Obstetric Topic 43. Licit and illicit drug use in pregnancy

I. General Principles

Definitions

• Licit drugs: legal/prescribed/OTC drugs; may still be harmful in pregnancy.
• Illicit drugs: illegal drugs or prescription drugs used non-medically.
• Risk depends on gestational age, dose, duration, placental transfer and fetal susceptibility.
• Rule: do not stop necessary maternal therapy automatically; use the safest effective drug and avoid known teratogens/polypharmacy.

II. Common Licit Drugs

Hypertension and Cardiovascular Disease

• HT drugs of choice: labetalol, nifedipine, α-methyldopa; hydralazine for acute severe HT.
• Avoid: ACE inhibitors/ARBs → fetal renal failure/dysgenesis, oligohydramnios, skull hypoplasia, neonatal renal failure/death.
• CHF: beta-blocker, digoxin and specialist care; avoid ACEi/ARB/ARNI and SGLT inhibitors if possible.

Diabetes Mellitus

• Drug of choice: insulin.
• Oral antidiabetics: many are avoided/limited in pregnancy; metformin may be used in selected GDM protocols.
• Hyperglycemia itself is teratogenic early → cardiac, neural tube and caudal regression defects.

Anticoagulation

• Drug of choice: LMWH (e.g. dalteparin/enoxaparin) → does not cross placenta.
• Avoid: warfarin/coumarins → nasal and limb hypoplasia, CNS anomalies, fetal hemorrhage.
• DOACs/NOACs: avoid because pregnancy safety data are limited.

Thyroid Disorders

• Hypothyroidism: levothyroxine.
• Hyperthyroidism: PTU in 1st trimester; methimazole often after 1st trimester.
• Methimazole in 1st trimester: aplasia cutis, esophageal/choanal atresia, dysmorphic defects.

Analgesics

• Drug of choice: paracetamol/acetaminophen.
• NSAIDs: fetal renal dysfunction/oligohydramnios after ~20 weeks; premature ductus arteriosus closure after ~30 weeks.
• Opioids: short indicated use may be necessary; chronic use → neonatal abstinence/respiratory depression.

Immunosuppressants and Rheumatologic Drugs

• Drugs of choice when indicated: prednisolone, azathioprine; hydroxychloroquine/sulfasalazine may also be used.
• Avoid: methotrexate → antifolate teratogenicity; mycophenolate mofetil → malformations; leflunomide.

Antibiotics

• Preferred when appropriate: penicillins, cephalosporins, selected macrolides, clindamycin, metronidazole, fosfomycin, nitrofurantoin.
• Avoid/caution drugs:
• Tetracyclines after midpregnancy → tooth discoloration, enamel/bone effects.
• Sulfonamides near term → kernicterus risk.
• Aminoglycosides → ototoxicity/nephrotoxicity risk.
• Chloramphenicol → gray baby syndrome.
• Fluoroquinolones → cartilage toxicity concern; avoid if alternatives exist.

Antifungals

• Drugs of choice: topical/vaginal azoles or nystatin; low-dose azoles may be used when needed.
• Avoid: high-dose/prolonged systemic azoles and griseofulvin → teratogenicity.

Psychiatric Drugs

• Do not abruptly stop needed therapy; untreated psychiatric disease is also risky.
• Preferred examples: sertraline; antipsychotics such as olanzapine/risperidone when indicated.
• Avoid/not preferred if starting: paroxetine → cardiac malformations; lithium → classically Ebstein anomaly.

Anticonvulsants

• Drugs of choice: lamotrigine, levetiracetam.
• Avoid if possible: valproate, phenytoin, phenobarbital → neural tube defects, cleft palate, cognitive impairment.
• Give high-dose folic acid before conception/early pregnancy.

Other Important Teratogens

• Retinoids/isotretinoin: CNS, cardiac, craniofacial and thymic defects.
• Thalidomide: severe limb/skeletal malformations.
• Radioactive iodine: fetal thyroid destruction.

III. Illicit Drugs and Substance Use

Alcohol

• No safe amount or safe time in pregnancy.
• Fetal alcohol syndrome: growth restriction, microcephaly, facial abnormalities, intellectual disability/mental retardation.

Tobacco / Nicotine

• Nicotine + carbon monoxide → vasoconstriction and fetal hypoxia.
• Risks: IUGR/FGR, low birth weight, preterm labor, placenta previa, placental abruption, stillbirth.

Cocaine and Amphetamines

• Mechanism: intense vasoconstriction → placental ischemia and fetal hypoxia.
• Cocaine: IUGR, prematurity, placental abruption, stillbirth.
• Amphetamine/methamphetamine: IUGR, prematurity, placental abruption, possible cardiac anomalies.

Opioids

• Risks: poor prenatal care, infections, FGR, preterm birth, stillbirth, neonatal abstinence syndrome.
• Treatment: methadone or buprenorphine + behavioral/social support; avoid repeated withdrawal cycles.

IV. Management Approach

At Prenatal Visits

• Ask routinely and nonjudgmentally about prescription/OTC drugs, supplements, alcohol, nicotine and illicit drugs.
• If exposure occurred: clarify drug, dose, route, timing and duration.
• Continue safer necessary therapy or substitute contraindicated drugs; offer teratology/genetic counseling and targeted US/fetal echo when indicated.
• Substance use disorder: addiction referral, social support and neonatal observation plan when needed.