Do gastric acidity inhibitors increase the risk of necrotising enterocolitis in preterm babies?

June 11, 2011

June 15, 2011

VENKATA PUNAGANTI, ST6 (HULL ROYAL INFIRMARY)

[In preterm baby], does [gastric acidity inhibitor ]increases the risk of [necrotising enterocolitis]?

You are a neonatal Registrar and called by the nurse to review a 10 days old preterm baby born at 27weeks gestation for vomiting. Baby is otherwise well in self with normal systemic examination. Baby is receiving expressed breast milk with thickener. You planned to commence the baby on Ranitidine for suspected gastro oesophageal reflux. You wonder whether ranitidine can increase the risk of necrotising enterocolitis (NEC) in this baby.

The Cochrane Library, MEDLINE (1948 to April 2011) and EMBASE (1947 to 2011).

‘Ranitidine’, ‘cimetidine’, ‘famotidine’, ‘histamine H2 antagonist’, ‘proton pump inhibitor’, ‘omeprazole’, ‘anti ulcer agent’, ‘gastric acid inhibitor’ and ‘necroti#ing enterocolitis’ are the keywords used for the search.

3 relevant papers identified

There is one retrospective case control study addressing the association of H2 blocker therapy and development of NEC in very low birth weight babies. The controls were matched for birth weight, race and neonatal network centre. Conditional logistic regression method was used to determine the effect H2 blocker use on the incidence of NEC but controlled for gender, site of birth, Apgar score of <7 at 5minutes and post natal steroids. They found that H2 blocker use was associated with an increased incidence of NEC when data collection was truncated by postmenstrual age (Odds ratio: 1.71) or when data collection was truncated by chronological age (Odds ratio: 1.49). There was no information available regarding type of milk (breast milk or formula milk). Data was not analysed controlling for confounding factors like gestational age and intrauterine growth retardation. Douglas etal study was again a retrospective case control study which had 3 controls for each case. Infants were primarily matched by gestational age at birth, birth weight, and, when possible, ethnicity. Significantly more infants who had H2 blockers added to their TPN solution developed NEC than did infants who did not have an H2 blocker added to their TPN solution, 58% versus 21%. Multiple logistic regression method was used and found that parenteral H2 Blocker use increases the risk of developing NEC with p = 0.01. But oral H2 Blocker use did not show any significant difference. Carrion V etal study was a prospective double blinded study in which babies with birth weight < 1,250gm were either receiving HCL or water supplement with the milk. The gastric enteric bacterial count was strongly correlated with gastric pH over 4 (p < 0.001). Incidence of NEC was significantly lower in HCL supplemented group (p< 0.02). But this was a small study with a sample size of only 68 babies. Unfortunately there is no good quality randomised controlled study looking at whether gastric acidity inhibitors increase the risk of NEC in preterm babies.

There is some evidence but not strong enough to suggest definite causal relation between the use of gastric acidity inhibitors and NEC in preterm babies. But gastric acid is present for a purpose and caution should be taken before commencing gastric acidity inhibitors in preterm babies. Avoid using them as routine prophylaxis and use only when there is clear clinical indication.

1. Guillet R, Stoll BJ, Cotton M, et al.. Association of H2-blocker therapy and higher incidence of necrotizing enterocolitis in very low birth weight infants
2. Douglas Drenckpohl, Lisa Knaub, Catherine Schneider etal. Risk Factors That May Predispose Premature Infants to Increased Incidence of Necrotizing Enterocolitis
3. Carrion V, Egan EA. Prevention of neonatal necrotizing enterocolitis