title: Ranitidine is Associated With Infections, Necrotizing Enterocolitis, and Fatal Outcome in Newborns Effect of gastric acid suppressants on human gastric motility Stress-induced gastric findings in critically ill newborn infants: frequency and risk factors Nosocomial pneumonia risk and stress ulcer prophylaxis: a comparison of pantoprazole vs ranitidine in cardiothoracic surgery patients. Upper GI bleeding in healthy full-term infants: a case-control study Prevention of Neonatal Necrotizing Enterocolitis Protective effects of vitamin E and omeprazole on the hypoxia/reoxygenation induced intestinal injury in newborn rats Effect of Omeprazole on Acid Gastroesophageal Reflux and Gastric Acidity in Preterm Infants With Pathological Acid Reflux A randomized, controlled study of prophylactic ranitidine in preventing stress-induced gastric mucosal lesions in neonatal intensive care unit patients. Bloodstream infections in neonatal intensive care unit patients: results of a multicenter study. The effect of H2-receptor antagonist and proton pump inhibitor on microbial proliferation in the stomach. Very low birth weight outcomes of the National Institute of Child health and human development neonatal research network, January 1995 through December 1996. NICHD Neonatal Research Network. High prevalence of asymptomatic esophageal and gastric lesions in preterm infants in intensive care Pharmacodynamics and systemic exposure of esomeprazole in preterm infants and term neonates with gastroesophageal reflux disease. Single-dose, multiple-dose, and population pharmacokinetics of pantoprazole in neonates and preterm infants with a clinical diagnosis of gastroesophageal reflux disease (GERD) Association of H2-Blocker Therapy and Higher Incidence of Necrotizing Enterocolitis in Very Low Birth Weight Infants Bacterial translocation and intestinal injury in experimental necrotizing enterocolitis model. Alteration of normal gastric flora in neonates receiving ranitidine. Altered bowel function and duodenal bacterial overgrowth in patients treated with omeprazole
abstract: Background And Objective : 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 prospect i ve 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 Background —The effect of histamine H2receptor antagonists on gastric emptying is controversial . Aims —To determine the effects of ranitidine , famotidine , and omeprazole on gastric motility and emptying . Patients and methods —Fifteen normal subjects underwent simultaneous antroduodenal manometry , electrogastrography ( EGG ) , and gastric emptying with dynamic antral scintigraphy ( DAS ) . After 30 minutes of fasting manometry and EGG recording , subjects received either intravenous saline , ranitidine , or famotidine , followed by another 30 minutes recording and then three hours of postpr and ial recording after ingestion of a radiolabelled meal . Images were obtained every 10–15 minutes for three hours to measure gastric emptying and assess antral contractility . Similar testing was performed after omeprazole 20 mg daily for one week . Results —Fasting antral phase III migrating motor complexes ( MMCs ) were more common after ranitidine ( 9/15 subjects , 60 % ) , famotidine ( 12/15 , 80 % ) , and omeprazole ( 8/12 , 67 % ) compared with placebo ( 4/14 , 29 % ; p<0.05 ) . Postpr and ially , ranitidine , famotidine , and omeprazole  slowed gastric emptying , increased the amplitude of DAS contractions , increased the EGG power , and increased the antral manometric motility index . Conclusions —Suppression of gastric acid secretion with therapeutic doses of gastric acid suppressants is associated with delayed gastric emptying but increased antral motility Objective : To evaluate whether infants treated in neonatal intensive care units have stress-induced bleeding from gastrointestinal tract or gastric lesions and to define risk factors for these findings . Design : Part one : retrospective ; part two : prospect i ve . Setting : Tampere University Hospital , neonatal intensive care unit . Patients and interventions : In part one , 100 consecutive newborn infants treated in intensive care were retrospectively evaluated for gastrointestinal tract bleeding and risk factors , and in part two 89 gastroscopied and mechanically ventilated infants were prospect ively evaluated for further risk factors for gastric mucosal lesions . The statistical evaluation of risk factors was made by multivariate analysis using logistic regression modeling . Main results : Of infants treated in the neonatal intensive care unit 20 % had signs of gastrointestinal bleeding .  Mechanical ventilation was the only risk factor ( OR = 4.06 , 95 % confidence interval 1.21–12.3 ) . In part two , when mechanically ventilated infants were prospect ively evaluated , 53 % had remarkable gastric mucosal lesions . The analysis showed three other risk factors : abnormal and delayed delivery and hypotension after birth . Conclusions : Newborn infants treated in the intensive care unit had a high frequency of stress-induced gastric hemorrhage with gastric lesions similar to adults and children treated in intensive care .  Mechanical ventilation is the main risk factor . Also mode of delivery and hypotension after birth increase the risk of stress-induced gastric lesions . These infants should be the target for prophylactic gastroprotective treatment BACKGROUND Stress ulcer prophylaxis ( SUP ) using ranitidine , a histamine H2 receptor antagonist , has been associated with an increased risk of ventilator-associated pneumonia . The proton pump inhibitor ( PPI ) pantoprazole is also commonly used for SUP . PPI use has been linked to an increased risk of community-acquired pneumonia . The objective of this study was to determine whether SUP with pantoprazole increases pneumonia risk compared with ranitidine in critically ill patients . METHODS The cardiothoracic surgery data base at our institution was used to identify retrospectively all patients who had received SUP with pantoprazole or ranitidine , without crossover between agents . From January 1 , 2004 , to March 31 , 2007 , 887 patients were identified , with 53 patients excluded ( pantoprazole , 30 patients ; ranitidine , 23 patients ) . Our analysis compared the incidence of nosocomial pneumonia in 377 patients who received pantoprazole with 457 patients who received ranitidine .  RESULTS Nosocomial pneumonia developed in 35 of the 377 patients ( 9.3 % ) who received pantoprazole , compared with 7 of the 457 patients ( 1.5 % ) who received ranitidine ( odds ratio [ OR ] , 6.6 ; 95 % confidence interval [ CI ] , 2.9 to 14.9 ) . Twenty-three covariates were used to estimate the probability of receiving pantoprazole as measured by propensity score ( C-index , 0.77 ) . Using this score , pantoprazole and ranitidine patients were stratified according to their probability of receiving pantoprazole . After propensity adjusted , multivariable logistic regression , pantoprazole treatment was found to be an independent risk factor for nosocomial pneumonia ( OR , 2.7 ; 95 % CI , 1.1 to 6.7 ; p = 0.034 ) . CONCLUSION The use of pantoprazole for SUP was associated with a higher risk of nosocomial pneumonia compared with ranitidine . This relationship warrants further study in a r and omized controlled trial OBJECTIVE : The aim of this case-control study was to evaluate the frequency and the type of mucosal lesions in newborn babies with upper GI bleeding ( UGIB ) , the diagnostic role and safety of upper GI endoscopy , and the recognition of risk factors associated with the hemorrhagic event . METHODS : A population of 5180 infants born from June , 1988 to May , 1997 was examined . A case was defined as any patient who had UGIB within 4 days of delivery . The diagnosis was made by endoscopic examination in an endoscopy room . The following parameters were determined : amniotic fluid features , funicular blood pH , Apgar index at 5 min , neonatal weight , body length , gestational age , and the presence of other pathologies . Biochemical profiles were also evaluated . Clinical and demographic data of the mothers of the newborn babies were analyzed . Sera of cases and the respective parents were tested for gastrin and pepsinogen . As a control group , 53 full-term healthy infants matched for sex and age were r and omly selected from the population of infants born in our pediatric department . RESULTS : Sixty-four of 5180 newborn babies ( 1.23 % ) suffered from UGIB within 26.5 ± 20 h of life . In 53 of 64 cases ( mean age = 24.2 ± 25.5 h ) it was possible to carry out an endoscopic examination . In one case , endoscopy was limited to the esophagus because of the presence of multiple mucosal ulcers and substenosis of the viscus . Esophageal damage was observed in 24/53 patients . The esophageal lesions were isolated in nine cases , and occurred jointly with gastric or duodenal damage in 14 cases and one , respectively . Gastric and duodenal lesions were seen in 43/52 and 1/52 patients , respectively . There were 17 cases of gastric ulcers and one case of duodenal ulcer . Blood clots were observed in 14 gastric ulcer patients ; in one case there was evidence of active bleeding at the margins of a gastric ulcer . There was no significant difference with regard to the demographic and clinical characteristics of the cases and controls . Median values of serum gastrin of the cases and controls were similar . Median serum pepsinogen was significantly higher in the case group . CONCLUSIONS : UGIB in the newborn babies is often associated with clinical ly relevant mucosal lesions of the upper GI tract . The evolution , after treatment with antisecretory drugs , is generally rapid and favorable , with clinical recovery usually obtained within 24–48 h. The higher serum pepsinogen levels may only represent a significant risk factor of mucosal lesions and complications Small premature infants are often hypochlorhydric , and frequently their stomachs are colonized by enteric , gram-negative bacteria . We tested a hypothesis that gastric pH affected the colonization of the stomach with enteric bacteria and that this colonization was causally related to the risk or severity of necrotizing enterocolitis . A prospect i ve , double-blind study was conducted that compared a group of infants supplemented with 0.01–0.02 ml of 1 N HCl/ml of milk to a group with a similar supplement of water .  Gastric pH , gastric enteric bacteria counts , and the incidence and severity of necrotizing enterocolitis were monitored . The median gastric pH of the HCl-supplemented group was lower ( 3.0 ) than controls ( 4.0 ) throughout the study ( p < 0.001 ) . The gastric enteric bacterial colonization rate and the quantitative bacterial counts were strongly correlated with gastric pH over 4 ( p < 0.001 ) . Somatic growth rates in infants in the HCl-supplemented group were equal to , or exceeded , those in the control group . There was 1 case of necrotizing entero-colitis among the 34 infants in the HCl-supplemented group and 8 cases among the 34 in the control group ( p = 0.02 ) . It appears that acidifying the feedings of small premature infants to a pH low enough to inhibit bacterial proliferation in the stomach significantly lowers the risk of necrotizing enterocolitis Evaluation of prophylactic effects of omeprazole and /or vitamin E on the formation of free oxygen radicals ( FOR ) and bowel histopathology in the newborn rat model of hypoxia/reoxygenation ( H/R ) that resembles human necrotizing enterocolitis ( NEC ) . Eighty newborn rats were r and omly divided into eight groups . H/R was done using airtight chamber . Rats were exposed to 100 % CO2 for 15 min followed by a reoxygenation for the next 15 min with 100 % O2 . Group 1 ( n = 10 ) was the control group . Group 2 ( n = 10 ) rats received vitamin E. In Group 3 ( n = 10 ) omeprazole was administrated . Group 4 ( n = 10 ) rats received omeprazole and vitamin E. Group 5 ( n = 10 ) rats were subjected to H/R two times for 2 days and one time for 3 days . Group 6 ( n = 10 ) received vitamin E in addition to H/R for 5 days and in Group 7 ( n = 10 ) omeprazole in addition to H/R for 5 days . In Group 8 ( n = 10 ) , vitamin E and omeprazole and H/R were applied for 5 days . Rats were killed at the end of the each process and bowel specimens were harvested for histopathological and biochemical investigations . We administrated vitamin E intramuscularly 300 unit/kg per day and omeprazole orally 20 mg/kg per day . Malondialdehyde ( MDA ) , xanthine oxidase ( XO ) , xanthine dehydogenase ( XDH ) and XO/(XO + XDH ) were measured . Vitamin E and /or omeprazole treated rats had significantly less XO% levels than H/R only group ( 0.36 , 0.38 and 0.57 , respectively ) . Similarly , the MDA levels were significantly lower in vitamin E and /or omeprazole received rats than H/R only rats ( 88.8 , 97.9 and 122.6 , respectively ) . All rats treated with omeprazole and /or vitamin E had better biochemical and histopathological levels compared to H/R rats ( p < 0.05 ) . Histopathological results show that Group 5 ( H/R only ) had significantly more intestinal damage when compared with Group 6 ( vitamin E + H/R ) , Group 7 ( omeprazole + R/H ) and Group 8 ( vitamin E + omeprazole + H/R ) ( p < 0.001 ) . Grade 2 and 3 intestinal damages were only in Group 5 and there were no statistical difference between in Groups 6 , 7 and 8 ( p > 0.001 ) . Omeprazole and /or vitamin E may protect the biochemical and histopathological intestinal damage of H/R injury in rats . These drugs may be beneficial in the prophylaxis of NEC in humans as well Introduction : Proton pump inhibitor ( PPI ) therapy is increasingly being used to treat premature infants with gastroesophageal reflux disease ( GERD ) ; however , the efficacy of PPI on acid production in this population has yet to be assessed in this patient group . The aim of this study was to determine the effect of 0.7 mg/kg/d omeprazole on gastric acidity and acid gastroesophageal reflux in preterm infants with reflux symptoms and pathological acid reflux on 24-h pH probe . Methods : A r and omized , double blind , placebo-controlled , crossover design trial of omeprazole therapy was performed in 10 preterm infants ( 34–40 weeks postmenstrual age ) . Infants were given omeprazole for 7 d and then placebo for 7 d in r and omized order . Twenty-four-hour esophageal and gastric pH monitoring was performed on days 7 and 14 of the trial . Results : Compared to placebo , omeprazole therapy significantly reduced gastric acidity ( % time pH < 4 , 54 % vs 14 % , P < 0.0005 ) , esophageal acid exposure ( % time pH < 4 , 19 % vs 5 % , P < 0.01 ) and number of acid GER episodes ( 119 vs 60 episodes , P < 0.05 ) . Conclusions : Omeprazole is effective in reducing esophageal acid exposure in premature infants with pathological acid reflux on 24-h pH probe ; however , the far more complex issues of safety and efficacy have yet to be addressed OBJECTIVE To assess endoscopically the effect of prophylactic short-term ranitidine treatment in the prevention of  stress-induced gastric lesions  in neonatal intensive care unit ( ICU ) patients . DESIGN Prospect i ve , r and omized study . SETTING Department of Neonatal Intensive Care , University Hospital of Tampere . PATIENTS Fifty-three infants were enrolled in a r and omized , controlled study . Forty-eight ( 90 % ) of these patients underwent endoscopic examination and were evaluated . INTERVENTIONS A histamine-2-receptor blocker , ranitidine , was given prophylactically after birth for 4 days to infants mechanically ventilated and treated in the neonatal ICU . The gastric mucosa was both visually and histologically evaluated after 3 to 6 days , and the outcome of the infants was registered . MEASUREMENTS AND MAIN RESULTS In the 23 infants prophylactically treated with ranitidine , the gastric mucosa was visually classified as normal in 14 ( 61 % ) infants as compared with five ( 20 % ) of 25 controls ( p < .004 ) . Histologic lesions showed parallel results ( 57 % vs. 16 % , p < .004 ) . Eight gastric ulcers were diagnosed endoscopically in the control group vs. none in the treatment group . The ulcers were all clinical ly " silent " at the time of endoscopy . According to logistic regression modeling , the decreased risk for gastric mucosal lesions in infants receiving prophylactic ranitidine was 0.03 ( 95 % confidence interval 0.003 to 0.178 ) . Surfactant treatment for infant respiratory distress syndrome also decreased the risk for stress-induced gastric mucosal lesions ( odds ratio 0.083 ; 95 % confidence interval 0.009 to 0.788 ) , whereas other variables ( birth weight , gestational age , Apgar scores , cord blood pH , and duration of intubation ) had no significant effect . No side effects could be attributed to the ranitidine treatment . CONCLUSION We conclude that short-term prophylactic ranitidine treatment prevents gastric mucosal lesions in newborn infants under stress For identification of risk factors for bloodstream infection ( BSI ) among neonatal intensive care unit patients , prospect i ve 6-month studies in three neonatal intensive care units were conducted . BSI was diagnosed in 42 of 376 ( 11.2 % ) enrolled infants . Pathogens included coagulase-negative staphylococci , C and ida sp. , Group B streptococci and Gram-negative species . Patients with BSIs were more likely to die during their neonatal intensive care unit stay than were patients who did not acquire BSIs ( 6 of 42 vs. 11 of 334 , P = 0.007 ) . BSI rate was highest in infants with birth weight < 1500 g ( relative risk ( RR ) = 6.8 , P < 0.001 ) , those treated with H-2 blockers ( RR = 4.2 , P < 0.001 ) or theophylline ( RR = 2.8 , P < 0.001 ) and those with admission diagnoses referable to the respiratory tract ( RR = 3.7 , P < 0.001 ) . Infants who developed BSI were more severely ill on admission than other infants ( median physiologic stability index 13 vs. 10 ( P < 0.001 ) and were of lower gestational age ( 28 vs. 35 weeks , P < 0.001 ) . In logistic regression analysis , risk of BSI was independently associated only with very low birth weight , respiratory admission diagnoses and receipt of H-2 blockers . Risk of isolation of a pathogen from blood culture was independently associated with Broviac , umbilical vein or peripheral venous catheterization > 10 , 7 or 3 days , respectively , at one insertion site . Rate of isolation of a pathogen was higher ( 9 of 59 ( 15 % ) ) within 48 hours of a measurable serum interleukin 6 concentration than an interleukin 6 level of 0 pg/ml ( 10 of 159 ( 6 % ) , P = 0.04 ) . ( ABSTRACT TRUNCATED AT 250 WORDS BACKGROUND / AIMS Intra-gastric bacterial proliferation is frequent in patients with hypochlohydria . However , status of gastric bacterial infection in patients receiving proton pump inhibitor or H2-receptor antagonist  remains controversial . The purpose of this study was to investigate the microbial condition of the stomach in patients who received H2-receptor antagonist or proton pump inhibitor .  METHODOLOGY Between November 2000 and January 2002 , 102 patients were enrolled in this study . Of these , 52 did not receive any treatment ( group I ) , 26 received H2-receptor antagonist ( group II ) , and 24 received proton pump inhibitor ( group III ) . Ten mL of gastric juice were aspirated for culture during endoscopic examination . The aerobic and anaerobic bacterial and fungal cultures were performed immediately . A glass pH meter measured the pH of the gastric juice . RESULTS The intra-gastric pH was 2.91+/-2.06 ( mean + /- SD ) , 4.12+/-2.83 , and 5.11+/-2.47 for groups I , II , and III , respectively ( p=0.001 between groups I and III , p>0.05 between groups I and II , and groups II and III ) . The positive bacterial culture rates were 66.7 % ( 16/24 ) in group III , 46.2 % ( 12/26 ) in group II , and 28.8 % ( 15/52 ) in group I ( p=0.007 between groups III and I , p>0.05 between groups I and II , and groups II and III ) . The positive c and idal culture rates were 12.5 % ( 3/24 ) in group III , 11.5 % ( 3/26 ) in group II , and 17.3 % ( 9/52 ) in group I ( p>0.05 ) . CONCLUSIONS Patients who received proton pump inhibitor had more acid suppression and intra-gastric bacterial infection than those of the control group . The intra-gastric c and idal infection was not related to intra-gastric pH or anti-secretory medication in this study OBJECTIVES To determine the mortality and morbidity for infants weighing 401 to 1500 g ( very low birth weight [ VLBW ] ) at birth by gestational age , birth weight , and gender . STUDY DESIGN Perinatal data were collected prospect ively on an inborn cohort from January 1995 through December 1996 by 14 participating centers of the National Institute of Child Health and Human Development Neonatal Research Network and were compared with the corresponding data from previous reports . Sociodemographic factors , perinatal events , and the neonatal course to 120 days of life , discharge , or death were evaluated . RESULTS Eighty four percent of 4438 infants weighing 501 to 1500 g at birth  survived until discharge to home or to a long-term care facility ( compared with 80 % in 1991 and 74 % in 1988 ) . Survival to discharge was 54 % for infants 501 to 750 g at birth , 86 % for those 751 to 1000 g , 94 % for those 1001 to 1250 g , and 97 % for those 1251 to 1500 g . The incidence of chronic lung disease ( CLD ; defined as receiving supplemental oxygen at 36 weeks ' postmenstrual age ; 23 % ) , proven necrotizing enterocolitis ( NEC ; 7 % ) , and severe intracranial hemorrhage ( ICH ; grade III or IV ; 11 % ) remained unchanged between 1991 and 1996 . Furthermore , 97 % of all VLBW infants and 99 % of infants weighing < 1000 g at birth had weights less than the 10th percentile at 36 weeks ' postmenstrual age . Mortality for 195 infants weighing 401 to 500 g was 89 % , with nearly all survivors developing CLD . Mortality in infants weighing 501 to 600 g was 71 % ; among survivors , 62 % had CLD , 35 % had severe ICH , and 15 % had proven NEC . CONCLUSIONS Survival for infants between 501 and 1500 g at birth continued to improve , particularly for infants weighing < 1000 g at birth . This improvement in survival was not associated with an increase in major morbidities , because the incidence of CLD , proven NEC , and severe ICH did not change . However , poor postnatal growth remains a major concern , occurring in 99 % of infants weighing < 1000 g at birth . Mortality and major morbidity ( CLD , severe ICH , and NEC ) remain high for the smallest infants , particularly those weighing < 600 g at birth To establish the prevalence of upper gastrointestinal mucosal lesions in full-term and preterm infants under stress . Design : A prospect i ve , cohort study . Setting : Neonatal intensive care unit at a university teaching hospital . Patients : Seventeen ( 14 preterm , 3 term ; median gestational age 29.7 wks ; median birth weight 1230 g ) consecutive , unselected infants treated in intensive care . Interventions : Gastroscopy , using a prototype fiberoptic gastroscope design ed for newborns , was performed for the first time at the age of 3 to 7 days . Biopsy specimens were taken when possible . Ranitidine treatment and follow-up endos-copies were performed in selected patients . Blood pressure , heart rate , oxygen saturation by pulse oximeter , and the general condition of the infants were monitored at 1-min intervals during the endoscopy .  Central nervous system ultra-sonography examination was repeatedly performed before and after the procedure . Measurements and Main Results : At the time of first endoscopy , 15 of 17 infants were asymptomatic for gastrointestinal tract problems , one had melena , and one hematemesis . Upper gastrointestinal endoscopy revealed pathology in 16 ( 94 % ) infants , macroscopic esophagitis in six infants , hemorrhagic gastritis in nine infants , and gastritis with ulcers in six infants . Microscopically , the lesions were also clear . A peculiar finding was acute gastritis with cystic gl and deformation ( “ cystic gastritis ” ) seen in five of the infants under stress ; one of these infants also had intestinal metaplasia in the gastric mucosa . Seven infants were treated with ranitidine without side-effects . Follow-up endoscopies demonstrated normalization of the lesions in five of six infants studied . The procedure , including biopsies , seemed to be safe , even for very low-birth weight infants . Conclusions : Gastric mucosal lesions are highly prevalent in preterm infants in intensive care before any symptoms occur . Further research on preterm infants under stress is needed in order to determine the risk factors and optimal treatment for the esophageal and gastric mucosal lesions described here . ( Crit Care Med 1993 ; 21:1863–1867 OBJECTIVE To characterize the pharmacodynamics and systemic exposure of esomeprazole in 26 preterm infants and term neonates with symptoms of gastroesophageal reflux and pathologic acid exposure . STUDY DESIGN Enrolled patients received oral esomeprazole 0.5 mg/kg once daily for 7 days . Twenty-four-hour esophagogastric pH-impedance monitoring was performed at baseline and on day 7 . Pharmacokinetic analysis was performed on day 7 . Symptoms occurring during the baseline and day 7 studies were recorded on a symptom chart . RESULTS There were no significant differences from baseline to day 7 of therapy in the frequency of bolus reflux , consistency of bolus reflux ( liquid , mixed , or gas ) , extent of bolus reflux , or bolus clearance time . Acid bolus reflux episodes were reduced on therapy ( median 30 vs 8 , P < .001 ) , as was the reflux index ( mean % time esophageal pH < 4 , 15.7 % vs 7.1 % , P < .001 ) . The estimated geometric mean of area under the plasma concentration time curve during the dosing interval and observed maximum plasma concentration was 2.5 micromol x h/L and 0.74 micromol/L , respectively . The number of gastroesophageal reflux symptoms recorded over 24 hours was lower on therapy ( median 22 vs 12 , P < .05 ) . CONCLUSIONS In preterm infants and term neonates esomeprazole produces no change in bolus reflux characteristics despite significant acid suppression Purpose The pharmacokinetic profile of pantoprazole granules was assessed in neonates and preterm infants with gastroesophageal reflux disease ( GERD ) in a multicenter , r and omized , open-label trial . Methods Patients were r and omly assigned to either the pantoprazole 1.25 mg ( approx . 0.6 mg/kg ) or 2.5 mg ( approx . 1.2-mg/kg ) group and treated for ≥5 consecutive days . Blood was sample d either at 0 , 2 , 8 , and 18 h postdose or at 0 , 1 , 4 , and 12 h postdose on day 1 and at 3 and 6 h postdose after ≥5 consecutive doses . Cytochrome P450 2C19 ( CYP2C19 ) and CYP3A4 genotypes were determined . Safety was monitored . Population pharmacokinetics ( popPK ) analyses were conducted using nonlinear mixed-effects modeling . Results The popPK modeling of the pantoprazole 1.25 mg and 2.5 mg groups obtained mean ( ±st and ard deviation ) estimates for the area under the plasma concentration versus time curve ( AUC ) of 3.54 ( ±2.82 ) and 7.27 ( ±5.30 ) µg h/mL , respectively , and mean estimates for half-life of 3.1 ( ±1.5 ) and 2.7 ( ±1.1 ) h , respectively . Pantoprazole did not accumulate following multiple-dose administration . The two patients with the CYP2C19 poor metabolizer genotype had a substantially higher AUC than extensive metabolizers . No safety-related discontinuations occurred . Conclusions In preterm infants and neonates , pantoprazole granules were generally well tolerated , mean exposures with pantoprazole 2.5 mg were slightly higher than that in adults who received 40 mg . While the half-life was longer , accumulation did not occur OBJECTIVE . We sought to determine if an association exists between the use of histamine-2 receptor ( H2 ) blockers and the incidence of  necrotizing enterocolitis ( NEC ) in infants of 401 to 1500 g in birth weight . STUDY DESIGN . Data from the National Institute of Child Health and Human Development Neonatal Research Network very low birth weight ( 401–1500 g ) registry from September 1998 to December 2001 were analyzed . The relation between the diagnosis of NEC ( Bell stage II or greater ) and antecedent H2-blocker treatment was determined by using case-control methodology . Conditional logistic regression was implemented , controlling for gender , site of birth ( outborn versus inborn ) , Apgar score of < 7 at 5 minutes , and postnatal steroids . RESULTS . Of 11072 infants who survived for at least 12 hours , 787 ( 7.1 % ) developed NEC ( 11.5 % of infants 401–750 g , 9.1 % of infants 751–1000 g , 6.0 % of infants 1001–1250 g , and 3.9 % of infants 1251–1500 g ) . Antecedent H2-blocker use was associated with an increased incidence of NEC ( P < .0001 ) . CONCLUSIONS . H2-blocker therapy was associated with higher rates of NEC , which is in agreement with a previous r and omized trial of acidification of infant feeds that result ed in a decreased incidence of NEC . In combination , these data support the hypothesis that gastric pH level may be a factor in the pathogenesis of NEC OBJECTIVE To study the occurrence of bacterial translocation and to assess the impact of breastfeeding on bacterial translocation in the animal model of necrotizing enterocolitis . METHODS A total of 20 neonate Sprague-Dawley rats were enrolled in the study . Rats were r and omly allocated into either control or study group just after birth . Ten newborn rats in the control group were left with their mother to be breast-fed . In contrary , necrotizing enterocolitis group consisted of neonates that were separated from their mothers , housed in an incubator and were gavaged with a special rodent formula three times daily .  Survival rates , weight changes , and morphologic scoring obtained after microscopic evaluation were determined as microbiologic evaluation criteria . RESULTS All the rats in the control group survived , while 1 ( 10 % ) rat died in the necrotizing enterocolitis group . Mortality rates of the two groups were similar . All the formula-fed animals in the necrotizing enterocolitis group had significant weight loss compared to the breast milk-fed rats in the control group ( p<0.05 ) . A total of 7 ( 70 % ) and 2 ( 20 % ) E. coli growths were identified in the bowel lumen , liver , and spleen of necrotizing enterocolitis and control groups , respectively . This difference was statistically significant . In peritoneal smear cultures , a total of 3 ( 30 % ) growths were detected in the necrotizing enterocolitis group and 1 ( 10 % ) growth in the control group . CONCLUSION As the result of a disturbance in the intestinal flora and impairment of the intestinal barrier in necrotizing enterocolitis , microrganisms in the bowel pass through the intestinal barrier and reach the liver and the spleen via the hematogenous route . This condition is closely related to the impairment of physiological and functional features of the intestinal barrier and is independent from the degree of intestinal injury . Bacterial translocation should be remembered in cases suspected of necrotizing enterocolitis , and a rapid and effective treatment algorithm should be applied in such circumstances ( Tab . 3 , Fig. 3 , Ref . 21 ) . Full Text in PDF www.elis.sk OBJECTIVES To determine if the administration of ranitidine to neonates leads to an increase in gastric pH to > or = 4 and if this increase in gastric pH correlates with gastric colonization . STUDY DESIGN 628 pH measurements and 276 gastric cultures were obtained from 86 neonates . Twenty-three patients received ranitidine and 63 patients served as controls .  RESULTS Treated patients had a mean gastric pH of 5.6 compared with a control mean pH of 4.4 ( p < 0.0001 ) . Gastric pH was significantly affected by feeding and postnatal age . 54 patients were colonized with pathogenic bacteria and /or yeast ( n = 20 treated , n = 34 control ) . Length of hospitalization ( p < 0.0001 ) , increase in gastric pH ( p < 0.01 ) , days of antibiotics before culture ( p < 0.0001 ) , and ranitidine use ( p < 0.0001 ) were associated with an increased rate of colonization . CONCLUSIONS The use of ranitidine did lead to a significant increase in gastric pH and with this increase in gastric pH gastric colonization rates increased . No increased frequency of infection was found in ranitidine-treated infants Background : The dramatic inhibitory effect of proton pump inhibitors on acid secretion has raised concern about possible side‐effects , such as small bowel bacterial overgrowth , which may result in further gut dysfunction . The aim of this study was to assess the effect of proton pump inhibitors on duodenal bacteriology , carbohydrate absorption and bowel habit
target: Exposure to H2 receptor antagonists may be associated with increased risk of NEC and infections in preterm infants
background: BACKGROUND Inhibitors of gastric acid ( IGA ) are used for upper gastrointestinal bleeding or gastroesophageal reflux in preterm infants .
  The result ant increase in gastric pH may enhance the growth of pathogens and increase the risk of necrotizing enterocolitis ( NEC ) .
  Our systematic review examined the association between  IGA and NEC in preterm infants .