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Personalized Profiling Reveals Donor- and Lactation-Specific Trends in the Human Milk Proteome and Peptidome.
Zhu, J, Dingess, KA, Mank, M, Stahl, B, Heck, AJR
The Journal of nutrition. 2021;(4):826-839
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Abstract
BACKGROUND Human milk is the most genuine form of personalized nutrition, whereby its nutritional and bioactive constituents support the changing needs of the growing infant. Personalized proteome profiling strategies may provide insights into maternal-infant relationships. Proteins and endogenous peptides in human milk play an important role as nutrients for growth and have distinct functionality such as immune defense. Comprehensive monitoring of all of the human milk proteinaceous components, including endogenous peptides, is required to fully understand the changing role of the human milk proteome throughout lactation. OBJECTIVE We aimed to investigate the personalized nature of the human milk proteome and peptidome for individual mother-infant dyads. METHODS Two individual healthy milk donors, aged 29 and 32 y and both of a normal BMI, were longitudinally observed over weeks 1, 2, 3, 4, 6, 8, 10, 12, and 16 postpartum. Milk collection was standardized. Comprehensive variations in the human milk proteinaceous components were assessed using quantitative LC-MS/MS methods. RESULTS We longitudinally profiled the concentrations of >1300 milk proteins and 2000 endogenous milk peptides spanning 16 wk of lactation for 2 individual donors. We observed many gradual and alike changes in both donors related to temporal effects, for instance early lactation was marked by high concentrations of proteins and peptides involved in lactose synthesis and immune development. Uniquely, in 1 of the 2 donors, we observed a substantial anomaly in the milk composition, exclusively at week 6, likely indicating a response to inflammation and/or infection. CONCLUSIONS Here, we provide a resource for characterizing the lactational changes in the human milk proteome, encompassing thousands of proteins and endogenous peptides. Further, we demonstrate the feasibility and benefit of personalized profiling to monitor the influence of milk on the development of the newborn, as well as the health status of each individual mother-infant pair.
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The Optimal Prepregnancy Body Mass Index for Lactation in Japanese Women with Neonatal Separation as Analyzed by a Differential Equation.
Tada, K, Miyagi, Y, Nakamura, K, Yorozu, M, Fukushima, E, Kumazawa, K, Nakamura, M, Kageyama, M
Acta medica Okayama. 2021;(1):63-69
Abstract
We used a differential equation to identify the biological relationship between the maternal prepregnancy body mass index (BMI) and lactation on postpartum day 4 in Japanese women with neonatal separation. This retro-spective observational study included 252 mothers (135 primiparas, 117 multiparas) whose singleton neonates were admitted to a neonatal ICU. We formulated hypotheses based on breast anatomy to analyze the relation-ship between the expressed milk obtained on postpartum day 4 and the maternal prepregnancy BMI with the following differential equation: y'(x) = k y(x)/x, where k is the constant, x is the prepregnancy BMI, and y is the expressed milk volume. The formula was then obtained as y(x) = axk, where a is the constant. The Akaike information criterion (AIC) was used to estimate the regression equation with the maximum likelihood for primiparas and multiparas. The best criteria for BMI determined by the AIC were 20.89 kg/m2 in primiparas and 20.19 kg/m2 in multiparas. These were the optimal BMI values for lactation, coinciding with the median prepregnancy BMI in the study population (20.78 kg/m2 in primiparas and 20.06 kg/m2 in multiparas). The formula based on biomathematics might help establish the biological relationship between prepregnancy BMI and breastmilk volume.
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Human milk immunomodulatory proteins are related to development of infant body composition during the first year of lactation.
Gridneva, Z, Lai, CT, Rea, A, Tie, WJ, Ward, LC, Murray, K, Hartmann, PE, Geddes, DT
Pediatric research. 2021;(4):911-921
Abstract
BACKGROUND To investigate relationships between infant body composition (BC) and human milk (HM) immunomodulatory proteins (IMPs) during the first 12 months of lactation. METHODS BC of breastfeeding dyads (n = 20) was measured with ultrasound skinfolds (infants) and bioimpedance spectroscopy (infants/mothers) at 2, 5, 9, and/or 12 months post partum. Breastfeeding frequency, 24-h milk intake, and IMP concentrations (lactoferrin, lysozyme, secretory immunoglobulin A (sIgA)) were measured, and calculated daily intakes (CDIs) were determined. We used linear regression/mixed-effects models and adjusted results for multiple comparisons. RESULTS No associations were seen between maternal characteristics and IMP concentrations/CDIs or between IMP concentrations and infant BC. Lactoferrin CDI was negatively associated with infant fat-free mass index (P = 0.002); lysozyme CDI was positively associated with infant fat mass (P = 0.004) and fat mass index (P = 0.004) measured with ultrasound skinfolds. CONCLUSION In this small cohort of infants breastfed on demand during first year of life, we report differential associations of HM IMPs with infant BC, showing that in addition to their critical role in shaping infant immunity, lactoferrin, and lysozyme also influence development of infant BC, highlighting the importance of breastfeeding for 12 months and beyond. IMPACT HM IMPs (concentrations and, most importantly, daily intakes) time-dependently and differentially associate with development of infant lean mass and adiposity during first 12 months of lactation. There is no information on how intakes and concentrations of these components affect development of infant BC. HM contains IMPs-lactoferrin, lysozyme, and sIgA, which not only play a critical role in shaping infant's immunity, but also influence infant growth and development of BC, highlighting the importance of breastfeeding for 12 months and beyond and warranting careful consideration of the dose effects of supplemented formula.
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Risk Factors for Delayed Onset of Lactogenesis II Among Primiparous Mothers from a Brazilian Baby-Friendly Hospital.
Rocha, BO, Machado, MP, Bastos, LL, Barbosa Silva, L, Santos, AP, Santos, LC, Ferrarez Bouzada, MC
Journal of human lactation : official journal of International Lactation Consultant Association. 2020;(1):146-156
Abstract
BACKGROUND Low milk supply is frequently reported as a reason for exclusive breastfeeding cessation. RESEARCH AIMS To determine the occurrence of, and the risk factors associated with, delayed onset of lactogenesis II among primiparas seen at a Baby-Friendly Hospital in Brazil. METHOD We conducted a prospective longitudinal observational cohort study of 224 primiparas who had a singleton delivery. Data were first collected at the hospital. We assessed the onset of lactogenesis on day four postpartum, based on maternal reports of changes in breast fullness. Breastfeeding practices and Edinburgh Postnatal Depression Scale were evaluated on day seven postpartum. Using Poisson regression, we assessed significant factors associated with delayed onset of lactogenesis II. RESULTS Delayed lactogenesis II occurred in 18.8% (n = 42) of participants and was significantly associated with alcohol drinking during pregnancy (IRR = 2.710, 95% CI [1.469, 4.996]); Edinburgh Postnatal Depression Scale scores ≥ 10 (IRR = 2.092, 95% CI [1.118, 3.916]), and the age of the mother (IRR: 1.081, 95% CI [1.039, 1.125]). CONCLUSION Postpartum depression and alcohol ingestion during pregnancy may be associated with lactogenesis II delay, but more research is needed to elucidate the directionality of these relationships. Older mothers are at risk of delayed lactogenesis II onset. The frequency of delayed lactogenesis in this population is similar to the rates seen in previous Latin America studies and much lower than the ranges seen in North America, possibly because of the low proportion of obesity and severe gestational diabetes in this sample.
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Association of Maternal Secretor Status and Human Milk Oligosaccharides With Milk Microbiota: An Observational Pilot Study.
Cabrera-Rubio, R, Kunz, C, Rudloff, S, García-Mantrana, I, Crehuá-Gaudiza, E, Martínez-Costa, C, Collado, MC
Journal of pediatric gastroenterology and nutrition. 2019;(2):256-263
Abstract
BACKGROUND AND OBJECTIVES Breast milk contains several bioactive factors including human milk oligosaccharides (HMOs) and microbes that shape the infant gut microbiota. HMO profile is determined by secretor status; however, their influence on milk microbiota is still uncovered. This study is aimed to determine the impact of the FUT2 genotype on the milk microbiota during the first month of lactation and the association with HMO. METHODS Milk microbiota from 25 healthy lactating women was determined by quantitative polymerase chain reaction and 16S gene pyrosequencing. Secretor genotype was obtained by polymerase chain reaction-random fragment length polymorphisms and by HMO identification and quantification. RESULTS The most abundant bacteria were Staphylococcus and Streptococcus, followed by Enterobacteriaceae-related bacteria. The predominant HMO in secretor milk samples were 2'FL and lacto-N-fucopentaose I, whereas non-secretor milk was characterized by lacto-N-fucopentaose II and lacto-N-difucohexaose II. Differences in microbiota composition and quantity were found depending on secretor/non-secretor status. Lactobacillus spp, Enterococcus spp, and Streptococcus spp were lower in non-secretor than in secretor samples. Bifidobacterium genus and species were less prevalent in non-secretor samples. Despite no differences on diversity and richness, non-secretor samples had lower Actinobacteria and higher relative abundance of Enterobacteriaceae, Lactobacillaceae, and Staphylococcaceae. CONCLUSIONS Maternal secretor status is associated with the human milk microbiota composition and is maintained during the first 4 weeks. Specific associations between milk microbiota, HMO, and secretor status were observed, although the potential biological impact on the neonate remains elusive. Future studies are needed to reveal the early nutrition influence on the reduction of risk of disease.
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Changes in Human Milk Fatty Acid Composition During Lactation: The Ulm SPATZ Health Study.
Siziba, LP, Lorenz, L, Stahl, B, Mank, M, Marosvölgyi, T, Decsi, T, Rothenbacher, D, Genuneit, J
Nutrients. 2019;(12)
Abstract
The lipid fraction of human milk provides the infant with the fatty acids that are necessary for optimal growth and development. The aim of this study was to investigate the fatty acid composition of human milk at three time points during lactation and its change over time using appropriate statistical methods. Human milk samples from breastfeeding mothers at 6 weeks (n = 706), 6 months (n = 483), and 12 months (n = 81 with all three time points) were analyzed. Centered log-ratio (clr) transformation was applied to the fatty acid data. Principal component analysis (PCA) and generalized linear model-based repeated measure analysis were used to assess changes over time. The total lipid content was significantly higher at 6 months (β = 0.199, p < 0.029) and 12 months of lactation (β = 0.421, p < 0.001). The constituents of C20:3n-6 and C20:3n-3 were lower at 6 months (p < 0.001). Four distinct sub-compositional fatty acid groups were only identified at 12 months of lactation. The inclusion of small fatty acids of small constituent size in the analysis resulted in a shift in the balance between fatty acid constituents. Human milk fatty acid composition during prolonged lactation is different from that of human milk during a short duration of lactation. Our findings support the hypothesis that a combination of multiple fatty acids is important in fatty acid profiling beyond the presentation of individual fatty acids. Furthermore, the high variability of small fatty acids warrants attention because a compositional analysis may show more pronounced changes.
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Effects of daytime versus night-time cesarean deliveries on Stage II lactogenesis.
İlhan, G, Atmaca, FV, Çümen, A, Zebitay, AG, Güngör, ES, Karasu, AFG
The journal of obstetrics and gynaecology research. 2018;(4):717-722
Abstract
AIM: The circadian timing system has a rhythm and one of the roles of this system is the mediation of hormonal and metabolic adaptations to lactation. This study was conducted to determine whether the time to stage II lactogenesis differed in women who underwent cesarean section (CS) in the daytime (DT) or night-time (NT). METHODS This study was conducted at Süleymaniye Research and Education Hospital between June and December 2016. Two hundred and eighty-eight mothers who had a cesarean delivery and their healthy singleton neonates were included. Clinical and demographic data of the mothers and neonates, time of initiation of breastfeeding and time to stage II lactogenesis were analyzed according to DT or NT CS groups. RESULTS There were no statistically significant differences in age, gravida, parity, body mass index, week of gestation at birth, postoperative hemoglobin level, cesarean indications, anesthesia type, previous history of breastfeeding, transfusion need, Apgar scores or birth weight-height of neonates between the DT and NT CS groups. While the time of initiation of breastfeeding did not differ statistically in terms of DT or NT CS groups, the time to stage II lactogenesis was significantly longer in the NT CS group. CONCLUSIONS NT cesarean delivery is a risk factor for the delayed onset of lactogenesis. The results of this study may be useful to clinical practitioners counseling mothers who undergo NT cesarean delivery.
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Obesity as a Predictor of Delayed Lactogenesis II.
Preusting, I, Brumley, J, Odibo, L, Spatz, DL, Louis, JM
Journal of human lactation : official journal of International Lactation Consultant Association. 2017;(4):684-691
Abstract
BACKGROUND Lactogenesis II is the onset of copious milk production. A delay in this has been associated with an increased risk of formula supplementation and early cessation of breastfeeding. Prepregnancy obesity has also been associated with decreased breastfeeding rates and early cessation. Research aim: This study aimed to evaluate the effect of prepregnancy obesity on self-reported delayed lactogenesis II. METHODS We conducted a prospective observational cohort study of 216 women with a singleton pregnancy and who planned to breastfeed. We compared the onset of lactogenesis II between women with a body mass index (BMI) < 30 kg/m2 and women with a BMI ≥ 30 kg/m2. Using multivariate logistic regression analyses, we assessed the relationship between maternal BMI and delay of lactogenesis II. RESULTS The prevalence of delayed lactogenesis II among women with prepregnancy BMI < 30 kg/m2 and BMI ≥ 30 kg/m2 was 46.4% and 57.9%, respectively. Delayed lactogenesis II occurred more frequently among women who were obese at the time of delivery ( p < .05). After controlling for the covariates, age, prepregnancy BMI, and gestational weight gain were positively associated with delayed lactogenesis II. CONCLUSION Prepregnancy obesity and excessive gestational weight gain are associated with an increased risk of delayed lactogenesis II. Women who are at risk for delay in lactogenesis II and early breastfeeding cessation will need targeted interventions and support for them to achieve their personal breastfeeding goals.
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ABM Clinical Protocol #20: Engorgement, Revised 2016.
Berens, P, Brodribb, W
Breastfeeding medicine : the official journal of the Academy of Breastfeeding Medicine. 2016;(4):159-63
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Abstract
A central goal of The Academy of Breastfeeding Medicine is the development of clinical protocols for managing common medical problems that may impact breastfeeding success. These protocols serve only as guidelines for the care of breastfeeding mothers and infants and do not delineate an exclusive course of treatment or serve as standards of medical care. Variations in treatment may be appropriate according to the needs of an individual patient.
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Are Prolactin Levels Linked to Suction Pressure?
Zhang, F, Xia, H, Shen, M, Li, X, Qin, L, Gu, H, Xu, X
Breastfeeding medicine : the official journal of the Academy of Breastfeeding Medicine. 2016;:461-468
Abstract
BACKGROUND Suction pressure has been reported to be a key driving force of lactation. An infant's sucking at its mother's breasts is the major stimulus to post-natal prolactin (PRL) secretion, and PRL is the essential hormone for lactation and milk production. It is unknown what role suction pressure has in PRL secretion and milk supply postnatally. OBJECTIVES To explore the relationship between the suction pressure, PRL level, lactation, and milk supply in breastfeeding mother-infant dyads. METHODS Healthy women with normal full-term infants were enrolled (n = 122). Data collection included suction pressure, PRL level, and the mother's perception of both the onset of her lactation and her milk supply at 1 month. Suction pressure was measured with a pressure sensor connected to a tube placed alongside the nipple. The chemiluminescence method was used to quantify maternal serum PRL level both before and after a breastfeed to explore the effect of suckling on PRL increment. The mother's perception of the onset of her lactation was evaluated by the mother's sense of fullness in her breast. The mother's perception of milk supply was evaluated by using the H&H Lactation Scale. RESULTS Data from 117 participants were included in this analysis. Low suction pressure, a shorter gestational age, a high pre-gestational body mass index (BMI), and high infant birth weight were associated with a smaller than average PRL increment. High suction pressure, longer sucking duration, and a low gestational weight gain were related to a mother's perception of an earlier onset of her lactation. However, low suction pressure, a high frequency of giving formula, a small PRL increment, and the mother's perception of a later onset of her lactation were correlated with her perception of an insufficient milk supply. CONCLUSIONS Suction pressure varied directly with the post-natal PRL increment. Suction pressure was associated with the timing of the mother's perception of her lactation. Strong suction pressure by the infant is likely to enhance the mother's confidence in her lactation. Additionally, sucking duration, frequency of giving formula, maternal BMI, and infant birth weight played a role in early breastfeeding success.