Aspirin 81 mg (Bayer Aspirin Low Dose) — most widely used LDA formulation in North America · Ecotrin (enteric-coated aspirin 81 mg and 325 mg) — note: enteric coating delays and reduces peak absorption; some evidence suggests plain (non-enteric) aspirin may produce more reliable antiplatelet effect · Disprin (dispersible aspirin 75 mg) — widely used in UK and Commonwealth countries for LDA · Micropirin 75 mg (modified-release aspirin) — UK formulation · Cardiprin 100 mg — Australia · Aspro Clear (effervescent aspirin) — UK/Europe · Nu-Seals 75 mg and 300 mg (enteric-coated) — UK · Acetylsalicylic acid (generic, multiple manufacturers) — 75 mg, 81 mg, 100 mg, 150 mg, 300 mg, 325 mg, 500 mg tablets available globally · Note: Plain (non-enteric-coated) aspirin 75–150 mg is pharmacokinetically preferred for antiplatelet effect in pregnancy — enteric coating delays absorption and may reduce peak platelet inhibition, though steady-state platelet inhibition at once-daily dosing is equivalent with either formulation in most studies
Clinical safety rating: caution
Positive evidence of fetus risks but benefits may outweigh risks in some cases
Aspirin exerts its pharmacological effects through irreversible acetylation of the active site serine residue (Ser530) of cyclooxygenase (COX) enzymes — specifically COX-1 and, at higher doses, COX-2. Antiplatelet mechanism (low-dose, 75–150 mg): At low doses, aspirin preferentially and irreversibly acetylates platelet COX-1, blocking the conversion of arachidonic acid to prostaglandin G2/H2 and ultimately to thromboxane A2 (TXA2) — a potent platelet aggregation agonist and vasoconstrictor. Because platelets are anucleate and cannot synthesise new COX-1, this inhibition is permanent for the platelet's lifespan (8–10 days). A single 75 mg dose produces near-complete (>95%) suppression of platelet TXA2 synthesis within 1 hour. Vascular endothelial cells can regenerate COX-2 and synthesise prostacyclin (PGI2) — an antiaggregatory, vasodilatory prostaglandin — relatively sparing the TXA2:PGI2 balance in favour of PGI2 at low doses. This is the mechanistic basis for the selective antiplatelet effect without full anti-inflammatory activity at low doses. Anti-inflammatory / analgesic mechanism (high dose, ≥325 mg): At higher doses, aspirin inhibits both COX-1 and COX-2 across multiple cell types (macrophages, endothelium, synoviocytes), reducing prostaglandin E2 (PGE2) and PGI2 synthesis systemically, providing anti-inflammatory, analgesic, and antipyretic effects. The COX-2 inhibition in the kidney mediates the renal prostaglandin-dependent effects (sodium retention, reduced GFR, oliguria) and in the ductus arteriosus mediates premature ductal constriction (the ductus is tonically maintained by PGE2 — COX inhibition reduces PGE2 and promotes constriction). Preeclampsia prevention mechanism: The pathophysiology of preeclampsia involves impaired trophoblast invasion and spiral artery remodelling, leading to placental ischaemia, excessive sFlt-1 release, and endothelial dysfunction with a pro-thrombotic, pro-inflammatory state. LDA is postulated to reduce preeclampsia risk through multiple complementary mechanisms: (1) inhibition of platelet-derived TXA2, shifting the TXA2:PGI2 balance toward vasodilation and anti-aggregation in the uteroplacental circulation; (2) early trophoblastic COX-2 inhibition modulating implantation and placentation; (3) anti-inflammatory effects on the systemic endothelial response. The greatest benefit of early initiation (before 16 weeks) aligns with the critical window of second-wave trophoblast invasion and spiral artery remodelling (10–18 weeks gestation).
| Metabolism | Aspirin is rapidly hydrolysed by plasma and intestinal esterases to salicylate (salicylic acid) — the primary active circulating metabolite — with an aspirin half-life of only 15–20 minutes. Salicylate is then metabolised in the liver via multiple pathways: 1. Glycine conjugation to salicyluric acid (primary pathway at low doses; saturable — Michaelis-Menten/zero-order kinetics at higher doses). 2. Glucuronide conjugation to salicyl phenolic glucuronide and salicyl acyl glucuronide (UGT enzymes). 3. Ring hydroxylation to gentisic acid (minor pathway, CYP-mediated). Dose-dependent (Michaelis-Menten) kinetics: At low doses (75–325 mg), salicylate follows first-order kinetics (half-life ~2–3 hours). At high/toxic doses (≥4 g/day), glycine conjugation is saturated and metabolism shifts to zero-order kinetics — a small increase in dose produces a disproportionately large increase in plasma salicylate concentration, with half-life extending to 15–30 hours. This is the pharmacokinetic basis for salicylate toxicity (salicylism) and why analgesic dosing carries fundamentally different risks than LDA. Pregnancy-specific changes: Pregnancy increases plasma volume and albumin concentration changes (albumin falls in late pregnancy, affecting protein binding of salicylate). Renal clearance of salicylate is influenced by urinary pH (alkaline urine promotes ionisation and reduced tubular reabsorption, increasing salicylate excretion). The expanded GFR in pregnancy modestly increases salicylate clearance, which, combined with larger volume of distribution, may lower steady-state salicylate plasma concentrations — one consideration in the debate about whether 150 mg/day achieves superior antiplatelet effects in pregnancy compared to 81 mg. CYP450: Aspirin and salicylate are not significantly metabolised by CYP3A4 or CYP2C19. Salicylate is a weak inhibitor of CYP2C9, which is the basis for its interaction with warfarin (CYP2C9-mediated warfarin metabolism impairment plus direct antiplatelet/anticoagulant synergy). |
Dosing varies by indication and patient profile. Always follow your institution's current prescribing guidelines.
| Renal impairment | Consult protocols for adjustment. |
| Liver impairment | Consult protocols for adjustment. |
| 1st trimester | Low-dose aspirin (75–150 mg/day): Safe and recommended. Initiate between 12+0 and 16+0 weeks (optimally by 12–13 weeks based on ASPRE data) for preeclampsia prevention in women meeting high-risk criteria (prior preeclampsia, chronic hypertension, diabetes, renal disease, autoimmune disease, multifetal gestation, or combined first-trimester screening-based risk ≥1:100). Evening bedtime dosing preferred. No increased risk of miscarriage at LDA doses — reassuring data from ASPRE (n=1,776) and the CLASP trial. High-dose aspirin: some case-control studies have associated first-trimester high-dose NSAID/aspirin use with gastroschisis and cardiac septal defects; data are not conclusive but the precautionary principle applies. Paracetamol is the preferred analgesic in T1. Aspirin should not be used for fever management in T1 (or any trimester) when paracetamol is available. |
| 2nd trimester | Low-dose aspirin: Safe. Continue LDA throughout T2 for preeclampsia prevention and APS management. No ductal or renal fetal toxicity at low doses — prostaglandin inhibition insufficient at 75–150 mg to affect ductal tone or fetal renal function. Monitor uterine artery Doppler at 20–24 weeks as part of preeclampsia surveillance. High-dose aspirin (≥325 mg): should be avoided after 20 weeks per FDA 2020 Drug Safety Communication. If NSAID-level aspirin was used before 20 weeks, reassess and discontinue or switch to paracetamol. If continued between 20–30 weeks for compelling indications (rare), serial ultrasound for amniotic fluid volume and ductal Doppler is recommended per FDA guidance. |
| 3rd trimester | Low-dose aspirin: Continue until 36 weeks (ACOG) or 37 weeks (some guidelines) if prescribed for preeclampsia prevention, then discontinue to reduce bleeding risk at delivery. Women with APS or mechanical heart valves may continue under specialist guidance with anaesthetic team communication. Neuraxial anaesthesia (epidural/spinal) is generally considered safe with LDA alone per OAA/AAGBI and ASRA guidelines — no mandatory washout period required for 75–100 mg/day if no other anticoagulants co-prescribed. High-dose aspirin: absolutely contraindicated in T3. After 32 weeks, the risk of premature ductal arteriosus closure is high and the ductus is exquisitely sensitive to prostaglandin inhibition — even short courses of analgesic-dose aspirin can cause rapid and potentially irreversible ductal constriction, neonatal pulmonary hypertension, and death. Additionally, high-dose aspirin inhibits myometrial prostaglandin synthesis, potentially prolonging labour and increasing postpartum haemorrhage risk. |
inflammation
Loading safety data…
Clinical note
Aspirin has a profoundly dose-dependent safety and indication profile in pregnancy that mandates clear clinical distinction between low-dose (75–100 mg/day, antiplatelet) and high-dose (≥325 mg, analgesic/anti-inflammatory) use. Low-dose aspirin (LDA) is a cornerstone intervention in obstetric medicine: ACOG, USPSTF (Grade B recommendation), WHO, NICE, and FIGO all recommend initiating LDA at 12–16 weeks gestation (optimally before 16 weeks, ideally by 12 weeks) in women at increased risk of preeclampsia, reducing its incidence by approximately 10–24% overall and by up to 62% when initiated before 16 weeks in high-risk women (ASPRE trial). LDA is also used for antiphospholipid syndrome (APS), prevention of recurrent pregnancy loss in APS, and thromboprophylaxis in specific haematological conditions. High-dose aspirin functions as a full NSAID and carries the class risks of premature closure of the ductus arteriosus (particularly after 20 weeks, critically so after 32 weeks), fetal renal impairment, oligohydramnios, inhibition of labour, and maternal and fetal haemostatic compromise. High-dose aspirin should be avoided after 20 weeks of gestation and is contraindicated after 32 weeks. The FDA issued a Drug Safety Communication in 2020 strengthening warnings against NSAID use (including high-dose aspirin) from 20 weeks onwards.
| Placental transfer | Yes — aspirin and its primary metabolite salicylate cross the placenta readily by passive diffusion, facilitated by aspirin's low molecular weight (180 g/mol) and moderate lipophilicity. Umbilical cord blood salicylate concentrations approximate maternal plasma levels, with cord:maternal ratios approaching 1.0 with sustained maternal exposure. Fetal plasma protein binding of salicylate is lower than maternal (fetal albumin has reduced salicylate-binding affinity), resulting in higher free salicylate fractions in fetal plasma — potentially amplifying fetal exposure relative to total plasma concentrations. At low doses (75–100 mg/day), transplacental salicylate exposure is clinically minimal and does not cause measurable fetal platelet inhibition at term under standard monitoring. At analgesic doses, particularly with prolonged use, fetal salicylate accumulation can occur. Aspirin itself (the acetylated form) is rapidly hydrolysed to salicylate in plasma and at the intestinal wall, so the primary transplacental species is salicylate rather than aspirin per se. |
| Breastfeeding | Aspirin is excreted into breast milk as salicylate. Following a single 650 mg maternal dose, peak milk salicylate concentrations of approximately 1.1–10 mg/L have been reported, with milk:plasma ratios of approximately 0.03–0.08. At low doses (75–100 mg/day), infant salicylate exposure via breast milk is minimal and the relative infant dose (RID) is estimated to be well below 1% of the maternal weight-adjusted dose — considered negligible. The primary concern with aspirin in breastfeeding is the theoretical risk of Reye syndrome — a rare but serious condition of hepatic encephalopathy associated with salicylate exposure during viral illness (influenza, varicella) in infants and children. No cases of Reye syndrome have been specifically attributed to breast milk aspirin exposure at low doses, but the theoretical risk is the basis for caution. Practical guidance: low-dose aspirin (75–100 mg/day) for maternal indications (preeclampsia prevention, APS, cardiac) is compatible with breastfeeding. High-dose or repeated analgesic-dose aspirin should be avoided — use paracetamol (acetaminophen) instead. Avoid breastfeeding during maternal influenza or varicella illness if taking any aspirin dose. Monitor infant for unusual bruising or bleeding (theoretical antiplatelet effect via breast milk is negligible at low doses but theoretically possible at high doses). |
