Indomethacin is a nonsteroidal anti-inflammatory drug (NSAID) that inhibits prostaglandin synthesis. While NSAIDs are avoided during pregnancy, indomethacin is sometimes prescribed for specific, urgent medical situations under close supervision. Its application requires balancing therapeutic benefits against potential fetal risks, which are managed through strict protocols.
Medical Reasons for Use in Pregnancy
One of the primary applications for indomethacin in pregnancy is to arrest preterm labor, a practice known as tocolysis. Labor involves the release of prostaglandins, which cause the uterus to contract. By inhibiting prostaglandin production, indomethacin can reduce the intensity and frequency of uterine contractions. This intervention is intended to delay delivery for 48 to 72 hours, providing a window for other treatments like administering corticosteroids to help mature the fetal lungs.
Another medical reason for its use is the management of polyhydramnios, a condition of excessive amniotic fluid. A significant portion of amniotic fluid is composed of fetal urine. Indomethacin crosses the placenta and can reduce blood flow to the fetal kidneys, which in turn decreases fetal urine production. This reduction in urine output helps lower the overall volume of amniotic fluid, alleviating maternal discomfort and reducing risks like uterine overdistension and preterm labor.
Gestational Timing and Associated Risks
The safety of indomethacin is highly dependent on the gestational age of the fetus. Medical guidelines recommend its use only before 32 weeks of gestation. Treatment is limited to a short duration, not exceeding 48 to 72 hours, to minimize fetal risks that increase as the pregnancy progresses.
The most significant risk, particularly after 32 weeks, is the premature closure of a fetal blood vessel called the ductus arteriosus. In the fetus, this vessel connects the pulmonary artery to the aorta, allowing blood to bypass the non-functioning lungs. Prostaglandins are responsible for keeping this vessel open, so indomethacin’s inhibition of them can cause it to constrict prematurely.
This premature closure forces blood into the lungs at high pressure, a condition known as pulmonary hypertension. This can lead to right ventricular hypertrophy and other serious cardiovascular complications for the newborn. The sensitivity of the ductus arteriosus to prostaglandin inhibitors increases as gestation advances, which is why indomethacin is strongly advised against in the third trimester.
The drug’s effect on reducing fetal kidney blood flow can also lead to oligohydramnios, a condition of abnormally low amniotic fluid. This occurs because the reduction in fetal urine output is too pronounced. This side effect is often reversible once the medication is stopped.
Potential Effects on the Newborn
When a mother has been treated with indomethacin, the neonatal care team prepares for specific monitoring after birth. A primary concern is the newborn’s cardiovascular status due to the drug’s effect on the ductus arteriosus. Pediatricians perform an echocardiogram, an ultrasound of the heart, to assess the ductus arteriosus for signs of pulmonary hypertension, allowing for prompt intervention if any abnormalities are detected.
Newborns may also experience transient kidney issues related to the drug’s reduction of renal blood flow in the fetus. The infant’s kidney function is monitored to ensure it returns to normal following delivery. In most cases, these effects on the kidneys are temporary and resolve without long-term consequences.
A potential link between indomethacin exposure and an increased risk of necrotizing enterocolitis (NEC), a serious intestinal disease affecting premature infants, has been studied. NEC involves inflammation and injury to the gut tissue. Research into this association has produced mixed results, with some studies finding no significant link with short-term maternal use. The risk is most relevant for infants who are already premature and vulnerable.
Monitoring During Treatment
When a pregnant individual is treated with indomethacin, they are placed under a strict monitoring protocol in a hospital setting. Healthcare providers use regular ultrasounds to assess fetal well-being and to measure the amniotic fluid index (AFI). This monitoring ensures that the drug’s effect on fetal urine output does not lead to a harmful drop in fluid levels.
Fetal echocardiography is also a component of the monitoring process. This specialized ultrasound focuses on the fetal heart and associated major blood vessels. It allows clinicians to directly visualize the ductus arteriosus and measure blood flow through it. If any signs of constriction or narrowing are detected, the dosage of indomethacin may be reduced or the treatment discontinued entirely to prevent pulmonary hypertension.