Should All Premature Infants Be Treated with Nitric Oxide?

A new study from Johns Hopkins Children’s Center challenges the common practice of treating premature infants with nitric oxide gas to prevent lung problems, neurological damage, and death. The research, based on analysis of 22 major studies of the effect of nitric oxide in babies born before 34 weeks of age, found no evidence of benefit in most infants.

Overall, the review found that infants who received nitric oxide in the neonatal intensive care unit didn’t fare any better than those who did not receive it, and were no less likely to die, develop chronic lung disease of prematurity, suffer cerebral palsy, or have neurological or cognitive impairments.

The findings, which will be published in the February issue of Pediatrics, refute the routine use of inhaled nitric oxide in all premature infants and call for careful, case-by-case evaluation of each infant’s degree of brain and lung maturation to determine if nitric oxide would help, hurt, or do nothing for a patient.

“What we call for is careful evaluation by a team of clinicians of each patient’s risk-benefit profile, factoring in birth weight, degree of prematurity and degree of lung and brain maturation,” said lead investigator Pamela Donohue, ScD, in a press release.

Because the investigators noticed a small, yet sufficiently intriguing difference in risk in some infants, the researchers stopped short of advocating complete abandonment of the treatment.

Infants who did not receive nitric oxide had no greater risk of dying than those who got the treatment, and were no more likely to develop chronic lung disease of prematurity. However, when the researchers analyzed the data differently and looked at whether an infant had a greater risk of either dying or developing lung disease, a small difference emerged. The combined risk of death and lung disease was 7% percent higher among infants who didn’t get the treatment.

“We can’t say whether this small difference signals a true clinical benefit, but we have to at least allow for the possibility that it might portend better outcomes for at least some babies,” said senior investigator Marilee Allen, MD.

The efficacy of nitric oxide has been well documented in near-term babies, or those born after 34 weeks, but the new Hopkins Children’s findings show that nitric oxide gas has no therapeutic value in most premature babies born at 34 weeks or earlier.

None of the 14 trials that analyzed the risk of death found differences in death rates between preemies who received nitric oxide and those who did not. Nine studies compared long-term death rates among children after one year and up to five years after birth, and again, none found a difference in death rates. The dose of nitric oxide had no bearing on how well an infant fared and neither did the infant’s weight at the time of birth, the researchers found. One study found a higher death rate among infants born weighing 1,000 grams or more and treated with inhaled nitric oxide.

None of the 12 trails that analyzed the risk for developing chronic lung disease found differences among babies regardless of whether they received nitric oxide after birth or not. Four studies, however, revealed a 25% lower risk for lung disease among babies treated with a dose of 10 parts per million, a difference that vanished with lower and higher doses.

The analysis showed no differences in the risk of brain damage, neurological deficits, cerebral palsy, or developmental impairment between babies who received nitric oxide and those who did not.

To read the Pediatrics study, click here.