Indomethacin Prophylaxis Associated With Substantially Improved Survival in Extremely Preterm Babies

Columbus, OH — November 2017

A number of well-known studies completed in the 1990s – most notably the Trial of Indomethacin Prophylaxis in Preterm Infants (TIPP) – showed a decreased incidence of intraventricular hemorrhage and patent ductus arteriosus for preterm infants who received prophylactic indomethacin (PI). Those studies did not tend to show, however, improvement in long-term outcomes.

The findings led to variation in PI use, even among providers in a single center. A recent study from physician-researchers at Nationwide Children’s Hospital has used those variations to look at PI outcomes in a more recent group of babies born extremely preterm, and discovered a clear reduction of mortality.

“Those earlier studies continue to influence how we use PI, even though neonatal care and outcomes have improved since that time,” says Leif Nelin, MD, chief of the Division of Neonatology at Nationwide Children’s and senior author of the recent publication in the Journal of Perinatology. “We wanted to see if PI would still benefit our patients in the same ways, and what we found was striking and unexpected.”

In contrast to those earlier studies, the authors found substantially improved survival in a group of infants born at less than 27 weeks of gestational age who received PI. Their risk of mortality was 48 percent less than similar babies who did not receive PI. The number needed to treat was only 7.4.

The entire cohort of 671 babies was born outside of Nationwide Children’s and admitted to the hospital between 2005 and 2014 after the decision to administer PI had been made at delivery hospitals. Current practice in the hospital’s region is to encourage but not require PI in extremely preterm infants. The cohort was made up of 530 patients who received PI and 141 who did not.

Because mortality may have changed over the retrospective nine-year period, the authors divided it into smaller epochs. All epochs showed survival improvement for babies who received PI, but babies born more recently had a more significant benefit.

Certain benefits that earlier studies had shown or suggested were not found in this more recent study, however. There was no difference in incidence of severe intraventricular hemorrhage or patent ductus arteriosus ligation between the cohort groups. The recent study also found no significant difference in scores on the Bayley Scales of Infant Development.

“Our results show the need for a large randomized controlled trial to provide definitive evidence regarding the use of PI in these extremely preterm infants,” says Dr. Nelin, who is also a professor of Pediatrics at The Ohio State University College of Medicine.

Nelin TD, Pena E, Giacomazzi T, Lee S, Logan JW, Moallem M, Bapat R, Shepherd EG, Nelin LD. Outcomes following indomethacin prophylaxis in extremely preterm infants in an all-referral NICU. Journal of Perinatology. 2017 Aug;37(8): 932-937.