From the Journals

Many premature infants receive reflux medication after NICU discharge

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Widespread use of post-NICU GER medication unwarranted

“Medications are frequently used to treat gastroesophageal reflux in premature infants,” wrote P. Brian Smith, MD, but “a number of these medications have been associated with significant harm” and the “short- or long-term benefits of GER medications in this population are undocumented.”

Histamine-2 receptor blockers, the most common GER medications, induce alterations to the fecal microbiota of premature infants by lowering microbial diversity and promoting overgrowth of Proteobacteria. “These alterations weaken the gastrointestinal tract’s protective barrier and render very low birth weight infants, already predisposed to [necrotizing enterocolitis] and other infections, even more vulnerable,” he noted.

“Infants receiving antacid therapy are also at increased risk of bacteremia, lower respiratory tract infections, aspiration pneumonia, and death,” he added.

“Pediatrics has a long history of widespread use of medications for which the risks did not outweigh the benefits. All drugs should be shown to be both safe and effective before use. [This study] has documented widespread, long-term use of medications that are likely neither,” he said.

Dr. Smith is with Duke University Medical Center, Durham, N.C. These comments are taken from an accompanying editorial (Pediatrics. 2016 Nov 23. doi: 10.1542/peds.2016-2849). Dr. Smith is a consultant for Astellas Pharma and Abbvie and receives grant support from Cempra Pharmaceuticals and Shionogi. Dr Smith receives salary support from the National Institutes of Health and the U.S. Food and Drug Administration.



Three-quarters of premature infants who receive gastroesophageal reflux medications get those drugs after being discharged from neonatal intensive care units, despite questions about the safety and efficacy of the medications in premature infants.

In a retrospective study of 2,217 premature infants treated within the Children’s Hospital of Philadelphia primary care network from 2005 to 2009, 812 were treated with gastroesophageal reflux (GER) medications. Of this group, 77% were started on GER medication after neonatal intensive care unit (NICU) discharge, according to Jo Ann D’Agostino, DNP, CRNP, and her associates (Pediatrics. 2016 Nov 23. doi: 10.1542/peds.2016-1977).

Histamine-2 receptor antagonists were the most commonly prescribed GER medication, received by 90% of infants. Proton pump inhibitors were prescribed to 37% of infants, 22% received prokinetics, and 2% received cholinergics. During the first year of life, 40% of treated infants received multiple GER medications, with 73% of these infants receiving at least two medications simultaneously.

Risk factors associated with the use of multiple GER medications include a gestation period less than 32 weeks, feeding difficulty, tube feeding, a need for supplemental oxygen, and asthma.

“Because premature infants are a medically fragile group, the need for 1 acid suppression medication, let alone 2 or more in combination, should be given careful consideration. The potential impact of acid suppression on community-acquired illnesses has yet to be explored for this vulnerable population,” said Dr. D’Agostino of the department of pediatrics at the Children’s Hospital of Philadelphia, and her coauthors.

Infants who received GER treatment after NICU discharge were started on medication at a mean chronological age of 95 days and received medication for a mean of 294 days. Infants who started GER treatment while in the NICU received medication for a mean of 375 days.

A total of 743 infants were started on GER medications before the age of 6 months, and of this group, 43% were still being treated at the age of 1 year. Extended medication usage was associated with a gestational age under 32 weeks, chronic lung disease, airway malacia, and reactive airways disease.

A gestation period of less than 32 weeks was associated with a 31% increase in GER medication duration, compared with infants with a gestation period of 34-35 weeks, and a gestation period of less than 28 weeks was associated with a 50% increase in medication duration.

“Physiologic reflux symptoms are reported to peak at 4 months of age. Feeding issues are also common for premature infants. Whether this combination of issues is influencing the decision to start treatment, as opposed to actual GER disease, is an important distinction for providers to consider before starting medication,” Dr. D’Agostino and her associates noted.

“With uncertain evidence of efficacy, the rationale for using these medications in this high-risk population should be carefully evaluated,” they concluded.

The study was funded by the National Institutes of Health. The authors had no relevant financial disclosures.

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