Background/Purpose: Women with anti-Ro antibodies face the risk of having a child with cardiac Neonatal Lupus (NL), characterized by congenital heart block and/or cardiomyopathy.  Biomarkers in maternal and/or fetal blood may provide insight into pathogenesis, treatment, and risk of disease.  Vitamin D has anti-fibrotic properties, and in a Swedish cohort, low maternal levels were postulated to contribute to an increase in cardiac NL cases since gestational susceptibility weeks 18-24 occurred more commonly during the winter.  C-reactive protein (CRP) is known to be activated by macrophages, which have been shown to infiltrate the AV node in cardiac NL autopsy cases.  Brain Natriuretic Peptide (BNP) is a predictor of cardiac disease in adults and associates with both ventricular dysfunction and cumulative damage index in Systemic Lupus Erythematosus.  Troponin I is associated with myocardial damage and is elevated in autoimmune myocarditis. 

Methods: Maternal and cord blood samples were obtained from the Research Registry for Neonatal Lupus.  Samples were analyzed using standard laboratory assays for Vitamin D, CRP, BNP and Troponin I. Levels were then evaluated for associations with cardiac NL development, fetal echocardiographic evidence of endocardial fibroelastosis (EFE), dilated cardiomyopathy (DCM), and hydrops, as well as child’s need for a pacemaker, and maternal use of fluorinated steroids (FS) at the time of blood draw. 

Results: Maternal samples closest to gestational week 20 were analyzed for Vitamin D in 36 cardiac NL and 35 unaffected pregnancies.  Mean vitamin D levels from affected cases were lower than unaffected pregnancies (40.8 ng/mL ± 28 vs. 53.8 ± 36, p=0.075). This trend became significant in comparing 9 cases with fetal EFE vs. 58 without (26.1 ng/mL ± 6.4 vs. 52.0 ± 32.3, p=0.010).  Maternal CRP in 49 cardiac NL and 51 unaffected cases closest to week 20 did not associate with disease. Cord blood was analyzed for CRP and Troponin I in 38 affected and 52 unaffected children, and BNP in 30 affected and 42 unaffected children.  Mean cord blood CRP was significantly higher in cardiac NL cases compared to unaffected children (12.9 ± 68.1 mg/L vs. 0.59 ± 1.8, p<0.001).  In 28 affected and 32 unaffected cases where both cord blood and maternal blood from the time of delivery were available, cardiac NL was associated with higher CRP in cord blood (16.5 mg/L ± 79.3 vs. 0.39 ± 0.70, p<0.001), while maternal blood did not have a significant association (47.2 mg/L  ± 43.8 vs. 37.2 ± 38.4, p=0.265).  Mean cord blood BNP was higher in cardiac NL cases compared to unaffected children (237.2 ng/mL ± 412 vs. 127.9 ± 292, p=0.04).  Troponin I in cord blood did not associate with disease.   No blood tests associated with DCM, hydrops, pacemaker or FS use.

Conclusion: Maternal vitamin D levels may play a role in the development of cardiac NL. Perhaps lower values, albeit in the normal range, confer reduced “protection” from fibrosis.  Increased cord blood CRP in cardiac NL cases independent of maternal levels suggests an ongoing fetal inflammatory response at the time of birth.  This supports close postnatal follow up to identify worsening of disease.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/maternal-vitamin-d-fetal-c-reactive-protein-and-brain-natriuretic-peptide-associate-with-the-development-and-morbidity-of-cardiac-neonatal-lupus/