Non-steroidal anti-inflammatory drugs (NSAIDs) like such as ibuprofen, naproxen, diclofenac and celecoxib are commonly used in pregnancy for treating fever and pain. The proportion of self medication is probably higher than that of prescribed medication. One study reported presence of NSAIDs in meconium in nearly 50% newborns. Of these, 22.8% had ibuprofen, 18.8% had naproxen, 7.9% had indomethacin, and 43.6% had aspirin. Presence of at least one NSAID in meconium, particularly aspirin, ibuprofen, or naproxen was associated with primary pulmonary hypertension (PPHN) of newborn.
The NSAIDs readily cross the placenta and can cause adverse effects on the embryo, fetus and neonate. NSAIDs block the synthesis of prostaglandins and thromboxane. The prostaglandins are required for successful implantation of the embryo. Thus their deficiency can cause an early abortion. The odds ratios of women who develop a miscarriage is 6.99 when an NSAID is taken in the week preceding a miscarriage and 2.69 when it is taken 7 to 9 weeks before miscarriage. After correction for other factors which can increase the risk of a miscarriage, use of NSAIDS is associated with a 59 percent greater risk of miscarriage than women who took no medication and 45 percent greater risk than women who took acetaminophen. The risk is greater when the medication is taken for at least 2 weeks than when it is taken for shorter period. The risk increases directly proportional to the dosage of the drug. Women with lower body mass index (BMI) are more vulnerable as compared to those with greater BMI.
The prostaglandins and thromboxane are required to keep the fetal ductus arterious open. NSAIDs can cause its closure and oligohydramnios. Its early closure causes neonatal persistent pulmonary hypertension, as when the drug is used to control preterm labor after 30 weeks of gestation. The effect depends on the gestational age, the dose and duration of treatment, and the interval between the administration and time of delivery.
It is found from animal studies that nonselective NSAIDs (which inhibit both cyclooxegenase-1 and -2) like aspirin, ibuprofen, and naproxen might cause congenital malformations like midline defects, diaphragmatic hernia, and ventricular septal defects. The use of specific NSAIDs might cause a small to moderate increase in risk of congenital anomalies like eye defects, oral clefts, neural tube defects, limb or body wall defects, pulmonary valvular stenosis.
Use of NSAIDs has not been reported to cause fetal growth restriction, stillbirth or preterm delivery.
If severe and persistent pain is not treated effectively during pregnancy, the gravida may develop anxiety, depression, and hypertension. The patient may be on NSAID medication for chronic painful conditions like arthritis, when she gets pregnant. In such cases exposure to the drug during the early first trimester is unavoidable. It is difficult to strike a balance between treating the patient adequately for her pain and not treating her out of fear of effects of the drug on the fetus. NSAIDs should be used in pregnancy only if the maternal benefits outweigh the fetal risks. Furthermore the lowest effective dose should be used, for the shortest duration required. Counseling of gravidas should be done about risks associated with the use of NSAIDs, before prescribing the drugs. Self medication should be discouraged. It is found that the product insert is not present when strips of tablets are sold. If it is present, the print is so small that a normal person may not be able to read the contents without the use of a magnifying lens. Such practices by pharmaceuticals should be banned.