What are the guidelines for using hydroxychloroquine (HCQ) in pregnancy?

Hydroxychloroquine in Pregnancy

Hydroxychloroquine should be continued throughout pregnancy in women already taking it for systemic lupus erythematosus or rheumatoid arthritis, and should be started if not already prescribed, as it reduces disease flares and pregnancy complications without increasing fetal risk. 1, 2

Guideline-Based Recommendations

Continue or Initiate HCQ During Pregnancy

• The American College of Rheumatology strongly recommends continuing hydroxychloroquine during pregnancy if already taking it, and conditionally recommends starting it if not already prescribed (unless contraindicated by allergy or intolerance). 1
• The KDIGO 2024 guidelines explicitly state that hydroxychloroquine should be continued during pregnancy to reduce the risk of pregnancy complications. 3
• The EULAR guidelines list hydroxychloroquine as a pregnancy-compatible antirheumatic drug that should be continued for maintenance of remission or treatment of disease flares. 1, 4

Add Low-Dose Aspirin

• Low-dose aspirin (81-100 mg daily) should be started before 16 weeks of gestation and continued until delivery to reduce the risk of preeclampsia and intrauterine growth retardation. 3, 2
• This combination of hydroxychloroquine plus low-dose aspirin provides optimal protection against pregnancy complications in women with SLE. 3, 2

Maternal and Fetal Benefits

Disease Activity Control

• Hydroxychloroquine significantly reduces lupus disease flares during pregnancy, with cessation associated with significantly increased disease activity and flare rates. 1, 5
• Women who stopped HCQ during pregnancy had higher lupus activity scores and increased flare rates compared to those who continued treatment. 5
• Continuing HCQ allows maintenance on lower average doses of prednisone during pregnancy. 5

Pregnancy Outcome Improvements

• Hydroxychloroquine decreases rates of preterm birth and intrauterine growth retardation in pregnant women with systemic lupus erythematosus. 3, 1
• When combined with low-dose aspirin, HCQ may reduce the risk of preeclampsia. 3, 1

Safety Profile

Fetal Safety Data

• The FDA label states that prolonged clinical experience over decades and available published data have not identified a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. 6
• More than 250 pregnancies resulting in live births have been reported with no increase in the rate of birth defects. 7, 8
• A large real-world evidence study of 288 pregnancies exposed to chloroquine/hydroxychloroquine found no increased risk of prematurity, low birth weight, or major congenital malformations. 9
• A controlled study of 133 pregnancies with HCQ exposure (117 live births) found no statistical difference in pregnancy outcomes, malformations, or cardiac abnormalities compared to controls. 10

Long-Term Child Safety

• No retinal toxicity, ototoxicity, cardiotoxicity, or growth and developmental abnormalities have been observed in children exposed to hydroxychloroquine in utero. 1, 6, 7, 10
• Follow-up of children exposed in utero showed no visual, hearing, growth, or developmental abnormalities at ages ranging from 12-108 months. 10

Placental Transfer

• Hydroxychloroquine readily crosses the placenta with cord blood levels corresponding to maternal plasma levels, but this has not resulted in adverse fetal outcomes. 6, 10

Dosing

• Typical doses are 200-400 mg daily (most commonly 400 mg daily in divided doses), which have been extensively studied and found safe. 1, 10

Absolute Contraindications

• Known allergy to hydroxychloroquine or chloroquine. 1, 4
• Severe adverse effects or intolerance to hydroxychloroquine. 1, 4
• G6PD deficiency is a relative contraindication due to hemolysis risk, though recent data suggest lower risk than previously thought. 1

Breastfeeding Compatibility

• Hydroxychloroquine is present in human milk at low levels with no adverse reactions reported in breastfed infants. 6
• The American Academy of Pediatrics considers hydroxychloroquine compatible with breastfeeding. 4
• Hydroxychloroquine has limited transfer into breast milk and is considered safe with breastfeeding. 3

Critical Pitfall to Avoid

The most common and dangerous error is discontinuing hydroxychloroquine when a patient becomes pregnant or is planning pregnancy. 1, 4

• This can precipitate disease flares and increase maternal morbidity without providing any fetal benefit. 1
• Active rheumatic disease during pregnancy increases the risk of adverse pregnancy outcomes including preterm delivery, low birth weight, spontaneous abortion, fetal death, preeclampsia, and intrauterine growth restriction. 3, 4, 6
• Abrupt discontinuation of medications when pregnancy is diagnosed can harm both mother and fetus. 4

Preconception Counseling

• Patients with active lupus nephritis should be counseled to avoid pregnancy while disease is active or when treatment with potentially teratogenic drugs is ongoing, and for at least 6 months after disease becomes inactive. 3
• Hydroxychloroquine should be continued during the preconception period as it is safe and helps maintain disease control. 1, 4