Volume 120, Issue 8 p. 948-959
Original Article

Effects of ibuprofen, diclofenac, naproxen, and piroxicam on the course of pregnancy and pregnancy outcome: a prospective cohort study

K Nezvalová-Henriksen

Corresponding Author

K Nezvalová-Henriksen

Division of Pharmacy, School of Pharmacy, University of Oslo, Oslo, Norway

Correspondence: K Nezvalová-Henriksen, School of Pharmacy, Faculty of Mathematics and Natural Sciences, University of Oslo, PO Box 1065, Blindern, Oslo, N-0316, Norway. Email [email protected]Search for more papers by this author
O Spigset

O Spigset

Department of Clinical Pharmacology, St Olav's University Hospital, Trondheim, Norway

Department of Laboratory Medicine, Children's and Women's Health, Norwegian University of Science and Technology, Trondheim, Norway

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H Nordeng

H Nordeng

Division of Pharmacy, School of Pharmacy, University of Oslo, Oslo, Norway

Division of Mental Health, The Norwegian Institute of Public Health, Oslo, Norway

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First published: 14 March 2013
Citations: 73

Abstract

Objective

To investigate the individual effects of ibuprofen, diclofenac, naproxen, and piroxicam on pregnancy outcome.

Design

Cohort study.

Setting

Norwegian population.

Population

A total of 90 417 women and singleton child pairs.

Methods

The Norwegian Mother and Child Cohort Study and Medical Birth Registry of Norway data sets were used.

Main outcome measures

Infant survival, congenitalmalformations, structural heart defects, neonatal complications, haemorrhage during pregnancy and postpartum, asthma at age of 18 months.

Results

One or more of the four nonsteroidal anti-inflammatory drugs (NSAIDs) were used by 6511 pregnant women (7.2%). No effect on rates of infant survival, congenital malformation, or structural heart defects was found. The use of ibuprofen in the second trimester was significantly associated with low birthweight (adjusted OR 1.7, 95% CI 1.3–2.3), and ibuprofen use in the second and third trimesters was significantly associated with asthma in 18–month—old children (adjusted OR 1.5, 95% CI 1.2–1.9; adjusted OR 1.5, 95% CI 1.1–2.1). The use of diclofenac in the second trimester was significantly associated with low birthweight (adjusted OR 3.1, 95% CI 1.1–9.0), whereas diclofenac use in the third trimester was significantly associated with maternal vaginal bleeding (adjusted OR 1.8, 95% CI 1.1–3.0). No associations with other neonatal complications were found.

Conclusions

The lack of associations with congenital malformations is reassuring. The significant association between diclofenac and ibuprofen use late in pregnancy, and maternal bleeding and asthma in the child, respectively, is consistent with their pharmacological effects. The increased risk of low birthweight may partly have been caused by underlying inflammatory conditions, and was reassuringly similar to the expected baseline risk of low birthweight.