Which tocolytic can cause patent ductus arteriosus in a patient with preterm labor?

Which Tocolytic Causes Patent Ductus Arteriosus?

Indomethacin (Option D) is the tocolytic that causes patent ductus arteriosus—specifically, it causes premature closure of the ductus arteriosus in utero during pregnancy, and paradoxically increases the incidence and severity of postnatal PDA in exposed preterm infants.

Mechanism and Clinical Evidence

In Utero Effects of Indomethacin

Indomethacin, as a prostaglandin inhibitor, causes constriction and premature closure of the fetal ductus arteriosus when used as a tocolytic agent during pregnancy. 1

• The FDA labeling explicitly warns that indomethacin's known effects on the fetal cardiovascular system include constriction of the ductus arteriosus prenatally, tricuspid incompetence, and pulmonary hypertension 1
• Complete in utero ductal closure has been documented, even after cessation of therapy, resulting in nonimmune hydrops fetalis and neonatal death 2
• The Society for Maternal-Fetal Medicine guidelines note that prostaglandin inhibitors used for polyhydramnios management carry potential complications including in utero constriction of the ductus arteriosus 3

Postnatal Paradox: Increased PDA After Antenatal Exposure

Counterintuitively, antenatal indomethacin exposure significantly increases both the incidence and severity of postnatal PDA in preterm infants who survive to delivery. 4, 5

• Infants exposed to antenatal indomethacin have a 2.1-fold increased risk of developing postnatal PDA (52% vs 24% in unexposed infants) 5
• These infants are 1.9 times more likely to require postnatal indomethacin treatment for symptomatic PDA 5
• Exposed infants show greater resistance to medical PDA closure and higher rates of surgical ligation requirement (19% required ligation vs 0% in unexposed infants) 5
• A 2020 study confirmed the association between antenatal indomethacin and early ductal closure in utero (OR: 2.52), while also noting increased risks of intraventricular hemorrhage and sepsis 4

Why Other Options Are Incorrect

Atosiban (Option A)

• An oxytocin receptor antagonist with no known effects on prostaglandin synthesis or ductal patency
• Does not affect the ductus arteriosus

Ritodrine (Option B)

• A beta-adrenergic agonist tocolytic
• No documented effects on ductal patency

Nifedipine (Option C)

• A calcium channel blocker used for tocolysis
• Does not cause ductal constriction or affect PDA incidence
• Generally considered safer than indomethacin regarding fetal cardiovascular effects

Critical Clinical Implications

The FDA explicitly contraindicates indomethacin use during late pregnancy due to these ductal effects. 1

• Indomethacin should be avoided in the third trimester because it may cause premature closure of the ductus arteriosus 1
• When used earlier in pregnancy for tocolysis, frequent fetal echocardiography is essential both during and after treatment to monitor ductal patency 2
• The American Thoracic Society notes that prophylactic low-dose indomethacin in the first 24 hours postnatally does not reduce chronic lung disease incidence, despite its effects on PDA 3

Clinical Monitoring Recommendations

For infants exposed to antenatal indomethacin: 4, 5

• Perform echocardiography within 24-72 hours of life to assess ductal status
• Maintain heightened vigilance for symptomatic PDA requiring intervention
• Anticipate potential resistance to standard postnatal indomethacin therapy
• Consider earlier escalation to surgical ligation if medical management fails

The answer is D: Indomethacin causes both in utero ductal constriction during maternal use and paradoxically increases postnatal PDA incidence and severity in exposed preterm infants.