Neonatal Lupus Erythematosus Risk Not Linked to Ethnicity

“In this large, multiethnic, single-center, cohort study of children born to anti-Ro antibody positive mothers, the child’s ethnicity was not associated with NLE risk, nor specific NLE manifestations,” stated investigators.

There was no association between a child’s ethnicity and the risk of contracting neonatal lupus erythematosus (NLE), nor any specific NLE symptoms and conditions, according to an article published in The Journal of Rheumatology.1 These findings contradict previous studies that alluded to more frequent adverse cardiac NLE outcomes in children of Non-European heritage.

We were able to examine the attributable risk of maternal disease status and medication exposure with NLE,” explained investigators. “Since our data was prospectively collected from infants undergoing routine screening for NLE manifestations, our reported prevalence of NLE and specific manifestations likely reflects the true prevalence of NLE in children born to mothers positive for anti-Ro antibodies.”

NLE, an autoimmune disorder obtained through the transplacental passage of maternal anti-Ro, can manifest in both cardiac and non-cardiac conditions. Examples of cardiac symptoms include congenital heart block, myocarditis, and valvular abnormalities, while non-cardiac manifestations may involve rash, elevated liver enzymes, and macrocephaly.

Eligible children were enrolled between January 2011 and April 2019 in the NLE clinic at The Hospital for Sick Children, were aged ≤1 year, and had mothers with positive anti-Ro antibodies. Mothers had anti-Ro antibody status checked during the first trimester of pregnancy. Fetal echocardiograms began at 16-18 weeks gestational age, and at 2, 4, and 12 months of age. Demographic characteristics of mothers and children were collected from the NLE database, and ethnicity information was collected via questionnaires. Ethnicity was grouped into the following categories: European, East Asian, South Asian, African, Latin American and Mixed (2 or more ethnicities). Investigators grouped participants into 3 categories: European, Non-European, and Mixed European/Non-European.

NLE diagnosis was classified as 1 or more of the following categories: cardiac and/or myocardial disease, cutaneous rash, hepatic, hematologic, and neurologic. Investigators analyzed maternal rheumatic disease status and antimalarial usage during pregnancy, as well as any anti-La antibodies.

A total of 324 children and 270 mothers were included in the study. Both NLE and its specific manifestations were compared between the ethnic groups using the Fisher’s exact test. Logistic regression models accounted for the child’s sex, the rheumatic disease status of the mother, and maternal use of antimalarials during her pregnancy.

Most children were Non-European (48%), followed by European (34%), and Mixed European/Non-European (18%). The majority of children had NLE (54%, n=175) and 13% (n=23) had cardiac involvement.

Investigators found no significant link between Non-European ethnicity (OR 1.18 95% CI 0.71 -1.94, p=0.51) or Mixed European/Non-European ethnicity (OR 1.13, 95% CI 0.59-2.16, p=0.70) and an increased NLE risk or specific NLE manifestations when compared with European ethnicity. Further, Non-European and Mixed European/Non-European groups were not at an increased risk for cardiac NLE or cutaneous NLE when compared with the European cohort.

The study was limited by the number of patients with cardiac NLE manifestations, which hinders comparisons between Non-European subgroups, such as those with Asian or African ancestries. However, it boasted the largest Non-European sample size to date as well as the largest study of children born to positive anti-Ro mothers both with and without rheumatic disease.

“In this large, multiethnic, single-center, cohort study of children born to anti-Ro antibody positive mothers, the child’s ethnicity was not associated with NLE risk, nor specific NLE manifestations,” concluded investigators. “Further studies in multiethnic cohorts are needed to validate our findings. Future genetic studies will enable identification of more precise mechanisms influencing NLE risk and manifestations.”

Reference:

Diaz T, Dominguez D, Jaeggi E, et al. Ethnicity and Neonatal Lupus Erythematosus Manifestations Risk in a Large Multi-Ethnic Cohort [published online ahead of print, 2021 Apr 1]. J Rheumatol. 2021;jrheum.201338. doi:10.3899/jrheum.201338