Prescribing During the Third Trimester

The third trimester, from 28 weeks to birth, brings maximal maternal physiological change and the transition to neonatal life. Medicines given now can affect the ductus arteriosus, foetal kidney, labour and the newborn, who must clear or withdraw from drugs after the cord is cut.

Neonatal consequences. Benzodiazepines, opioids, antidepressants, antipsychotics, beta-blockers and sulphonamides near term can cause sedation, withdrawal, hypoglycaemia, bradycardia or jaundice in the newborn.

Ductus arteriosus. NSAIDs from 30 weeks can constrict the ductus and cause foetal pulmonary hypertension; avoid them.

Preterm birth. Corticosteroids, magnesium sulphate for neuroprotection and short tocolysis improve neonatal outcome when birth before 34 weeks is likely.

Antenatal corticosteroids. Between 24 weeks and 34 weeks and 6 days when birth is expected within 7 days:

• Betamethasone 12 mg IM, 2 doses 24 hours apart.
• Alternative: dexamethasone 6 mg IM every 12 hours for 4 doses (or 12 mg IM 2 doses 24 hours apart).
• Consider from 22 weeks after senior discussion; consider at 34 to 36 weeks only in selected cases and not in pre-existing diabetes because of neonatal hypoglycaemia.

Magnesium sulphate for neuroprotection. Offer under 30 weeks and consider at 30 weeks to 33 weeks and 6 days when birth is expected within 24 hours: 4 g IV over 15 minutes, then 1 g/hour until birth or for 24 hours, whichever comes first. A higher loading dose of 6 g with 2 g/hour is used in some regions.

Tocolysis (to allow corticosteroids or transfer, 24 to 34 weeks).

• Nifedipine 20 mg orally, then 10 to 20 mg 3 to 4 times daily adjusted to contractions, maximum 160 mg daily, for up to 48 hours.
• Alternative: atosiban 6.75 mg IV over 1 minute, then 18 mg/hour for 3 hours, then 6 mg/hour for up to 45 hours; maximum 48 hours and 330 mg in total.
• Indometacin under 32 weeks only, 50 to 100 mg loading then 25 mg every 6 hours for no more than 48 hours.

Pre-eclampsia with severe features. Magnesium sulphate 4 g IV over 5 to 15 minutes, then 1 g/hour for 24 hours after birth or the last seizure, whichever is later. Recurrent seizure: further 2 g IV (4 g if over 70 kg) over 5 to 15 minutes.

Intramuscular magnesium regimen (common where infusion pumps are limited). Magnesium sulphate 4 g IV over 5 minutes plus 10 g deep IM (5 g into each buttock with 1 mL of 2% lidocaine), then 5 g deep IM every 4 hours into alternate buttocks for 24 hours.

Anti-D. Continue the 28 and 34 week schedule and give within 72 hours of any sensitising event, sized by Kleihauer test.

Chronic conditions. Plan intrapartum doses of insulin, anticoagulants, antiepileptics and lithium by 36 weeks with a written birth plan.

Avoid. NSAIDs from 30 weeks (and from 20 weeks unless specialist use), ACE inhibitors and angiotensin receptor blockers, sulphonamides and co-trimoxazole close to birth unless benefit outweighs jaundice risk, nitrofurantoin from 36 weeks (neonatal haemolysis, especially with G6PD deficiency), chloramphenicol near term (grey baby syndrome).

Monitor the newborn after. Long-term SSRIs and SNRIs, benzodiazepines, opioids including opioid substitution, antipsychotics, beta-blockers (glucose and heart rate for 24 to 48 hours), lithium, insulin and sulphonylureas (neonatal hypoglycaemia).

Magnesium sulphate toxicity. Loss of patellar reflexes (over 3.5 to 5 mmol/L), respiratory depression (over 5 to 6.5 mmol/L), cardiac arrest (over 7.5 mmol/L). Antidote: calcium gluconate 10%, 10 mL (1 g) IV over 10 minutes.

Interactions. Nifedipine with magnesium sulphate can cause hypotension and neuromuscular weakness; use together with close observation. Magnesium potentiates non-depolarising neuromuscular blockers at caesarean birth.

Special groups.

• Kidney impairment: halve or stop the magnesium maintenance infusion if urine output falls under 100 mL in 4 hours or creatinine rises; check serum magnesium.
• Asthma: avoid labetalol; use nifedipine or hydralazine.
• Twins: corticosteroid and magnesium regimens unchanged.
• Regional: G6PD deficiency is common in East Africa; avoid nitrofurantoin, sulphonamides and primaquine near term when status is unknown.

Monitoring. Magnesium sulphate: patellar reflexes, respiratory rate and oxygen saturation hourly, urine output hourly with a catheter; serum magnesium if renal function is impaired or toxicity is suspected (therapeutic range 2 to 4 mmol/L). After corticosteroids: capillary glucose for 72 hours in diabetes and insulin adjustment.

Lithium. Weekly levels from 36 weeks; omit at the onset of labour or 24 to 48 hours before planned birth; restart at the pre-pregnancy dose after birth once fluid balance is stable, with a level within 1 week.

Stopping rules. Stop magnesium if reflexes are absent, respiratory rate is under 12 a minute or urine output is under 100 mL in 4 hours. Stop tocolysis at 48 hours, with membrane rupture and infection, or with maternal compromise.

Referral and escalation. Transfer threatened preterm birth under 32 weeks in utero to a unit with neonatal intensive care where possible. Escalate any eclamptic seizure, severe hypertension not controlled within 1 hour or magnesium toxicity to senior obstetric and anaesthetic staff at once.