegaly and cm to coastal border). 

3. NIRS is installed at our institution (cerebral and somatic) for monitoring.

4. Baby is kept NPO and TFI is at 65 mL/kg/day. Starter TPN and SMOF (lipids) may be considered to optimize nutrition.

5. Initial blood work include: gaz, crossmatch and Coombs, CBC, liver enzymes, albumin, creatinine, bilirubin (for cholestasis), baseline NT-proBNP, baseline troponin, baseline creatine kinase. 

6. Blood gaz is then followed q 4-6 hours for the first day of life (to monitor glucose, calcium, pH, CO2, electrolytes and lactate)

7. Mg, PO4, Triglycerides (TPN labs) with liver enzymes (AST, ALT) and Bili at 24 hours of age to rule out autoimmune hepatitis, cholestasis and routine screening of neonatal jaundice 

8. Chest and abdominal radiography, as well as abdominal shoot-through for line placement and cardio-thoracic silhouette

9. Consultation with cardiology with echocardiography and formal 12-lead ECG. 

10. We obtain consent with parents for the admission, pasteurized human milk (if eventually needed), PICC line and transfusion.

11. Hydrocortisone initiated at 30 mg/m2/day (average newborn BSA is 0.25 m2) = 1 mg IV q8hr. This dose should be kept until clarification of the plan (i.e. need for pacemaker or not). It should then be tapered to 10 mg/m2/day and eventually an ACTH-stimulation test should be performed. 

12. The role of ongoing postnatal steroid therapy for modulating cardiac inflammation and cardiomyopathy remains controversial, as potential adverse effects in the neonatal period must be weighed against the uncertain benefits. Current research does not provide strong evidence that post-natal steroids improve or reverse congenital heart block in infants with maternal lupus. While some observational data suggest possible improved outcomes, complete heart block remains largely irreversible, and most infants require pacemakers. Steroids may help with other neonatal lupus symptoms, but their role in treating established heart block is unproven. While postnatal corticosteroids have been proposed as a means of mitigating persistent cardiac inflammation and improving the cardiomyopathy phenotype associated with prolonged in utero injury, this potential benefit remains theoretical. Any consideration of therapy must be carefully balanced against a wide range of adverse effects. Steroids can exacerbate cardiac workload through vascular remodeling and increased afterload, promote myocardial hypertrophy that raises myocardial oxygen demand without a proportional enhancement in stroke volume, and alter coronary perfusion. Systemic complications include hyperglycemia, impaired immunity and increased infection risk, neurotoxicity and neurodevelopmental concerns, adrenal suppression, and activation of mineralocorticoid pathways that may further disturb cardio-renal interactions. Given these risks, the decision to pursue postnatal steroid therapy requires strong clinical rationale, close hemodynamic monitoring, and a clear assessment of risk versus potential benefit. Unfortunately, in infants with established endocardial fibroelastosis (EFE - (hyperechogenicity: edema, inflammation and fibrosis)), the extent of myocardial injury and fibrosis is typically advanced and unlikely to regress with corticosteroid therapy. Moreover, prolonged or high-dose steroid exposure can itself promote a steroid-induced cardiomyopathy phenotype, which may further compromise an already vulnerable myocardium. Overall, the evidence supporting postnatal steroids as an effective means of reducing ongoing cardiac inflammation (especially when it has been ongoing and peaked prenatally for a prolonged period of time) remains highly controversial, and any potential benefit is uncertain. A summary of the available literature is provided below:

    • See: Trucco SM, Jaeggi E, Cuneo B, et al. Use of intravenous gamma globulin and corticosteroids in the treatment of maternal autoantibody-mediated cardiomyopathy. J Am Coll Cardiol. 2011;57(6):715-723

    • A poster described a cohort of 33 children with cardiac neonatal lupus who received postnatal immunosuppressive therapy (including corticosteroids and IVIG). Most had good long-term outcomes, with a 9% mortality rate—lower than historical rates (13–30%). However, progression from first/second-degree to complete heart block still occurred in some, and most children with complete heart block required pacemakers. The study suggests postnatal immunosuppression may improve outcomes, but causality is not established and the data are not from randomized trials. 

      1. Reference: Yathiraju, C., Thompson, K., Diaz, T., Dominguez, D., Freud, L., Hamilton, R., Jaeggi, E., Knight, A., Laskin, C., Silverman, E., & Hiraki, L. (2025). Long-term outcomes of postnatal immunosuppressive therapy in children with cardiac neonatal lupus erythematosus. The Journal of Rheumatology. https://doi.org/10.3899/jrheum.2025-0390.pv154.

    • Case reports and small series describe transient improvements in cardiac function (e.g., ejection fraction) after postnatal steroids and IVIG, but these are anecdotal and do not demonstrate reversal of established complete heart block. 

      1. Ref 1: Ali, M., Beheri, R., Alheraish, Y., Almuqri, R., Alarwan, K., Alomair, M., Sangi, R., & Alawi, A. (2025). A case of neonatal lupus presenting with myocardial dysfunction with complete heart block: early identification and management results in excellent outcome. International Journal of Contemporary Pediatrics. https://doi.org/10.18203/2349-3291.ijcp20251767.

      2. Ref 2: Rider, L., Buyon, J., Rutledge, J., & Sherry, D. (1993). Treatment of neonatal lupus: case report and review of the literature.. The Journal of rheumatology, 20 7, 1208-11 .

    • Reviews and guidelines consistently state that, once complete congenital heart block is established, it is generally irreversible and postnatal steroids have not been shown to reverse it. Steroids may be beneficial for other neonatal lupus manifestations (hepatic, hematologic), but not for established heart block.

      1. Ref: Sun, W., Fu, C., Jin, X., Lei, C., & Zhu, X. (2025). Neonatal lupus erythematosus: an acquired autoimmune disease to be taken seriously. Annals of Medicine, 57. https://doi.org/10.1080/07853890.2025.2476049.

13. IVIG should only considered with approval of cardiology if there is a significant concern for carditis and cardiac dysfunction. 

14. Newborn may also require inotropic support with epinephrine (or dobutamine) infusion (which also has chronotropic action) depending on the hemodynamic status / perfusion and cardiac evaluation. Dobutamine can be pro-arrhythmogenic, as such epinephrine may be a more optimal choice in the context of decreased cardiac function. 

15. Will likely require a double-lumen PICC line during admission. 

16. Follow CBC before discharge to rule out SLE-related thrombocytopenia, anemia and leucopenia

17. Consultation with social worker, lactation consultant. 

18. Consultation pharmacy: may not be eligible to rotavirus (live) vaccine considering the prolong exposure to steroids during fetal life. As such, baby may not be eligible to live vaccines in first year of life. 

19. The family may be eligible to Neonatal Follow-up. 

20. Avoid sun light exposure to minimized risk of developing neonatal cutaneous lupus. Neonatal cutaneous lupus manifestation may occur in the first few days of life, but is typically appearing after sun exposure due to photosensitivity. It is transient and typically benign.

Summary of data on postnatal corticosteroid therapy in the treatment of neonatal cardiac lupus

Summary statement The following summary was compiled by Ms. Josianne Malo (Neonatal Pharmacist) and translated by Dr. Gabriel Altit, and reviews the available evidence regarding the use of postnatal corticosteroid therapy in infants with cardiac neonatal lupus. 

Local practice note (Dr. Altit): At our institution, we have generally not adopted the routine use of postnatal systemic corticosteroids in infants exposed to anti-Ro antibodies who develop myocardial hyperechogenicity and/or congenital heart block, even when the intent is to limit progression of cardiomyopathy or to delay or avoid cardiac transplantation. This cautious approach reflects the absence of convincing evidence demonstrating a clear benefit of postnatal corticosteroids in this setting, together with concerns regarding cumulative steroid exposure and potential adverse effects. These include myocardial hypertrophy with increased myocardial oxygen consumption, increased vascular stiffness, and unfavorable ventricular loading conditions in an already vulnerable myocardium, as well as systemic effects on other organs, particularly the developing brain.

CARDIAC NEONATAL LUPUS

A comprehensive and detailed review of the etiology and pathogenesis of cardiac neonatal lupus was recently published (Silverman 2025); key points are summarized below.

Pathogenesis

The Ro60 and La48 proteins are present in all cells. During apoptosis, these normally intracellular proteins become exposed on the cell surface. This phenomenon plays an important role in the pathophysiology, as apoptosis is an essential step in cardiogenesis, particularly during cardiac remodeling. When these proteins expressed on the surface of apoptotic cardiomyocytes are targeted by maternal autoantibodies, immune complexes form. This interaction disrupts the physiological clearance of apoptotic cells, inducing local inflammation followed by fibrosis, which contributes to the development of congenital atrioventricular/heart block (AVB / CHB) (Silverman 2025). From a diagnostic standpoint, anti-Ro60 antibodies are highly sensitive but poorly specific for predicting cardiac neonatal lupus, whereas anti-La48 antibodies, although less common, have higher specificity for this condition (Silverman 2025). The majority of mothers of infants affected by cardiac neonatal lupus are asymptomatic and unaware that they carry anti-Ro/La antibodies. The risk is higher when maternal antibody titers are elevated or after a previous pregnancy complicated by AVB, but not all exposed fetuses develop the disease. This suggests variable individual vulnerability and the involvement of additional, still poorly defined, predisposing factors (Silverman 2025).

Two biological mechanisms – two types of involvement

Cardiac neonatal lupus encompasses two manifestations: CHB and cardiac hyperechogenicity (previously called "EFE", although echocardiography cannot evaluate for fibrosis). These may coexist or occur independently. They share a common etiology (mainly maternal anti-Ro antibodies) but affect different tissues through partially distinct mechanisms.

Congenital Heart - Atrioventricular block (AVB / CHB)

CHB is primarily explained by the interaction of maternal anti-Ro/SSA antibodies with L-type and T-type calcium channels. These antibodies can cross-react with fetal calcium channels and inhibit their currents, which are fundamentally involved in action potential generation in cardiomyocytes of the sinus and AV nodes. Prolonged blockade disrupts calcium homeostasis in nodal cells, activating apoptosis and inflammatory mechanisms, and leading to irreversible fibrosis of the conduction system (Gryka-Marton 2021). AVB is readily identifiable on fetal echocardiography. However, it can be very difficult to distinguish second-degree from third-degree AVB. In some cases, the fetal heart rhythm may fluctuate between second- and third-degree AVB (Costedoat-Chalumeau 2020). These features introduce assessment bias in studies. Favorable outcomes have been reported in patients with pacemakers. Nevertheless, secondary cardiomyopathy is a possible complication, particularly in the presence of electromechanical dyssynchrony.

Hyperechogenicity and dilated cardiomyopathy

In the case of hyperechogenicity (also referred to as "fibroelastosis"), there is diffuse IgG infiltration and the presence of a T-lymphocyte infiltrate throughout the myocardium. Transplacental passage of maternal autoantibodies is thought to induce an immune reaction within the myocardium, involving activation of transforming growth factor-β (TGF-β) and leading to fibroelastosis (Gryka-Marton 2021). This process may extend to the junction between the endocardium and myocardium, referred to as endomyocardial thickening. Hyperechogenicity, myocarditis, and dilated cardiomyopathy are more complex to assess by echocardiography.

Critical period

Cardiac manifestations of neonatal lupus typically occur between 14 and 28 weeks’ gestation. Vulnerability appears to decrease after 26 weeks’ gestation, making a new inflammatory insult less likely (Buyon 2025; Carlucci 2025).

A rare and difficult condition to study

Congenital AVB, the most common manifestation of neonatal lupus, remains a rare condition, affecting 0.005–0.007% of births (Silverman 2025). The low prevalence of this pathology poses methodological challenges for studies, limiting the strength of recommendations and leading to variable, often debated, clinical practices.

Possibility of spontaneous regression

Second-degree AVB may remain stable or be spontaneously reversible, but in most cases it progresses to third-degree block (Buyon 2025). Incomplete block is considered a critical and potentially reversible inflammatory state in which the AV node has not yet undergone irreversible fibrosis. Thus, the goal of dexamethasone and IVIG in cases of second-degree AVB is to reduce inflammation and prevent progression to third-degree AVB. Third-degree AVB is generally irreversible, with only rare cases of transient reversal reported (Buyon 2025). This variable clinical course further complicates the interpretation of published studies.

REPORTED BENEFITS OF POSTNATAL CORTICOSTEROID THERAPY

Case report

In a hospital in Saudi Arabia, a newborn with third-degree AVB, heart failure, pulmonary arterial hypertension, hypoxemia, and hemodynamic instability despite pacemaker implantation was treated with ECMO. Four days after IVIG and corticosteroid pulse therapy, left ventricular ejection fraction improved rapidly (from 15% to 55%). The authors suggest that the rapid and marked clinical improvement may be explained by treatment of myocarditis with corticosteroids (Ali 2025). A single case report does not establish causality.

Cohorts

The only cohorts addressing postnatal corticosteroid therapy have been published by, or in collaboration with, the SickKids team. They are briefly summarized here, with a focus on the proposed potential benefits: reduction in hyperechogenicity, dilated cardiomyopathy, and severe heart failure, and improvement in survival.

1) Jaeggi 2004

1. • Pre/post study from 2 centers

   • 16 cases before vs 21 cases after adoption of an antenatal corticosteroid + IVIG protocol

   • Maternal dexamethasone: 19% vs 90%

   • Postnatal steroids (not described): 13% vs 24%

   • Outcomes:

     • Higher neonatal survival: 80% vs 95%

     • Higher 1-year survival: 47% vs 95%

     • Fewer autoimmune-related deaths or transplants
       (4/9 vs 8/18 live births, p = 0.007)

   • Interpretation

     • No evidence that postnatal corticosteroids had a significant impact on:

1. • 1. • Extent of hyperechogenicity

        • Dilated cardiomyopathy

        • Severe heart failure

        • Survival

   • The authors attribute improved survival and reduced autoimmune complications to antenatal corticosteroid therapy.

   • Postnatal steroids were used in a few cases, without demonstrated efficacy.

2) Trucco 2011

• Retrospective cohort from 1 canadian and three other U.S. centers

• 20 newborns with cardiac neonatal lupus (AV block and/or hyperechogenicity)

• Antenatal or postnatal corticosteroids and IVIG

• No control group

• Among 19 live-born infants, 15 received postnatal corticosteroids

• Outcomes

• Median follow-up: 2.9 years (range 1.1–9.8)

• Normal cardiac function in 16 surviving patients (80%)

• 10 patients had pacemakers

• Limitations

  • Highly heterogeneous postnatal treatment (methylprednisolone, prednisone, dexamethasone, or hydrocortisone; at birth, later, or for several months)

  • No data on hyperechogenicity evolution

  • Impossible to draw conclusions on efficacy without a control group

  • Difficult to isolate the effect of postnatal corticosteroids from IVIG and pacing

3) Mawad 2022

1. • Retrospective cohort from four Canadian centers (including SickKids and CHU Sainte-Justine) and three U.S. centers

   • 130 pregnancies affected by cardiac neonatal lupus (mostly third-degree AV block)

   • All treated antenatally with dexamethasone ± IVIG ± beta-agonists

   • External international cohorts used for comparison

   • Reported favorable outcomes

     • Survival:

   • Fetal: 96%

• • Neonatal: 93%

  • End of follow-up (median 5.9 years): 90%

• Dilated cardiomyopathy:

  • 3% incidence (3/99 children with third-degree AV block)

  • Compared with 18–29% in other published cohorts

• Severe heart failure:

  • Normal ventricular function at last follow-up in 97/100 children

  • Interpretation

• • • Postnatal practices varied between centers, but no analysis evaluated the isolated impact of postnatal steroids

    • Use of external comparator cohorts introduces major bias

    • Favorable outcomes attributed to antenatal corticosteroids ± IVIG ± beta-agonists, not postnatal corticosteroids

    • No postnatal data on regression of hyperechogenicity

4) Yathiraju 2025

• Retrospective cohort from SickKids

• 33 children, median follow-up 6 years (IQR 2.5–11.4)

• 85% of mothers received antenatal immunosuppression

• All infants received postnatal corticosteroids

• 52% received pulse therapy

• Postnatal protocol

• IVIG 2 g/kg × 1

• Corticosteroid pulse 30 mg/kg/day × 3 days, then 2 mg/kg/day × 4 weeks, with taper guided by troponin levels

• Outcomes

  • Vast majority had favorable outcomes

  • Mortality 9%, lower than other cohorts (13–30%)

  • Authors suggest postnatal immunosuppression may explain good cardiovascular outcomes

• Limitations

• • Data presented as an abstract; some inconsistencies in reported numbers

  • No control group → no causal inference

  • Difficult to isolate postnatal steroid effect from combined prenatal and postnatal therapies

  • No postnatal data on hyperechogenicity regression

It is possible that postnatal corticosteroid therapy could improve outcomes, but the available data are too limited to evaluate this. No study can establish a causal relationship because of the observational nature of the evidence, historical comparisons, and multiple sources of bias, including:

• Temporal bias (some registries began in the 1960s, 1970s, or 2000s, and evolving clinical practice over time may have influenced outcomes)

• Variable diagnostic criteria

• Heterogeneity of interventions and variable quality of care across centers (making it impossible to isolate the effect of a single intervention)

• Indication bias, which can influence results in both directions:

  • The most severe cases often receive more aggressive treatments, which could falsely associate treatment with worse prognosis

  • Conversely, less severe cases may be overrepresented in cohorts treated systematically, which could falsely associate treatment with better prognosis

• In published data, the absence of a comparator group limits possible conclusions, as do small sample sizes

SAFETY OF POSTNATAL CORTICOSTEROID THERAPY

The tolerability of postnatal corticosteroid therapy for the treatment of congenital cardiac neonatal lupus has not been evaluated in detail. The usual adverse effects of corticosteroids apply: hyperglycemia, arterial hypertension, impaired wound healing, and adrenal insufficiency (Micromedex). Impaired wound healing is a particular concern if pacemaker implantation is required. 

In a Cochrane overview of systematic reviews on corticosteroids for the prevention and treatment of BPD, the following complications were associated with early dexamethasone (van de Loo 2024):

• Cerebral palsy: RR 1.85, 95% CI 1.31–2.61; NNTH 9 (95% CI 6–19); I² 52%; 7 studies, 587 infants

• Overall neurodevelopmental impairment (including motor, cognitive, and sensory deficits): RR 1.36, 95% CI 1.05–1.77; NNTH 10 (95% CI 5–48); I² 34%; 4 studies, 469 infants

• Gastrointestinal perforation: RR 1.73, 95% CI 1.20–2.51; NNTH 32 (95% CI 19–96); I² 0%; 9 studies, 1,936 infants

In that overview, newborns were generally <32 weeks’ gestation and weighed <1.5 kg at birth. Cumulative dexamethasone doses ranged from 0.2 to 14 mg/kg, administered over a few days to several weeks, typically starting in the first week of life (van de Loo 2024).

Data on prednisone and methylprednisolone in neonatology are limited. A secondary observational analysis of the multicenter PENUT trial (Preterm Erythropoietin Neuroprotection Trial) did not find a significant association between postnatal prednisone or methylprednisolone and cerebral palsy (OR 1.5, 95% CI 0.8–2.8), nor with worse neurodevelopment at 2 years (Puia-Dumitrescu 2022). In that study, methylprednisolone was started later (median day 29; IQR day 20–44) and for a relatively short duration (median 13 days; IQR 6–25), and statistical power was limited by small numbers exposed to these agents.

Considerations when interpreting safety data

The external validity of safety data on postnatal corticosteroids for BPD prevention/treatment is affected by gestational age: BPD data come from a more immature population with higher baseline risks of adverse outcomes, compared with infants who are generally 35–37 weeks’ gestation in the context of cardiac neonatal lupus. Dexamethasone-related neurotoxicity is linked to its potent, prolonged glucocorticoid effect with no mineralocorticoid activity. In the brain, this can disrupt the balance between mineralocorticoid and glucocorticoid signaling, leading to pro-apoptotic effects on neurons (Lodygensky 2005; Watterberg 2012; Htun 2021). Methylprednisolone, like dexamethasone, has exclusively glucocorticoid activity (Nicolaides 2018), so a similar neurotoxic effect is conceivable. Based on animal and pharmacokinetic data, methylprednisolone is expected to have less transfer to the central nervous system than dexamethasone, but neonatal-specific data are lacking (Inaba 2010). Transfer of methylprednisolone into the brain may still be clinically meaningful, particularly in neonates.

Synthesis
The role of ongoing postnatal steroid therapy to modulate cardiac inflammation and cardiomyopathy remains controversial, as potential adverse effects in the neonatal period must be weighed against uncertain benefits. Current research does not provide strong evidence that postnatal steroids improve or reverse congenital heart block in infants exposed to maternal lupus antibodies. While some observational data suggest possible improved outcomes, complete heart block is largely irreversible, and most infants require pacemakers. Steroids may help other neonatal lupus manifestations, but their role in treating established heart block is unproven. Postnatal corticosteroids have been proposed to mitigate persistent cardiac inflammation and improve the cardiomyopathy phenotype associated with prolonged in-utero injury, but this potential benefit remains theoretical. Any consideration of therapy must be balanced against a broad range of adverse effects. Steroids can increase cardiac workload through vascular remodeling and increased afterload, promote myocardial hypertrophy that raises myocardial oxygen demand without proportional improvement in stroke volume, and alter coronary perfusion. Systemic complications include hyperglycemia, immunosuppression and infection risk, neurotoxicity and neurodevelopmental concerns, adrenal suppression, and activation of mineralocorticoid pathways that may further disturb cardio-renal interactions. Given these risks, the decision to use postnatal steroid therapy requires strong clinical rationale, close hemodynamic monitoring, and a clear risk–benefit assessment. In infants with established endocardial fibroelastosis, myocardial injury and fibrosis are typically advanced and unlikely to regress with corticosteroid therapy. Moreover, prolonged or high-dose steroid exposure can itself promote a steroid-induced cardiomyopathy phenotype, potentially worsening an already vulnerable myocardium. Corticosteroid therapy may additionally induce myocardial hypertrophy, leading to increased myocardial oxygen demand, while simultaneously increasing afterload through enhanced vascular stiffness and systemic vascular resistance. Together, these effects may further compromise cardiac performance in an already vulnerable myocardium. Overall, evidence supporting postnatal steroids as an effective approach to reduce ongoing cardiac inflammation—especially when inflammation has peaked prenatally over a prolonged period—remains highly controversial, and any benefit is uncertain.

WHAT NEXT?

Slow Heart Registry of Fetal Immune-mediated High-Degree Heart Block - ClinicalTrials.gov NCT04559425 from PI Dr Edgar Jaeggi, The Hospital for Sick Children. A prospective multicenter observational study of fetuses diagnosed with high-degree immune-mediated AV block. The goal is to build an international database on management and outcomes, publish results of currently available prenatal care strategies, and assess the need for further research.

• 27 centers across 11 countries in North America, Europe, and Asia

• Primary objective: determine transplant-free survival to 1 year of age, according to prenatal strategy: fluorinated glucocorticoids vs no glucocorticoids

• Secondary objectives:

  • Compare evolution of clinical parameters (AV conduction, fetal heart rate, other neonatal lupus manifestations, fetal growth)

  • Evaluate use of additional prenatal treatments (corticosteroids, beta-agonists, IVIG)

  • Describe postnatal management (pacemaker, corticosteroids, IVIG)

  • Follow clinical evolution from birth to 1–3 years
    
    

Rozanolixizumab as innovative antenatal secondary prevention? Carlucci 2025
A woman with systemic lupus erythematosus and three previous pregnancies complicated by neonatal lupus (including two cardiac forms) was treated with rozanolixizumab, a monoclonal antibody that blocks the neonatal Fc receptor (FcRn), to reduce maternal IgG and prevent placental transfer. Treatment was given weekly from 14 to 28 weeks’ gestation: the pregnancy had no cardiac complications, and a healthy infant was delivered at 37 weeks.

References:

• Ali M, Beheri RM, Alheraish YA, et al. A case of neonatal lupus presenting with myocardial dysfunction with complete heart block: early identification and management results in excellent outcome. Int J Contemp Pediatr 2025;12(7):1208-11.

• Buyon JP. Neonatal lupus: Management and outcomes. In: UpToDate [Internet]. Waltham (MA): UpToDate Inc.; 2025 [cité le 16 décembre 2025]. Available on : https://www.uptodate.com/contents/neonatal-lupus-management-and-outcomes

• Carlucci PM, Masson M, Cuneo BF, et al. Blocking the neonatal Fc receptor as a novel approach to prevent cardiac neonatal lupus: a proof-of-concept study. Ann Rheum Dis 2025:S0003-4967(25)04417-6.

• Costedoat-Chalumeau N, Morel N. Commentary: First Report of the Italian Registry on Immune-Mediated Congenital Heart Block (Lu.Ne Registry). Front Cardiovasc Med 2020;7:83.

• Gryka-Marton M, Szukiewicz D, Teliga-Czajkowska J, Olesinska M. An Overview of Neonatal Lupus with Anti-Ro Characteristics. Int J Mol Sci 2021;22(17):9281.

• Htun ZT, Schulz EV, Desai RK, et al.Postnatal steroid management in preterm infants with evolving bronchopulmonary dysplasia. J Perinatol 2021;41(8):1783-96.

• Inaba H, Pui CH. Glucocorticoid use in acute lymphoblastic leukaemia. Lancet Oncol 2010;11(11):1096-106.

• Jaeggi ET, Fouron JC, Silverman ED, et al. Transplacental fetal treatment improves the outcome of prenatally diagnosed complete atrioventricular block without structural heart disease. Circulation 2004;110(12):1542-8.

• Lodygensky GA, Rademaker K, Zimine S, et al. Structural and functional brain development after hydrocortisone treatment for neonatal chronic lung disease. Pediatrics 2005;116(1):1-7.

• Mawad W, Hornberger L, Cuneo B, et al. Outcome of Antibody-Mediated Fetal Heart Disease With Standardized Anti-Inflammatory Transplacental Treatment. J Am Heart Assoc 2022;11(3):e023000.

• Nicolaides NC, Pavlaki AN, Maria Alexandra MA, et al. Glucocorticoid Therapy and Adrenal Suppression. [Updated 2018 Oct 19]. In: Feingold KR, Ahmed SF, Anawalt B, et al., editors. Endotext [Internet]. South Dartmouth (MA): MDText.com, Inc.; 2000-. Available on : https://www.ncbi.nlm.nih.gov/books/NBK279156/table/adrenal_glucocorticoid-therapy-and-adrenal-suppression.T./

• PredniSONE, 2025. IBM Micromedex [DRUGDEX]. Consulté le 16 décembre 2025. Available on : https://www.micromedexsolutions.com

• Puia-Dumitrescu M, Wood TR, Comstock BA, et al. Dexamethasone, Prednisolone, and Methylprednisolone Use and 2-Year Neurodevelopmental Outcomes in Extremely Preterm Infants. JAMA Netw Open 2022;5(3):e221947.

• Silverman E, Jaeggi E, Barsalou J. Neonatal lupus erythematosus. Dans : Petty RE, Laxer RM, Lindsley CB, Wedderburn LR, éditeurs. Textbook of Pediatric Rheumatology. 8e édition. Philadelphie : Elsevier; 2025. p. 346‑59.

• Trucco SM, Jaeggi E, Cuneo B, et al. Use of intravenous gamma globulin and corticosteroids in the treatment of maternal autoantibody-mediated cardiomyopathy. J Am Coll Cardiol 2011;57(6):715-23.

• Van de Loo M, van Kaam A, Offringa M, et al. Corticosteroids for the prevention and treatment of bronchopulmonary dysplasia: an overview of systematic reviews. Cochrane Database of Systematic Reviews 2024, Issue 4. Art. No.: CD013271. DOI: 10.1002/14651858.CD013271.pub2.

• Watterberg K, Walsh M, Kennedy K, et al. A randomized controlled trial of the effect of hydrocortisone on survival without bronchopulmonary dysplasia and on neurodevelopmental outcomes at 22-26 months of age in intubated infants (On web). 2012. Available on: https://www.nichd.nih.gov/sites/default/files/about/Documents/Hydrocortisone_Protocol.pd

• Yathiraju C, Thompson K, Diaz T, et al. Long-term outcomes of postnatal immunosuppressive therapy in children with cardiac neonatal lupus erythematosus. J Rheumatol 2025;52(Suppl 1):171.

Important Articles on fetal cardiac manifestations of Anti-Ro (SSa) / Anti-La (SSb) pregnancies

From: Donofrio, Mary T., et al. "Diagnosis and treatment of fetal cardiac disease: a scientific statement from the American Heart Association." Circulation 129.21 (2014): 2183-2242.