Prenatal predisposing factors associated with neonatal lupus erythematosus

Objectives To identify the prenatal predisposing factors related to neonatal lupus erythematosus (NLE). Materials and Methods A retrospective case-control study was made of 131 pregnant women with positive anti-Ro or anti-La autoantibodies and known neonatal outcomes between January 2002 and December 2019 at Siriraj Hospital, Bangkok, Thailand. There were 101 unaffected neonates and 30 NLE cases confirmed postnatally. Demographic and clinical data of the mothers and neonates with and without NLE were statistically compared. Results NLE was diagnosed in 30 out of 131 cases. A multivariate analysis identified the following significant factors for NLE: maternal anti-La antibodies (odds ratio (OR), 3.591; p = 0.030); and maternal treatment with either hydroxychloroquine (OR, 0.082; p = 0.001) or prednisolone (OR, 0.136; p = 0.017). Of the significant variables examined in the multivariate analysis models, high levels of maternal anti-La antibodies were found to be the strongest predictor of noncardiac NLE (OR, 4.558; p = 0.032), while a female baby was significantly higher in pregnancies complicated by cardiac NLE (OR, 5.374; p = 0.046). Hydroxychloroquine still provided a protective effect for both cardiac and noncardiac NLE ( p = 0.039 and 0.032, respectively). Conclusions The maternal anti-La antibodies were a beneficial predictor for NLE, especially as their high titers were influentially associated with noncardiac features. A female fetus seemed to present an increased risk for developing a congenital heart block. Nevertheless, the treatment with hydroxychloroquine during the pregnancies demonstrated a potentially protective factor against both cardiac and noncardiac manifestations.

An Isolated Thrombocytopenia in a Newborn

Isolated thrombocytopenia is a common finding in neonates and infants. Physicians should rule out infection at first. Meanwhile, neonatal lupus erythematosus is classically revealed by cutaneous and cardiac manifestations. Hematological involvement is possible but rare. In this article, we report the case of a one-month-old boy who had been suffering from isolated thrombocytopenia and was diagnosed with neonatal lupus.

An Overview of Neonatal Lupus with Anti-Ro Characteristics

Neonatal lupus erythematosus (NLE) is a syndrome of clinical symptoms observed in neonates born to mothers with antibodies to soluble antigens of the cell nucleus. The main factors contributing to the pathogenesis of this disease are anti-Sjögren Syndrome A (anti-SS-A) antibodies, known as anti-Ro, and anti-Sjögren Syndrome B (anti-SS-B) antibodies, known as anti-La. Recent publications have also shown the significant role of anti-ribonucleoprotein antibodies (anti-RNP). Seropositive mothers may have a diagnosed rheumatic disease or they can be asymptomatic without diagnosis at the time of childbirth. These antibodies, after crossing the placenta, may trigger a cascade of inflammatory reactions. The symptoms of NLE can be divided into reversible symptoms, which concern skin, hematological, and hepatological changes, but 2% of children develop irreversible symptoms, which include disturbances of the cardiac stimulatory and conduction system. Preconceptive care and pharmacological prophylaxis of NLE in the case of mothers from the risk group are important, as well as the monitoring of the clinical condition of the mother and fetus throughout pregnancy and the neonatal period. The aim of this manuscript is to summarize the previous literature and current state of knowledge about neonatal lupus and to discuss the role of anti-Ro in the inflammatory process.

Cytomegalovirus-Associated Hemolytic Anemia in an Infant Born to a Mother with Lupus

A 31-day-old infant was admitted to the pediatric intensive care unit due to shock and anemia. The mother had systemic lupus erythematosus and direct antiglobulin test (DAT)-positive hemolytic anemia. The perinatal course of this infant and the mother was uneventful. Regular health check screenings revealed that activity, growth, and development were unremarkable at birth, 5, and 28 days of life. Passive immune hemolytic anemia due to neonatal lupus erythematosus was diagnosed based on a positive DAT for warm-type IgG antibodies, reticulocytosis, and lupus-specific antibodies at rehospitalization. It was complicated by cytomegalovirus (CMV) antigenemia. Umbilical cord blood and peripheral blood samples obtained from the infant at 5 days after birth were negative for CMV DNA. The infant was curatively treated by intensive care with repeated blood transfusions and antiviral therapy. This is the first report indicating that CMV infection exacerbates hemolytic anemia in patients with maternal red blood cell alloantibodies.

Ethnicity and Neonatal Lupus Erythematosus Manifestations Risk in a Large Multi-Ethnic Cohort

Objective To evaluate the association between ethnicity and neonatal lupus erythematosus (NLE), as well as specific NLE manifestations in a large multi-ethnic population. Methods We conducted a cohort study of the children (≤1 year of age) seen in the NLE clinic at SickKids, between January 2011 and April 2019. The cohort was divided into European, non-European and Mixed European–Non-European groups according to parent reported child’s ethnicity (Canada census categories). Outcomes were NLE and specific NLE manifestations (cardiac, cutaneous, cytopenias, transaminitis and macrocephaly). The frequency of NLE and specific manifestations were compared between ethnic groups (Fisher’s exact test). We tested the association between ethnicity and 1) NLE risk and 2) specific NLE manifestations with logistic regression models, including covariates for child’s sex, maternal rheumatic disease status during pregnancy, and maternal use of antimalarials during pregnancy (multiple comparisons threshold p-value<0.008). Results We included 324 children born to 270 anti-Ro antibody positive mothers. Median age at first visit: 1.8 months (IQR: 1.4, 2.3 months). Median follow-up time: 12 months (IQR: 2,24months). The majority were non-European (48%), with 34% European, and 18% Mixed European–Non-European. There was no significant association between non-European ethnicity (OR 1.14, 95% CI:0.69-1.89, p=0.59), Mixed European-Non-European ethnicity (OR 1.06, 95% CI:0.55-2.06, p=0.84) and NLE risk compared with European ethnicity. We also did not find an association between ethnicity and specific NLE manifestations, in univariate or multivariable adjusted models. Conclusion In a large multiethnic cohort, there was no association between child’s ethnicity and NLE risk, nor specific NLE manifestations.