Human milk cortisol and immune factors over the first three postnatal months: Relations to maternal psychosocial distress.

BACKGROUND: Many biologically active factors are present in human milk including proteins, lipids, immune factors, and hormones. The milk composition varies over time and shows large inter-individual variability. This study examined variations of human milk immune factors and cortisol concentrations in the first three months post-partum, and their potential associations with maternal psychosocial distress. METHODS: Seventy-seven healthy mothers with full term pregnancies were enrolled, of which 51 mothers collected morning milk samples at 2, 6 and 12 weeks post-delivery. Maternal psychosocial distress was assessed at 6 weeks post-delivery using questionnaires for stress, anxiety, and depressive symptoms. Immune factors were determined using multiplex immunoassays and included innate immunity factors (IL1ß, IL6, IL12, IFNγ, TNFα), acquired immunity factors (IL2, IL4, IL10, IL13, IL17), chemokines (IL8, Groα, MCP1, MIP1ß), growth factors (IL5, IL7, GCSF, GMCSF, TGFß2) and immunoglobulins (IgA, total IgG, IgM). Cortisol was quantified using liquid chromatography-tandem mass spectrometry. A linear mixed effects model was fit to test whether stress, anxiety, and depressive symptoms individually predicted human milk cortisol concentrations after accounting for covariates. Repeated measurement analyses were used to compare women with high (n = 13) versus low psychosocial distress (n = 13) for immune factors and cortisol concentrations. RESULTS: Virtually all immune factors and cortisol, with the exception of the granulocyte-macrophage colony-stimulating factor (GMCSF), were detected in the human milk samples. The concentrations of the immune factors decreased during the first 3 months, while cortisol concentrations increased over time. No correlation was observed between any of the immune factors and cortisol. No consistent relationship between postnatal psychosocial distress and concentrations of immune factors was found, whereas higher psychosocial distress was predictive of higher cortisol concentrations in human milk. CONCLUSION: In the current study we found no evidence for an association between natural variations in maternal distress and immune factor concentrations in milk. It is uncertain if this lack of association would also be observed in studies with larger populations, with less uniform demographic characteristics, or with women with higher (clinical) levels of anxiety, stress and/or depressive symptoms. In contrast, maternal psychosocial distress was positively related to higher milk cortisol concentrations at week 2 post-delivery. Further investigation on maternal psychosocial distress in relation to human milk composition is warranted.

The association between breastmilk oligosaccharides and faecal microbiota in healthy breastfed infants at two, six, and twelve weeks of age.

Several factors affect gut microbiota development in early life, among which breastfeeding plays a key role. We followed 24 mother-infant pairs to investigate the associations between concentrations of selected human milk oligosaccharides (HMOs) in breastmilk, infant faeces, and the faecal microbiota composition in healthy, breastfed infants at two, six and 12 weeks of age. Lactation duration had a significant effect on breastmilk HMO content, which decreased with time, except for 3-fucosyllactose (3FL) and Lacto-N-fucopentaose III (LNFP III). We confirmed that microbiota composition was strongly influenced by infant age and was associated with mode of delivery and breastmilk LNFP III concentration at two weeks, with infant sex, delivery mode, and concentrations of 3'sialyllactose (3'SL) in milk at six weeks, and infant sex and Lacto-N-hexaose (LNH) in milk at 12 weeks of age. Correlations between levels of individual breastmilk HMOs and relative abundance of OTUs found in infant faeces, including the most predominant Bifidobacterium OTUs, were weak and varied with age. The faecal concentration of HMOs decreased with age and were strongly and negatively correlated with relative abundance of OTUs within genera Bifidobacterium, Parabacteroides, Escherichia-Shigella, Bacteroides, Actinomyces, Veillonella, Lachnospiraceae Incertae Sedis, and Erysipelotrichaceae Incertae Sedis, indicating the likely importance of these taxa for HMO metabolism in vivo.

Human Milk Microbiome and Maternal Postnatal Psychosocial Distress.

Human milk contains many bioactive components, including bacteria, which are transferred to the developing infant through breastfeeding. Milk bacteria appear to, amongst others, originate from the maternal gut. A mother's postnatal psychosocial distress may alter maternal gut microbiota, which in turn may affect the bacteria present in milk. The aim of this study was to explore whether maternal postnatal psychosocial distress was related to alterations in the relative abundances of specific bacteria and to milk microbial diversity. Healthy mothers (N = 77; N = 51 with complete data) collected breast milk samples at 2, 6, and 12 weeks postpartum and filled in mood questionnaires on experienced stress, anxiety, and depressive symptoms at 6 weeks postpartum. A metataxonomic approach (16S rRNA gene sequencing (region V3 and V4) using Illumina MiSeq technology) was used to assess bacterial abundances and diversity. For the group as a whole, an increase in diversity of the milk bacterial community was observed during the first 3 months of breastfeeding (Shannon index). This general increase in diversity appears to be explained by an increase of Lactobacillus and other minor genera, together with a decrease in Staphylococcus. With respect to psychological distress and milk microbial composition, no significant differences in the relative abundance of major bacterial genera were detected between women with high (N = 13) and low (N = 13) psychosocial distress. However, progressive and distinct changes in the content of Firmicutes, Proteobacteria, and Bacteroidetes at the phylum level and Acinetobacter, Flavobacterium, and Lactobacillus at the genera level were observed in milk samples of women with low psychosocial distress. With respect to milk microbial diversity, high maternal psychosocial distress, compared to low maternal psychosocial distress, was related to significantly lower bacterial diversity in milk at 3 months post-delivery. Anxiety, stress, and depressive symptoms separately were unrelated to specific bacterial profiles. The current study suggests a potential relation between maternal psychosocial distress and milk microbiota, providing first evidence of a possible mechanism through which post-partum psychological symptoms may affect infant development and health.

The effect of prebiotic fortified infant formulas on microbiota composition and dynamics in early life.

Gastrointestinal (GI) microbiota composition differs between breastfed and formula-fed infants. Today's infant formulas are often fortified with prebiotics to better mimic properties of human milk with respect to its effect on GI microbiota composition and function. We used Illumina HiSeq sequencing of PCR-amplified 16S rRNA gene fragments to investigate the composition of faecal microbiota in 2-12 week old infants receiving either breastmilk, infant formulas fortified with prebiotics, or mixed feeding. We compared these results with results from infants fed traditional formulas used in the Netherlands in 2002-2003, which contained no added prebiotics. We showed that today's formulas supplemented with either scGOS (0.24-0.50 g/100 ml) or scGOS and lcFOS (at a 9:1 ratio; total 0.6 g/100 ml) had a strong bifidogenic effect as compared to traditional formulas, and they also resulted in altered patterns of microbial colonisation within the developing infant gastrointestinal tract. We identified three microbial states (or developmental stages) in the first 12 weeks of life, with a gradual transition pattern towards a bifidobacteria dominated state. In infants receiving only fortified formulas, this transition towards the bifidobacteria dominated state was accelerated, whereas in infants receiving mixed feeding the transition was delayed, as compared to exclusively breastfed infants.

Prenatal and postnatal cortisol and testosterone are related to parental caregiving quality in fathers, but not in mothers.

Testosterone and cortisol have both been implicated in human parenting behavior. We investigated the relations between observed quality of caregiving during parent-child interactions and pre- and postnatal testosterone and cortisol levels, in both mothers (N = 88) and fathers (N = 57). Testosterone and cortisol were measured before and after interaction with an infant simulator (prenatal) and with their own child (postnatal) to index basal levels as well as steroid reactivity to the interaction. Our findings are that in fathers, interactions between cortisol and testosterone are related to quality of caregiving both pre- and postnatally. Prenatally there was a stronger negative relation between T and quality of caregiving in fathers with lower cortisol levels, and postnatally there was a stronger negative relation between cortisol and quality of caregiving in fathers high in testosterone levels. Furthermore, prenatal cortisol levels were related to paternal quality of caregiving during interaction with their own child. In mothers, no associations between quality of caregiving and our endocrine measures were observed. We interpret our findings in the context of hyperreactive physiological responses observed in parents at risk for insensitive caregiving, and in light of the dual-hormone hypothesis. The current findings contribute to the growing literature on the endocrine antecedents of human caregiving behavior.

Are cortisol concentrations in human breast milk associated with infant crying?

The present longitudinal study is the first to investigate the association between human breast milk cortisol and infant crying over the first three months of life. Higher concentrations of breast milk cortisol were expected to be differentially associated with fussing and crying in boys and girls. At 2, 6, and 12 weeks of infant age, mothers (N = 70) collected a morning sample of their milk and kept a 3-day diary to measure infant fussing and crying. Cortisol was extracted and quantified from milk samples. Results showed that breast milk cortisol concentrations increased from 2 weeks through 12 weeks of infant age. Milk cortisol was unrelated to the total duration, frequency, and bout length of infant fussing and crying for both boys and girls. Directions for future research aiming to extend our knowledge on the biology of milk cortisol in relation to infant behavior and development are discussed.

Young adults' reactions to infant crying.

AIM: To determine whether young childless adults show negative emotions and cognitive disturbances when listening to infant crying, compared to other disturbing noises, and whether negative emotions and cognitive disturbances are associated. METHODS: We tested the cognitive performances and emotional reactions of 120 childless participants on a working memory task while being subjected to different disturbing noises including infant crying. RESULTS: Participants had the least correct trials on the working memory task, and showed the most negative emotions, when hearing infant crying as compared to the other noises. Participants also showed less positive emotions when hearing infant crying as compared to working in silence. Overall, negative emotions were associated with less correct trials on the working memory task, except in the infant crying condition. Furthermore, cognitive performance and emotional reactions to infant crying were unrelated to personality characteristics. CONCLUSION: Negative emotions and cognitive disturbances may be general adult responses to infant crying that are not limited to parents. These results suggest a broadly present human emotional and cognitive response to infant crying, that may underlie a general predisposition to care for infants in distress.