Review question
Does providing a very small volume of maternal colostrum into the mouth of preterm babies (oropharyngeal colostrum (OPC)) prevent complications and improve health outcomes?
Background
Placing a small volume of colostrum - the first milk produced by the mother during the first few days of life - directly onto the inside of the cheeks of preterm infants may provide immunological and growth factors that stimulate the immune system and enhance growth of the intestine. These benefits could potentially reduce infections, including severe infections in the intestine known as necrotising enterocolitis (NEC), thereby improving survival and long-term outcomes.
Study characteristics
We searched for both published and unpublished studies comparing oropharyngeal colostrum versus a control such as water, placebo, or no oral priming. We included only clinical trials reporting outcomes in preterm babies (< 37 weeks' gestation). The evidence is up-to-date as of August 2017. We did not limit the review to any particular region or language.
Key results
Six studies were eligible for inclusion, involving 335 preterm infants with gestational ages ranging from 25 to 32 weeks' gestation and birth weights of 410 to 2500 grams. Reviewers noted no differences between OPC and control for rate of NEC, infection, or death before hospital discharge. Similarly, they observed no difference in length of hospital stay between OPC and control babies. Infants who received OPC achieved full milk feeds on average 2.5 days earlier than those given placebo or no intervention. However, included studies were small, data were insufficient, and study designs were not ideal. Combining study data did not provide sufficient evidence to recommend the use of colostrum for oral priming to prevent complications in preterm infants. Five of the included studies reported no harms (adverse effects); however, no numerical data are available from these studies. Included studies were of very low quality; therefore the effects of OPC remain uncertain.
Conclusions
Larger, better quality clinical trials would be needed to evaluate more precisely and reliably the effects of OPC on important outcomes for preterm infants. .
Large, well-designed trials would be required to evaluate more precisely and reliably the effects of oropharyngeal colostrum on important outcomes for preterm infants.
Placing a small volume of colostrum directly onto the buccal mucosa of preterm infants during the early neonatal period may provide immunological and growth factors that stimulate the immune system and enhance intestinal growth. These benefits could potentially reduce the risk of infection and necrotising enterocolitis (NEC) and improve survival and long-term outcome.
To determine if early (within the first 48 hours of life) oropharyngeal administration of mother’s own fresh or frozen/thawed colostrum can reduce rates of NEC, late-onset invasive infection, and/or mortality in preterm infants compared with controls. To assess trials for evidence of safety and harm (e.g. aspiration pneumonia). To compare effects of early oropharyngeal colostrum (OPC) versus no OPC, placebo, late OPC, and nasogastric colostrum.
We used the standard search strategy of the Cochrane Neonatal Review Group to search the Cochrane Central Register of Controlled Trials (CENTRAL; 2017, Issue 8), MEDLINE via PubMed (1966 to August 2017), Embase (1980 to August 2017), and the Cumulative Index to Nursing and Allied Health Literature (CINAHL; 1982 to August 2017). We also searched clinical trials registries for ongoing and recently completed trials (clinicaltrials.gov; the World Health Organization International Trials Registry (www.whoint/ictrp/search/en/), and the ISRCTN Registry), conference proceedings, and the reference lists of retrieved articles for randomised controlled trials and quasi-randomised trials. We performed the last search in August 2017. We contacted trial investigators regarding unpublished studies and data.
We searched for published and unpublished randomised controlled trials comparing early administration of oropharyngeal colostrum (OPC) versus sham administration of water, oral formula, or donor breast milk, or versus no intervention. We also searched for studies comparing early OPC versus early nasogastric or nasojejunal administration of colostrum. We considered only trials that included preterm infants at < 37 weeks' gestation. We did not limit the review to any particular region or language.
Two review authors independently screened retrieved articles for inclusion and independently conducted data extraction, data analysis, and assessments of 'Risk of bias' and quality of evidence. We graded evidence quality using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. We contacted study authors for additional information or clarification when necessary.
We included six studies that compared early oropharyngeal colostrum versus water, saline, placebo, or donor, or versus no intervention, enrolling 335 preterm infants with gestational ages ranging from 25 to 32 weeks' gestation and birth weights of 410 to 2500 grams. Researchers found no significant differences between OPC and control for primary outcomes - incidence of NEC (typical risk ratio (RR) 1.42, 95% confidence interval (CI) 0.50 to 4.02; six studies, 335 infants; P = 0.51; I² = 0%; very low-quality evidence), incidence of late-onset infection (typical RR 0.86, 95% CI 0.56 to 1.33; six studies, 335 infants; P = 0.50; I² = 0%; very low-quality evidence), and death before hospital discharge (typical RR 0.76, 95% CI 0.34 to 1.71; six studies, 335 infants; P = 0.51; I² = 0%; very low-quality evidence). Similarly, meta-analysis showed no difference in length of hospital stay between OPC and control groups (mean difference (MD) 0.81, 95% CI -5.87 to 7.5; four studies, 293 infants; P = 0.65; I² = 49%). Days to full enteral feeds were reduced in the OPC group with MD of -2.58 days (95% CI -4.01 to -1.14; six studies, 335 infants; P = 0.0004; I² = 28%; very low-quality evidence).
The effect of OPC was uncertain because of small sample sizes and imprecision in study results (very low-quality evidence).
No adverse effects were associated with OPC; however, data on adverse effects were insufficient, and no numerical data were available from the included studies.
Overall the quality of included studies was low to very low across all outcomes. We downgraded GRADE outcomes because of concerns about allocation concealment and blinding, reporting bias, small sample sizes with few events, and wide confidence intervals.