Can hydroxychloroquine and vitamin D supplementation be given during the first trimester of pregnancy?

Hydroxychloroquine and Vitamin D in First Trimester: Safety and Recommendations

Yes, both hydroxychloroquine (HCQ) and vitamin D supplementation can be safely given during the first trimester of pregnancy. The evidence strongly supports their use, with HCQ being explicitly pregnancy-compatible for rheumatic diseases and vitamin D supplementation being conditionally recommended for all pregnant women.

Hydroxychloroquine (HCQ) Safety in First Trimester

HCQ is explicitly listed as pregnancy-compatible and should be continued throughout pregnancy, including the first trimester 1. The 2025 EULAR guidelines clearly state that HCQ is among the conventional synthetic disease-modifying antirheumatic drugs compatible with pregnancy and should be continued for maintenance of remission or treatment of disease flares 1.

Key Safety Evidence:

• FDA labeling confirms safety: Decades of clinical experience and published epidemiologic studies have not identified a drug-associated risk of major birth defects, miscarriage, or adverse maternal/fetal outcomes 2

• No organ toxicity in exposed infants: Children exposed to HCQ in utero show no retinal toxicity, ototoxicity, cardiotoxicity, or growth/developmental abnormalities 2

• Disease control benefits outweigh minimal risks: Untreated rheumatic disease during pregnancy carries significant risks including preterm birth, preeclampsia, and fetal death 2

Nuanced Risk Assessment:

While one 2021 study suggested a small increased risk of malformations (adjusted RR 1.26,95% CI 1.04-1.54), particularly at doses ≥400 mg daily 3, this must be weighed against:

• A larger 2021 Danish cohort study (1,487 exposed pregnancies) found no increased risk of major birth defects, preterm birth, or small-for-gestational-age infants 4
• The absolute risk increase, if real, is small and likely outweighed by disease control benefits 3
• Stopping HCQ during pregnancy significantly increases lupus activity and flare rates 5

Clinical recommendation: Continue HCQ at standard doses (≤5.0 mg/kg/day real weight, typically ≤400 mg/day) throughout pregnancy, including the first trimester, for patients with rheumatic diseases 1, 6.

Vitamin D Supplementation in First Trimester

Vitamin D supplementation should be given empirically during pregnancy, including the first trimester, without routine baseline testing 7. The 2024 Endocrine Society guidelines conditionally recommend this approach based on moderate evidence of benefit.

Dosing Recommendations:

• Standard supplementation: 600 IU/day minimum for all pregnant women 8
• Higher doses may be beneficial: 1,000-4,000 IU/day to achieve better maternal and infant outcomes 8
• For deficiency: Studies show 5,000 IU daily or 50,000 IU weekly are equally effective and safe 9

Evidence for Benefits:

The 2024 Endocrine Society guideline found that vitamin D supplementation during pregnancy may reduce 7:

• Preeclampsia
• Low birth weight
• Preterm birth
• Small-for-gestational-age births

The median effective dose in studies was approximately 2,600-3,400 IU daily 7, substantially higher than the traditional 600 IU recommendation.

Important Caveats:

• Evidence certainty is low to moderate, hence the conditional recommendation 7
• The 95% confidence intervals in studies included potential for both benefit and harm 7
• Vitamin D deficiency is highly prevalent in first trimester (70.4% in one study) 10
• Supplementation significantly increases 25(OH)D levels by approximately 0.51 nmol/L per 40 IU daily 10

Practical Implementation Algorithm

For patients with rheumatic disease:

1. Continue HCQ at ≤5.0 mg/kg/day (max 400 mg/day typically)
2. Add vitamin D 1,000-2,000 IU daily empirically
3. No need for baseline 25(OH)D testing unless clinically indicated
4. Monitor for disease activity, not drug levels

For patients without rheumatic disease (vitamin D only):

1. Start vitamin D 600-2,000 IU daily in first trimester
2. Consider higher doses (up to 4,000 IU daily) if risk factors for deficiency exist (darker skin, limited sun exposure, obesity)
3. No routine testing needed if doses remain within tolerable upper limits

Critical Safety Points

• Do not stop HCQ due to pregnancy concerns - this increases disease flare risk significantly 5, 6
• Vitamin D is inexpensive and low-risk - the potential benefits justify empiric supplementation 7
• Shared decision-making is essential - discuss risks/benefits with patients 1
• HCQ crosses the placenta but decades of data show safety 2

Both medications represent evidence-based, guideline-supported interventions that can and should be used during the first trimester when clinically indicated.