Prescribing during pregnancy

Case vignette

Thandi, a 22-year-old physiotherapy student, presented with severe cystic acne that significantly affected her confidence and quality of life. After trying various topical and oral antibiotics without success, she was prescribed isotretinoin by a general practitioner (GP). Thandi, keen to start treatment, overlooked the need for contraception, assuming her infrequent sexual activity posed minimal risk. A few weeks into treatment, she discovered she was 6 weeks pregnant during a routine consultation. The news was devastating, as isotretinoin is known for its high teratogenic potential, including risks of craniofacial, cardiac, and central nervous system abnormalities in the developing foetus. Thandi was immediately referred to a multidisciplinary team, including a physician, obstetrician, dermatologist, and counsellor, to address her medical and emotional needs.

This case underscores the critical need for strict adherence to pregnancy prevention programmes and patient education when prescribing medications with teratogenic potential to women of childbearing age. It also highlights the importance of early pregnancy detection in patients receiving such treatments to mitigate risks to both the mother and foetus.

Introduction

Prescribing during pregnancy is a delicate and complex process that requires healthcare professionals (HCPs) to carefully balance the therapeutic benefits to the mother against potential risks to the developing foetus. Certain medications, while effective for treating chronic or severe conditions, may have significant teratogenic effects that can result in serious congenital abnormalities.

A critical example is isotretinoin (CAP or GEL), a highly effective treatment for severe acne vulgaris but associated with severe teratogenic risks if taken during pregnancy. This highlights the importance of careful medication review, patient education, and contraception counselling for women of childbearing potential.

Applications of prescribing during pregnancy

Neurological medications

• Certain antiepileptic drugs (AEDs), such as sodium valproate, pose significant risks during pregnancy, including teratogenic effects and neurodevelopmental disorders in the foetus. For example:
  • Sodium valproate: Associated with neural tube defects like spina bifida and developmental delays. Alternative AEDs like lamotrigine or levetiracetam should be considered where clinically appropriate.
  • Carbamazepine: Though safer, it still carries a risk for neural tube defects, warranting folic acid supplementation and close monitoring.
• Balancing maternal seizure control with foetal safety is crucial. When prescribing AEDs, HCPs must weigh risks, adjust doses as needed, and prioritise medications with a lower teratogenic profile.

Antimicrobial medications

• The use of antimicrobials during pregnancy requires careful consideration to avoid adverse effects on foetal development:
  • Chloramphenicol (INJ/CAP) or (EYO/OPD): This may cause foetal bone marrow suppression, making it unsuitable during pregnancy.
  • Tetracyclines: Linked to permanent tooth discolouration and inhibited bone growth in the foetus. Avoid these, especially after the first trimester.
  • Fluoroquinolones: Associated with musculoskeletal abnormalities; safer alternatives like penicillins or cephalosporins are preferred.
• Prescribing safer options and limiting antimicrobial use to necessary cases can significantly reduce risks to both mother and baby.

Antifungal medications

• Certain antifungal drugs are teratogenic and should be prescribed cautiously:
  • Fluconazole: High doses are linked to congenital anomalies, including heart defects and skeletal abnormalities.
  • Itraconazole: Associated with developmental defects similar to fluconazole.
  • Topical antifungals, when effective, are a safer alternative during pregnancy.

Anticoagulant medications

• The use of anticoagulants in pregnancy is challenging due to the risks posed by certain agents:
  • Warfarin: Associated with warfarin embryopathy, characterised by nasal hypoplasia, bone defects, and increased miscarriage risk.
  • Low-molecular-weight heparins (LMWH): For example, enoxaparin, is a safer alternative (condition-based, use with caution).
• HCPs must carefully balance maternal health needs against foetal risks, often transitioning patients to safer options early in pregnancy.

Vitamin A and hormonal medications

• High doses of vitamin A and certain hormonal therapies present significant risks:
• Vitamin A derivatives: Linked to craniofacial defects such as cleft palate and microcephaly.
• Diethylstilbestrol (DES): Historical use caused vaginal and cervical cancers in offspring, illustrating the long-term consequences of prenatal exposure.
• Monitoring vitamin and supplement intake during pregnancy is essential to prevent teratogenic effects.

Insights for practice

Prescribing during pregnancy requires careful consideration to ensure maternal and foetal safety. HCPs should:

• Review medication histories to identify teratogenic drugs, such as isotretinoin or valproate.
• Prescribe safer alternatives when possible, tailored to the patient’s condition.
• Adjust dosages based on physiological changes during pregnancy that affect drug metabolism.
• Educate patients on medication risks and the importance of treatment adherence.
• Ensure contraception and monitoring for women on teratogenic medications, with regular pregnancy testing.
• Collaborate with specialists to provide comprehensive and safe care.
• Use digital tools like EDD calculators to guide medication decisions based on gestational age.

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References

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2. Mitchell AA, Gilboa SM, Werler MM, et al. Medication use during pregnancy, with particular focus on prescription drugs: 1976-2008. Am J Obstet Gynecol. 2011;205(1):51.e1-51.e518.
3. Costantine MM. Physiologic and Pharmacokinetic Changes in Pregnancy. Front Pharmacol. 2014;5:65.
4. Tsamantioti ES, Hashmi MF. Teratogenic Medications. In: StatPearls. Treasure Island (FL): StatPearls Publishing; 2024.
5. Zaki NM, Albarraq AA, Fatani AJ, El Hadi MA. Use, attitudes and knowledge of medications among pregnant women: A Saudi study. Saudi Pharm J. 2014;22(5):419-428.