Associations of maternal plasma and infant umbilical cord blood plasma metabolomics profiles with anthropometric measures at birth: a prospective cohort study.

BackgroundThe metabolomics profiles of maternal plasma during pregnancy and cord plasma at birth might influence fetal growth and birth anthropometry. The objectives of this study are to examine how metabolites measured in maternal plasma samples collected during pregnancy and umbilical cord plasma samples collected at birth are associated with newborn anthropometric measures, a known predictor of future health outcomes.MethodsPregnant women between 24 and 28 weeks of gestation were recruited from prenatal clinics in New Hampshire as part of a prospective cohort study. Blood samples from 413 women at enrollment and 787 infant cord blood samples were analyzed using the Biocrates AbsoluteIDQ® p180 kit . Multivariable linear regression models were used to examine association of cord and maternal metabolites with infant anthropometry at birth.ResultsIn cord blood samples, several acylcarnitines, a phosphatidylcholine, and a custom metabolite indicator were negatively associated with birth weight Z-score, and lysophosphatidylcholines as well as three custom metabolite indicators were positively associated with birth weight Z-score. Acylcarnitine C5 was negatively associated with birth length Z-score, and several lysophosphatidylcholines and a custom metabolite indicator were positively associated with birth length Z-score. Maternal blood metabolites did not show significant associations with birth weight and length Z scores, however, a custom metabolite indicator, the ratio of kynurenine over tryptophan, was negatively associated with weight-for-length Z-score.ConclusionsSeveral cord blood metabolites associated with newborn weight and length Z-scores; in particular, consistent findings were observed for several acylcarnitines that play a role in utilization of energy sources, and a lysophosphatidylcholine that is part of oxidative stress and inflammatory response pathways. Fewer associations were observed with maternal metabolomic profiles.

Combined Effect of Telomere Length and Mitochondrial DNA Copy Number As a Potential Biomarker Indicating PE Risk: a Case-Control Study in a Chinese Population

Purpose To explore changes of Telomere length (TL) and mitochondrial copy number (mtDNA-CN) in preeclampsia (PE) and to evaluatethe combined effect of maternal TL and mtDNA-CN on PE risk.Methods A case-control study of 471 subjects (130 PE cases and 341 age frequency matched controls) was conducted in Nanjing Drum Tower Hospital, Jiangsu Province of China. Relative telomere length (RTL) and mtDNA-CN were measured using quantitative polymerase chain reaction (qPCR) and PE risk was calculated between groups by logistic regression analyses.Results PE patients displayed longer RTL (0.48 versus 0.30) and higher mtDNA-CN (3.02 versus 2.00) in maternal bloodas well as longer cord blood RTL(0.61 versus 0.35) but lower mtDNA-CN (1.69 versus 5.49) in cord blood (all p<0.001). Exercise during pregnancy exerted an obvious effect of prolonging maternal telomere length. Multiparous, women with folic acid intake during early pregnancy and those delivered vaginally showed longer telomere length while those factors imposed no or opposite effect on RTL in PE cases. Furthermore, RTL and mtDNA-CN were positively correlated in controls (in maternal blood r=0.18, p<0.01; in cord blood r=0.19, p<0.001), but this correlation was disrupted in PE cases, no matter in maternal blood or in cord blood. Longer maternal RTL and higher mtDNA-CN were associated with higher risk of PE, and the ROC curve of RTL and mtDNA-CN in predicting PE risk presented an AUC of 0.755(95%CI: 0.698-0.812).Conclusions Interaction of TL and mtDNA-CN may play an important role in pathogenesis of PE and it could be a potential biomarker indicating PE risk.

Mapping the cord blood transcriptome of pregnancies affected by early maternal anemia to identify signatures of fetal programming

Objective Anemia during early pregnancy (EP) is common in developing countries and is associated with adverse health consequences for both mother and children. Offspring of women with EP anemia often have low birth-weight, the latter being a risk factor for cardiometabolic diseases including type 2 diabetes (T2D) later in life. Mechanisms underlying developmental programming of adult cardiometabolic disease include epigenetic and transcriptional alterations potentially detectable in umbilical cord blood (UCB) at time of birth. Methods We leveraged global transcriptome- and accompanying epigenome-wide changes in 48 UCB from newborns of EP-anemic Tanzanian mothers and 50 controls to identify differentially expressed genes (DEG) in UCB exposed to maternal EP-anemia. DEGs were assessed for association with neonatal anthropometry and cord insulin levels. These genes were further studied in expression data from human fetal pancreas and adult islets to understand their role in beta-cell development and/or function. Results The expression of 137 genes was altered in UCB of newborns exposed to maternal EP anemia. These putative signatures of fetal programming which included the birth-weight locus LCORL, were potentially mediated by epigenetic changes in 27 genes and associated with neonatal anthropometry. Among the DEGs were P2RX7, PIK3C2B, and NUMBL which potentially influence beta-cell development. Insulin levels were lower in EP anemia exposed UCB, supporting the notion of developmental programming of pancreatic beta-cell dysfunction and subsequently increased risk of T2D in offspring of EP anemic mothers. Conclusions Our data provide proof-of-concept on distinct transcriptional and epigenetic changes detectable in UCB from newborns exposed to maternal EP anemia.

Optimization of human umbilical cord blood-derived mesenchymal stem cell isolation and culture methods in serum- and xeno-free conditions

Background Although umbilical cord blood (UCB) is identified as a source of mesenchymal stem cells (MSCs) with various advantages, the success in cell isolation is volatile. Therefore, it is necessary to optimize methods of cord blood-derived MSC (UCB-MSC) isolation and culture. In this study, we evaluated the efficiency of UCB-MSC isolation and expansion using different commercially available serum- and xeno-free media and investigated the capacity of autologous serum and plasma as a supplement to support cell proliferation. Additionally, we defined the presence of multilineage-differentiating stress-enduring (Muse) cells in the UCB-MSC population. Functions of UCB-MSC in in vitro angiogenesis processes and anti-cancer were also verified. Methods Mononuclear cells were isolated using density gradient separation and cultured in four commercial media kits, as well as four surface coating solutions. UCB-MSCs were characterized and tested on tube formation assay, and co-cultured with SK-MEL cells in a transwell system. Results The results showed that only StemMACS™ MSC Expansion Media is more appropriate to isolate and culture UCB-MSCs. The cells exhibited a high cell proliferation rate, CFU forming capability, MSC surface marker expression, trilineage differentiate potential, and chromosome stability. In addition, the culture conditions with autologous serum coating and autologous plasma supplement enhanced cell growth and colony forming. This cell population contained Muse cells at rate of 0.3%. Moreover, UCB-MSCs could induce the tube formation of human umbilical vein endothelial cells and inhibit more than 50% of SK-MEL cell growth. Conclusions UCB-MSCs could be high-yield isolated and expanded under serum- and xeno-free conditions by using the StemMACS™ MSC Expansion Media kit. Autologous serum coating and plasma supplement enhanced cell proliferation. These UCB-MSCs had effected the tube formation process and an anti-cancer impact.

Detection of pathogens associated with early-onset neonatal sepsis in cord blood at birth using quantitative PCR

Background: Early onset neonatal sepsis (EONS) typically begins prior to, during or soon after birth and may be rapidly fatal. There is paucity of data on the aetiology of EONS in sub-Saharan Africa due to limited diagnostic capacity in this region, despite the associated significant mortality and long-term neurological impairment. Methods: We compared pathogens detected in cord blood samples between neonates admitted to hospital with possible serious bacterial infection (pSBI) in the first 48 hours of life (cases) and neonates remaining well (controls). Cord blood was systematically collected at Kilifi County Hospital (KCH) from 2011-2016, and later tested for 21 bacterial, viral and protozoal targets using multiplex PCR via TaqMan Array Cards (TAC). Results: Among 603 cases (101 [17%] of whom died), 179 (30%) tested positive for ≥1 target and 37 (6.1%) tested positive for multiple targets. Klebsiella oxytoca, Escherichia coli/Shigella spp., Pseudomonas aeruginosa, and Streptococcus pyogenes were commonest. Among 300 controls, 79 (26%) tested positive for ≥1 target, 11 (3.7%) were positive for multiple targets, and K. oxytoca and P. aeruginosa were most common. Cumulative odds ratios across controls: cases (survived): cases (died) were E. coli/Shigella spp. 2.6 (95%CI 1.6-4.4); E. faecalis 4.0 (95%CI 1.1-15); S. agalactiae 4.5 (95%CI 1.6-13); Ureaplasma spp. 2.9 (95%CI 1.3-6.4); Enterovirus 9.1 (95%CI 2.3-37); and Plasmodium spp. 2.9 (95%CI 1.4-6.2). Excluding K. oxytoca and P. aeruginosa as likely contaminants, aetiology was attributed in 9.4% (95%CI 5.1-13) cases using TAC. Leading pathogen attributions by TAC were E. coli/Shigella spp. (3.5% (95%CI 1.7-5.3)) and Ureaplasma spp. (1.7% (95%CI 0.5-3.0)). Conclusions: Cord blood sample may be useful in describing EONS pathogens at birth, but more specific tests are needed for individual diagnosis. Careful sampling of cord blood using aseptic techniques is crucial to minimize contamination. In addition to culturable bacteria, Ureaplasma and Enterovirus were causes of EONS.