Oral immunoglobulin for preventing necrotizing enterocolitis in preterm and low birth weight neonates

Review question: Does the use of oral immunoglobulin reduce the incidence of necrotizing enterocolitis and other complications in preterm or low birth weight (or both) neonates?

Background: Immunoglobulin given orally for preventing emergency intestinal problems (necrotizing enterocolitis) in premature and low birth weight newborn infants. Destructive inflammation of the intestine (called necrotizing enterocolitis, NEC) is caused by gas-producing bacteria that ferment milk. It is a potential problem for newborn preterm (born before their due date) and low birth weight (born at less than 2500 grams) infants. Even after leaving hospital, affected infants may need frequent and prolonged hospitalisation because of continuing nutritional problems. This makes it difficult for parents both emotionally and financially. Immunoglobulins are proteins found in the blood that give the body immunity to disease. Immunoglobulins (types IgA and IgG) taken by mouth (orally) may protect susceptible infants from developing NEC.

Study characteristics: We searched the medical literature through January 2016 and found three randomized controlled trials (clinical studies where people are randomly put into one of two or more treatment groups) (with 2095 newborn infants). Treatment was started either in the first 24 hours following birth (two small studies) or following commencement of oral feeding (enteral) (one large well-controlled study). In this large study, infants generally received breast milk, whereas they received formula milk in the other two studies.

Results: Giving immunoglobulin (IgG alone or IgG plus IgA combination) did not reduce the incidence of NEC, need for surgery related to NEC or death from NEC, either during or after the study period. Immunoglobulins could possibly cause breakdown of red blood cells (called haemolysis) (red blood cells are common cells in the blood that delivery oxygen to organs), but no clinically important haemolysis was apparent. There were no other reported side effects.

Quality of the evidence: There was low-very low evidence for all the major outcomes. The major factor that affected the quality of evidence was the lack of precision in the result estimates, as the calculated plausible range of the effects (the 95% confidence intervals) were wide.

Authors' conclusions: 

Based on the available trials, the evidence does not support the administration of oral immunoglobulin for the prevention of NEC. There are no randomized controlled trials of oral IgA alone for the prevention of NEC.

Read the full abstract...

Necrotizing enterocolitis (NEC) is the most common emergency involving the gastrointestinal tract occurring in the neonatal period. There have been published reports that suggest that oral immunoglobulins (Ig)A and IgG produce an immunoprotective effect in the gastrointestinal mucosa.


To determine the effect of oral immunoglobulin on the incidence of necrotizing enterocolitis and other complications in preterm or low birth weight (or both) neonates.

Search strategy: 

We used the standard search strategy of the Cochrane Neonatal Group. We searched the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library 2016, Issue 1), PubMed (1966 to January 2016), CINAHL (1982 to January 2016) and EMBASE (1980 to January 2016) and conference proceedings.

Selection criteria: 

All randomized or quasi-randomised controlled trials where oral immunoglobulins were used as prophylaxis against NEC in preterm (less than 37 weeks' gestation) or low birth weight (less than 2500 gram), or both, neonates.

Data collection and analysis: 

We performed data collection and analysis in accordance with the standard methods of the Cochrane Neonatal Review Group.

Main results: 

The search identified five studies on oral immunoglobulin for the prevention of NEC of which three met the inclusion criteria. In this review of the three eligible trials (including 2095 neonates), the oral administration of IgG or an IgG/IgA combination did not result in a significant reduction in the incidence of definite NEC (typical risk ratio (RR) 0.84, 95% confidence interval (CI) 0.57 to 1.25; typical risk difference (RD) -0.01, 95% CI -0.03 to 0.01; 3 studies, 1840 infants), suspected NEC (RR 0.84, 95% CI 0.49 to 1.46; RD -0.01, 95% CI -0.02 to 0.01; 1 study, 1529 infants), need for surgery (typical RR 0.21, 95% CI 0.02 to 1.75; typical RD -0.03, 95% CI -0.06 to 0.00; 2 studies, 311 infants) or death from NEC (typical RR 1.10, 95% CI 0.47 to 2.59; typical RD 0.00, 95% CI -0.01 to 0.01; 3 studies, 1840 infants).