Oropharyngeal colostrum in preventing mortality and morbidity in preterm infants

Nasuf, Amna Widad A., Ojha, Shalini and Dorling, Jon (2018) Oropharyngeal colostrum in preventing mortality and morbidity in preterm infants. Cochrane Database of Systematic Reviews, 2018 (9), [CD011921]. (doi:10.1002/14651858.CD011921.pub2).

Record type: Review

Abstract

Background: 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. Objectives: 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. Search methods: 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 We contacted trial investigators regarding unpublished studies and data. Selection criteria: We searched for published and unpublished randomised controlled trials comparing early administration of oropharyngeal colostrum (OPC) versus sham administration of water, oral formula, or donor breast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. Data collection and analysis: 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. Main results: 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. Authors' conclusions: Large, well-designed trials would be required to evaluate more precisely and reliably the effects of oropharyngeal colostrum on important outcomes for preterm infants.

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Published date: 7 September 2018

Additional Information: Funding Information: This study was funded by the National Institutes of Health and by Medela, Inc., USA Funding Information: Change in salivary secretory IgA concentration from baseline to 2 weeks of age Necrotising enterocolitis (Bell’s stage 2 or 3) Culture-positive sepsis Time to full enteral feeding (defined as 140 mL/kg/d) Children’s Miracle Network Research Grant National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) of the National Institutes of Health under award number 1R01DK099350. USA Results were initially available as a conference abstract, and further information was provided by Dr Karen Glass. Data included in the review included information from the subsequent publication - Glass 2017 - and information provided by Dr Glass Funding Information: • National Institute for Health Research, UK. Editorial support for Cochrane Neonatal has been funded by a UK National Institute of Health Research (NIHR) Cochrane Programme Grant (16/114/03). The views expressed in this publication are those of the review authors and not necessarily those of the National Health Service, the NIHR, or the UK Department of Health. • Vermont Oxford Network, USA. Cochrane Neonatal Reviews are produced with support from Vermont Oxford Network, a worldwide collaboration of health professionals dedicated to providing evidence-based care of the highest quality for newborn infants and their families. Funding Information: Supported by The Minas Gerais State Research Support Foundation (FAPEMIG), Brazil Publisher Copyright: © 2018 The Cochrane Collaboration.