Nonsteroidal anti-inflammatory drugs in early pregnancy
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
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