title: 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.
abstract: 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.
authors.affiliation: Division of Rheumatology, Department of Medicine, New York University School of Medicine, TH-407, New York, NY 10016, USA. Peter.Izmirly@nyumc.org
authors.forename: Peter M
authors.initials: PM
authors.lastname: Izmirly
authors.forename: Mimi Y
authors.initials: MY
authors.lastname: Kim
authors.forename: Carolina
authors.initials: C
authors.lastname: Llanos
authors.forename: Phuong U
authors.initials: PU
authors.lastname: Le
authors.forename: Marta M
authors.initials: MM
authors.lastname: Guerra
authors.forename: Anca D
authors.initials: AD
authors.lastname: Askanase
authors.forename: Jane E
authors.initials: JE
authors.lastname: Salmon
authors.forename: Jill P
authors.initials: JP
authors.lastname: Buyon
mesh_terms: 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
chemical_list: D018501:Antirheumatic Agents; D001323:Autoantibodies; D001324:Autoantigens; D006886:Hydroxychloroquine; D012261:Ribonucleoproteins; D000097585:SS-B Antigen; D000099207:SS-A Antigen
references.citation: J Immunol. 2010 Feb 15;184(4):2148-55
references.pmid: 20089705
references.citation: Circulation. 2008 Jan 29;117(4):485-93
references.pmid: 18195175
references.citation: J Pediatr. 2003 Jun;142(6):678-83
references.pmid: 12838197
references.citation: Ann Intern Med. 1994 Apr 1;120(7):544-51
references.pmid: 8116991
references.citation: Arthritis Rheum. 2006 Nov;54(11):3640-7
references.pmid: 17075810
references.citation: Arch Otolaryngol. 1968 Oct;88(4):370-2
references.pmid: 5302911
references.citation: Arthritis Rheum. 2001 Aug;44(8):1832-5
references.pmid: 11508435
references.citation: Arthritis Res Ther. 2006;8(3):209
references.pmid: 16712713
references.citation: J Am Coll Cardiol. 2002 Aug 21;40(4):796-802
references.pmid: 12204513
references.citation: Arthritis Rheum. 2009 Oct;60(10):3091-7
references.pmid: 19790064
references.citation: Ann Rheum Dis. 2010 Jan;69(1):20-8
references.pmid: 19103632
references.citation: Arthritis Rheum. 2006 Oct;54(10):3068-70
references.pmid: 17009223
references.citation: J Am Coll Cardiol. 1998 Jun;31(7):1658-66
references.pmid: 9626848
references.citation: Biometrics. 1986 Mar;42(1):121-30
references.pmid: 3719049
references.citation: Bull Soc Ophtalmol Fr. 1969 Apr;69(4):466-7
references.pmid: 5403305
references.citation: Autoimmun Rev. 2005 Feb;4(2):111-5
references.pmid: 15722258
references.citation: Am J Cardiol. 2009 Apr 15;103(8):1102-6
references.pmid: 19361597
references.citation: Lupus. 2001;10(6):401-4
references.pmid: 11434574
references.citation: Arthritis Rheum. 2010 Apr;62(4):1153-7
references.pmid: 20131261