NSAIDs or
cyclooxygenase inhibitors (COX inhibitors), including
aspirin, are widely used to treat
pain,
fever and the articular symptoms of chronic
rheumatic diseases. Manifestations of connective tissue or
autoimmune diseases are commonly treated with glucocorticosteroids. The effect and side effects of
NSAIDs depend on the
isoforms of
cyclooxygenases that they preferentially or selectively inhibit. The use of COX inhibitors has recently been associated with
infertility and
miscarriage. The classical nonselective COX inhibitors, including
aspirin, do not increase the risk of congenital malformations in humans but administered in the latter part of gestation, they can affect pregnancy and the fetus. The ability of nonselective and selective COX inhibitors to prolong gestation has been used by obstetricians to inhibit premature delivery. The vascular effects of
prostaglandin inhibitors can cause constriction of the fetal ductus arteriosus and reduce renal blood flow. These complications have been described for most nonselective COX inhibitors but are increasingly reported also for the selective
COX-2 inhibitors.
Aspirin, which causes irreversible inhibition of
cyclooxygenases, differs from other
NSAIDs with regard to indication, effects and side effects. Prematurity, which is increased in pregnancies of women with
connective tissue diseases, is an additional risk factor for adverse effects of antenatal exposure to
NSAIDs. Therefore, treatment with COX inhibitors should be discontinued at week 32 of gestation. The ability of
NSAIDs to compromise reproductive function by inhibition of ovulation and as causative agents for
miscarriage is still under debate. Glucocorticosteroids given in early pregnancy are a risk factor for the development of oral clefts. Therefore, the daily dose should be kept to <or= 15 mg during the first trimester. High doses of glucocorticosteroids in the second and third trimester are reserved for flares of
autoimmune diseases. Intrauterine
fetal growth restriction and premature delivery are possible side effects of high doses.