NEW YORK (Reuters Health) – Antenatal indomethacin given to prevent preterm labor is associated with a significantly increased risk of necrotizing enterocolitis in premature infants, investigators report in the July issue of Pediatrics.

The report notes that “Indomethacin tocolysis continues to be used despite little evidence of improved neonatal outcomes.” Postnatal indomethacin has been linked to necrotizing enterocolitis in preemies, but since it readily crosses the placenta it may also pose a risk when used for tocolysis, the authors note.

To investigate, Dr. Beena G. Sood, with Children’s Hospital of Michigan in Detroit, and colleagues reviewed the records of 628 infants born between 23 and 32 weeks’ gestational age. In this cohort, 23 infants developed necrotizing enterocolitis in the 15 days after delivery. In the group as a whole, 63 infants had received antenatal indomethacin within 15 days before delivery.

The team found that antenatal indomethacin exposure was associated with numerous factors, including multiple gestation, antenatal corticosteroids and magnesium sulfate use, respiratory distress syndrome, and sepsis – as well as necrotizing enterocolitis.

On multivariate analysis controlling such covariates, however, indomethacin remained independently associated with necrotizing enterocolitis (adjusted odds ratio 7.2). In fact, the investigators calculated that the number-needed-harm was only 5.

Still, Dr. Sood and colleagues note that a large cohort study is needed to confirm the findings, pointing out that the potential for harm precludes a randomized trial.

“In the meantime, indomethacin tocolysis should be used after carefully weighing the potential benefits and risks,” they conclude. “In cases where indomethacin tocolysis is used, patients should be educated regarding fetal risks and benefits and the neonatologist informed of fetal exposure to indomethacin at delivery.”

Reference:
The Risk of Necrotizing Enterocolitis After Indomethacin Tocolysis
Pediatrics 2011;128:e54–e62.