Proton Pump Inhibitors, H2 Blocker Use, and Risk of Inflammatory Bowel Disease in Children

Abstract

OBJECTIVES Evidence suggests use of proton pump inhibitors (PPIs) and H2 blockers may provoke disease flares in individuals with established inflammatory bowel disease (IBD); however, there are no studies investigating the relationship of these medications with risk of developing pediatric IBD. The hypothesis was that use of acid suppression therapy in children might be associated with development of pediatric IBD. METHODS This was a nested case-control study of 285 Kaiser Permanente Northern California members, age ≤21 years diagnosed with IBD from 1996 to 2016. Four controls without IBD were matched to each case on age, race, and membership status at the case's index date. Disease risk scores (DRS) were computed for each subject. Odds ratios and 95% confidence intervals were calculated by using conditional logistic regression models adjusted for DRS. RESULTS The children's mean age was 15.1 ± 2.6 years and 49.5% were female. Six cases (n = 3 Crohn's disease [CD], n = 3 ulcerative colitis [UC]) and 6 controls were prescribed PPIs and 10 cases (n = 7 CD, n = 3 UC) and 28 controls were prescribed H2 blockers. The OR for the association of at least 1 PPI or H2 blocker prescription with subsequent IBD was 3.6 (95% CI, 1.1–11.7) for PPIs and 1.6 (95% CI, 0.7–3.7) for H2 blockers. CONCLUSIONS Early-life PPI use appears to be associated with subsequent IBD risk. These findings have implications for clinical treatment of children with gastrointestinal symptoms and warrant further investigation in a larger cohort.

Regular Use of Proton Pump Inhibitor and the Risk of Inflammatory Bowel Disease: Pooled Analysis of 3 Prospective Cohorts

“…Out results were in line with a recent nested case-control study of 286 patients with pediatric IBD and 1144 controls, which showed that PPI was significantly associated with increased risk (odds ratio, 3.6; 95% CI, 1.1-11.7), and no sufficient evidence of increased risk was observed for H2RAs (odds ratio, 1.6; 95% CI, 0.7-3.7). 16 In patients with established IBD, many studies have reported that PPIs might increase the severity of the disease and lead to treatment escalation. [21][22][23] For example, a meta-analysis of 5 randomized trials found that patients with IBD taking PPIs were less likely to achieve remission while on infliximab therapy.…”

“…A recent nested case-control study found that PPI was significantly associated with increased risk of pediatric IBD. 16 A large randomized controlled trial 8 and meta-analyses of observational studies [17][18][19] have demonstrated that PPI use could facilitate gastrointestinal infections, such as C difficile infection, which are known to associate with development of IBD. 5,20 In patients with IBD, PPIs may provoke disease flares, 21,22 and were associated with lower remission rate.…”

Parentally reported early childhood upper gastrointestinal symptoms alleviate at school age

“…The increased use of PPI medication in children has raised concerns among paediatric gastroenterologists. 10 Long-term PPI use has been associated with potentially harmful alteration of the gut microbiome, 21 increased risk of inflammatory bowel disease 22 and bacterial infections in the GI tract. 5 Therefore, it is essential to restrain the medication for patients with objective proof of excessive acidic GOR.…”

Peculiarities of influence of single intragastric administration of H2-histamine receptor blockers of the second (nisatidine) and third (famotidine) generation on acid-peptic and mucoid-electrolyte secretion of the stomach in patients with duodenal ulcer

“…У базових схемах лікування кислотнозалежних хвороб ШКК переважають БПП завдяки більш високій кислотоблокувальній здатності [9]. Однак БПП мають низку недоліків, серед яких великий відсоток пацієнтів, резистентних до тих чи інших БПП, а також можливість так званого нічного кислотного прориву [5,24]. Крім цього, застосовуючи БПП лікар-інтерніст мусить оцінювати не тільки кислотнознижувальний ефект ЛЗ, а й інші впливи на орґанізм [9].…”

“…Вільну й загальну кислотність шлункового соку визначали титраційним методом [7], а також проводили титрування шлункового соку з використанням рН-метра для оцінки активності іонів водню [14]. Уміст пепсиноґену визначали колориметричним методом [11,26], сіалових кислот (N-acetylneuraminicacid-NANA), як маркера мукоїдної секреції -резорциновим методом у шлунковому соці та нерозчинному слизі [13,24]. Концентрацію натрію, як маркера гідрокарбонатної секреції, в шлунковому соці та нерозчинному слизі визначали полуменево-фотометричним методом [14].…”