Prescribing During the Second Trimester

The second trimester, from 14 weeks to 27 weeks and 6 days, follows completion of organogenesis. Structural risk falls, but medicines can still impair foetal growth, renal function, bone and tooth development and neurodevelopment, and maternal pharmacokinetic changes approach their peak.

Shift in risk. Functional rather than structural toxicity dominates: renin-angiotensin blockade, NSAIDs after 20 weeks, tetracyclines after 15 weeks, iodine excess and antithyroid overtreatment.

Pharmacokinetics. Glomerular filtration and hepatic enzyme induction near their maximum; doses of renally cleared and UGT-metabolised drugs often need upward adjustment.

Preventive window. Most preventive interventions start or continue here: malaria prevention, iron and calcium, aspirin, glucose screening at 24 to 28 weeks and maternal vaccination.

Malaria prevention. Sulfadoxine-pyrimethamine 1500 mg/75 mg orally as a single observed dose monthly from 13 weeks until birth in endemic areas, unless taking co-trimoxazole prophylaxis.

Pre-eclampsia prevention. Continue aspirin 75 to 150 mg at night until 36 weeks; calcium 1.5 to 2 g elemental daily from 20 weeks where intake is low.

Iron deficiency anaemia. Elemental iron 100 to 200 mg orally daily (or on alternate days to improve absorption and tolerance). Intravenous iron from the second trimester if haemoglobin fails to rise by 10 g/L in 2 to 3 weeks or oral iron is not tolerated: ferric carboxymaltose 20 mg/kg (booking weight) up to 1000 mg as a single infusion over at least 15 minutes, or iron sucrose 200 mg IV up to 3 times weekly to the calculated deficit.

Gestational diabetes after screening.

• Metformin 500 mg orally once daily with food, increasing weekly to 2 g daily in divided doses (maximum 2.5 to 3 g daily).
• Insulin when targets are not met within 1 to 2 weeks of diet, or if fasting glucose is 7.0 mmol/L or more at diagnosis: isophane or long-acting analogue at night (start 0.1 to 0.2 units/kg) plus rapid-acting analogue with meals, titrated every 2 to 3 days.
• Targets: fasting under 5.3 mmol/L, 1 hour after meals under 7.8 mmol/L or 2 hours under 6.4 mmol/L.

Rhesus D negative, non-sensitised. Anti-D immunoglobulin 1500 units IM at 28 weeks as a single dose, or 500 units at 28 and 34 weeks. Give 250 units (under 20 weeks) or at least 500 units (from 20 weeks) within 72 hours of any sensitising event, with a Kleihauer test from 20 weeks.

Maternal vaccination. Tetanus, diphtheria and acellular pertussis from 16 weeks, ideally 20 to 32 weeks (27 to 36 weeks in some regions); inactivated influenza in any trimester; tetanus toxoid series where pertussis vaccine is unavailable. Live vaccines are contraindicated.

Preterm labour risk. Vaginal progesterone 200 mg at night from diagnosis of a cervix 25 mm or less (16 to 24 weeks) until 34 to 36 weeks.

Hyperthyroidism. Switch propylthiouracil to carbimazole 5 to 15 mg orally once daily (methimazole about 3 to 10 mg daily, roughly 60% of the carbimazole dose) at the start of the second trimester, keeping free T4 at or just over the upper limit of normal.

Avoid. ACE inhibitors, angiotensin receptor blockers and direct renin inhibitors (oligohydramnios, renal tubular dysgenesis). Tetracyclines and doxycycline from 15 weeks. NSAIDs from 20 weeks except short specialist courses. Warfarin (central nervous system abnormalities remain possible). Iodine-containing antiseptics in large amounts.

Acceptable. Penicillins, cephalosporins, macrolides, metronidazole, nitrofurantoin, paracetamol, short-course opioids, labetalol, nifedipine, methyldopa, insulin, metformin, low molecular weight heparins, inhaled asthma therapy, most SSRIs and continued antipsychotics.

Interactions. Iron with levothyroxine, quinolones or tetracyclines: separate by 4 hours. Calcium with iron: separate by 2 hours. Sulfadoxine-pyrimethamine with co-trimoxazole: additive antifolate and sulphonamide toxicity, never co-prescribe.

Special groups.

• Twins and multiples: higher iron and folate needs; earlier insulin requirement in diabetes.
• Kidney impairment: metformin dose reduced when eGFR is 30 to 45 mL/min and stopped when under 30 mL/min.
• Liver impairment: intravenous iron is safe; avoid metformin in decompensated liver disease.
• Regional: in HIV on co-trimoxazole, do not give sulfadoxine-pyrimethamine; malaria prevention is the co-trimoxazole itself.

Monitoring. Haemoglobin 2 to 4 weeks after starting iron and at 28 weeks; capillary glucose 4 times daily on treatment for diabetes; free T4 and TSH every 4 weeks on antithyroid drugs; antiepileptic levels against baseline if seizures recur or adverse effects appear.

Foetal checks. Growth scans every 2 to 4 weeks from 28 weeks when a medicine or condition affects growth (beta-blockers at high dose, diabetes, hypertension). Liquor volume after any NSAID exposure after 20 weeks.

Stopping rules. Stop NSAIDs at once if oligohydramnios is detected. Stop intravenous iron infusion for any hypersensitivity sign. Reduce antithyroid dose as free T4 falls into range; many can stop by the third trimester.

Referral and escalation. Refer to the diabetes antenatal clinic within 1 week of a diagnosis of gestational diabetes; refer haemoglobin under 70 g/L, or symptomatic anaemia, for urgent review and possible transfusion.