Prescribing During the First Trimester

The first trimester, up to 13 weeks and 6 days, spans implantation and organogenesis, when structural teratogenic risk is highest. Many exposures happen before pregnancy is recognised, so prescribing here means preventing harmful exposure, assessing exposure already sustained and treating common early conditions safely.

Critical window. Gestational weeks 5 to 10 (days 15 to 60 after conception) carry the greatest structural risk: neural tube closes by about day 28 after conception, heart forms over weeks 5 to 8, palate fuses by about week 12.

Recognition gap. Around half of pregnancies are unplanned. Treat every person of reproductive potential as possibly pregnant before prescribing a teratogen.

Common needs. Nausea and vomiting (up to 80%), hyperemesis gravidarum (about 1%), urinary infection, malaria in endemic areas, threatened miscarriage, thyroid dose adjustment and continuation of chronic therapy.

Nausea and vomiting, first line.

• Doxylamine 10 mg with pyridoxine 10 mg delayed release: 2 tablets at bedtime; add 1 tablet in the morning on day 3 and 1 mid-afternoon on day 4 if needed; maximum 4 tablets daily.
• Cyclizine 50 mg orally, IM or IV up to 3 times daily; maximum 150 mg daily.
• Promethazine 25 mg orally at night, up to 100 mg daily in divided doses.
• Prochlorperazine 5 to 10 mg orally 2 to 3 times daily, or 12.5 mg IM.

Nausea and vomiting, second line.

• Metoclopramide 10 mg orally, IM or IV up to 3 times daily; maximum 30 mg daily (0.5 mg/kg daily) for no more than 5 days because of extrapyramidal effects.
• Ondansetron 4 to 8 mg orally or IV up to 3 times daily; a single IV dose must not exceed 16 mg. A small rise in orofacial clefts (about 3 extra in 10,000) is reported with first trimester use, so discuss and reserve for failure of first-line agents.

Hyperemesis gravidarum. Intravenous fluids with potassium replacement, thiamine 100 mg IV or orally daily before any dextrose, antiemetic combination and thromboprophylaxis if admitted. For refractory cases prednisolone 40 to 50 mg orally daily (or hydrocortisone 100 mg IV twice daily), tapered over weeks once vomiting settles.

Urinary infection and asymptomatic bacteriuria.

• Nitrofurantoin modified release 100 mg orally twice daily for 7 days (avoid if eGFR under 45 mL/min).
• Cefalexin 500 mg orally 2 to 3 times daily for 7 days.
• Amoxicillin 500 mg orally 3 times daily for 7 days only if the organism is sensitive.
• Avoid trimethoprim in the first trimester (folate antagonist) unless no alternative and folic acid 5 mg is given.

Malaria.

• Uncomplicated: artemether-lumefantrine 20 mg/120 mg, 4 tablets orally at 0, 8, 24, 36, 48 and 60 hours with fatty food (weight 35 kg or more). Now advised in all trimesters, including the first.
• Alternative uncomplicated: quinine 10 mg/kg (salt) orally 8-hourly with clindamycin 10 mg/kg orally 12-hourly, both for 7 days.
• Severe: artesunate 2.4 mg/kg IV or IM at 0, 12 and 24 hours, then daily until oral therapy is tolerated, then a full artemisinin combination course. Use in all trimesters.

Threatened miscarriage. With bleeding and at least one previous miscarriage, vaginal micronised progesterone 400 mg twice daily from presentation until 16 weeks.

Thyroid. On confirmation of pregnancy, raise levothyroxine by about 25 to 30% (for example 2 extra daily doses each week). Hyperthyroidism: propylthiouracil 50 to 150 mg orally 3 times daily in the first trimester, switching to carbimazole or methimazole from the second trimester.

Avoid or replace. Valproate, isotretinoin, mycophenolate, methotrexate, warfarin (switch before 6 weeks), ACE inhibitors, angiotensin receptor blockers, statins, carbimazole and methimazole (aplasia cutis, choanal and oesophageal atresia, highest risk at 6 to 10 weeks), misoprostol, leflunomide.

Usually acceptable. Paracetamol, penicillins, cephalosporins, erythromycin, azithromycin, clindamycin, insulin, metformin, levothyroxine, labetalol, nifedipine, methyldopa, inhaled corticosteroids and bronchodilators, low molecular weight heparins, most SSRIs (sertraline preferred for new starts), lamotrigine and levetiracetam.

Use with care. Ibuprofen and other NSAIDs (possible miscarriage association, avoid around conception and early pregnancy where alternatives exist), paroxetine (small cardiac defect signal), fluconazole at high or prolonged doses, codeine for more than a few days.

Interactions. Iron and calcium reduce levothyroxine absorption; separate by 4 hours. Ondansetron with other QT-prolonging drugs (macrolides, some antipsychotics) needs ECG review when electrolytes are deranged.

Special groups.

• Adolescents: confirm dates and consent; folic acid uptake is often low.
• Kidney impairment: avoid nitrofurantoin when eGFR is under 45 mL/min.
• Liver impairment: avoid propylthiouracil when transaminases are raised; it can cause fulminant hepatitis.
• Regional: in sickle cell disease continue folic acid 5 mg daily and stop hydroxycarbamide (ideally 3 months before conception).

Exposure assessment. Date by ultrasound, convert to days after conception, list every medicine with dose and dates, and compare with the critical window for each. Offer a detailed scan at 18 to 22 weeks after any teratogen exposure.

Monitoring. Hyperemesis: weight, ketones, urea, electrolytes, magnesium, liver tests and thyroid function. Levothyroxine: TSH 4 weeks after any change. Propylthiouracil: liver tests at baseline and with any symptoms of hepatitis.

Stopping rules. Stop metoclopramide at 5 days or at the first extrapyramidal sign. Stop propylthiouracil at once if jaundice, dark urine or transaminases over 3 times the upper limit.

Referral and escalation. Admit for hyperemesis with ketonuria and weight loss over 5% despite oral antiemetics, inability to keep down fluids or medicines, or electrolyte derangement. Refer exposures to valproate, mycophenolate, isotretinoin, methotrexate or warfarin to a specialist the same week.