Elsevier

Reproductive Toxicology

Volume 15, Issue 4, July–August 2001, Pages 371-375
Reproductive Toxicology

Nonsteroidal anti-inflammatory drugs in early pregnancy

https://doi.org/10.1016/S0890-6238(01)00137-XGet rights and content

Abstract

A study was performed of congenital malformations in infants whose mothers used nonsteroidal anti-inflammatory drugs (NSAIDs) in early pregnancy. Data were obtained from an ongoing prospective recording of drug use during the first trimester. During the period July 1, 1995 through December 31, 1998, 2557 infants were born to women who reported the use of NSAIDs in early pregnancy. The OR (after consideration of maternal age, parity, and smoking habits) for any congenital malformation was 1.04 (95%CI 0.84–1.29), but the OR for cardiac defects reported to the Medical Birth Registry was 1.86 (1.32–2.62) based on 36 instances, and for orofacial clefts 2.61 (1.01–6.78) based on only six instances. By using other information sources, another four infants with cardiac defects were identified. There was no drug specificity for cardiac defects but among six mothers of infants with orofacial clefts, five had used naproxen.

Introduction

Nonsteroid anti-inflammatory drugs (NSAIDs) are in common use, both for rheumatic and degenerative joint diseases, sports injuries, and temporary pain, e.g. dysmenorrhoea or migraine. First trimester exposures are therefore relatively common. NSAIDs have a documented effect on the fetus toward the end of the pregnancy by causing a premature closure of the ductus arteriosus leading to pulmonary hypertension and respiratory problems. An effect on kidney function also has been observed leading to oligohydramnios and neonatal anuria [1]. These effects make NSAID use unsuitable during the third trimester and notably just before expected delivery.

Relatively little is known about possible teratogenic effects and first trimester use is usually regarded as safe [1], [2]. Recently a study [3] was published based on 1106 women who had received a prescription for an NSAID drug 30 days before pregnancy or during the first trimester of pregnancy. The risk for a congenital malformation was 1.27 (95% CI 0.93–1.75). A case-control study (using as cases women who had been hospitalized for miscarriage and as controls primiparous women who had live births) indicated an excess risk for miscarriage after the use of NSAID but the confounding effect of induced abortions was not taken into consideration.

We used a data base to evaluate the possibility that use of NSAID drugs in early pregnancy could increase the risk for congenital malformations.

Section snippets

Materials and methods

Since July 1, 1994, information on first trimester drug use has been collected in Sweden for all pregnant women at their first visit to the maternity care center. This visit usually takes place at 10 to 12 weeks gestation at which time a midwife conducts a 30 to 60 min long interview with the woman on conditions related to her previous reproductive history, her present situation, and her pregnancy since the last menstrual period (LMP). Among the questions asked is whether the woman has used any

Results

Table 1 shows that women using NSAIDs in early pregnancy may deviate from others with respect to age, parity, and smoking habits in early pregnancy. A trend of increasing use of NSAID with maternal age was identified at a P value of 0.10. Use was higher at parity 1 than at parity 2 (P = 0.02) and increased with higher parity (P for trend = 0.05). Maternal smoking was significantly related to the use of NSAIDs.

Table 2 lists the congenital malformations identified among infants whose mothers used

Discussion

The present study is based on prospectively collected information on drug use in early pregnancy as part of the routine recording of pregnancies in a Medical Birth Registry. Such data have previously been utilized in the analysis of the use of acid-suppressive drugs [9], of inhaled corticosteroids (budesonide) [10], and of antidepressants [11]. A weakness of the data are that exact exposure time or dosage is often not known, but at least in the majority of cases, exposure occurred during the

References (13)

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