Is the use of Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) such as indomethacin or ibuprofen recommended for promoting ductal closure in cases of patent ductus arteriosus (PDA) diagnosed in utero?

From the Guidelines

The use of NSAIDs such as indomethacin or ibuprofen is not recommended for promoting ductal closure in cases of patent ductus arteriosus (PDA) diagnosed in utero. These medications are only used after birth, typically in premature infants, when the ductus arteriosus fails to close naturally. During fetal development, the ductus arteriosus is meant to remain open as it serves a critical function in fetal circulation by allowing blood to bypass the non-functioning lungs. Attempting to close the ductus arteriosus before birth would be harmful to the fetus as it would disrupt normal fetal circulation, potentially causing fetal distress or death.

According to the most recent evidence, particularly from 1, NSAIDs can cause premature closure of the fetal ductus arteriosus and oligohydramnios, especially if administered for more than 48 hours, which further supports the avoidance of these medications in utero for promoting ductal closure. The potential risks associated with NSAID use in pregnancy, as outlined in 1 and 1, include increased cutaneous and intracranial bleeding, pulmonary hypertension, impaired renal function, reduced urine output, and reduced amniotic fluid volume, emphasizing the need for caution.

After birth, when the infant begins breathing independently, the ductus arteriosus should close naturally within the first few days of life. Only if it remains open beyond this period (particularly in premature infants) would medical intervention with NSAIDs be considered, typically at doses of indomethacin 0.1-0.2 mg/kg given intravenously every 12-24 hours for 3 doses, or ibuprofen 10 mg/kg followed by two doses of 5 mg/kg at 24-hour intervals. Management of PDA diagnosed prenatally involves monitoring and appropriate postnatal care rather than prenatal pharmacological intervention. Key considerations include:

• Monitoring fetal development and well-being
• Planning for appropriate postnatal care, including potential surgical intervention if necessary
• Avoiding NSAIDs during pregnancy due to potential fetal risks, as highlighted in 1 and 1
• Ensuring multidisciplinary care involving obstetrics, pediatrics, and potentially pediatric cardiology for optimal outcomes.

From the FDA Drug Label

Use of NSAIDs, including ibuprofen tablets, can cause premature closure of the fetal ductus arteriosus and fetal renal dysfunction leading to oligohydramnios and, in some cases, neonatal renal impairment Premature Closure of Fetal Ductus Arteriosus: Avoid use of NSAIDs in women at about 30 weeks gestation and later in pregnancy, because NSAIDs, including ibuprofen tablets, can cause premature closure of the fetal ductus arteriosus

The use of NSAIDs such as ibuprofen is not recommended for promoting ductal closure in cases of patent ductus arteriosus (PDA) diagnosed in utero, as it can cause premature closure of the fetal ductus arteriosus. In fact, the FDA label advises to avoid use of NSAIDs in women at about 30 weeks gestation and later in pregnancy due to this risk 2, 2.

From the Research

NSaID and Patent Ductus Arteriosus In Utero

• The use of Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) such as indomethacin or ibuprofen for promoting ductal closure in cases of patent ductus arteriosus (PDA) diagnosed in utero is a topic of interest.
• Studies have compared the efficacy and safety of ibuprofen and indomethacin in the treatment of PDA in preterm infants 3.
• Ibuprofen has been shown to be as effective as indomethacin in closing PDA, with fewer hemodynamic effects and reduced risk of gastrointestinal complications 3, 4.
• A Cochrane review found that ibuprofen probably decreases the risk of PDA on day 3 or 4, and decreases the need for rescue treatment with cyclo-oxygenase inhibitors and surgical ductal ligation 5, 6.
• However, the review also found that ibuprofen may increase the risk of oliguria and gastrointestinal bleeding, and that current evidence does not support the use of ibuprofen for prevention of patent ductus arteriosus 5, 6.

Treatment Options

• Ibuprofen and indomethacin are both used to treat PDA, but ibuprofen may be preferred due to its reduced risk of side effects 3, 4.
• Oral ibuprofen may be as effective as intravenous ibuprofen in closing PDA, and may reduce the risk of necrotizing enterocolitis (NEC) 4.
• The optimal dosage and timing of ibuprofen treatment for PDA are still being studied, and more research is needed to determine the long-term effects of ibuprofen treatment on infants with PDA 4.

Safety and Efficacy

• Ibuprofen has been shown to be safe and effective in treating PDA in preterm infants, with a reduced risk of NEC and transient renal insufficiency compared to indomethacin 4.
• However, ibuprofen may increase the risk of oliguria and gastrointestinal bleeding, and may not be suitable for all infants with PDA 5, 6.
• Further research is needed to fully understand the safety and efficacy of ibuprofen in treating PDA, and to determine the optimal treatment strategy for infants with this condition 5, 6, 4.