Rachel Robertson.CPAP.Poster.v3MU.pdf

Does continuous positive airway pressure (CPAP) alter the fecal microbiota of very low birth weight infants? A Pilot Study.

Rachel Robertson, MD BSc Hons; Diana Taft, PhD; Kara Kuhn-Riordon, MD; David Mills, PhD; Mark Underwood, MD

Background: CPAP is commonly used to treat Respiratory Distress Syndrome (RDS), pneumonia and meconium aspiration. This continuous positive airway pressure (CPAP) however, leads to the common side effect of gaseous abdominal distension. Whether “CPAP belly” alters the intestinal microbiota in premature infants is unknown. Distal intestinal microbiota differs between healthy term and preterm infants. In term infants, their microbiota is dominated by strict anaerobes like Bifidobacteria, Lactobacilli and Clostridia. However in a Preterm infant facultative anaerobe Enterobacteriaceae predominates which often precedes necrotizing enterocolitis and sepsis.

Methods: A single center cohort study of infants with gestational age >33 weeks and <1500g fecal samples were collected twice weekly. Gene sequencing of 16S rRNA in fecal samples from 15 infants who received CPAP for 4 or more days (15 samples) and from 15 infants not receiving CPAP therapy (15 samples). The comparison groups were matched by DOL. Alpha diversity (AD) was measured using the Shannon Index and was normally distributed (Shapiro-Wilks p=0.25); an unpaired t-test was used to analyze for group difference. Beta diversity (BD) was measured using Bray-Curtis and PERMANOVA plotted into NMDS between the two groups. P>0.05 was considered statistically significant.

Results: Among 41 infants in the cohort, those receiving <4 days of CPAP were more preterm, smaller, had greater incidence of bronchopulmonary dysplasia and longer hospital stays versus infants not receiving CPAP. AD is a measure of diversity within a community (e.g. how many different species are present). There were no differences between groups in AD as p=0.15. BD measures similarity between communities. There were no differences between groups in BD as p=0.64. At the family level the dominant bacteria did not differ in relative abundance between matched individual samples. The probiotic administered had a greater effect than CPAP.

Conclusions: Significant differences were discovered in key confounders (gestational age and degree of illness) between groups requiring an alternative analytical approach (matching of infants with a resultant decrease in numbers of samples). Pilot studies are useful for sample size calculations. Based on these data, to demonstrate a significant decrease in AD with CPAP would require a sample size of 70 in each group (assuming alpha 0.05 and power 0.90).

Resident Statement of Involvement: Discussion with Dr. Underwood regarding microbiota interest, selected study question. Created Access DB from raw study data, extracted EMR data for ~70 infants including each protracted course in NICU and respiratory support throughout each infants stay. Compiled the data, produced report of results.