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Congenital Heart Block: Dangers Ahead

Children of autoantibody-positive mothers who were born with congenital heart block were at high risk for developing later cardiovascular and autoimmune disorders, as were their siblings, Swedish researchers reported.

In a cohort that included 119 patients with congenital heart block, 16.8% were diagnosed with cardiomyopathy and/or heart failure compared with 0.3% of controls, for a hazard ratio of 70 (95% CI 20.8-235.4), according to Marie Wahren-Herlenius, MD, PhD, and colleagues from the Karolinska Institute in Stockholm. 

In addition, both patients and their siblings had an increased risk for developing any of 15 common autoimmune diseases such as thyroid disease, psoriasis, arthritis, and multiple sclerosis, with hazard ratios of 5.7 (95% CI 2.83-11.69) for patients and 3.6 (95% CI 1.7-8) for siblings, the researchers reported online in Annals of the Rheumatic Diseases.

Congenital heart block is estimated to occur in 1% to 2% of babies born to mothers with anti-Ro/SSA and anti-La/SSB autoantibodies, which cross the placenta and can cause neonatal lupus with third-degree atrioventricular block. The mothers may have been diagnosed with systemic lupus erythematosus or Sjogren's syndrome, although some are asymptomatic.

Most of these children require placement of a pacemaker early in life, but this in turn can increase the likelihood of future cardiomyopathy.

Previous studies have suggested that affected children face various complications, including growth restriction, neuropsychiatric deficits, and rheumatic diseases, which tend to run in families.

To more closely examine long-term outcomes in children with congenital heart block, Wahren-Herlenius and colleagues undertook a cohort study that enrolled 119 patients and 128 siblings born to antibody-positive mothers from 1948 to 2010.

Each patient was matched with 10 controls from the general population (n=1,190) along with siblings of the controls (n=1,071).

Patients' mean age was 7.5 years, and their siblings' mean age was 11.7 years. Mean follow-up was 17.1 years for patients and 18.4 years for the siblings. Total exposure times for patients and siblings were 2,036 and 2,352 years, respectively, while exposure times for the controls and their siblings were 20,078 and 19,534 years.

A total of 14 cases of cardiomyopathy were diagnosed in the congenital heart block group but none among controls (HR >100), and 10 cases of heart failure versus three among controls (HR 34.4, 95% CI 9.5-125.2). Moreover, 46.2% of patients in the heart block group were diagnosed with "other arrhythmias" compared with 0.4% of controls (HR>100). Sick sinus syndrome was detected in 4.2% of patients and 0.1% of controls, while atrial fibrillation and flutter were found in 7.6% of patients.

And "notably," according to the authors, 3.4% of patients had a cerebral infarction compared with 0.08% of controls (HR 39.9, 95% CI 4.5-357.3).

Connective tissue diseases also were increased among patients (2.5% vs 0.3%, HR 7.5, 95% CI 1.7-33.4). "This risk of systemic connective tissue disorders later in life was increased in patients with congenital heart block (6%) as well as their siblings (4%), albeit the risk was relatively low," commented Jill P. Buyon, MD, director of the Division of Rheumatology at NYU Langone Health in New York City.

"This increased risk is likely reflective of inherited genes conferring overall risk of autoimmunity," said Buyon, who was not involved in the study, but whose group has reported on more than 300 patients at NYU's Research Registry for Neonatal Lupus.

Risks also were elevated for multiple infectious diseases:

  • Infections of the skin and subcutaneous tissue: HR 20.1 (95% CI 6.1-66.9, P<0.01)
  • Bacterial infection of unspecified site: HR 14.9 (95% CI 2.5-89.1, P=0.05)
  • Acute bronchitis: HR 9.2 (95% CI 3.7-22.6, P<0.01)
  • Pneumonia: HR 6.4 (95% CI 2.5-16.5, P<0.01)
  • Acute tonsillitis: HR 3.7 (95% CI 1.8-7.7, P<0.01)
  • Acute upper respiratory infections: HR 2.3 (95% CI 1.3-4, P=0.04)

The researchers also considered the impact of pacemaker treatment, and found that it was protective against cerebral infarction (HR 0.1, 95% CI 0.01-0.8) and arrhythmias (HR 0.4, 95% CI 0.1-0.9), but worsened risk for cardiomyopathy/heart failure (HR 3.8, 95% CI 1.1-12.6) and infections (HR 5.5, 95% CI 2.7-11.3).

Several possible reasons may help explain the increased risk of infection in these patients, including the recognized complication of post-pacemaker-implantation infection and risks associated with prematurity, Wahren-Herlenius and colleagues noted.

"This paper is of interest although it is limited by data being derived from a national register," Buyon told MedPage Today.

Nonetheless, "these data will be informative for both physicians and patients dealing with cardiac complications secondary to in utero exposure to maternal anti-Ro antibodies," she said.

The study was supported by the Swedish Research Council, the Swedish Rheumatism Association, the King Gustaf the Vth 80-year Foundation, the Heart-Lung Foundation, the Freemason's in Stockholm Foundation for Children's Welfare, the Stockholm County Council, the Karolinska Institute, and the Torsten and Ragnar Soderberg Foundation.

Wahren-Herlenius and co-authors disclosed no relevant relationships with industry.

The author has no conflicts of interest to disclose related to this subject

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