Ranitidine is Associated With Infections, Necrotizing Enterocolitis, and Fatal Outcome in Newborns

Abstract

WHAT'S KNOWN ON THIS SUBJECT: Although still off-label for newborns, the use of inhibitors of gastric acid secretion continues to increase. Acid-suppressive drugs could facilitate the onset of infections in adults and children. Evidence for efficacy is weak in newborns, particularly if preterm. WHAT THIS STUDY ADDS:This is the first prospective study demonstrating an association between the use of ranitidine and infections, necrotizing enterocolitis, and fatal outcome in very low birth weight newborns. Caution is advocated in using ranitidine in newborns.abstract BACKGROUND AND OBJECTIVES: Gastric acidity is a major nonimmune defense mechanism against infections. The objective of this study was to investigate whether ranitidine treatment in very low birth weight (VLBW) infants is associated with an increased risk of infections, necrotizing enterocolitis (NEC), and fatal outcome. METHODS:Newborns with birth weight between 401 and 1500 g or gestational age between 24 and 32 weeks, consecutively observed in neonatal intensive care units, were enrolled in a multicenter prospective observational study. The rates of infectious diseases, NEC, and death in enrolled subjects exposed or not to ranitidine were recorded. RESULTS:We evaluated 274 VLBW infants: 91 had taken ranitidine and 183 had not. The main clinical and demographic characteristics did not differ between the 2 groups. Thirty-four (37.4%) of the 91 children exposed to ranitidine and 18 (9.8%) of the 183 not exposed to ranitidine had contracted infections (odds ratio 5.5, 95% confidence interval 2.9-10.4, P , .001). The risk of NEC was 6.6-fold higher in ranitidine-treated VLBW infants (95% confidence interval 1.7-25.0, P = .003) than in control subjects. Mortality rate was significantly higher in newborns receiving ranitidine (9.9% vs 1.6%, P = .003).CONCLUSIONS: Ranitidine therapy is associated with an increased risk of infections, NEC, and fatal outcome in VLBW infants. Caution is advocated in the use of this drug in neonatal age. Infections are a common cause of morbidity and mortality in premature infants. 1 Gastric juice is a major nonimmune defense mechanism against infections. 2 Treatment with inhibitors of gastric acid secretion leads to insufficient elimination of several ingested pathogens. [3][4][5][6][7][8][9][10][11] Many studies show that these drugs facilitate the onset of infections in adults [3][4][5][6][7]12 and children, as we recently demonstrated. 10 There is evidence of an increased risk of infections and necrotizing enterocolitis (NEC) related to the use of histamine-2 receptor (H2-R) blockers and proton pump inhibitors in neonates. [13][14][15] These medications, like many others administered in neonatology, have not been approved by the US Food and Drug Administration for use in this population and are prescribed in an off-label manner because of the perceived safety and potential benefit demonstrated for older populations. Despite these aspects, the use of these drugs has progressively increased. 12,16 In the NICU, the most common i...

Prognostic Values of Multichannel Intraluminal Impedance and pH Monitoring in Newborns with Symptoms of Gastroesophageal Reflux Disease

“…In fact, these drugs have been described as inefficient in newborns (24), (25) and potentially harmful to preterm newborns. (26) CONCLUSION MII/pH performed in first weeks of life has a prognostic value for duration of GERD symptoms.…”

Apnea of Prematurity

“…32 In addition, recent data suggest harmful effects (including an increased incidence of necrotizing enterocolitis, late-onset sepsis, and death) of medications to reduce gastric acidity in preterm infants. 33 …”

Perioperative Care of the Neonate

“…Antirelux medications should be avoided in the neonate unless for speciic surgical cases such as tracheoesophageal istula where such medications have proven to be necessary. Relux medications lead to abnormalities of intestinal lora and have been shown to increase neonatal mortality [37].…”