Paracetamol is an antipyretic analgesic indicated for the treatment of mild-to-moderate pain and pyrexia. For the purpose of this monograph, ‘therapeutic’ use of oral paracetamol is regarded as 500-1000mg up to four times a day, with a maximum dose of 4g within a 24-hour period. Where this dose is exceeded or other factors such as prolonged use or low maternal weight are present, an assessment for paracetamol overdose may need to be considered. Please refer to our monograph ‘Paracetamol overdose in pregnancy’ for further information.
Animal studies have indicated that a rise in maternal core body temperature of 1.5°C may be associated with teratogenicity and there are limited human data that suggest that maternal fever, specifically a rise in temperature of 2°C, in the first trimester of pregnancy may increase the risk of neural tube defects (NTDs) in the offspring, however data are conflicting. Severe or chronic pain, if inadequately treated, may also impact on maternofetal outcome through alteration of both maternal cardiovascular function and uteroplacental perfusion. Adverse effects on maternal and fetal outcome due to the underlying maternal condition for which paracetamol is used should therefore be considered when interpreting pregnancy safety data.
Several studies which have investigated overall congenital malformation rates following in utero exposure found no increase in risk. No increase in risk has been reported for miscarriage, small for gestational age/low birth weight infants or preterm delivery.
A large number of studies have investigated neurodevelopmental outcomes following in utero exposure to paracetamol, with conflicting results. Three meta-analyses have analysed the prevalence of ADHD. Although these meta-analyses identified an increased likelihood of ADHD in children exposed to paracetamol in utero, when one of the meta-analyses accounted for unmeasured confounding, no statistically significant difference in the rates of ADHD in paracetamol-exposed and unexposed cohorts was found. Additionally, evidence of familial confounding has been described. Therefore, residual confounding cannot be excluded. Due to significant methodological limitations of these studies, the conclusions that can be drawn are limited and a causal association remains unproven.
Frequent paracetamol use during late pregnancy (20-32 weeks) has been associated with an increased incidence of wheezing or childhood asthma in some studies but not others.
Exposure to paracetamol at any stage of pregnancy is not regarded as medical grounds for termination of pregnancy or any additional fetal monitoring. However, other risk factors may 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.
This is a summary of the full UKTIS monograph for health care professionals and should not be used in isolation. The full UKTIS monograph and access to any hyperlinked related documents is available to NHS health care professionals who are logged in.
If you have a patient with exposure to a drug or chemical and require assistance in making a patient-specific risk assessment, please telephone UKTIS on 0344 892 0909 to discuss the case with a teratology specialist.
If you would like to report a pregnancy to UKTIS please click here to download our pregnancy reporting form. Please encourage all women to complete an online reporting form.