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 increases the risk of NTDs in the offspring, however other 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 investigated overall congenital malformation rates following in utero exposure found no increase in risk. Findings regarding a possible increased risk of cryptorchidism in male offspring following paracetamol use during pregnancy are conflicting.
A number of studies have examined the effects of in utero paracetamol exposure on various aspects of neurodevelopment. While single studies have shown no association with IQ, attention disorders, or psychosis respectively, one study found that children exposed in utero to paracetamol were more likely to have poorer gross motor development, communication skills, externalising and internalising behaviours, and to have higher activity levels than siblings who had not been exposed to paracetamol. Four studies have analysed the prevalence of behaviour subtypes that may be indicative of ADHD. Although three of these studies identified an increased likelihood of these behaviours in children exposed to paracetamol in utero, associations were generally only of marginal statistical significance. One study found that boys exposed to paracetamol in utero were more likely to exhibit symptoms of autism spectrum disorder (ASD) but did not observe the association in girls, while a further study found an increased risk of ASD with hyperkinetic symptoms in children gestationally exposed to paracetamol, but no increased risk of ASD without hyperkinetic symptoms. In most studies, risk of abnormal neurodevelopment correlated with duration of paracetamol exposure. However, significant methodological limitations of these studies limit the conclusions that can be drawn 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, some of which were included in a recent meta-analysis which showed a weak association.
Data regarding other fetal effects of maternal paracetamol use in pregnancy are limited and conflicting. An association with an increased risk of any adverse fetal outcome following therapeutic paracetamol use in pregnancy remains to be proven.
Exposure to paracetamol at any stage of pregnancy would not usually be 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.