No role of the third-trimester inflammatory factors in the association of gestational diabetes mellitus with postpartum cardiometabolic indicators.

BACKGROUND: The influence of gestational diabetes mellitus (GDM) on postpartum cardiometabolic indicators is primarily restricted to glucose and lipid metabolism, however the indicators for liver and kidney function have been rarely explored, and the role of the third-trimester inflammatory factors in these associations has never been investigated. METHODS: Based on the Ma'anshan birth cohort (MABC), women with or without GDM history were selected and invited to participate in a 6-year postpartum follow-up. The fasting blood samples were collected to measure 16 comprehensive metabolic indicators during a 6-year postpartum follow-up: fasting plasma glucose (FPG), glycosylated hemoglobin (HbA1c), triglycerides (TG), total cholesterol (TC), uric acid (UA), blood urea nitrogen (BUN), serum creatinine (SCR), etc. Seven inflammatory factors, including TNF-α, IFN-γ, IL-1ß, IL-6, IL-10, IL-12p70, and IL-17 A, were measured with serum samples collected during the third trimester of pregnancy. Linear regression models were used to analyze the associations between GDM and 6-year postpartum metabolic indicators, GDM and third-trimester inflammatory factors, and the third-trimester inflammatory factors and 6-year postpartum metabolic indicators. Mediating and moderating effect analyses were further performed to explore if the third-trimester inflammatory factors mediate or modify the association between GDM and postpartum cardiometabolic indicators. RESULTS: From July 2021 to August 2022, 307 participants have been followed up, with 99 women with a prior GDM history. Compared with those without GDM, individuals with a prior history of GDM had significantly elevated levels of FPG (ß = 0.40, 95% CI: 0.18 to 0.62, PFDR < 0.001), HbA1c (ß = 0.22, 95% CI: 0.09 to 0.34, PFDR = 0.009), TyG (ß = 0.22, 95% CI: 0.07 to 0.37, PFDR = 0.024) at 6 years postpartum, and the association between GDM and SCR (ß = 2.43, 95% CI: 0.02 to 4.85, PFDR = 0.144) reached nominal significance level. GDM history was associated with a decreased level of third-trimester IL-17 A (ß = -0.58, 95% CI: -0.99 to -0.18, PFDR = 0.035). No significant association between third-trimester inflammatory factors and 6-year postpartum metabolic indicators was observed. And no mediating or moderating effect of third-trimester inflammatory factors was observed in those associations. CONCLUSION: A prior history of GDM was significantly associated with elevated FPG, HbA1c, and TyG in women at 6 years postpartum, whereas third-trimester inflammatory factors had no role in mediating or moderating these associations.

Variations of blood metabolites in single- and multiple-bearing Ossimi ewes during the transition period.

Evaluation of the metabolic profile indices allows early detection and treatment of various metabolic disorders during the transition period in ewes. This study aimed to determine the variations in the blood metabolites around lambing in Ossimi ewes. The blood metabolites were investigated in ewes with single (n = 27) and multiple (n = 9) lambs at 3- and 1-week pre-lambing and 3-week post-lambing. The plasma concentrations of glucose were higher in single-bearing ewes than those in multiple-bearing ewes (p < .05), moreover, its lowest value was measured at 1-week prepartum in both groups. Throughout the study period, the serum concentrations of non-esterified fatty acids (NEFA) were significantly increased in ewes with multiple lambs compared to ewes with single lambs (p < .05), and the highest value was found at 1-week before parturition in both groups. In addition, the serum level of beta-hydroxybutyric acid (BHBA) was higher at 3-week postpartum, and it was significantly increased in multiple-bearing ewes than that in single-bearing ones (p < .05) at 3-week pre-lambing. In both groups, the lowest values of total proteins were determined 1-week before lambing, and its concentrations, at 3- and 1-week prepartum, were higher in ewes with single lambs than those with multiple lambs (p < .05). In contrast, the serum concentrations of albumin were significantly lowered 1-week postpartum (p < .05), and without significant differences between both groups (p > .05). The serum activities of aspartate aminotransferase (AST) and gamma-glutamyltransferase (GGT) were significantly increased at 1-week after parturition in both groups (p < .05). Furthermore, the serum activities of AST were higher in multiple-bearing ewes than those in single-bearing ones at 3-week pre-lambing and 3-week post-lambing (p < .05). Variable positive and negative correlations were determined among the blood metabolites. In conclusion, physiological adaptations are associated with the fluctuation of the blood metabolites around lambing. The higher the number of foetuses the higher the metabolic variations in Ossimi ewes. Therefore, regular metabolic profiling for health monitoring may be necessary to avoid disease development during the transition period.

Association between serum mineral levels and reproductive performance in primiparous dairy cows during the peripartum period.

To the best of the authors' knowledge, no study has previously investigated whether the concentration of minerals is related to reproductive outcomes in primiparous cows. For this reason, two objectives were set in the present study: (i) to assess serum mineral levels, macrominerals, and trace elements during the transition period (period of high nutritional requirements) in primiparous cows, considering reproductive efficiency, and (ii) to address if the serum mineral levels of primiparous cows are related to reproductive efficiency. Blood samples were taken (i) one month before calving, (ii) one week before calving, (iii) one week postpartum, and (iv) one month postpartum. At the beginning and the end of the study, a body condition score (BCS) was assigned to each lactating cow with no clinical signs of disease. The difference between one month before and one month after calving was the body condition loss (ΔBCS). Optimal prepartum concentrations of K and Cl were associated with fewer days open and a shorter interval calving. Furthermore, macrominerals in the serum decreased immediately after calving (one week) but recovered at one month postpartum. In contrast, the highest concentration of trace elements was found at one week postpartum. Primiparous cows with higher postpartum Se, Mn, Co, and Mo concentrations exhibited better reproductive efficiency, and the concentrations of trace elements in serum were correlated with interval calving and the number of inseminations. Finally, primiparous cows with a greater ΔBCS (at least one point) in period 4 exhibited both a longer calving interval and a greater number of days open. In summary, this study showed, for the first time in primiparous cows, that the concentration of some serum minerals not only plays a crucial role during the transition period but is also related to crucial reproductive parameters, such as interval calving and days open.

Inflammatory and immune marker trajectories from pregnancy to one-year post-birth.

BACKGROUND: Pregnancy is an immunomodulatory state, with reported systematic changes in inflammatory and immune activity by pregnancy stage. Published data are inconsistent as to how inflammatory and immune markers change and recover across pregnancy and the postpartum period, or the sociodemographic, health and pregnancy-related factors that could affect biomarker trajectories. The purpose of this study is to describe inflammatory and immune marker trajectories from pregnancy to a year post-birth, and to test associations with sociodemographic, health and pregnancy-related variables. METHODS: A sample of 179 pregnant women were assessed three times during pregnancy (between 8 and 36 weeks gestation) and three times during the postpartum period (between 1 and 12 months). Maternal sociodemographic characteristics, health, and pregnancy factors were obtained at study entry. Blood samples from each assessment were assayed for interleukin(IL)-6, tumor necrosis factor(TNF)α, IL-8, IL-10, and interferon(IFN)γ. Multilevel modelling was used to characterize biomarker trajectories and associations with sociodemographic and health variables. RESULTS: Distinct trajectories over time emerged for each biomarker. Male pregnancies were associated with higher TNFα, IL-10, and IFNγ; higher pre-pregnancy BMI was associated with higher IL-6 and IFNγ. Nulliparity was associated with greater increases in IL-6 and TNFα. CONCLUSIONS: Patterns observed for inflammatory and immune markers from pregnancy to a year postpartum support the hypothesis that the maternal immune system changes systematically across pregnancy and through an extended postpartum period. Parity, pre-pregnancy BMI and child sex are associated with inflammatory marker patterns over time. These results contribute to our understanding of how immune system activity changes from pregnancy to the post-birth period, and the factors that could affect those changes.

Glucose levels during gestational diabetes pregnancy and the risk of developing postpartum diabetes or prediabetes.

BACKGROUND: Blood glucose levels during pregnancy may reflect the severity of insulin secretory defects and/or insulin resistance during gestational diabetes mellitus (GDM) pregnancy. We hypothesized that suboptimal glycemic control in women with GDM could increase the risk of postpartum type 2 diabetes mellitus (T2DM) or prediabetes. Our objective was to evaluate the impact of plasma glucose levels throughout GDM pregnancy on the risk of postpartum T2DM or prediabetes. METHODS: The medical records of 706 women with GDM who underwent a postpartum 75-g, 2-hour oral glucose tolerance test at our institution between January 2011 and December 2018 were reviewed. These women were classified into 2 groups according to glycemic control during pregnancy: ≤ 1 occasion of either fasting glucose ≥ 95 mg/dL or 2-hour postprandial glucose ≥ 120 mg/dL was defined as optimal glycemic control or else was classified as suboptimal glycemic control. Rates of postpartum T2DM and prediabetes were compared between women with optimal (n = 505) and suboptimal (n = 201) glycemic control. RESULTS: The rates of postpartum T2DM and prediabetes were significantly higher in the suboptimal glycemic control group than in the optimal glycemic control group: 22.4% vs. 3.0%, P < 0.001 for T2DM and 45.3% vs. 23.5%, P < 0.001 for prediabetes. In a multivariate analysis, suboptimal glucose control during pregnancy was an independent risk factor for developing either postpartum T2DM or prediabetes. The adjusted odds ratios were 8.4 (95% confidence interval, 3.5-20.3) for T2DM and 3.9 (95% confidence interval, 2.5-6.1) for prediabetes. CONCLUSION: Our findings suggest that blood glucose levels during GDM pregnancy have an impact on the risk of postpartum T2DM and prediabetes.

Postpartum circulating microRNA enhances prediction of future type 2 diabetes in women with previous gestational diabetes.

AIMS/HYPOTHESIS: Type 2 diabetes mellitus is a major cause of morbidity and death worldwide. Women with gestational diabetes mellitus (GDM) have greater than a sevenfold higher risk of developing type 2 diabetes in later life. Accurate methods for postpartum type 2 diabetes risk stratification are lacking. Circulating microRNAs (miRNAs) are well recognised as biomarkers/mediators of metabolic disease. We aimed to determine whether postpartum circulating miRNAs can predict the development of type 2 diabetes in women with previous GDM. METHODS: In an observational study, plasma samples were collected at 12 weeks postpartum from 103 women following GDM pregnancy. Utilising a discovery approach, we measured 754 miRNAs in plasma from type 2 diabetes non-progressors (n = 11) and type 2 diabetes progressors (n = 10) using TaqMan-based real-time PCR on an OpenArray platform. Machine learning algorithms involving penalised logistic regression followed by bootstrapping were implemented. RESULTS: Fifteen miRNAs were selected based on their importance in discriminating type 2 diabetes progressors from non-progressors in our discovery cohort. The levels of miRNA miR-369-3p remained significantly different (p < 0.05) between progressors and non-progressors in the validation sample set (n = 82; 71 non-progressors, 11 progressors) after adjusting for age and correcting for multiple comparisons. In a clinical model of prediction of type 2 diabetes that included six traditional risk factors (age, BMI, pregnancy fasting glucose, postpartum fasting glucose, cholesterol and triacylglycerols), the addition of the circulating miR-369-3p measured at 12 weeks postpartum improved the prediction of future type 2 diabetes from traditional AUC 0.83 (95% CI 0.68, 0.97) to an AUC 0.92 (95% CI 0.84, 1.00). CONCLUSIONS: This is the first demonstration of miRNA-based type 2 diabetes prediction in women with previous GDM. Improved prediction will facilitate early lifestyle/drug intervention for type 2 diabetes prevention.

Significant increases of the amygdala between immediate and late postpartum: Pronounced effects within the superficial subregion.

Research exploring the underlying neuroanatomical correlates of early motherhood seems to suggest that the period after giving birth is marked by tissue increases in the mother's brain. While some studies point to the amygdala as one of the areas undergoing postpartum changes, existing analyses did not discriminate between the different subregions of this functionally heterogeneous structure. Thus, to further extend this understudied field of research and to better understand the potential role of the amygdala when transitioning to motherhood, we applied an advanced region-of-interest technique that enabled us to analyze the amygdala as a whole as well as its different subareas, specifically the left and right centromedian (CM), laterobasal (LB), and superficial (SF) regions. Comparing the brains of 14 healthy women between immediate postpartum (within 1-2 days of childbirth) and late postpartum (at 4-6 weeks after childbirth), we revealed increases of the amygdala. However, effects manifested differentially across subareas, with particularly strong effects for the SF region, moderate effects for the CM region, and no effects for the LB region. These findings might reflect region-specific adaptations of the mother's brain tuning into the distinct and ever-changing needs of a newborn, either as a cause for it or as a consequence thereof.

Influence of Bowel Habit and Hormonal Changes on the Development of Hemorrhoidal Disease During Pregnancy and the Postdelivery Period: A Prospective Cohort Study.

BACKGROUND: Hemorrhoidal disease in women during pregnancy is common in clinical practice. However, prospective data on its real prevalence and women's demographics are scarce. OBJECTIVE: The aim of this study was to determine the prevalence of hemorrhoidal disease during pregnancy and to assess its impact on quality of life. In addition, this study aimed to identify the relationship between patients' characteristics, bowel habits, hormonal changes, and the presence of symptomatic hemorrhoids. DESIGN: This is a prospective longitudinal cohort study. SETTING: This study was conducted in the Obstetrics Department for pregnancy follow-up. PATIENTS: The patients evaluated were a cohort of pregnant women. INTERVENTION: The study was designed to follow a homogeneous cohort of women for 15 months. Visits took place in the first and third trimesters of pregnancy, and 3 and 6 months after delivery. Women's demographics (age, medical history, bowel habit, Bristol stool scale) and serum determination of pregnancy-related hormones (estrogen, progesterone, and relaxin) were determined. MAIN OUTCOME MEASURES: The primary outcome was the development of hemorrhoidal disease. RESULTS: Overall, 109 women (mean age, 31.2 ± 5.4 years) were included in the study. The prevalence of symptoms and physical findings of hemorrhoidal disease was present in 11% in the first trimester, 23% in the third trimester, 36.2% at 1 month after delivery, and 16.9% at 3 months after delivery. A medical history of hemorrhoidal disease was significantly associated with the diagnosis of hemorrhoids in the first trimester (p < 0.0001) and third trimester (p = 0.005). Symptoms of constipation were associated with this clinical disorder in the first trimester (p = 0.011) and the third trimester of pregnancy (p = 0.022). No association was found between hormonal changes and the development of hemorrhoidal disease. LIMITATIONS: A larger sample would provide more information. CONCLUSIONS: The prevalence of women with hemorrhoidal disease increases during pregnancy and after delivery. A history of hemorrhoidal disease and constipation is significantly associated with the diagnosis of symptomatic hemorrhoidal disease. See Video Abstract at http://links.lww.com/DCR/B504. INFLUENCIA DEL HBITO INTESTINAL Y LOS CAMBIOS HORMONALES EN EL DESARROLLO DE LA ENFERMEDAD HEMORROIDAL DURANTE EL EMBARAZO Y EL PERODO POSTERIOR AL PARTO UN ESTUDIO DE COHORTE PROSPECTIVO: ANTECEDENTES:La enfermedad hemorroidal en mujeres durante el embarazo es común en la práctica clínica. Sin embargo, hay escasos datos prospectivos sobre su prevalencia real y la demografía de las mujeres.OBJETIVO:El objetivo fue determinar la prevalencia de enfermedad hemorroidal durante el embarazo y evaluar su impacto en la calidad de vida. Además, identificar la relación entre las características de los pacientes, los hábitos intestinales, los cambios hormonales y la presencia de hemorroides sintomáticas.DISEÑO:Estudio prospectivo de cohorte longitudinal.AJUSTE:Este estudio se realizó en el Departamento de Obstetricia para el seguimiento del embarazo.PACIENTES:Una cohorte de mujeres embarazadas.INTERVENCIÓN:El estudio se diseñó para realizar un seguimiento de una cohorte homogénea de mujeres durante 15 meses. Las visitas se realizaron en el primer y tercer trimestre del embarazo, y a los 3 y 6 meses después del parto. Se determinaron los datos demográficos de las mujeres (edad, antecedentes médicos, hábito intestinal, escala de heces de Bristol) y la determinación sérica de hormonas relacionadas con el embarazo (estrógeno, progesterona y relaxina).PRINCIPALES MEDIDAS DE RESULTADO:El resultado principal fue el desarrollo de enfermedad hemorroidal.RESULTADOS:Se incluyó en el estudio a 109 mujeres (edad media, 31,2 ± 5,4 años). La prevalencia de síntomas y hallazgos físicos de enfermedad hemorroidal estuvo presente en 11% en el primer trimestre, 23% en el tercer trimestre, 36,2% 1 mes después del parto y 16,9% 3 meses después del parto. Un historial médico previo de enfermedad hemorroidal se asoció significativamente con el diagnóstico de hemorroides en el primer trimestre (p <0,0001) y tercer trimestre (p = 0,005). Los síntomas de estreñimiento se asociaron con este trastorno clínico en el primer trimestre (p = 0,011) y el tercer trimestre del embarazo (p = 0,022), respectivamente. No se encontró asociación entre los cambios hormonales y el desarrollo de enfermedad hemorroidal.LIMITACIONES:Una muestra más grande proporcionaría más información.CONCLUSIONES:La prevalencia de mujeres con enfermedad hemorroidal aumentó durante el embarazo y el posparto. El antecedente de enfermedad hemorroidal y estreñimiento se asociaron significativamente con el diagnóstico de enfermedad hemorroidal sintomática. Consulte Video Resumen en http://links.lww.com/DCR/B504.

Changes in metabolic and hormonal profiles during transition period in dairy cattle - the role of spexin.

BACKGROUND: This study aimed to evaluate spexin as a novel blood marker and to describe the relationship of this peptide with selected biochemical metabolites measured during the transition period in dairy cows. Additionally, mRNA expression of the spexin gene as well as spexin receptors - galanin receptor type 2 and galanin receptor type 3, was investigated in several bovine tissues. Blood samples were collected at weekly intervals starting at 21 days before the estimated parturition day until 21 days in milk to determine concentrations of spexin, nonesterified fatty acids, ß-hydroxybutyrate acid, total and active ghrelin, progesterone, glucose, insulin, IGF-I, triglycerides, cholesterol, leptin, corticosterone and 17-ß-estradiol as well as the activity of aspartate transaminase, alkaline phosphatase and gamma-glutamyl transferase. RESULTS: Spexin concentration decreased from 21 d before parturition to calving day and next it rose during the first 14 d of lactation. The lowest concentration of spexin was recorded on the calving day and it differed from the mean level of this peptide before parturition as well as postpartum. Moreover, differences were observed between mean spexin concentrations before and after calving. Spexin levels were moderately negatively correlated with NEFA (r = - 0.39) and total ghrelin contents (r = - 0.41), weakly correlated with BHBA (r = - 0.35) while they showed a moderate positive relationship with progesterone concentrations (r = 0.42). Moreover, we detected that mRNA expression of GALR2, GALR3 and SPX is present in various bovine tissues (kidney, bowel, rumen, spinal cord, lung, skeletal muscle, liver, heart, fat and spleen). CONCLUSION: A negative correlation between spexin concentration and NEFA, BHBA and total ghrelin contents as well as a positive relationship with levels of progesterone, metabolites and hormones, which are key players in the dairy cow transition period, may confirm an important function of this peptide in metabolism regulation. Thus measurement of spexin concentration could provide useful supplementary information for dairy cow herd health monitoring.

Association between serum calcium dynamics around parturition and common postpartum diseases in dairy cows.

The objective of this study was to compare periparturient serum Ca dynamics (CaDyn) in cows with and without diseases in early lactation. The study enrolled 1,949 cows from a commercial dairy farm in northern Germany. Blood samples were drawn 7 d before expected calving date and on d 0, 1, 3, and 7 after calving and analyzed for serum Ca concentration. Cows were monitored for clinical hypocalcemia (CH), ketosis, left displaced abomasum (LDA), retained placenta, acute puerperal metritis (APM), mastitis, and pneumonia. To evaluate the association between CaDyn and diseases during the transition period, repeated measures ANOVA with first-order autoregressive covariance were performed. Serum CaDyn of healthy cows (i.e., without any of the aforementioned diseases) was compared with CaDyn of cows with one of the aforementioned diseases (CH, ketosis, APM, mastitis, LDA, and pneumonia), and cows with multiple diseases (CH+, ketosis+, APM+, mastitis+, LDA+, and pneumonia+). Separate models were built for primiparous and multiparous cows. For primiparous cows, we evaluated the association between CaDyn and ketosis (healthy cows vs. cows with ketosis vs. cows with ketosis+) and CaDyn and APM (healthy cows vs. cows with APM vs. cows with APM+). The same models were built for multiparous cows. Three additional models were built for multiparous cows to evaluate the association between CaDyn and CH (healthy cows vs. cows with CH vs. cows with CH+), mastitis (healthy cows vs. cows with mastitis vs. cows with mastitis+), or LDA (healthy cows vs. cows with LDA vs. cows with LDA+). In primiparous cows, serum Ca concentrations of cows with ketosis, APM, and APM+ were significantly reduced on d 3 and 7 after calving, compared with healthy cows. Serum Ca concentrations of primiparous cows with ketosis+ were reduced on d 3, but not on d 7 after calving. Multiparous cows with CH had significantly reduced serum Ca concentrations on d 0, 1, and 3 compared with healthy cows. On d 3 and 7, serum Ca concentration of CH+ cows was significantly reduced compared with healthy multiparous cows. Multiparous cows with ketosis and ketosis+ had significantly reduced serum Ca concentrations on d 1 and 3 compared with healthy cows. Cows with APM+ had significantly increased serum Ca concentrations on d 0 and reduced serum Ca concentrations on d 3, compared with healthy cows. Whereas multiparous cows with mastitis had a reduced serum Ca concentration on d 1, mastitis+ cows had a reduced serum Ca concentration on d 1 and 3, compared with healthy multiparous cows. Overall, multiparous cows with LDA+ had reduced serum Ca concentrations. Especially a delayed onset of hypocalcemia (d 3 and 7) was indicative for the development of disease in primiparous cows. In multiparous cows, reduced serum Ca concentrations on d 1 and 3 were associated with occurrence of diseases. Future studies should evaluate whether reduced serum Ca concentrations are a cause or concomitant circumstance of diseases in early lactation.

Subfoveal Choroidal Thickness and Associated Changes of Angiogenic Factors in Women with Severe Preeclampsia.

OBJECTIVE: Severe preeclampsia complicates roughly 1% of all pregnancies. One defining feature of severe preeclampsia is new onset visual disturbance. The accessibility of the choroid to high-resolution, noninvasive imaging makes it a reasonable target of investigation for disease prediction, stratification, or monitoring in preeclampsia. This study aimed to compare subfoveal choroidal thickness between women with severe preeclampsia and those with normotensive pregnancies, and to investigate associations between such findings and other indicators of disease severity, including gestational age and serum angiogenic factors. STUDY DESIGN: We designed a case-control study comprised of 36 women diagnosed with severe preeclampsia (cases) matched to 37 normotensive women (controls) by race/ethnicity and parity, all diagnosed in the postpartum period. All patients underwent enhanced depth imaging spectral-domain optical coherence tomography and serum analysis. RESULTS: Cases showed no difference in subfoveal choroidal thickness compared with controls (p = 0.65). Amongst cases, subfoveal choroidal thickness and gestational age at delivery were inversely related (r = 0.86, p < .001). There was a positive association of placental growth factor with subfoveal choroidal thickness amongst cases (r = 0.54, p = 0.002). CONCLUSION: This study suggests a relationship between the degree of disease severity and the magnitude of choroidal thickening. We also show an association between this index and placental growth factor level in the postpartum period.

Biological changes in the pregnancy-postpartum period and subsequent cardiometabolic risk-UPSIDE MOMS: A research protocol.

Multiple physiological changes occur in pregnancy as a woman's body adapts to support the growing fetus. These pregnancy-induced changes are essential for fetal growth, but the extent to which they reverse after pregnancy remains in question. For some women, physiological changes persist after pregnancy and may increase long-term cardiometabolic disease risk. The National Institutes of Health-funded study described in this protocol addresses a scientific gap by characterizing weight and biological changes during pregnancy and an extended postpartum period in relation to cardiometabolic risk. We use a longitudinal repeated measures design to prospectively examine maternal health from early pregnancy until 3 years postpartum. The aims are: (1) identify maternal weight profiles in the pregnancy-postpartum period that predict adverse cardiometabolic risk profiles three years postpartum; (2) describe immune, endocrine, and metabolic biomarker profiles in the pregnancy-postpartum period, and determine their associations with cardiometabolic risk; and (3) determine how modifiable postpartum health behaviors (diet, physical activity, breastfeeding, sleep, stress) (a) predict weight and cardiometabolic risk in the postpartum period; and (b) moderate associations between postpartum weight retention and downstream cardiometabolic risk. The proposed sample is 250 women. This study of mothers is conducted in conjunction with the Understanding Pregnancy Signals and Infant Development study, which examines child health outcomes. Biological and behavioral data are collected in each trimester and at 6, 12, 24, and 36 months postpartum. Findings will inform targeted health strategies that promote health and reduce cardiometabolic risk in childbearing women.

Circulatory Neutrophils Exhibit Enhanced Neutrophil Extracellular Trap Formation in Early Puerperium: NETs at the Nexus of Thrombosis and Immunity.

Pregnancy is associated with elevated maternal levels of cell-free DNA of neutrophil extracellular trap (NET) origin, as circulatory neutrophils exhibit increased spontaneous NET formation, mainly driven by G-CSF and finely modulated by sex hormones. The postpartum period, on the other hand, involves physiological alterations consistent with the need for protection against infections and fatal haemorrhage. Our findings indicate that all relevant serum markers of neutrophil degranulation and NET release are substantially augmented postpartum. Neutrophil pro-NETotic activity in vitro is also upregulated particularly in post-delivery neutrophils. Moreover, maternal puerperal neutrophils exhibit a strong pro-NETotic phenotype, associated with increased levels of all key players in the generation of NETs, namely citH3, MPO, NE, and ROS, compared to non-pregnant and pregnant controls. Intriguingly, post-delivery NET formation is independent of G-CSF in contrast to late gestation and complemented by the presence of TF on the NETs, alterations in the platelet activity status, and activation of the coagulation cascade, triggered by circulating microparticles. Taken together, our results reveal the highly pro-NETotic and potentially procoagulant nature of postpartum neutrophils, bridging an overt immune activation with possible harmful thrombotic incidence.

Comparative biochemical profiles, utero-ovarian function, and fertility of the postpartum buffalo with and without subclinical endometritis.

In postpartum buffaloes, the process of uterine involution and changes in blood metabolic profile has not been studied in relation to development of subclinical endometritis (SCE). In this study, buffaloes (n = 100) approaching calving were identified. Weekly blood samples were collected on the day of calving up to 6 weeks post-calving. The diameter of uterine horns and onset of ovarian cyclicity (corpus luteum) were recorded through ultrasonography. On the basis of polymorphonuclear cell (PMN) cell count in endometrial cytology at days 45-50 postpartum, buffaloes were divided into two groups, viz., with SCE (> 5% PMN; n = 38) and without SCE (≤ 5% PMN; n = 62). Buffaloes with SCE took longer (P < 0.05) time to complete uterine involution and had larger (P < 0.05) uterine horn diameter between 3rd and 6th weeks postpartum and lower prostaglandin F2α metabolite (PGFM) concentration on the day of calving (P < 0.05) and 1 week (P < 0.001) post-calving than without SCE group. Buffaloes with SCE had lower (P < 0.001) concentration of glucose at weeks 2 and 3, higher (P < 0.001) ß-hydroxybutyric acid (BHBA) at week 3, and lower serum albumin concentration throughout the sampling period (P < 0.05 to 0.001) except at 1 week post-calving as compared to without SCE group. The urea concentration was significantly lower (P < 0.05 to 0.001) in buffaloes with SCE from 4 weeks post-calving onwards than without SCE group. The calcium concentration was lower in buffaloes with SCE at weeks 5 (P < 0.001) and 6 (P < 0.05) postpartum, whereas the concentration of magnesium and phosphorus was uniform between the two groups. No significant (P > 0.05) difference in onset of ovarian cyclicity between the 2 groups was observed, whereas buffaloes with SCE had longer (P = 0.001) median days open (141 days) than their counterpart (117 days). The first service conception rate, cumulative pregnancy rate, and pregnancy rate at 150 days postpartum were lower (P < 0.05) in buffaloes with SCE than without SCE group. In summary, higher BHBA and lower serum concentrations of glucose, albumin, urea, and calcium control onset of subclinical endometritis which in turn has negative impact on fertility of buffaloes.

Longitudinal changes in glucose metabolism in women with gestational diabetes, from late pregnancy to the postpartum period.

AIMS/HYPOTHESIS: This study aimed to determine, in women with gestational diabetes (GDM), the changes in insulin sensitivity (Matsuda Insulin Sensitivity Index; ISOGTT), insulin response and disposition index (DI) from late pregnancy (34-37 weeks gestation, T1), to early postpartum (1-5 days, T2) and late postpartum (6-12 weeks, T3). A secondary aim was to correlate the longitudinal changes in maternal lipids, adipokines, cytokines and weight in relation to the changes in ISOGTT, insulin response and DI. METHODS: ISOGTT, insulin response and DI were calculated at the three time points (T1, T2 and T3) using the results of a 75 g OGTT. Adipokines, cytokines and lipids were measured prior to each OGTT. Linear mixed-effects models were used to compare changes across each time point. Changes in ISOGTT, insulin response and DI were correlated with changes in maternal adipokines, cytokines and lipids at each time point. RESULTS: A total of 27 women completed all assessments. Compared with T1, ISOGTT was 11.20 (95% CI 8.09, 14.31) units higher at 1-5 days postpartum (p < 0.001) and was 5.49 (95% CI 2.38, 8.60) units higher at 6-12 weeks postpartum (p < 0.001). Compared with T1, insulin response values were 699.6 (95% CI 957.5, 441.6) units lower at T2 (p < 0.001) and were 356.3 (95% CI 614.3, 98.3) units lower at T3 (p = 0.004). Compared with T1, the DI was 6434.1 (95% CI 2486.2, 10,381.0) units higher at T2 (p = 0.001) and was 4262.0 (95% CI 314.6, 8209.3) units higher at T3 (p = 0.03). There was a decrease in mean cholesterol, triacylglycerol, LDL-cholesterol and VLDL-cholesterol from T1 to T2 (all p < 0.001), and an increase in mean C-reactive protein, IL-6 and IL-8 from T1 to T2 (all p < 0.001). Mean leptin decreased from T1 to T2 (p = 0.001). There was no significant change in mean adiponectin (p = 0.99) or TNF-α (p = 0.81) from T1 to T2. The mean maternal BMI decreased from T1 to T2 (p = 0.001) and T3 (p < 0.001). There were no significant correlations between any measure of change in ISOGTT, insulin response and DI and change in maternal cytokines, adipokines, lipids or weight from T1 to T2. CONCLUSIONS/INTERPRETATION: In women with GDM, delivery was associated with improvement in both insulin sensitivity and insulin production within the first few days. Improvement in insulin production persisted for 6-12 weeks, but insulin sensitivity deteriorated slightly. These changes in glucose metabolism were not associated to changes in lipids, leptin, inflammation markers or body weight. TRIAL REGISTRATION: ClinicalTrials.gov NCT02082301.

Postpartum plasma metabolomic profile among women with preeclampsia and preterm delivery: implications for long-term health.

BACKGROUND: Preeclampsia and preterm delivery (PTD) are believed to affect women's long-term health including cardiovascular disease (CVD), but the biological underpinnings are largely unknown. We aimed to test whether maternal postpartum metabolomic profiles, especially CVD-related metabolites, varied according to PTD subtypes with and without preeclampsia, in a US urban, low-income multi-ethnic population. METHODS: This study, from the Boston Birth Cohort, included 980 women with term delivery, 79 with medically indicated PTD (mPTD) and preeclampsia, 52 with mPTD only, and 219 with spontaneous PTD (sPTD). Metabolomic profiling in postpartum plasma was conducted by liquid chromatography-mass spectrometry. Linear regression models were used to assess the associations of each metabolite with mPTD with preeclampsia, mPTD only, and sPTD, respectively, adjusting for pertinent covariates. Weighted gene coexpression network analysis was applied to investigate interconnected metabolites associated with the PTD/preeclampsia subgroups. Bonferroni correction was applied to account for multiple testing. RESULTS: A total of 380 known metabolites were analyzed. Compared to term controls, women with mPTD and preeclampsia showed a significant increase in 36 metabolites, mainly representing acylcarnitines and multiple classes of lipids (diacylglycerols, triacylglycerols, phosphocholines, and lysophosphocholines), as well as a decrease in 11 metabolites including nucleotides, steroids, and cholesteryl esters (CEs) (P < 1.3 × 10-4). Alterations of diacylglycerols, triacylglycerols, and CEs in women with mPTD and preeclampsia remained significant when compared to women with mPTD only. In contrast, the metabolite differences between women with mPTD only and term controls were only seen in phosphatidylethanolamine class. Women with sPTD had significantly different levels of 16 metabolites mainly in amino acid, nucleotide, and steroid classes compared to term controls, of which, anthranilic acid, bilirubin, and steroids also had shared associations in women with mPTD and preeclampsia. CONCLUSION: In this sample of US high-risk women, PTD/preeclampsia subgroups each showed some unique and shared associations with maternal postpartum plasma metabolites, including those known to be predictors of future CVD. These findings, if validated, may provide new insight into metabolomic alterations underlying clinically observed PTD/preeclampsia subgroups and implications for women's future cardiometabolic health.

Cell-free mitochondrial DNA increases in maternal circulation during healthy pregnancy: a prospective, longitudinal study.

Mitochondrial DNA (mtDNA) exposed to the extracellular space due to cell death has immunostimulatory properties. Case-control studies reported a positive association between odds of developing preeclampsia and circulating mtDNA. These findings are based on relative quantification protocols that do not allow determination of absolute concentrations of mtDNA and are highly sensitive to nuclear DNA contamination. Furthermore, circulating mtDNA concentrations in response to normal pregnancy, which is an inflammatory state characterized by continuous placental cell apoptosis, have not been established. The main objective of this study was to determine longitudinal changes in circulating mtDNA from preconception to first trimester, third trimester, and postpartum in healthy pregnant women. Absolute real-time PCR quantification of mtDNA and nuclear DNA (nDNA) was performed on whole genomic extracts from serum using TaqMan probes and chemistry. Serum cell-free mtDNA and nDNA concentrations were greater in late pregnancy as compared with early pregnancy and postpartum. Pregnant women carrying neonates at the upper quartile of birth length distribution had higher concentrations of mtDNA in late pregnancy compared with pregnancies carrying neonates at the lower quartile. The correlation between circulating mtDNA and nDNA concentrations varied by sex (i.e., pregnancies carrying female vs. male fetuses). This study is the first to establish temporal patterns of circulating cell-free mtDNA concentrations in normal human pregnancy using absolute DNA quantification techniques. Concentrations of circulating mtDNA in normal pregnancy may be used as reference values for the development of clinical prognostic or diagnostic tests in pregnant women with, or at risk of developing, gestational complications.

Examining the relationship between maternal body size, gestational glucose tolerance status, mode of delivery and ethnicity on human milk microbiota at three months post-partum.

BACKGROUND: Few studies have examined how maternal body mass index (BMI), mode of delivery and ethnicity affect the microbial composition of human milk and none have examined associations with maternal metabolic status. Given the high prevalence of maternal adiposity and impaired glucose metabolism, we systematically investigated the associations between these maternal factors in women ≥20 years and milk microbial composition and predicted functionality by V4-16S ribosomal RNA gene sequencing (NCT01405547;  https://clinicaltrials.gov/ct2/show/NCT01405547 ). Demographic data, weight, height, and a 3-h oral glucose tolerance test were gathered at 30 (95% CI: 25-33) weeks gestation, and milk samples were collected at 3 months post-partum (n = 113). RESULTS: Multivariable linear regression analyses demonstrated no significant associations between maternal characteristics (maternal BMI [pre-pregnancy, 3 months post-partum], glucose tolerance, mode of delivery and ethnicity) and milk microbiota alpha-diversity; however, pre-pregnancy BMI was associated with human milk microbiota beta-diversity (Bray-Curtis R2 = 0.037). Women with a pre-pregnancy BMI > 30 kg/m2 (obese) had a greater incidence of Bacteroidetes (incidence rate ratio [IRR]: 3.70 [95% CI: 1.61-8.48]) and a reduced incidence of Proteobacteria (0.62 [0.43-0.90]) in their milk, compared to women with an overweight BMI (25.0-29.9 kg/m2) as assessed by multivariable Poisson regression. An increased incidence of Gemella was observed among mothers with gestational diabetes who had an overweight BMI versus healthy range BMI (5.96 [1.85-19.21]). An increased incidence of Gemella was also observed among mothers with impaired glucose tolerance with an obese BMI versus mothers with a healthy range BMI (4.04 [1.63-10.01]). An increased incidence of Brevundimonas (16.70 [5.99-46.57]) was found in the milk of women who underwent an unscheduled C-section versus vaginal delivery. Lastly, functional gene inference demonstrated that pre-pregnancy obesity was associated with an increased abundance of genes encoding for the biosynthesis of secondary metabolites pathway in milk (coefficient = 0.0024, PFDR < 0.1). CONCLUSIONS: Human milk has a diverse microbiota of which its diversity and differential abundance appear associated with maternal BMI, glucose tolerance status, mode of delivery, and ethnicity. Further research is warranted to determine whether this variability in the milk microbiota impacts colonization of the infant gut.

Circulating irisin levels of prenatal and postnatal patients with gestational diabetes mellitus: A systematic review and meta-analysis.

AIMS: At present, there are few studies on the relationship between circulating irisin levels and gestational diabetes mellitus (GDM), and the results are inconsistent. Therefore, this study conducts a systematic review and meta-analysis to comprehensively discuss the role of irisin in the occurrence and development of GDM. METHODS: We searched the articles on the relationship between GDM and circulating irisin levels up to September 2019, using the CNKI, WANFANG-DATA, PubMed and the Web of Science databases. RESULTS: Twenty two articles including 3563 participants were selected in the meta-analysis. Meta-analysis found the blood irisin levels for GDM group were significantly lower than that for control group during pregnancy(SMD = -0.88, 95%CI: -1.34, -0.42, P < 0.001). However, there was no significant difference of irisin levels in the postpartum blood and cord blood between the two groups (SMD = -1.44, 95 %CI: -3.79, 0.92, P = 0.23; SMD = -0.17, 95 %CI: -0.59, 0.25, P = 0.42, respectively). CONCLUSIONS: Compared with the control group, irisin levels in the GDM group during pregnancy are lower. However, it is no significant difference of irisin levels in the postpartum blood and cord blood. Irisin may play an important role in the occurrence and development of GDM, which needs further research to demonstrate.

Phosphatidylethanol Levels in Postpartum Women and Their Newborns in Uruguay and Brazil.

BACKGROUND: There is increasing interest in the development of newborn screening tests to identify children at risk of fetal alcohol spectrum disorder (FASD) in order to provide these children with early intervention. Phosphatidylethanol (PEth) has emerged as a potential universal newborn screening candidate. METHODS: The aim of this report was to present the results of a study designed to compare PEth levels in 1,140 postpartum women and their newborn infants in Montevideo, Uruguay, and Sao Paulo, Brazil. Self-report alcohol use during pregnancy data was collected, along with both maternal and newborn dried blood spot samples for PEth analysis. RESULTS: The average age and parity of the women in the sample were 26 years of age and 2.3 pregnancies. For the Uruguay sample (n = 611), 45.8% of postpartum women had PEth levels ≥ 8 ng/ml with a mean positive PEth of 43.6 ng/ml. In contrast, 86.8% of the newborns had PEth levels ≥ 8 ng/ml, with a mean positive PEth of 77.4 ng/ml. For the Brazil sample (n = 529), 33.2% of women had PEth levels ≥ 8 ng/ml with a mean positive PEth of 31 ng/ml. In contrast, 76.9% of the Brazil newborns had PEth levels ≥ 8 ng/ml and 43.9% with a mean positive PEth of 61.1 ng/ml. PEth levels were significantly higher in newborns compared with their postpartum mothers in both the Uruguay and Brazil samples. Self-reported third-trimester alcohol was 6% in the Uruguay sample and 9.1% in the Brazil sample compared with positive maternal PEth levels in 45.8% and 33.2%, respectively. CONCLUSIONS: Clinicians may want to consider newborn PEth screening in high-risk populations where prenatal alcohol use is common. The mechanism underlying significantly higher PEth levels in newborns compared with their mothers is not known.