Evaluation of the risk of anti-SSA/Ro-SSB/La antibody-associated cardiac manifestations of neonatal lupus in fetuses of mothers with systemic lupus erythematosus exposed to hydroxychloroquine.
BACKGROUND
Based on the potential involvement of Toll-like receptor (TLR) signalling in the pathogenesis of neonatal lupus (NL), it was hypothesised that fetal exposure to hydroxychloroquine (HCQ), a TLR inhibitor, might reduce the risk of anti-SSA/Ro/SSB/La antibody-associated cardiac manifestations of NL (cardiac-NL).


METHODS
Cardiac-NL children (N=50) and controls (N=151) were drawn from the following overlapping pregnancy studies: Research Registry for NL; PR Interval and Dexamethasone Evaluation in Cardiac-NL; and Predictors of Pregnancy Outcomes: Biomarkers in Antiphospholipid Syndrome and Systemic Lupus Erythematosus (SLE). Pregnancies met the following inclusion criteria: documentation of maternal anti-SSA/Ro/SSB/La antibodies at pregnancy, confirmation of medication use and child's outcome, a diagnosis of SLE before pregnancy and birth by 31 December 2007.


RESULTS
Seven (14%) of the cardiac-NL children were exposed to HCQ compared with 56 (37%) of the controls (p=0.002; OR 0.28; 95% CI 0.12 to 0.63). Cases and controls were similar with respect to demographic and antibody status. Multivariable analysis adjusting for birth year, maternal race/ethnicity, antibody status, non-fluorinated steroid use and prior cardiac-NL risk yielded an OR associated with HCQ use of 0.46 (95% CI 0.18 to 1.18; p=0.10).


CONCLUSIONS
This case-control study suggests that, in mothers with SLE with anti-SSA/Ro/SSB/La antibodies, exposure to HCQ during pregnancy may decrease the risk of fetal development of cardiac-NL. Prospective studies are needed for confirmation.
Izmirly
Peter M
PM
Division of Rheumatology, Department of Medicine, New York University School of Medicine, TH-407, New York, NY 10016, USA. Peter.Izmirly@nyumc.org
Kim
Mimi Y
MY
Llanos
Carolina
C
Le
Phuong U
PU
Guerra
Marta M
MM
Askanase
Anca D
AD
Salmon
Jane E
JE
Buyon
Jill P
JP
D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001323:Autoantibodies / Q000097:blood; D001324:Autoantigens / Q000276:immunology; D016022:Case-Control Studies; D005260:Female; D006331:Heart Diseases / Q000209:etiology / Q000276:immunology / Q000517:prevention & control*; D006801:Humans; D006886:Hydroxychloroquine / Q000627:therapeutic use*; D007231:Infant, Newborn; D008180:Lupus Erythematosus, Systemic / Q000150:complications / Q000188:drug therapy* / Q000276:immunology; D008297:Male; D008431:Maternal-Fetal Exchange; D011247:Pregnancy; D011248:Pregnancy Complications / Q000188:drug therapy* / Q000276:immunology; D011297:Prenatal Exposure Delayed Effects; D012261:Ribonucleoproteins / Q000276:immunology; D000097585:SS-B Antigen; D000099207:SS-A Antigen
D018501:Antirheumatic Agents; D001323:Autoantibodies; D001324:Autoantigens; D006886:Hydroxychloroquine; D012261:Ribonucleoproteins; D000097585:SS-B Antigen; D000099207:SS-A Antigen
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