Maternal and pregnancy-related factors affecting human milk cytokines among Peruvian mothers bearing low-birth-weight neonates

Abstract

Several cytokines have been detected in human milk but their relative concentrations differ among women and vary over time in the same person. The drivers of such differences have been only partially identified, while the effect of luminal cytokines in the fine-regulation of the intestinal immune system is increasingly appreciated. The aim of this study was to investigate the associations between obstetrical complications and human milk cytokine profiles in a cohort of Peruvian women giving birth to Low Birth Weight (LBW) infants. Colostrum and mature human milk samples were collected from 301 Peruvian women bearing LBW infants. The concentration of twenty-three cytokines was measured using the Luminex platform. Ninety-nine percent of women had at least one identified obstetrical complication leading to intra-uterine growth restriction and/or preterm birth. Median weight at birth was 1,420 grams; median gestational age 31 weeks. A core of 12 cytokines, mainly involved in innate immunity and epithelial cell integrity, was detectable in most samples. Maternal age, maternal infection, hypertensive disorders, preterm labor, and premature rupture of membranes were associated with specific cytokine profiles both in colostrum and mature human milk. Mothers of Very LBW (VLBW) neonates had significantly higher concentrations of chemokines and growth factor cytokines both in their colostrum and mature milk compared with mothers of larger neonates. Thus, maternal conditions affecting pregnancy duration and in utero growth are also associated with specific human milk cytokine signatures.

Breast Milk, a Source of Beneficial Microbes and Associated Benefits for Infant Health

“…In addition to providing correct nutrients required for energy, human milk provides many bioactive components and immune factors such as antibodies, immunoglobulins, lactoferrin, lysozyme, antimicrobial peptides, growth factors, white blood cells, microRNAs, and human milk oligosaccharides (HMOs) which play a vital role in boosting the developing infant immune system and providing defence against pathogens [72]. It has been reported that colostrum contains higher levels of immunoglobulins, cytokines, and immune cells when compared to mature milk [73][74][75]. Bioactive compounds in milk come from numerous sources, many are produced and secreted by the mammary epithelium and cells in milk while others are transferred across the mammary epithelium by receptor-mediated transport from maternal serum [76,77].…”

“Omics” in Human Colostrum and Mature Milk: Looking to Old Data with New Eyes

“…Furthermore, interest in cytokines and chemokines in HC content is increasing, especially to clarify which maternal or pregnancy-related factors can influence their concentrations [ 2 , 53 , 54 , 55 , 56 , 57 ]. The very recent study of Zambruni et al [ 2 ], even if conducted on a peculiar population of mothers ( n = 223 Peruvian mothers living in resource-limited conditions and giving birth to low birth weight neonates (LBW)), pointed out that the course of pregnancy showed a great influence on HM composition at birth and during the first weeks of lactation, potentially influencing infant mucosal immunomodulation and clinical outcomes. In particular, 13 cytokines and chemokines related to innate immunity were highly represented in HC instead of in mature milk (MM) [ 2 ].…”

“…The very recent study of Zambruni et al [ 2 ], even if conducted on a peculiar population of mothers ( n = 223 Peruvian mothers living in resource-limited conditions and giving birth to low birth weight neonates (LBW)), pointed out that the course of pregnancy showed a great influence on HM composition at birth and during the first weeks of lactation, potentially influencing infant mucosal immunomodulation and clinical outcomes. In particular, 13 cytokines and chemokines related to innate immunity were highly represented in HC instead of in mature milk (MM) [ 2 ]. Lower levels of pro-inflammatory cytokines in HC have been associated with peripartum infections, spontaneous preterm delivery and VLBW neonates, especially those related to the immune system, which could protect the newborn against the mucosal invasion of pathogens.…”

“…Human Breast Milk (HM) is a complex biological fluid which is considered the best source for infant nutrition, until at least the first six months of life [ 1 , 2 , 3 , 4 ]; it contains proteins, lipids, sugars, immune cells and bioactive molecules providing nutrition and also exerting anti-inflammatory and anti-infective functions; moreover, HM also promotes the formation of a correct immune system and supports organ development [ 5 , 6 , 7 , 8 ].…”

“…HM antimicrobial and immunomodulatory factors can give passive immunity to breastfed neonates [ 7 , 8 , 10 ]. In colostrum, there are higher levels of immunoglobulins (Ig) instead of mature milk (MM), because of their passage between the interstitial spaces of mammary epithelium, whose junctions show progressive increase in tightness during milk maturation [ 7 , 11 ]; higher levels of cytokines and immune cells have also been demonstrated [ 2 , 12 , 13 ].…”