Sexually Dimorphic Associations between Maternal Factors and Human Milk Hormonal Concentrations

Abstract

While human milk composition is characterised by marked dynamicity, we are far from having a clear picture of what factors drive this variation. Hormones in human milk are known to vary according to specific maternal phenotypes, but limited evidence shows the infant also has a role in determining milk composition. The present study aimed to investigate the interplay between maternal and infant characteristics in relation to human milk hormonal profile. In total, 501 human milk samples from mothers recruited in the Finnish STEPS cohort study (Steps to the healthy development) were analysed. Pre-pregnancy and pregnancy maternal data, socioeconomic status and infant characteristics at birth were collated. Leptin, adiponectin, insulin-like growth factor-1 and cyclic Glycine-Proline in milk were measured. Multivariate analysis of variance (MANOVA) and linear regression were utilised for statistical analysis. Sex-specific interactions with maternal factors were observed, as the infant sex mediated associations between gestational diabetes and milk adiponectin (p = 0.031), birth-mode and total protein (p = 0.003), maternal education and insulin-like growth factor-1: cyclic Glycine-Proline ratio (p = 0.035). Our results suggest that changes in human milk composition are associated with interactions between maternal and infant characteristics and pathophysiological factors. Future work should expand on these findings and further explore the link between hormonal profiles in human milk and infant outcomes.

Cholinergic-pathway-weakness-associated pancreatic islet dysfunction: a low-protein-diet imprint effect on weaned rat offspring

“…9,29 Additionally, sex dimorphism in regard to human milk composition has been shown to be associated with maternal and infant characteristics as well pathophysiological factors. 28 Although measurements were performed only 1 week after the maternal low-protein diet exposure, in the present study, the male weaned LP rats did not show changes in corticosterone plasma levels. High levels and/or local action of glucocorticoids in early life (cortisol 30,31 in humans and corticosterone 32 in rodents) have been shown to programme, among other diseases, metabolic malfunction later in life 4,33 .…”

“…Human milk adiponectin levels have been shown to change in a sex-dependent manner, where milk from gestational diabetic women presented higher adiponectin in mothers of female babies than in mothers of male babies. 28 In addition, we identified a reduced tonus of the superior vagus nerve and a decreased insulinotropic response by muscarinic potentiation and the insulinotropic role of M3mAChR in dysfunctional pancreatic islets from male weaned LP rats, as depicted in the schematic in Fig. 5.…”

Growth Factor Concentrations in Human Milk Are Associated With Infant Weight and BMI From Birth to 5 Years

“…This study utilizes HM samples obtained from 501 mothers and 507 children participating in the Finnish longitudinal cohort, Steps to healthy development of Children (the STEPS Study) between 2008 and 2010, as described previously (40). HM samples from consenting mothers were collected 2.6 ± 0.4 months after birth by manual expression in the morning, from a single breast, as detailed previously (41).…”

“…HM analysis was undertaken in 2018 as described previously (40). In brief, leptin, adiponectin and IGF-1 in HM were analyzed using commercially available ELISA kits (human sensitive leptin ELISA, human adiponectin ELISA, human IGF-1 ELISA, Mediagnost, Germany), while cGP was analyzed via liquid chromatography tandem mass spectrometry (LC-MS).…”

“…In a recent study we reported on the association between HM concentrations of adiponectin, leptin, IGF-1 and cGP with maternal-infant characteristics in the STEPS cohort (40). We identified significant differences in the concentrations of HM-borne total protein, IGF-1, leptin and adiponectin across mother-infant dyads, particularly in association with maternal/perinatal/infant characteristics including pre-pregnancy BMI, maternal education, birth mode, gestational diabetes (GDM), and infant sex.…”