A149: Does Prenatal Exposure to Antimalarial Decrease the Risk of Neonatal Lupus: a Bayesian Perspective
Authors: Barsalou Julie , Jaeggi Edgar , Tian Simon Yu , Hamilton Robert M. , Laskin Carl A. , Silverman Earl D. 
Published: March 2014

Background/Purpose:

It had been suggested that prenatal exposure to hydroxychloroquine reduced the risk of cardiac NLE. The primary aim was to assess if prenatal exposure to antimalarials (AM) decreased the risk of cardiac NLE. The secondary aim was to analyze the effect of AM exposure on the risk of non‐cardiac NLE.

Methods:

A retrospective cohort study was performed on a large single‐center cohort of children exposed to anti‐Ro and/or anti‐La antibodies on whom prospective data has been collected since 1984. Inclusion criteria were: 1) first child born from a woman positive for anti‐Ro and/or anti‐La antibodies with a diagnosis of cutaneous lupus, systemic lupus erythematosus, Sjogren's syndrome, dermatomyositis or rheumatoid arthritis, 2) the mother underwent fetal chocardiography screening during pregnancy and/or the child had a postnatal ECG and 3) the child was ≥6 months old as of October 2013. We used Bayesian analysis for the association between prenatal use of AM and NLE.

Results:

The study population consisted of 265 children, of whom 72 were exposed to AM throughout gestation. Full laboratory data was available on 216 infants: 101 (46.8%) developed NLE and 115 (53.2%) remained unaffected. Forty nine children were classified as having no cardiac NLE but could not be diagnosed as true unaffected children as one or more blood test components were missing. These children were only included when the outcome studied was cardiac NLE. On univariable analysis and under a non‐informative prior, the probability that prenatal AM exposure would be protective (RR < 1) was 97.1% for cardiac and 66.9% for non‐cardiac NLE. On multivariable analysis, the RRs obtained were numerically higher, but still suggestive of a protective effect (). Using a more stringent RR cutoff (RR < 0.75), the effect on the outcome cardiac NLE remained significant, unlike for non‐cardiac NLE for which probabilities dropped significantly.

Bayesian Analyses of the Effect of Prenatal Exposure to Antimalarial on the Risk of NLE

Outcome
Prior
Sample size (N)
RR (95% CrI)
Probability of RR <1 (%)
Probability of RR <0.75 (%)

Univariable analyses

Cardiac NLE
Non‐informative
265
0.17 (0.01, 1.05)
97.1
93.8

Cardiac NLE
Informative
265
0.34 (0.17, 0.66)
99.9
98.9

Non‐cardiac NLE
Non‐informative
214
0.93 (0.64, 1.29)
66.9
12.7

Multivariable analyses

Cardiac NLE
Non‐informative
230
0.31 (0.01, 1.91)
87.8
80.0

Cardiac NLE
Informative
230
0.36 (0.18, 0.72)
99.8
98.1

Non‐cardiac NLE
Non‐informative
190
0.94 (0.65, 1.31)
64.0
11.6

Independent variable: prenatal exposure to AM

Independent variables: prenatal exposure to AM, anti‐Ro ≥50 U/mL, anti‐La ≥50 U/mL and maternal diagnosis (Sjogren's syndrome vs all other diagnosis)

NLE: neonatal lupus; RR (95% CrI): relative risk (95% credible interval)

Conclusion:

In this study of the largest single‐center cohort of children born to anti‐Ro and/or anti‐La antibody positive women with a connective tissue disease, we have shown that the probability that AM exposure was associated with a decreased risk of cardiac NLE was >87%. A clinically significant beneficial effect from AM exposure on non‐cardiac NLE features was not present. These findings need to be confirmed in an independent cohort.