USE OF ASPIRIN AND ASPIRIN OVERDOSE IN PREGNANCY

Aspirin is an acetylated salicylate with analgesic, antipyretic, anti-inflammatory and antiplatelet properties. Low-dose aspirin (75-300mg/day) is used as an antiplatelet medication in the prophylaxis of thromboembolic cerebrovascular disease and myocardial infarction. Higher doses of aspirin (up to 4g/day) are used in the control of mild-to-moderate pain and pyrexia. 

The National Institute for Health and Care Excellence (NICE) guidelines state that pregnant women at high risk of pre-eclampsia should be offered low-dose aspirin from 12 gestational weeks. Low-dose aspirin is sometimes used from conception for women undergoing fertility treatment and those with a history of recurrent miscarriage or conditions such as antiphospholipid syndrome, as some studies have suggested an improvement in live birth rates.

There is no specific information on malformation rates following use of low-dose aspirin in pregnancy but in most cases this treatment is initiated after 12 weeks of pregnancy when fetal organogenesis is complete and there is little risk of medication-induced structural malformation. Increased risks of gastroschisis, cleft lip and palate, and neural tube defects have been reported following maternal use of aspirin during pregnancy (mainly at analgesic doses), however data are conflicting and may also be confounded, and a causal association with aspirin has not been proven. Data relating to risk of cardiac malformations are reassuring.

The majority of evidence suggests that there is no association between the use of low-dose aspirin and miscarriage, fetal growth restriction, or preterm delivery. Stillbirth data are limited to one small randomised-controlled trial that found no increased risk following exposure to low-dose aspirin. No data are available on pregnancy outcomes following aspirin use at analgesic doses, and data on neurodevelopmental outcomes following in utero aspirin exposure at any dose are too limited to facilitate an evidence-based assessment of risk.

Chronic exposure to analgesic doses of aspirin >300mg/day from 30 weeks of pregnancy may be associated with neonatal bleeding complications and premature closure of the ductus arteriosus (DA), resulting in pulmonary vasculature abnormalities and persistent pulmonary hypertension of the newborn (PPHN). These effects have not been reported with low-dose aspirin use.

Regular use of analgesic doses of aspirin in the third trimester should be avoided if possible. In circumstances where the maternal clinical condition requires treatment with analgesic doses of aspirin during the third trimester, fetal monitoring for oligohydramnios and ductus arteriosus patency is recommended. Exposure to analgesic doses of aspirin prior to the third trimester would not be considered an indication for any additional fetal monitoring. 

Aspirin overdose can result in severe maternal toxicity and consequently adverse fetal effects.  Pregnant women who have overdosed on aspirin should be managed as for the non-pregnant patient and may require additional interventions and/or fetal monitoring. Discussion with UKTIS and NPIS is recommended in all such cases.

Other risk factors may also be present in individual cases which may independently increase the risk of adverse pregnancy outcome. Clinicians are reminded of the importance of consideration of such factors when performing case-specific risk assessments.