Inflammatory Markers in Mother’s Own Milk and Infant Stool of Very Low Birthweight Infants

Abstract

Background: Mother’s breastmilk is the gold standard for feeding preterm infants. Preterm delivery may be precipitated by inflammatory maternal states, but little is known about milk cytokine profiles and how they correlate with markers of infant gut inflammation (i.e., stool calprotectin) in this vulnerable population. Research Aim: To assess cytokines and inflammatory markers in milk from parents of very preterm infants over time as well as correlations between milk and infant’s stool calprotectin. Method: This is a secondary analysis of milk samples collected during OptiMoM, a triple-blind randomized clinical trial of infants born < 1250 g (NCT02137473). Longitudinally collected samples were analyzed for cytokines, choline, and inflammatory markers (C-reactive protein [CRP], IFN-γ, IL-10, IL-1β, IL-1ra, IL-6, IL-8, TNF-α). Infant stools were collected for longitudinal calprotectin analysis. Generalized estimating equations quantified longitudinal profiles of milk markers and stool calprotectin, their associations, and the correlation between free choline and C-reactive protein over follow-up. Result: Participants included 92 parents and infants (median weeks of gestation 27.3, median birth weight 845 g, and prevalence of male infants 45%). In all, 212 milk samples and 94 corresponding stool calprotectin levels were collected 1–11 weeks postpartum. C-reactive protein was present in much higher concentrations than other markers, and was highest in Week 1 postpartum. It decreased over time. IL-8 and free choline also changed over time while other markers did not. There was no correlation between any milk markers and stool calprotectin. Conclusion: Milk from mothers of very preterm infants has detectable inflammatory markers, some of which change over time. Research is needed to determine if infant outcomes are associated with these markers.

Associations of maternal inflammatory states with human milk composition in mothers of preterm infants

“…A total of 226 MOM samples were analyzed and grouped into six time points: weeks 1, 2, 3, 4, 7–8, and 10–11. Inflammatory marker levels over time have been previously reported for the cohort in general ( 15 ). Subject characteristics are shown in Table 1 —maternal co-morbidities and pro-inflammatory states were frequent, with a mean of 2.3 and a maximum of 5 inflammatory diagnoses per mother; every mother carried at least one inflammatory diagnosis.…”

“…To visualize the potentially nonlinear time profile of serial MOM inflammatory markers (log-transformed) and FA profiles, in keeping with our previous studies, we modeled the time effect using natural cubic splines and generalized estimating equations (GEEs) with an identity link function and independent working correlation matrix. The corresponding pointwise 95% confidence intervals (CIs) were estimated using a robust sandwich estimator ( 15 ). Cytokines, CRP, and free choline were log-transformed; FAs were reported as percentages in the original data; FA values were multiplied by 100 to compensate for the large differences in units.…”

“…FAs studied included omega-6:omega-3 ratio, docosahexaenoic acid (DHA), arachidonic acid (ARA), linoleic acid, monounsaturated FAs, and saturated FAs. This was a preplanned analysis of a larger exploratory study ( 15 ) describing longitudinal cytokine and other inflammatory marker profiles in MOM from mothers of preterm infants.…”