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Over-the-counter analgesics during pregnancy: a comprehensive review of global prevalence and offspring safety

Zafeiri A, Mitchell R, Hay D, Fowler P (2021) Human Reproduction Update Jan 4;27(1):67-95 doi: 10.1093/humupd/dmaa042 

Web URL: Read this and related articles on PubMed

Abstract:

Background: 

Analgesia during pregnancy is often necessary. Due to their widespread availability, many mothers opt to use over-the-counter (OTC) analgesics. Those analgesic compounds and their metabolites can readily cross the placenta and reach the developing foetus.

Evidence for safety or associations with adverse health outcomes is conflicting, limiting definitive decision-making for healthcare professionals.

Objective and rationale: 

This review provides a detailed and objective overview of research in this field. We consider the global prevalence of OTC analgesia during pregnancy, explain the current mechanistic understanding of how analgesic compounds cross the placenta and reach the foetus, and review current research on exposure associations with offspring health outcomes.

Search methods: 

A comprehensive English language literature search was conducted using PubMed and Scopus databases. Different combinations of key search terms were used including 'over-the-counter/non-prescription analgesics', 'pregnancy', 'self-medication', 'paracetamol', 'acetaminophen', 'diclofenac', 'aspirin', 'ibuprofen', 'in utero exposure', 'placenta drug transport', 'placental transporters', 'placenta drug metabolism' and 'offspring outcomes'.

Outcomes: 

This article examines the evidence of foetal exposure to OTC analgesia, starting from different routes of exposure to evidence, or the lack thereof, linking maternal consumption to offspring ill health.

There is a very high prevalence of maternal consumption of OTC analgesics globally, which is increasing sharply. The choice of analgesia selected by pregnant women differs across populations. Location was also observed to have an effect on prevalence of use, with more developed countries reporting the highest consumption rates.

Some of the literature focuses on the association of in utero exposure at different pregnancy trimesters and the development of neurodevelopmental, cardiovascular, respiratory and reproductive defects. This is in contrast to other studies which report no associations.

Wider implications: 

The high prevalence and the challenges of reporting exact consumption rates make OTC analgesia during pregnancy a pressing reproductive health issue globally. Even though some healthcare policy-making authorities have declared the consumption of some OTC analgesics for most stages of pregnancy to be safe, such decisions are often based on partial review of literature.

Our comprehensive review of current evidence highlights that important knowledge gaps still exist. Those areas require further research in order to provide pregnant mothers with clear guidance with regard to OTC analgesic use during pregnancy.

FAB RESEARCH COMMENT:

This review shows that the use in pregnancy of over-the-counter pain-killing drugs in the UK and other developed countries is high, and appears to have increased dramatically in recent decades.

It also reveals gaps in the evidence for their safety and risk-benefit ratio, as previous reviews have also highlighted.  

Some studies indicate that use of these drugs in pregnancy may be associated with higher risks in the offsping for neurodevelopmental disorders (particularly ADHD and Autism Spectrum Disorders), and for cardiovascular, respiratory or reproductive defects.

Other studies do not find such links statistically significant - but the long-term systematic studies needed to establish the relative risks and benefits, so as provide more reliable guidance for pregnanct women and the professionals who adivse them, simply have not been done.

Meanwhile, a precautionary approach would be to limit their use as far as possible. and to explore other potential approaches to pain management, which include dietary changes:

Increasing intake of the long-chan omega-3 fats EPA and DHA from fish and seafood, and reducing omega-6 fats from vegetable was found to be as effective as some newly approved prescription medications for migraine

Evidence shows that many other aspects of nutrition and diet can also influence both inflammatory and neuropathic pain.

As usual, modern, western-type diets rich in hghly processed foods are likely to be the worst for promoting inflammation and pain, while Mediterranean or other traditional diets rich in whole, unprocessed foods and with a healthy omega-3/omega-6 balance, are likely to be best for minimising and managing inflammatory and chronic pain conditions.

For a review of the evidence for dietary approaches that may help in pain management, see:

 And for more information on the links between diet and pain, see: