Outcomes of children born to mothers with systemic lupus erythematosus exposed to hydroxychloroquine or azathioprine

John A Reynolds; Mary Gayed; Munther A Khamashta; Francesca Leone; Veronica Toescu; Ian N Bruce; Ian Giles; Lee-Suan Teh; Neil McHugh; Mohammed Akil; Christopher J Edwards; Caroline Gordon

doi:10.1093/rheumatology/keac372

Outcomes of children born to mothers with systemic lupus erythematosus exposed to hydroxychloroquine or azathioprine

John A Reynolds, Mary Gayed, Munther A Khamashta, Francesca Leone, Veronica Toescu, Ian N Bruce, Ian Giles, Lee-Suan Teh, Neil McHugh, Mohammed Akil, Christopher J Edwards, Caroline Gordon

Research output: Contribution to journal › Article › peer-review

7 Citations (SciVal)

Abstract

Objectives: HCQ and AZA are used to control disease activity and reduce risk of flare during pregnancy in patients with SLE. The aim of this study was to determine the outcomes of children born to mothers with SLE exposed to HCQ or AZA during pregnancy and breast-feeding. Methods: Women attending UK specialist lupus clinics with children ≤17 years old, born after SLE diagnosis, were recruited to this retrospective study. Data were collected using questionnaires and from clinical record review. Factors associated with the outcomes of low birth weight and childhood infection were determined using multivariable mixed-effects logistic regression models. Results: We analysed 284 live births of 199 mothers from 10 UK centres. The first pregnancies of 73.9% of mothers (147/199) were captured in the study; (60.4%) (150/248) and 31.1% (87/280) children were exposed to HCQ and AZA, respectively. There were no significant differences in the frequency of congenital malformations or intrauterine growth restriction between children exposed or not to HCQ or AZA. AZA use was increased in women with a history of hypertension or renal disease. Although AZA was associated with low birth weight in univariate models, there was no significant association in multivariable models. In adjusted models, exposure to AZA was associated with increased reports of childhood infection requiring hospital management [odds ratio 2.283 (1.003, 5.198), P = 0.049]. Conclusions: There were no significant negative outcomes in children exposed to HCQ in pregnancy. AZA use was associated with increased reporting of childhood infection, which warrants further study.

Original language	English
Pages (from-to)	1124–1135
Number of pages	12
Journal	Rheumatology (Oxford, England)
Volume	62
Issue number	3
Early online date	29 Jun 2022
DOIs	https://doi.org/10.1093/rheumatology/keac372
Publication status	Published - 1 Mar 2023

Bibliographical note

Funding Information:
Funding: The authors are most grateful for grant support from Lupus UK and support from Southampton Rheumatology Trust.

Funding Information:
Disclosure statement: C.G. reports personal fees for honoraria from consultancy work and/or advisory boards from the Center for Disease Control and Prevention, AbbVie, Amgen, Astra-Zeneca, BMS, GSK, MGP, Sanofi, and UCB; personal fees for speakers bureau from UCB and GSK; and previous educational grants from UCB to Sandwell and West Birmingham Hospitals NHS Trust that have supported her research work independent of any specific drug or pregnancy study. I.G. reports personal fees for honoraria from consultancy work and/or advisory boards from UCB; and an unrestricted research grant from UCB. C.J.E. reports personal fees for honoraria from consultancy work, advisory boards and speakers bureau from AbbVie, Astra-Zeneca, BMS, Celltrion, Chugai, Galapagos, Gilead, GSK, Lilly, Pfizer, and Roche. The remaining authors have declared no conflicts of interest.

Funding Information:
I.N.B. is a National Institute for Health Research (NIHR) Senior Investigator Emeritus and is funded by the NIHR Manchester Biomedical Research Centre. The views expressed in this publication are those of the author(s) and not necessarily those of the NHS, the NIHR, or the Department of Health.

Publisher Copyright:
© 2022 The Author(s). Published by Oxford University Press on behalf of the British Society for Rheumatology.

Keywords

AZA
HCQ
SLE
adverse outcomes
pregnancy

ASJC Scopus subject areas

Pharmacology (medical)
Rheumatology

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10.1093/rheumatology/keac372Licence: CC BY-NC

Cite this

Reynolds, J. A., Gayed, M., Khamashta, M. A., Leone, F., Toescu, V., Bruce, I. N., Giles, I., Teh, L.-S., McHugh, N., Akil, M., Edwards, C. J., & Gordon, C. (2023). Outcomes of children born to mothers with systemic lupus erythematosus exposed to hydroxychloroquine or azathioprine. Rheumatology (Oxford, England), 62(3), 1124–1135. https://doi.org/10.1093/rheumatology/keac372

Reynolds, JA, Gayed, M, Khamashta, MA, Leone, F, Toescu, V, Bruce, IN, Giles, I, Teh, L-S, McHugh, N, Akil, M, Edwards, CJ & Gordon, C 2023, 'Outcomes of children born to mothers with systemic lupus erythematosus exposed to hydroxychloroquine or azathioprine', Rheumatology (Oxford, England), vol. 62, no. 3, pp. 1124–1135. https://doi.org/10.1093/rheumatology/keac372

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abstract = "Objectives: HCQ and AZA are used to control disease activity and reduce risk of flare during pregnancy in patients with SLE. The aim of this study was to determine the outcomes of children born to mothers with SLE exposed to HCQ or AZA during pregnancy and breast-feeding. Methods: Women attending UK specialist lupus clinics with children ≤17 years old, born after SLE diagnosis, were recruited to this retrospective study. Data were collected using questionnaires and from clinical record review. Factors associated with the outcomes of low birth weight and childhood infection were determined using multivariable mixed-effects logistic regression models. Results: We analysed 284 live births of 199 mothers from 10 UK centres. The first pregnancies of 73.9% of mothers (147/199) were captured in the study; (60.4%) (150/248) and 31.1% (87/280) children were exposed to HCQ and AZA, respectively. There were no significant differences in the frequency of congenital malformations or intrauterine growth restriction between children exposed or not to HCQ or AZA. AZA use was increased in women with a history of hypertension or renal disease. Although AZA was associated with low birth weight in univariate models, there was no significant association in multivariable models. In adjusted models, exposure to AZA was associated with increased reports of childhood infection requiring hospital management [odds ratio 2.283 (1.003, 5.198), P = 0.049]. Conclusions: There were no significant negative outcomes in children exposed to HCQ in pregnancy. AZA use was associated with increased reporting of childhood infection, which warrants further study.",

keywords = "AZA, HCQ, SLE, adverse outcomes, pregnancy",

author = "Reynolds, {John A} and Mary Gayed and Khamashta, {Munther A} and Francesca Leone and Veronica Toescu and Bruce, {Ian N} and Ian Giles and Lee-Suan Teh and Neil McHugh and Mohammed Akil and Edwards, {Christopher J} and Caroline Gordon",

note = "Funding Information: Funding: The authors are most grateful for grant support from Lupus UK and support from Southampton Rheumatology Trust. Funding Information: Disclosure statement: C.G. reports personal fees for honoraria from consultancy work and/or advisory boards from the Center for Disease Control and Prevention, AbbVie, Amgen, Astra-Zeneca, BMS, GSK, MGP, Sanofi, and UCB; personal fees for speakers bureau from UCB and GSK; and previous educational grants from UCB to Sandwell and West Birmingham Hospitals NHS Trust that have supported her research work independent of any specific drug or pregnancy study. I.G. reports personal fees for honoraria from consultancy work and/or advisory boards from UCB; and an unrestricted research grant from UCB. C.J.E. reports personal fees for honoraria from consultancy work, advisory boards and speakers bureau from AbbVie, Astra-Zeneca, BMS, Celltrion, Chugai, Galapagos, Gilead, GSK, Lilly, Pfizer, and Roche. The remaining authors have declared no conflicts of interest. Funding Information: I.N.B. is a National Institute for Health Research (NIHR) Senior Investigator Emeritus and is funded by the NIHR Manchester Biomedical Research Centre. The views expressed in this publication are those of the author(s) and not necessarily those of the NHS, the NIHR, or the Department of Health. Publisher Copyright: {\textcopyright} 2022 The Author(s). Published by Oxford University Press on behalf of the British Society for Rheumatology.",

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AU - Leone, Francesca

AU - Toescu, Veronica

AU - Bruce, Ian N

AU - Giles, Ian

AU - Teh, Lee-Suan

AU - McHugh, Neil

AU - Akil, Mohammed

AU - Edwards, Christopher J

AU - Gordon, Caroline

N1 - Funding Information: Funding: The authors are most grateful for grant support from Lupus UK and support from Southampton Rheumatology Trust. Funding Information: Disclosure statement: C.G. reports personal fees for honoraria from consultancy work and/or advisory boards from the Center for Disease Control and Prevention, AbbVie, Amgen, Astra-Zeneca, BMS, GSK, MGP, Sanofi, and UCB; personal fees for speakers bureau from UCB and GSK; and previous educational grants from UCB to Sandwell and West Birmingham Hospitals NHS Trust that have supported her research work independent of any specific drug or pregnancy study. I.G. reports personal fees for honoraria from consultancy work and/or advisory boards from UCB; and an unrestricted research grant from UCB. C.J.E. reports personal fees for honoraria from consultancy work, advisory boards and speakers bureau from AbbVie, Astra-Zeneca, BMS, Celltrion, Chugai, Galapagos, Gilead, GSK, Lilly, Pfizer, and Roche. The remaining authors have declared no conflicts of interest. Funding Information: I.N.B. is a National Institute for Health Research (NIHR) Senior Investigator Emeritus and is funded by the NIHR Manchester Biomedical Research Centre. The views expressed in this publication are those of the author(s) and not necessarily those of the NHS, the NIHR, or the Department of Health. Publisher Copyright: © 2022 The Author(s). Published by Oxford University Press on behalf of the British Society for Rheumatology.

PY - 2023/3/1

Y1 - 2023/3/1

N2 - Objectives: HCQ and AZA are used to control disease activity and reduce risk of flare during pregnancy in patients with SLE. The aim of this study was to determine the outcomes of children born to mothers with SLE exposed to HCQ or AZA during pregnancy and breast-feeding. Methods: Women attending UK specialist lupus clinics with children ≤17 years old, born after SLE diagnosis, were recruited to this retrospective study. Data were collected using questionnaires and from clinical record review. Factors associated with the outcomes of low birth weight and childhood infection were determined using multivariable mixed-effects logistic regression models. Results: We analysed 284 live births of 199 mothers from 10 UK centres. The first pregnancies of 73.9% of mothers (147/199) were captured in the study; (60.4%) (150/248) and 31.1% (87/280) children were exposed to HCQ and AZA, respectively. There were no significant differences in the frequency of congenital malformations or intrauterine growth restriction between children exposed or not to HCQ or AZA. AZA use was increased in women with a history of hypertension or renal disease. Although AZA was associated with low birth weight in univariate models, there was no significant association in multivariable models. In adjusted models, exposure to AZA was associated with increased reports of childhood infection requiring hospital management [odds ratio 2.283 (1.003, 5.198), P = 0.049]. Conclusions: There were no significant negative outcomes in children exposed to HCQ in pregnancy. AZA use was associated with increased reporting of childhood infection, which warrants further study.

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Outcomes of children born to mothers with systemic lupus erythematosus exposed to hydroxychloroquine or azathioprine

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

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