TY - JOUR

T1 - Fetal safety of chloroquine and hydroxychloroquine use during pregnancy

T2 - A nationwide cohort study

AU - Andersson, Niklas Worm

AU - Skov, Lone

AU - Andersen, Jon Trærup

N1 - Publisher Copyright: © 2020 The Author(s). Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved.

PY - 2021

Y1 - 2021

N2 - Objective: The antimalaria 4-aminoquinoline drugs chloroquine and HCQ are used in the treatment of a wide range of CTDs. Data to inform on the safety of their use in pregnancy are limited. Methods: In a Danish nationwide cohort study from 1996 through 2016, we identified 4-aminoquinoline-exposed pregnancies from a cohort of 1240 875 pregnancies to investigate the associated risks of major birth defects, preterm birth, and small size for gestational age (SGA). Distinct study cohorts of propensity-score-matched 4-aminoquinoline-exposed and unexposed pregnancies (in a 1:1 ratio) were established for each outcome analysis. The association with the outcomes was assessed by prevalence odds ratios (ORs) estimated through logistic regression. The associated risks for chloroquine and HCQ were individually assessed through additional analyses. Results: A total of 1487 pregnancies exposed to 4-aminoquinolines (1184 chloroquine- A nd 303 HCQ-exposed) were identified. Among the 983 pregnancies exposed to 4-aminoquinolines in the first trimester, 34 infants (3.5%) were diagnosed with major birth defects as compared with 36 (3.7%) among the matched unexposed pregnancies (prevalence OR, 0.94; 95% CI: 0.59, 1.52). Exposure to 4-aminoquinolines in pregnancy was neither associated with an increased risk of preterm birth (prevalence OR, 0.97; 95% CI: 0.73, 1.28) or SGA (prevalence OR, 1.18; 95% CI: 0.93, 1.50), compared with unexposed pregnancies. No significant associations between exposure to chloroquine or HCQ individually and risk of the outcomes were identified. Conclusion: Among pregnancies exposed to 4-aminoquinolines (chloroquine and HCQ), no increased risk of major birth defects, preterm birth, or SGA was identified.

AB - Objective: The antimalaria 4-aminoquinoline drugs chloroquine and HCQ are used in the treatment of a wide range of CTDs. Data to inform on the safety of their use in pregnancy are limited. Methods: In a Danish nationwide cohort study from 1996 through 2016, we identified 4-aminoquinoline-exposed pregnancies from a cohort of 1240 875 pregnancies to investigate the associated risks of major birth defects, preterm birth, and small size for gestational age (SGA). Distinct study cohorts of propensity-score-matched 4-aminoquinoline-exposed and unexposed pregnancies (in a 1:1 ratio) were established for each outcome analysis. The association with the outcomes was assessed by prevalence odds ratios (ORs) estimated through logistic regression. The associated risks for chloroquine and HCQ were individually assessed through additional analyses. Results: A total of 1487 pregnancies exposed to 4-aminoquinolines (1184 chloroquine- A nd 303 HCQ-exposed) were identified. Among the 983 pregnancies exposed to 4-aminoquinolines in the first trimester, 34 infants (3.5%) were diagnosed with major birth defects as compared with 36 (3.7%) among the matched unexposed pregnancies (prevalence OR, 0.94; 95% CI: 0.59, 1.52). Exposure to 4-aminoquinolines in pregnancy was neither associated with an increased risk of preterm birth (prevalence OR, 0.97; 95% CI: 0.73, 1.28) or SGA (prevalence OR, 1.18; 95% CI: 0.93, 1.50), compared with unexposed pregnancies. No significant associations between exposure to chloroquine or HCQ individually and risk of the outcomes were identified. Conclusion: Among pregnancies exposed to 4-aminoquinolines (chloroquine and HCQ), no increased risk of major birth defects, preterm birth, or SGA was identified.

KW - 4-aminoquinolines

KW - fetal safety

KW - nationwide cohort study

KW - pregnancy

KW - propensity-score matching

UR - http://www.scopus.com/inward/record.url?scp=85104331072&partnerID=8YFLogxK

U2 - 10.1093/rheumatology/keaa592

DO - 10.1093/rheumatology/keaa592

M3 - Journal article

C2 - 33232466

AN - SCOPUS:85104331072

VL - 60

SP - 2317

EP - 2326

JO - Rheumatology

JF - Rheumatology

SN - 1462-0324

IS - 5

ER -