Predictors of Ductal Closure and Intestinal Complications in Very Low Birth Weight Infants Treated with Indomethacin

Abstract

Objective: To describe factors associated with failure of patent ductus arteriosus closure and development of gastrointestinal complications in subjects treated with indomethacin. Study Design: Infants ≤30 weeks and <1,500 g delivered between 1997–2003 with patent ductus arteriosus treated with indomethacin were included in this single-center retrospective study. Risk factors for failed ductal closure rates and gastrointestinal complications were identified with uni- and multivariable analyses. Results: Among 210 subjects treated with indomethacin, ductal closure increased from 43% at 23 weeks to 87% at 27 weeks (OR 1.51 per week gestation, 95% CI 1.14–2.01, p = 0.004) and was unchanged thereafter. Gastrointestinal complications decreased with increasing gestational age (OR 0.67/week, 95% CI 0.52–0.84) but increased with male gender (OR 2.41, 95% CI 1.07–5.45). SNAP-II (Score for Neonatal Acute Physiology-II) scores at birth and at the time of first indomethacin therapy were not associated with likelihood of closure or with gastrointestinal complications. Duration of ductal patency was not associated with risk of necrotizing enterocolitis or intestinal perforation after adjusting for gestational age and gender. Conclusions: Ductal closure with indomethacin is linearly associated with gestational age in infants ≤27 weeks. Illness severity at the time of treatment is not predictive of treatment outcome or gastrointestinal complications. The duration of ductal patency is not associated with an increase in adjusted risk of necrotizing enterocolitis or intestinal perforation in patients treated with indomethacin.

The Risk of Necrotizing Enterocolitis After Indomethacin Tocolysis

“…Awareness of the association of postnatal indomethacin and NEC and the debate regarding the need for treatment of PDA has led to decreased use of postnatal indomethacin in our institution and may account for the observed lack of association with NEC in our study. In the literature, there are conflicting reports, with increased, 4,5 decreased, 62 and unchanged [63][64][65] incidence of NEC being reported after postnatal indomethacin. Although an increased risk for NEC has been reported in black preterm infants, males, and after maternal cocaine use, we did not observe these associations.…”

Prenatal or postnatal indomethacin exposure and neonatal gut injury associated with isolated intestinal perforation and necrotizing enterocolitis

“…7 Despite its proven efficacy for both conditions, concern about the safety of indomethacin, particularly with respect to neonatal intestinal complications continues to influence its usage in the NICU. 5,12,13 Our investigation was designed to assess the risk of indomethacin on the two major neonatal gut injuries (IIP and NEC) that predominate the obstetrical and neonatal literature.…”

“…[3][4][5][6] Exposure to indomethacin can occur prenatally [3][4][5] and/or postnatally. 6,7 Indomethacin is used for tocolysis and acts via inhibition of prostaglandin synthetase. 8 Postnatally, indomethacin has been used to effect closure of a patent ductus arteriosus (PDA) 7 or to prevent severe intraventricular hemorrhage in very low birth weight infants.…”

“…6,7 Indomethacin is used for tocolysis and acts via inhibition of prostaglandin synthetase. 8 Postnatally, indomethacin has been used to effect closure of a patent ductus arteriosus (PDA) 7 or to prevent severe intraventricular hemorrhage in very low birth weight infants. 9,10 Before 1996, postnatal indomethacin administration at our center was used only to treat PDA, 7 but subsequently its use increased following reports that administration of indomethacin to very low birth weight infants within 6 to 12 h after birth was associated with a reduced rate of severe intraventricular hemorrhage.…”

“…8 Postnatally, indomethacin has been used to effect closure of a patent ductus arteriosus (PDA) 7 or to prevent severe intraventricular hemorrhage in very low birth weight infants. 9,10 Before 1996, postnatal indomethacin administration at our center was used only to treat PDA, 7 but subsequently its use increased following reports that administration of indomethacin to very low birth weight infants within 6 to 12 h after birth was associated with a reduced rate of severe intraventricular hemorrhage. 9,10 With increased frequency and early use of indomethacin several reports linking indomethacin exposure to IIP 6,[11][12][13] and/or to NEC 6,14 emerged.…”