Ibuprofen is a non-steroidal anti-inflammatory drug (NSAID) used to treat acute and chronic pain, and in the management of arthritis.
The use of NSAIDs in pregnancy has been associated with increased risks of miscarriage, malformation (including specific defects, such as cardiovascular defects, septal cardiac defects, and orofacial clefts), preterm delivery and fetal growth impairment. However, the available evidence is often conflicting, is likely confounded, and findings may have also been influenced by methodological limitations. Causal relationships between NSAID use in pregnancy and these outcomes are therefore unproven.
Twenty-two studies collectively including more than 75,000 ibuprofen-exposed pregnancies have investigated the risk of adverse fetal effects following in utero exposure. There is no robust evidence of associations with intrauterine death/stillbirth, preterm delivery or neurodevelopmental impairment. The data relating to other pregnancy outcomes are conflicting, with a small number of individual studies describing increased risks of miscarriage, overall and specific malformations, and low infant birth weight. However, it is possible that confounding has affected these data. Further studies are required before robust conclusions can be drawn.
Exposure to NSAIDs after 20 weeks of gestation has been associated with an increased risk of premature closure of the ductus arteriosus (DA) and oligohydramnios. These effects are thought to be mediated by the inhibitory effect of NSAIDs on prostaglandin production. There are conflicting findings regarding the risks of persistent pulmonary hypertension of the newborn (PPHN) following antenatal use of NSAIDs. Further evidence is required before this possible association can be confirmed. A possible class effect for these associations should be considered for all NSAIDs.
All NSAIDs should, where possible, be avoided after 20 weeks of pregnancy. In circumstances where the maternal clinical condition requires short-term treatment with ibuprofen (such as acute short-lived pain), treatment should be limited to the shortest duration possible. There is currently no evidence-based guidance about how long use should be restricted for but pragmatic advice is to limit use to no longer than three days. Longer term use at any stage of pregnancy, for example for treatment of chronic arthritis, or any use in the third trimester (28 weeks of gestation or beyond), should be avoided. As fetal urine production begins at approximately 10 weeks’ gestational age, UKTIS recommends referral to a Fetal Medicine Unit for monitoring of DA patency and oligohydramnios following prolonged NSAID use after the first trimester.
Please refer to the NSAID overview monograph for more information. 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.
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.