Abstract
Background There are no longitudinal studies regarding the long term cardiac health of children with cardiac manifestations of neonatal lupus (NL). This study was performed to evaluate risk factors for morbidity and provide evidence-based guidance regarding the course of cardiac NL.
Methods Echocardiograms throughout life were evaluated in 240 individuals born with cardiac NL from the Research Registry for Neonatal Lupus: 142 were available from ages 0–1 years, 174 from ages 1–17 years, and 65>17 years. A composite adverse outcome defined as qualitatively decreased left ventricular (LV) function or concurrent use of cardiac medications was assessed. Aortic dilation (root or ascending aorta z-score >2.0) was also recorded. Analyses were performed to associate the composite adverse outcome and aortic dilation with maternal medications, pacing, and fetal disease status, including a severity score based on mortality risk factors such as lower fetal heart rate and extranodal disease.
Results The composite adverse outcome for cardiac dysfunction was identified in 21.1% of echos in children ages 0–1, 13.2% ages 1–17% and 29.2% ages>17. In 89 children in which echos were available at ages 0–1 and 1–17, 6/16 with dysfunction at ages 0–1 were also affected at ages 1–17, while 10 reverted to normal. Among those without dysfunction at age 0–1, 8/90 developed new worsening of cardiac function during age 1–17. In 35 cases with echos at ages 1–17 and >17, 3/3 cases with dysfunction at age 1–17 were also affected at >17, and 2/32 developed new dysfunction in adulthood. Cardiac dysfunction was significantly associated with number of years paced at all ages (p<0.001, 0.001,<0.001). A lower fetal ventricular heart rate at the first time of heart block detection was associated with cardiac dysfunction age 0–1 and >17 (p=0.048, 0.005 respectively) and lowest heart rate in utero associated with dysfunction at age <1 and 1–17 (p<0.001, 0.015). Fetal extranodal cardiac disease was associated with dysfunction in ages1–17 and >17 (p=0.026, 0.023). Higher fetal severity score associated with postnatal dysfunction in ages 0–1 and 1–17 groups (p=0.013, 0.001). Aortic dilation was present in 13.4% at ages 0–1% and 14.9% at ages 1–17, but at >17, dilation only occurred in 9.2%. There was no association of postnatal cardiac dysfunction or aortic dilation with maternal medication use, maternal rheumatic disease, fetal age at heart block detection or gestational age of birth.
Conclusions Cardiac dysfunction in the first year normalizes by later childhood in the majority of cases, possibly due to the short term effects of cardiac pacing or resolution of inflammation with the clearance of maternal autoantibodies. However, new onset dysfunction can occur after the first year of life. Aortic dilation can continue for longer periods, but may decrease in frequency with age. Nevertheless, cardiac dysfunction is present in roughly 30%, and in adulthood there are associations with fetal extranodal disease and heart rate at detection. Patients who develop morbidity in utero may have subclinical damage or be more susceptible to future insults that manifest later in life, which can be exacerbated by prolonged pacing. Close monitoring and aggressive treatment of early extranodal disease in cardiac NL may have long term benefit in preventing subsequent morbidity.
