Gestational Diabetes Mellitus and Colostral Appetite-Regulating Adipokines.

Gestational diabetes mellitus (GDM) is a complex metabolic disorder that has short- and long-term effects on maternal and offspring health. This study aimed to assess the impact of maternal hyperglycemia severity, classified as GDM-G1 (diet treatment) and GDM-G2 (insulin treatment) on colostral appetite-regulating molecules. Colostrum samples were collected from hyperglycemic (N = 30) and normoglycemic (N = 21) mothers, and the concentrations of milk hormones were determined by immunoenzymatic assay. A difference was found for milk ghrelin, but not for molecules such as adiponectin, leptin, resistin, or IGF-I levels, in relation to maternal hyperglycemia. The colostral ghrelin in the GDM-G1 cohort (0.21 ng/mL) was significantly lower than for GDM-G2 (0.38 ng/mL) and non-GDM groups (0.36 ng/mL). However, colostral resistin was higher, but not significantly, for GDM-G1 (13.33 ng/mL) and GDM-G2 (12.81 ng/mL) cohorts than for normoglycemic mothers (7.89 ng/mL). The lack of difference in relation to hyperglycemia for milk leptin, adiponectin, leptin-adiponectin ratio, resistin, and IGF-I levels might be the outcome of effective treatment of GDM during pregnancy. The shift between ghrelin and other appetite-regulating hormones might translate into altered ability to regulate energy balance, affecting offspring's metabolic homeostasis.

Factors affecting total protein and lactoferrin in human milk.

The aim of this study was to investigate factors affecting total, true protein and lactoferrin (Lf) concentrations in human milk (HM) and to evaluate the changes in protein concentrations over the course of lactation (first to sixth month postpartum). HM samples were collected from exclusively breastfeeding mothers during six time periods (1-6 months postpartum); 198 breast milk samples were collected in total. The concentrations of total and true protein in HM were determined using the MIRIS human milk analyzer (HMA). The assessment of HM protein content was also performed in skim HM samples and quantified by bicinchoninic methods with the Bicinchoninic Acid Protein Assay Kit. In turn, Lf content in skim HM samples was determined by the enzyme-linked immunosorbent assay (ELISA) in accordance with a slightly modified procedure. In the first month of lactation total protein concentration was negatively correlated with maternal pre-pregnancy BMI (r = - 0.397; p = 0.022), whereas in the third month postpartum, positive correlation with maternal age was found (r = 0.399; p = 0.021). Considering Lf concentration, in the first month of lactation, it was positively correlated with baby's birth weight (r = 0.514; p = 0.002). In the next months (from second to sixth) no relationships between Lf concentration and maternal and infants' factors were observed. The concentration of protein and Lf in HM changes dynamically throughout lactation. Maternal and infant characteristics may impact the HM protein and Lf content, especially in the first month postpartum.

The Mother-Child Dyad Adipokine Pattern: A Review of Current Knowledge.

An important role in the network of interconnections between the mother and child is played by adipokines, which are adipose tissue hormones engaged in the regulation of metabolism. Alternations of maternal adipokines translate to the worsening of maternal insulin resistance as well as metabolic stress, altered placenta functions, and fetal development, which finally contribute to long-term metabolic unfavorable conditions. This paper is the first to summarize the current state of knowledge concerning the concentrations of individual adipokines in different biological fluids of maternal and cord plasma, newborn/infant plasma, milk, and the placenta, where it highlights the impact of adverse perinatal risk factors, including gestational diabetes mellitus, preeclampsia, intrauterine growth restriction, preterm delivery, and maternal obesity on the adipokine patterns in maternal-infant dyads. The importance of adipokine measurement and relationships in biological fluids during pregnancy and lactation is crucial for public health in the area of prevention of most diet-related metabolic diseases. The review highlights the huge knowledge gap in the field of hormones participating in the energy homeostasis and metabolic pathways during perinatal and postnatal periods in the mother-child dyad. An in-depth characterization is needed to confirm if the adverse outcomes of early developmental programming might be modulated via maternal lifestyle intervention.

Attitude and Level of COVID-19 Vaccination among Women in Reproductive Age during the Fourth Pandemic Wave: A Cross-Sectional Study in Poland.

COVID-19 vaccination, apart from the sanitary regime, is the most efficient strategy to limit the spread of the SARS-CoV-2 virus and significantly reduce the severity of the disease following infection. A cross-sectional survey was conducted during the fourth wave of the COVID-19 pandemic among pregnant Polish women and women who have already given birth to evaluate the level and attitude to vaccination. Briefly, 1196 women (256 pregnant and 940 mothers) participated in the study; 68.0% of pregnant women and 66.2% of mothers declared that they had received COVID-19 vaccination. The most frequently stated reasons not to get vaccinated were possible adverse effects on the mother, fetus or breastfed child, post-vaccination complications and limited scientific evidence on the safety of the COVID-19 vaccine. The identified predictors of avoiding COVID-19 vaccination are young age, residing in small cities or rural areas, cohabitation, low anxiety level regarding SARS-CoV-2 infection, and little knowledge concerning maternal vaccine-induced immune protection delivered to offspring. Despite the unlimited access to COVID-19 vaccination, the declared level of vaccination is worryingly low. The knowledge concerning the benefits of vaccination to mothers and their offspring is not satisfactory and requires urgent educational action, particularly among young women living outside big cities and single motherhood.

Fibronectin Molecular Status in Plasma of Women with Endometriosis and Fertility Disorders.

The diagnosis of endometriosis and fertility disorders is difficult; therefore, it is necessary to look for reliable biomarkers. Analysis of the molecular status of fibronectin as a key player in repair and wound healing processes, as well as in coagulation and fibrinolysis pathways, is justified. ELISA and SDS-agarose immunoblotting were applied to determine the fibronectin concentration and presence and occurrence of soluble FN-fibrin complexes in the blood plasma of women with endometriosis (n = 38), fertility disorders (n = 28) and the healthy group (n = 25). The concentration of fibronectin in the blood plasma of women with endometriosis (292.61 ± 96.17 mg/L) and fertility disorders (287.53 ± 122.68 mg/L) was significantly higher than in the normal group (226.55 ± 91.98 mg/L). The presence of FN-fibrin complexes of 750, 1000, 1300, 1600 and 1900 kDa in the plasma of women with endometriosis and fertility disorders was shown. The presence of FN-fibrin complexes with a molecular mass of more than 1300 kDa in women with endometriosis and infertility and the complete absence of these complexes in healthy women may indicate an increased and chronic activation of coagulation mechanisms in these patients. The presence of complexes of high molecular mass may be one of the biomarkers of fertility disorders in women.

Polish Women Have Moderate Knowledge of Gestational Diabetes Mellitus and Breastfeeding Benefits.

Gestational diabetes mellitus (GDM) is a multifaceted disease and is associated with complications for newborns and mothers. The aim of the study was to assess Polish women's knowledge concerning GDM and their attitude to breastfeeding. As a research tool, an anonymous online survey that included 33 questions, grouped into three main sections-sociodemographic and obstetric variables, risk factors for GDM and neonatal adverse outcomes, and knowledge about breastfeeding-was used and administered online. A total of 410 women aged from 18 to 45 participated in this study. Based on the survey, it was demonstrated that the women had moderate knowledge concerning the maternal risk factors and adverse neonatal outcomes associated with GDM and, additionally, the short- and long-term effects of breastfeeding. Significantly deeper knowledge about GDM, including breastfeeding by GDM mothers, was observed among hyperglycemic mothers in comparison to normoglycemic mothers. However, knowledge concerning the health benefits of breastfeeding was not related to the mothers' glycemic status. In conclusion, educational programs must include pre-pregnancy education of women and place emphasis on explaining the mechanism of development of GDM and the transformation of GDM to type 2 diabetes. This is crucial for changing the public's perception of GDM as a temporary, reversible clinical entity.

Lactoferrin and Immunoglobulin Concentrations in Milk of Gestational Diabetic Mothers.

Gestational diabetes mellitus (GDM) is associated with an increased risk of having a high-care newborn and has an impact on maternal wellbeing. This study aimed to assess the effect of GDM on the lactoferrin (LF), secretory immunoglobulin A (SIgA), immunoglobulin G (IgG), and immunoglobulin M (IgM) concentrations in early colostrum, colostrum, and transitional milk samples of hyperglycemic (n = 53) and normoglycemic (n = 49) mothers using enzyme-linked immunosorbent assay (ELISA). The concentrations of milk lactoferrin and SIgA, but not IgG and IgM, from hyperglycemic and normoglycemic mothers, showed a similar negative correlation with lactation from the first to the fifteenth day. Apart from early colostral IgG, there were no differences in concentrations of LF and immunoglobulins in milk from hyperglycemic and normoglycemic mothers. For hyperglycemia compensated by diet (GDM G1) or insulin treatment (GDM G2), slight differences were seen for LF and IgG, but not for SIgA and IgM, during an early stage of lactation only. Early colostral IgG and colostral LF of insulin-treated mothers were higher (10.01 ± 4.48 mg/L and 11.50 ± 0.58 g/L, respectively) than for diet-control diabetic mothers (7.65 ± 5.67 mg/L and 8.05 ± 1.38 g/L, respectively). GDM of mothers does not have a significant impact on immunological quality of early milk.

Changes in Human Milk Immunoglobulin Profile During Prolonged Lactation.

Mother's milk immunoglobulins (Igs) delivered to infants during breastfeeding are crucial in shaping and modulating immature infants' immune system and provide efficient protection against pathogens. The aim of the study was to evaluate the immunoglobulin concentrations in milk of 116 lactating mothers over prolonged lactation from the 1st to the 48th month using the ELISA method. The concentration of proteins, SIgA and IgG, but not IgM, showed a positive correlation (r = 0.69, p < 0.005; r = 0.54, p < 0.05; and r = 0.27, p < 0.05, respectively) with lactation from the 1st to the 48th month. The lowest concentrations of SIgA and IgG were observed for the first year (2.12 ± 0.62 g/L and 14.71 ± 6.18 mg/L, respectively) and the highest after the 2nd year of lactation (7.55 ± 7.16 g/L and 18.95 ± 6.76 mg/L, respectively). The IgM concentration remained stable during 2 years (2.81 ± 2.74 mg/L), but after 24 months it was higher (3.82 ± 3.05 mg/L), although not significantly. Moreover, negative correlations of protein (r = -0.24, p < 0.05) and SIgA (r = -0.47, p < 0.05) concentrations with the number of feedings were found. Human milk after the 2nd year of lactation contains significantly higher concentrations of protein, SIgA, and IgG. High concentration of immunoglobulins and protein during prolonged lactation is an additional argument to support breastfeeding even after introducing solid foods and should be one of the overarching goals in the protection of children's health.

The Impact of Dietary Fucosylated Oligosaccharides and Glycoproteins of Human Milk on Infant Well-Being.

Apart from optimal nutritional value, human milk is the feeding strategy to support the immature immunological system of developing newborns and infants. The most beneficial dietary carbohydrate components of breast milk are human milk oligosaccharides (HMOs) and glycoproteins (HMGs), involved in both specific and nonspecific immunity. Fucosylated oligosaccharides represent the largest fraction of human milk oligosaccharides, with the simplest and the most abundant being 2'-fucosyllactose (2'FL). Fucosylated oligosaccharides, as well as glycans of glycoproteins, as beneficial dietary sugars, elicit anti-adhesive properties against fucose-dependent pathogens, and on the other hand are crucial for growth and metabolism of beneficial bacteria, and in this aspect participate in shaping a healthy microbiome. Well-documented secretor status related differences in the fucosylation profile of HMOs and HMGs may play a key but underestimated role in assessment of susceptibility to fucose-dependent pathogen infections, with a potential impact on applied clinical procedures. Nevertheless, due to genetic factors, about 20% of mothers do not provide their infants with beneficial dietary carbohydrates such as 2'-FL and other α1,2-fucosylated oligosaccharides and glycans of glycoproteins, despite breastfeeding them. The lack of such structures may have important implications for a wide range of aspects of infant well-being and healthcare. In light of the above, some artificial mixtures used in infant nutrition are supplemented with 2'-FL to more closely approximate the unique composition of maternal milk, including dietary-derived fucosylated oligosaccharides and glycoproteins.

Lectin-Based Method for Deciphering Human Milk IgG Sialylation.

In light of the immunoprotective function of human milk and the incontestable impact of IgG glycosylation on its immune functions, characterization of the sialylation profile of human milk IgG is needed. Lectins as a molecular probe were applied in lectin-IgG-ELISA to analyze the sialylation and galactosylation pattern of skim milk IgG of mothers who delivered at term and prematurely. Well-defined biotinylated lectins were used: Maackia amurensis II (MAA II), Sambucus nigra (SNA), Ricinus communis I (RCA I), and Griffonia simplicifolia II (GSL II) specific to α2,3-Neu5Ac, α2,6-Neu5Ac, Gal(ß1,4)GlcNAc, and agalactosylated glycans, respectively. The sialylation pattern of milk IgG differs qualitatively and quantitatively from maternal plasma IgG and is related to lactation stage and perinatal risk factors. Expression of MAA-, SNA-, and GSL-reactive glycotopes on term milk IgG showed a positive correlation with milk maturation from days 1 to 55. Preterm birth was associated with an increase of MAA-reactive and a decrease of RCA-reactive IgG glycotopes. Moreover, higher SNA- and GSL-reactive and lower RCA-reactive glycoform levels of milk IgG were associated with infection of lactating mothers. Application of a specific and simple method, lectin-IgG-ELISA, reveals the sialylation pattern of milk IgG over milk maturation. However, further investigations are needed in this area.

Sialylated Oligosaccharides and Glycoconjugates of Human Milk. The Impact on Infant and Newborn Protection, Development and Well-Being.

Human milk not only has nutritional value, but also provides a wide range of biologically active molecules, which are adapted to meet the needs of newborns and infants. Mother's milk is a source of sialylated oligosaccharides and glycans that are attached to proteins and lipids, whose concentrations and composition are unique. Sialylated human milk glycoconjugates and oligosaccharides enrich the newborn immature immune system and are crucial for their proper development and well-being. Some of the milk sialylated oligosaccharide structures can locally exert biologically active effects in the newborn's and infant's gut. Sialylated molecules of human milk can be recognized and bound by sialic acid-dependent pathogens and inhibit their adhesion to the epithelial cells of newborns and infants. A small amount of intact sialylated oligosaccharides can be absorbed from the intestine and remain in the newborn's circulation in concentrations high enough to modulate the immunological system at the cellular level and facilitate proper brain development during infancy. Conclusion: The review summarizes the current state of knowledge on sialylated human milk oligosaccharides and glycoconjugates, discusses the significance of sialylated structures of human milk in newborn protection and development, and presents the advantages of human milk over infant formula.

Delivery-associated presence of supramolecular fibronectin-fibrin complexes in puerperal and cord plasma.

Objective: The variable fibronectin (FN) molecular forms are known to be engaged in coagulation and fibrinolysis pathways as well as tissue remodeling and repair processes. Some of them seem to be indispensable molecules within intensive biological processes associated with delivery. The aim of the study was to evaluate the FN molecular status in maternal and cord plasma after vaginal birth and cesarean section (C-section). Materials and methods: The study included nonpregnant women's plasma samples (n = 31) and puerperal and cord plasma samples collected from 49 mothers who delivered healthy newborns at term by vaginal birth (n = 25) and C-section (n = 24). The maternal and cord plasma FN concentrations and presence and relative ratios of different FN-fibrin complexes were determined by ELISA and sodium dodecyl sulfate (SDS) -agarose immunoblotting, respectively. Results: FN concentration in puerperal plasma after vaginal birth (232.08 ± 71.8 mg/L) and C-section (228.17 ± 71.2 mg/L) was significantly higher than in the plasma of nonpregnant women (190.00 ± 48.75 mg/L). In contrast, FN concentration in cord plasma of the C-section group (101.95 ± 30.3 mg/L) was significantly lower than that of the vaginal birth group (121.80 ± 22.2 mg/L). Immunoblotting of puerperal and cord plasma distinguished the most abundant dimeric plasma FN form, the 220-280-kDa FN degradation products and 750-1900-kDa FN-fibrin complexes, which occurred more frequently and in higher amounts in puerperal and cord plasma groups than the nonpregnant women group, although independently of the mode of delivery. Conclusions: Occurrence and relative amount of delivery-associated FN-fibrin complexes in both puerperal and cord plasmas might be bound with the physiological adaptive mechanisms reducing the risk of hemorrhage and intensive remodeling and repair processes after delivery.

Potential plasma biomarkers of bladder cancer identified by proteomic analysis: A pilot study.

BACKGROUND: Bladder cancer diagnosis and surveillance includes cystoscopy and cytology. New methods for the detection of bladder cancer are needed, because cystoscopy is invasive and expensive, and because urine cytology is not sensitive enough. OBJECTIVES: The aim of the study was to select potential plasma protein markers for bladder cancer which could be useful in developing a specific laboratory test to improve diagnosis and to establish treatment strategies in order to prevent the recurrence of the disease. MATERIAL AND METHODS: Plasma proteome maps were prepared based on 2-dimensional sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE), combined with image gel analysis and matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry of plasma samples from patients with urothelial bladder cancer, and they were compared to normal samples. RESULTS: The analyses of bladder cancer plasma samples allowed us to distinguish 3 groups of proteins whose relative abundance differed from that in normal samples. The 1st one comprised modified forms of plasma transferrin, fibrinogen gamma and complement C3b, which were absent in normal plasma. The 2nd group comprised haptoglobin, alpha-2-macroglobulin, vitamin D-binding protein, and pigment epithelium-derived factor, which occurred in the cancerous samples in large quantities. The 3rd group consisted of 3 molecular forms of immunoglobulin M (IgM), the relative abundance of which was significantly lower in the cancerous plasma samples. CONCLUSIONS: The data indicated potential plasma biomarkers associated with inflammation, immunity and coagulation processes accompanying bladder cancer. They could be used for the development of a laboratory test(s) useful in clinical practice.

Lectin-based analysis of fucosylated glycoproteins of human skim milk during 47 days of lactation.

Glycoproteins of human milk are multifunctional molecules, and their fucosylated variants are potentially active molecules in immunological events ensuring breastfed infants optimal development and protection against infection diseases. The expression of fucosylated glycotopes may correspond to milk maturation stages. The relative amounts of fucosylated glycotopes of human skim milk glycoproteins over the course of lactation from the 2(nd) day to the 47(th) day were analyzed in colostrums, transitional and mature milk samples of 43 healthy mothers by lectin-blotting using α1-2-, α1-6-, and α1-3-fucose specific biotinylated Ulex europaeus (UEA), Lens culinaris (LCA), and Lotus tetragonolobus (LTA) lectins, respectively. The reactivities of UEA and LCA with the milk glycoproteins showed the highest expression of α1-2- and α1-6-fucosylated glycotopes on colostrum glycoproteins. The level of UEA-reactive glycoproteins from the beginning of lactation to the 14(th) day was high and relatively stable in contrast to LCA-reactive glycoproteins, the level of which significantly decreased from 2-3 to 7-8 days then remained almost unchanged until the 12(th)-14(th) days. Next, during the progression of lactation the reactivities with both lectins declined significantly. Eighty percent of α1-2- and/or α1-6-fucosylated glycoproteins showed a high negative correlation with milk maturation. In contrast, most of the analyzed milk glycoproteins were not recognized or weakly recognized by LTA and remained at a low unchanged level over lactation. Only a 30-kDa milk glycoprotein was evidently LTA-reactive, showing a negative correlation with milk maturation. The gradual decline of high expression of α1-2- and α1-6-, but not α1-3-, fucoses on human milk glycoproteins of healthy mothers over lactation was associated with milk maturation.

[The significance of fucosylated glycoconjugates of human milk in nutrition of newborns and infants]. / Znaczenie fukozylowanych glikokoniugatów mleka ludzkiego w zywieniu noworodków i niemowlat.

Human milk is extremely complex secretion rich in biologically active glycoconjugates including free oligosaccharides, glycoproteins, glycolipids, and glycosaminoglycans. Alpha1-2-fucosylated glycoconjugates of human milk are component of the innate immune system and provide an additional defense for infants. Participation of fucosylated glycotopes in the inhibition of infections caused by some bacteria and/or viruses rely on blocking of lectin-receptors of pathogen. Free fucosylated glycoconjugates present in milk are recognized and bound by the lectin-receptors of bacteria and/or viruses, and prevent pathogens adhesion to host epithelial cells and development of infection. So far, the efficacy of fucosylated glycoconjugates of human milk in the inhibition of adhesion has been confirmed for Escherichia coli, Campylobacter jejuni, Salmonella enterica, Rotaviruses, HIV, and Noroviruses. In this process the secretor/nonsecretor status of mother plays an important role. This is particularly important for the women who are nonsecretors and whose milk does not contain α1-2-fucosylated glycoconjugates and has reduced anti-microbial properties. Fucosylated glycoconjugates of milk are also one of the energy sources for physiological bacterial flora (Bifidobacterium), and have a positive impact on the intestinal peristalsis, and indirectly stimulate the central nervous system of infants. Furthermore, compared to human milk, the content of fucosylated glycoconjugates of cow's milk is very low and does not provide adequate protection. This fact is particularly important in terms of nutrition and should be taken into consideration when artificial mixtures based on cows' milk are used. The paper presents the current state of knowledge on human milk glycoconjugates, particularly on α1-2-fucosylated free oligosaccharides and glycoproteins, and discusses the significance of fucosylated glycoconjugates of human milk in the nutrition of newborns and infants.