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1.
Effects of perinatal factors on sirtuin 3, 8-hydroxy-2'- deoxyguanosine, brain-derived neurotrophic factor and serotonin in cord blood and early breast milk: an observational study.
Nyárády, K, Turai, R, Funke, S, Györgyi, E, Makai, A, Prémusz, V, Bódis, J, Sulyok, E
International breastfeeding journal. 2020;(1):57
Abstract
BACKGROUND The profile of sirtuin 3 (SIRT3), 8-hydroxy-2'-deoxyguanosine (8-OHdG), brain-derived neurotrophic factor (BDNF) and serotonin (5-HT) in cord blood and in early breast milk was studied and it was related to perinatal factors. 5-HT and BDNF signalling systems have been claimed to play a critical role in intrauterine development, postnatal adaptation and lactation. Since prematurity and Caesarean birth are frequently associated with inflammation and related oxidative stress, an attempt was made to reveal the adaptive changes of the protective SIRT3 and the complex interplay among these bioactive components in cord blood and early breast milk. METHODS Three groups each consisting of 30 mothers were included in the study: mothers who underwent spontaneous vaginal birth at term (group I), Caesarean section at term (group II) and preterm birth (group III). Venous cord blood and early breast milk samples were collected for measuring the biomarkers. SIRT3, 8-OHdG, BDNF and 5-HT levels were determined by using commercially available ELISA kits. RESULTS It was demonstrated that cord blood levels of SIRT3, BDNF and 5-HT were markedly reduced whereas those of 8-OHdG were significantly elevated after preterm birth when compared with birth at term. The Caesarean section was associated with a moderate decrease in BDNF and 5-HT, however, both SIRT3 and 8-OHdG remained unaffected. Breast milk levels of all biomarkers studied proved to be independent of their corresponding cord blood concentrations. In response to preterm birth breast milk SIRT3, 8-OHdG and 5-HT increased significantly, while a drastic fall occurred in BDNF. A significant positive relationship was found of 5-HT with SIRT3 and 8-OHdG irrespective of the gestational age and the mode of delivery. CONCLUSIONS It is suggested that the selected biomarkers in the breast milk mostly derive from local production by the mammary glands and 5-HT may have an essential role in the control of this process.
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2.
A clinical research study on the respective relationships between visfatin and human fetuin A and pregnancy outcomes in gestational diabetes mellitus.
Lu, D, Yang, M, Yao, Y, Xie, Y
Taiwanese journal of obstetrics & gynecology. 2019;(6):808-813
Abstract
OBJECTIVE The aim was to determine the role of visfatin (VF) and human fetuin A (AHSG) in the development of gestational diabetes mellitus (GDM) and to explore the association between these variables and adverse outcomes. MATERIALS AND METHODS We carried out our study on 68 cases of GDM pregnant women and 42 cases of healthy pregnant women, including 56 cases with diet control and 12 cases with insulin treatment. Enzyme-linked immunoassay (ELISA) was used to test the expression levels of VF and AHSG in maternal and umbilical cord serum. Immunohistochemistry (ICH) was used to test the expression level of the VF protein in placental tissue. RESULTS The expression levels of VF and AHSG in maternal and umbilical cord serum and the expression level of VF in placental tissue in GDM pregnant women were higher than those in healthy pregnant women. The incidence of adverse outcomes in the GDM pregnant women was higher than that in healthy pregnant women, and these differences were statistically significant (P < 0.05). Those who had higher expression levels of VF or AHSG had a higher incidence of adverse outcomes (P < 0.05). CONCLUSION The expression of VF and AHSG may participate in the development of GDM. A test of VF and AHSG in GDM pregnant women may have some predictive value for the occurrence of adverse outcomes.
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3.
Multifactorial analysis of the stochastic epigenetic variability in cord blood confirmed an impact of common behavioral and environmental factors but not of in vitro conception.
Gentilini, D, Somigliana, E, Pagliardini, L, Rabellotti, E, Garagnani, P, Bernardinelli, L, Papaleo, E, Candiani, M, Di Blasio, AM, Viganò, P
Clinical epigenetics. 2018;:77
Abstract
BACKGROUND An increased incidence of imprint-associated disorders has been reported in babies born from assisted reproductive technology (ART). However, previous studies supporting an association between ART and an altered DNA methylation status of the conceived babies have been often conducted on a limited number of methylation sites and without correction for critical potential confounders. Moreover, all the previous studies focused on the identification of methylation changes shared among subjects while an evaluation of stochastic differences has never been conducted. This study aims to evaluate the effect of ART and other common behavioral or environmental factors associated with pregnancy on stochastic epigenetic variability using a multivariate approach. RESULTS DNA methylation levels of cord blood from 23 in vitro and 41 naturally conceived children were analyzed using the Infinium HumanMethylation450 BeadChips. After multiple testing correction, no statistically significant difference emerged in the number of cord blood stochastic epigenetic variations or in the methylation levels between in vitro- and in vivo-conceived babies. Conversely, four multiple factor analysis dimensions summarizing common phenotypic, behavioral, or environmental factors (cord blood cell composition, pre or post conception supplementation of folates, birth percentiles, gestational age, cesarean section, pre-gestational mother's weight, parents' BMI and obesity status, presence of adverse pregnancy outcomes, mother's smoking status, and season of birth) were significantly associated with stochastic epigenetic variability. The stochastic epigenetic variation analysis allowed the identification of a rare imprinting defect in the locus GNAS in one of the babies belonging to the control population, which would not have emerged using a classical case-control association analysis. CONCLUSIONS We confirmed the effect of several common behavioral or environmental factors on the epigenome of newborns and described for the first time an epigenetic effect related to season of birth. Children born after ART did not appear to have an increased risk of genome-wide changes in DNA methylation either at specific loci or randomly scattered throughout the genome. The inability to identify differences between cases and controls suggests that the number of stochastic epigenetic variations potentially induced by ART was not greater than that naturally produced in response to maternal behavior or other common environmental factors.
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4.
Oxidative stress and DNA damage in the cord blood of preterm infants.
Norishadkam, M, Andishmand, S, Zavar Reza, J, Zare Sakhvidi, MJ, Hachesoo, VR
Mutation research. Genetic toxicology and environmental mutagenesis. 2017;:20-24
Abstract
Preterm birth infants are more susceptible to oxidative stress and aftermaths unwanted outcomes such as DNA damage due to hyperoxic stress. In this study, we compared the DNA strand breaks as one of the results of DNA oxidation in white blood cells, malondialdehyde (oxidative stress marker), catalase and superoxide dismutase activity, and total antioxidant capacity (markers of antioxidant defense) in a cord blood plasma of a group of preterm (n=25) and full term births (n=25). The primary DNA damage and plasma oxidative stress markers were significantly higher in a preterm group (p<0.05). Cord plasma activity of superoxide dismutase was significantly lower in preterm infants (p≤0.001). However, there were no significant differences in the cord blood total antioxidant capacity, catalase activity and malondialdehyde in preterm and term infants. Among the oxidative stress markers, the malondialdehyde concentration showed the strongest effect size (1.54; 95%CI: 0.9-2.17). For comet parameters, the most powerful effect size was observed for tail length (5.24; 95% CI: 4.05-6.42). However, tail DNA percent and tail moment were also significantly higher in cases compared to controls. Significant negative correlation was observed between comet assay parameters and birth weight and gestational age when all cases and controls entered into the analysis. There was no significant association between the levels of oxidative stress markers and early DNA damage in cord blood plasma with future nutritional tolerance in preterm infants. In the present study, the primary DNA damage and plasma oxidative stress markers significantly were increased in a preterm group. Preterm babies are more prone to the outcomes related to the early DNA damage. Tail DNA percent does not depend on experimental conditions as other parameters (tail length and thus also tail moment) and can be used for comparison with other studies.
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5.
Wait a minute? An observational cohort study comparing iron stores in healthy Swedish infants at 4 months of age after 10-, 60- and 180-second umbilical cord clamping.
Askelöf, U, Andersson, O, Domellöf, M, Fasth, A, Hallberg, B, Hellström-Westas, L, Pettersson, K, Westgren, M, Wiklund, IE, Götherström, C
BMJ open. 2017;(12):e017215
Abstract
BACKGROUND AND OBJECTIVE Umbilical cord blood (UCB) is a valuable stem cell source used for transplantation. Immediate umbilical cord (UC) clamping is widely practised, but delayed UC clamping is increasingly advocated to reduce possible infant anaemia. The aim of this study was to investigate an intermediate UC clamping time point and to evaluate iron status at the age of 4 months in infants who had the UC clamped after 60 s and compare the results with immediate and late UC clamping. DESIGN Prospective observational study with two historical controls. SETTING A university hospital in Stockholm, Sweden, and a county hospital in Halland, Sweden. METHODS Iron status was assessed at 4 months in 200 prospectively recruited term infants whose UC was clamped 60 s after birth. The newborn baby was held below the uterine level for the first 30 s before placing the infant on the mother's abdomen for additional 30 s. The results were compared with data from a previously conducted randomised controlled trial including infants subjected to UC clamping at ≤10 s (n=200) or ≥180 s (n=200) after delivery. RESULTS After adjustment for age differences at the time of follow-up, serum ferritin concentrations were 77, 103 and 114 µg/L in the 10, 60 and 180 s groups, respectively. The adjusted ferritin concentration was significantly higher in the 60 s group compared with the 10 s group (P=0.002), while the difference between the 60 and 180 s groups was not significant (P=0.29). CONCLUSION In this study of healthy term infants, 60 s UC clamping with 30 s lowering of the baby below the uterine level resulted in higher serum ferritin concentrations at 4 months compared with 10 s UC clamping. The results suggest that delaying the UC clamping for 60 s reduces the risk for iron deficiency. TRIAL REGISTRATION NUMBER NCT01245296.
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6.
The Effects of Fetal Gender on Maternal and Fetal Insulin Resistance.
Walsh, JM, Segurado, R, Mahony, RM, Foley, ME, McAuliffe, FM
PloS one. 2015;(9):e0137215
Abstract
OBJECTIVE Gender plays a role in the development of a number of cardiovascular and metabolic diseases and it has been suggested that females may be more insulin resistant in utero. We sought to assess the relationship between infant gender and insulin resistance in a large pregnancy cohort. STUDY DESIGN This is a secondary analysis of a cohort from the ROLO randomized control trial of low GI diet in pregnancy. Serum insulin, glucose and leptin were measured in early pregnancy and at 28 weeks. At delivery cord blood C-peptide and leptin were measured. A comparison of maternal factors, fetal biometry, insulin resistance and leptin was made between male and female offspring. A multivariate regression model was built to account for the possible effects of maternal BMI, birthweight and original study group assignment on findings. RESULTS A total of 582 women were included in this secondary analysis, of whom 304 (52.2%) gave birth to male and 278 (47.8%) gave birth to female infants. Compared to male infants at birth, female infants were significantly lighter, (3945 ± 436 vs. 4081± 549g, p<0.001), shorter in length (52.36 ± 2.3 vs. 53.05 ± 2.4cm, p<0.001) and with smaller head circumferences (35.36 ± 1.5 vs. 36.10 ± 1.1cm, p<0.001) than males. On multiple regression analysis, women pregnant with female fetuses were less insulin resistant in early pregnancy, i.e. had lower HOMA indices (B = -0.19, p = 0.01). Additionally female fetuses had higher concentrations of both cord blood leptin and C-peptide at birth when compared to male offspring (B = 0.38, p<0.001 and B = 0.31, p = 0.03 respectively). CONCLUSION These findings suggest gender is a risk factor for insulin resistance in-utero. Additionally, carrying a female fetus decreases the risk of insulin resistance in the mother, from as early as the first trimester.
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7.
Effects of ethnicity and vitamin D supplementation on vitamin D status and changes in bone mineral content in infants.
Abrams, SA, Hawthorne, KM, Rogers, SP, Hicks, PD, Carpenter, TO
BMC pediatrics. 2012;:6
Abstract
BACKGROUND To evaluate the effects on serum 25(OH)D and bone mineralization of supplementation of breast-fed Hispanic and non-Hispanic Caucasian infants with vitamin D in infants in Houston, Texas. METHODS We measured cord serum 25(OH)D levels, bone mineral content (BMC), bone mineral density (BMD) and their changes over 3 months of life with 400 IU/day of vitamin D3 supplementation. RESULTS Cord serum 25(OH)D was significantly lower in Hispanic than non-Hispanic Caucasian infants (16.4 ± 6.5 ng/mL, n = 27, vs 22.3 ± 9.4 n = 22, p = 0.013). Among 38 infants who completed a 3 month vitamin D supplementation intervention, provision of 400 IU/day of vitamin D increased final 25(OH)D to a higher level in non-Hispanic Caucasian compared to Hispanic infants. There was no significant relationship between cord serum 25(OH)D and BMC or BMD in the first week of life (n = 49) or after 3 months of vitamin D supplementation. CONCLUSION Low cord 25(OH)D levels are seen in Hispanic infants, but their functional significance is uncertain related to bone health in a southern US setting. Daily vitamin D intake of 400 IU during the first months of life appears adequate to increase serum 25(OH)D and support BMC increases despite low initial 25(OH)D levels in some infants. TRIAL REGISTRATION ClincalTrials.gov NCT00697294.
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8.
Mild gestational diabetes in pregnancy and the adipoinsular axis in babies born to mothers in the ACHOIS randomised controlled trial.
Pirc, LK, Owens, JA, Crowther, CA, Willson, K, De Blasio, MJ, Robinson, JS
BMC pediatrics. 2007;:18
Abstract
BACKGROUND Mild gestational diabetes is a common complication of pregnancy, affecting up to 9% of pregnant women. Treatment of mild GDM is known to reduce adverse perinatal outcomes such as macrosomia and associated birth injuries, such as shoulder dystocia, bone fractures and nerve palsies. This study aimed to compare the plasma glucose concentrations and serum insulin, leptin and adiponectin in cord blood of babies of women (a) without gestational diabetes mellitus (GDM), (b) with mild GDM under routine care, or (c) mild GDM with treatment. METHODS 95 women with mild GDM on oral glucose tolerance testing (OGTT) at one tertiary level maternity hospital who had been recruited to the ACHOIS trial at one of the collaborating hospitals and randomised to either Treatment (n = 46) or Routine Care (n = 49) and Control women with a normal OGTT (n = 133) were included in the study. Women with mild GDM (treatment or routine care group) and OGTT normal women received routine pregnancy care. In addition, women with treated mild GDM received dietary advice, blood glucose monitoring and insulin if necessary. The primary outcome measures were cord blood concentrations of glucose, insulin, adiponectin and leptin. RESULTS Cord plasma glucose was higher in women receiving routine care compared with control, but was normalized by treatment for mild GDM (p = 0.01). Cord serum insulin and insulin to glucose ratio were similar between the three groups. Leptin concentration in cord serum was lower in GDM treated women compared with routine care (p = 0.02) and not different to control (p = 0.11). Adiponectin was lower in both mild GDM groups compared with control (Treatment p = 0.02 and Routine Care p = 0.07), while the adiponectin to leptin ratio was lower for women receiving routine care compared with treatment (p = 0.08) and control (p = 0.05). CONCLUSION Treatment of women with mild GDM using diet, blood glucose monitoring and insulin if necessary, influences the altered fetal adipoinsular axis characteristic of mild GDM in pregnancy.
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9.
[The effect of tobacco smoking during pregnancy on concentration of malondialdehyde in blood of mothers and in umbilical cord blood].
Chełchowska, M, Laskowska-Klita, T, Leibschang, J
Ginekologia polska. 2005;(12):960-5
Abstract
OBJECTIVES Maternal smoking during pregnancy is known to be associated with not only intrauterine fetal growth retardation or low birth weight but also causes disturbances in postnatal growth and development. The prime role of oxidative stress in the pathogenesis of adverse pregnancy outcomes is almost universally accepted. DESIGN The aim of the study was to estimate the effect of tobacco smoking during pregnancy on concentration of lipid peroxidation products (malondialdehyde - MDA) in blood of mother and newborns. MATERIALS AND METHODS 147 healthy, pregnant women were divided into non-smoking (n = 85) and smoking group (n = 62) according to questionnaire declaration and confirmed by cotinine concentration in serum and urine. Level of MDA was measured by fluorimetric method in plasma and in erythrocytes of mothers and umbilical cord blood. RESULTS We found that, in group of women smoking during pregnancy concentration of malondialdehyde was higher in plasma and in erythrocytes when compared to group of tobacco abstinent. Also in cord blood of newborns of smoking mothers level of MDA was significantly higher in plasma (p < 0.05) as well as in erythrocytes (p < 0.01) than in control group. CONCLUSION The presented results indicate that smoking during pregnancy may promotes free radical damage in growing fetus and newborns therefore stimulates metabolic disorders dependent on oxidative stress.
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10.
Low vitamin D status is associated with low cord blood levels of the immunosuppressive cytokine interleukin-10.
Zittermann, A, Dembinski, J, Stehle, P
Pediatric allergy and immunology : official publication of the European Society of Pediatric Allergy and Immunology. 2004;(3):242-6
Abstract
The cytokine interleukin-10 (IL-10) plays a pivotal regulatory role in tolerizing exogenous antigens. Experimental data indicate that low cellular availability of the vitamin D hormone 1,25-dihydroxyvitamin D [1,25(OH)2D] results in a down-regulation of IL-10 concentrations. The tissue production of an adequate amount of 1,25(OH)2D depends on a high circulating 25-hydroxyvitamin D (25-OHD) level. The present study was thus aimed at evaluating the associations between season of birth, vitamin D status, and the allergy risk markers IL-10 and total immunoglobulin (IgE) in newborns. Cord blood was obtained from 49 infants born during the summer half year (mid-April to mid-October, geographic latitude 51 degrees N) and from 47 infants born during the winter half year (mid-October to mid-April, geographic latitude of 51 degrees N). Serum levels of 25-OHD were 99% higher, and IL-10 levels were 43% higher in the summer half year compared with the winter half year (p < 0.001 and p = 0.018). Moreover, the ratio of IL-10 to total IgE was 124% higher in the summer half year compared with the winter half year (p = 0.039). Serum levels of 25-OHD were correlated with IL-10 levels (r = +0.22; p < 0.05). Mothers' age, gestational ages, birth weights and serum 1,25(OH)2D levels did not differ between study groups. We conclude that the low vitamin D status of infants born in winter may at least in part adversely affect biomarkers of allergy risk.