The impact of cesarean delivery on infant DNA methylation

Abstract Background Mounting evidence suggests that cesarean delivery may have a long-lasting effect on infant health. But the underlying mechanisms remain unclear. This study aims to examine whether cesarean delivery on maternal request without any medical indications (CDMR) impacts DNA methylation status in the umbilical cord blood of the infant. Methods A cross-sectional study was conducted in Shanghai, China. A total of 70 CDMR and 70 vaginal deliveries (VD) were recruited in 2012. The cord blood DNA methylation status was measured in 30 CDMR and 30 VD newborns using Illumina Infinium Human Methylation 450 K BeadChip. To validate the results, the cord blood DNA methylation status was measured in another 40 CDMR and 40 VD newborns using targeted bisulfite sequencing assay. A total of 497 CpG sites from 40 genes were included in the analysis. Results A total of 165 differentially methylated positions (DMPs) exhibited differences in DNA methylation by 10% or more between the CDMR and VD groups, many of which were related to the development of the immune system. Based on the targeted bisulfite sequencing assay, 16 genes (16/22, 72.7%) had higher methylation level in the CDMR group than the VD group. Among them, 5 genes were related to the immune system. After considering the estimation of cell type proportions, there was few significant differences in DNA methylation between CDMR and VD groups. Conclusions The DMPs identified between CDMR and VD groups might be largely explained by the cell type proportions. Further studies are needed to examine DNA methylation in each cell type separately.

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Differences in DNA methylation of white blood cell types at birth and in adulthood reflect postnatal immune maturation and influence accuracy of cell type prediction

10.1101/399279 ◽

2018 ◽

Cited By ~ 3

Author(s):

Meaghan J Jones ◽

Louie Dinh ◽

Hamid Reza Razzaghian ◽

Olivia de Goede ◽

Julia L MacIsaac ◽

...

Keyword(s):

Dna Methylation ◽

Immune System ◽

Blood Cell ◽

Cord Blood ◽

White Blood Cell ◽

Blood Cells ◽

Cell Types ◽

Cell Type ◽

Cell Type Specific ◽

The Impact

AbstractBackgroundDNA methylation profiling of peripheral blood leukocytes has many research applications, and characterizing the changes in DNA methylation of specific white blood cell types between newborn and adult could add insight into the maturation of the immune system. As a consequence of developmental changes, DNA methylation profiles derived from adult white blood cells are poor references for prediction of cord blood cell types from DNA methylation data. We thus examined cell-type specific differences in DNA methylation in leukocyte subsets between cord and adult blood, and assessed the impact of these differences on prediction of cell types in cord blood.ResultsThough all cell types showed differences between cord and adult blood, some specific patterns stood out that reflected how the immune system changes after birth. In cord blood, lymphoid cells showed less variability than in adult, potentially demonstrating their naïve status. In fact, cord CD4 and CD8 T cells were so similar that genetic effects on DNA methylation were greater than cell type effects in our analysis, and CD8 T cell frequencies remained difficult to predict, even after optimizing the library used for cord blood composition estimation. Myeloid cells showed fewer changes between cord and adult and also less variability, with monocytes showing the fewest sites of DNA methylation change between cord and adult. Finally, including nucleated red blood cells in the reference library was necessary for accurate cell type predictions in cord blood.ConclusionChanges in DNA methylation with age were highly cell type specific, and those differences paralleled what is known about the maturation of the postnatal immune system.

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Association between one-carbon metabolism indices and DNA methylation status in maternal and cord blood

Scientific Reports ◽

10.1038/s41598-018-35111-1 ◽

2018 ◽

Vol 8 (1) ◽

Cited By ~ 5

Author(s):

Anna K. Knight ◽

Hea Jin Park ◽

Dorothy B. Hausman ◽

Jennifer M. Fleming ◽

Victoria L. Bland ◽

...

Keyword(s):

Dna Methylation ◽

Cord Blood ◽

Carbon Metabolism ◽

Methylation Status ◽

One Carbon Metabolism

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Whole-Genome Methylation Analysis Revealed ART-Specific DNA Methylation Pattern of Neuro- and Immune-System Pathways in Chinese Human Neonates

Frontiers in Genetics ◽

10.3389/fgene.2021.696840 ◽

2021 ◽

Vol 12 ◽

Author(s):

Zongzhi Liu ◽

Wei Chen ◽

Zilong Zhang ◽

Junyun Wang ◽

Yi-Kun Yang ◽

...

Keyword(s):

Dna Methylation ◽

Immune System ◽

Cord Blood ◽

Genetic Model ◽

Housekeeping Genes ◽

Normal Pregnancy ◽

Methylation Pattern ◽

Whole Genome ◽

Maternal Cell ◽

Dna Methylation Pattern

The DNA methylation of human offspring can change due to the use of assisted reproductive technology (ART). In order to find the differentially methylated regions (DMRs) in ART newborns, cord blood maternal cell contamination and parent DNA methylation background, which will add noise to the real difference, must be removed. We analyzed newborns’ heel blood from six families to identify the DMRs between ART and natural pregnancy newborns, and the genetic model of methylation was explored, meanwhile we analyzed 32 samples of umbilical cord blood of infants born with ART and those of normal pregnancy to confirm which differences are consistent with cord blood data. The DNA methylation level was lower in ART-assisted offspring at the whole genome-wide level. Differentially methylated sites, DMRs, and cord blood differentially expressed genes were enriched in the important pathways of the immune system and nervous system, the genetic patterns of DNA methylation could be changed in the ART group. A total of three imprinted genes and 28 housekeeping genes which were involved in the nervous and immune systems were significant different between the two groups, six of them were detected both in heel blood and cord blood. We concluded that there is an ART-specific DNA methylation pattern involved in neuro- and immune-system pathways of human ART neonates, providing an epigenetic basis for the potential long-term health risks in ART-conceived neonates.

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DNA methylation of insulin-like growth factor 2 and H19 cluster in cord blood and prenatal air pollution exposure to fine particulate matter

Environmental Health ◽

10.1186/s12940-020-00677-9 ◽

2020 ◽

Vol 19 (1) ◽

Author(s):

Congrong Wang ◽

Michelle Plusquin ◽

Akram Ghantous ◽

Zdenko Herceg ◽

Rossella Alfano ◽

...

Keyword(s):

Dna Methylation ◽

Particulate Matter ◽

Growth Factor ◽

Cord Blood ◽

Gene Cluster ◽

Methylation Level ◽

Fine Particulate Matter ◽

Methylation Status ◽

Insulin Like Growth Factor ◽

Fine Particulate

Abstract Background The IGF2 (insulin-like growth factor 2) and H19 gene cluster plays an important role during pregnancy as it promotes both foetal and placental growth. We investigated the association between cord blood DNA methylation status of the IGF2/H19 gene cluster and maternal fine particulate matter exposure during fetal life. To the best of our knowledge, this is the first study investigating the association between prenatal PM2.5 exposure and newborn DNA methylation of the IGF2/H19. Methods Cord blood DNA methylation status of IGF2/H19 cluster was measured in 189 mother-newborn pairs from the ENVIRONAGE birth cohort (Flanders, Belgium). We assessed the sex-specific association between residential PM2.5 exposure during pregnancy and the methylation level of CpG loci mapping to the IGF2/H19 cluster, and identified prenatal vulnerability by investigating susceptible time windows of exposure. We also addressed the biological functionality of DNA methylation level in the gene cluster. Results Prenatal PM2.5 exposure was found to have genetic region-specific significant association with IGF2 and H19 during specific gestational weeks. The association was found to be sex-specific in both gene regions. Functionality of the DNA methylation was annotated by the association to fetal growth and cellular pathways. Conclusions The results of our study provided evidence that prenatal PM2.5 exposure is associated with DNA methylation in newborns’ IGF2/H19. The consequences within the context of fetal development of future phenotyping should be addressed.

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A smoothed EM-algorithm for DNA methylation profiles from sequencing-based methods in cell lines or for a single cell type

Statistical Applications in Genetics and Molecular Biology ◽

10.1515/sagmb-2016-0062 ◽

2017 ◽

Vol 16 (5-6) ◽

Cited By ~ 1

Author(s):

Lajmi Lakhal-Chaieb ◽

Celia M.T. Greenwood ◽

Mohamed Ouhourane ◽

Kaiqiong Zhao ◽

Belkacem Abdous ◽

...

Keyword(s):

Dna Methylation ◽

Em Algorithm ◽

Single Cell ◽

Cell Lines ◽

Methylation Status ◽

Embryonic Stem ◽

Cell Type ◽

Data Set ◽

Cpg Sites ◽

Single Cell Type

AbstractWe consider the assessment of DNA methylation profiles for sequencing-derived data from a single cell type or from cell lines. We derive a kernel smoothed EM-algorithm, capable of analyzing an entire chromosome at once, and to simultaneously correct for experimental errors arising from either the pre-treatment steps or from the sequencing stage and to take into account spatial correlations between DNA methylation profiles at neighbouring CpG sites. The outcomes of our algorithm are then used to (i) call the true methylation status at each CpG site, (ii) provide accurate smoothed estimates of DNA methylation levels, and (iii) detect differentially methylated regions. Simulations show that the proposed methodology outperforms existing analysis methods that either ignore the correlation between DNA methylation profiles at neighbouring CpG sites or do not correct for errors. The use of the proposed inference procedure is illustrated through the analysis of a publicly available data set from a cell line of induced pluripotent H9 human embryonic stem cells and also a data set where methylation measures were obtained for a small genomic region in three different immune cell types separated from whole blood.

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Abstract 5335: A highly efficient targeted bisulfite sequencing method for accurate DNA methylation profiling

10.1158/1538-7445.am2018-5335 ◽

2018 ◽

Author(s):

Quan Peng ◽

Daniel Kim ◽

Mohammad Nezami Ranjbar ◽

Sascha Strauss ◽

Scott Winter ◽

...

Keyword(s):

Dna Methylation ◽

Bisulfite Sequencing ◽

Targeted Bisulfite Sequencing ◽

Highly Efficient ◽

Sequencing Method ◽

Dna Methylation Profiling ◽

Methylation Profiling

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Altered DNA methylation in human placenta after (suspected) preterm labor

Epigenomics ◽

10.2217/epi-2019-0346 ◽

2020 ◽

Vol 12 (20) ◽

pp. 1769-1782

Author(s):

Jon Schoorlemmer ◽

Sofía Macías-Redondo ◽

Mark Strunk ◽

Ricardo Ramos-Ruíz ◽

Pilar Calvo ◽

...

Keyword(s):

Dna Methylation ◽

Preterm Birth ◽

Human Placenta ◽

Preterm Labor ◽

Bisulfite Sequencing ◽

Term Birth ◽

Targeted Bisulfite Sequencing ◽

Per Se ◽

Methylation Patterns

Aim: The aim of this study was to determine if alterations in DNA methylation in the human placenta would support suspected preterm labor as a pathologic insult associated with diminished placental health. Methods: We evaluated placental DNA methylation at seven loci differentially methylated in placental pathologies using targeted bisulfite sequencing, in placentas associated with preterm labor (term birth after suspected preterm labor [n = 15] and preterm birth [n = 15]), and controls (n = 15). Results: DNA methylation levels at the NCAM1 and PLAGL1 loci in placentas associated with preterm labor did differ significantly (p < 0.05) from controls. Discussion: Specific alterations in methylation patterns indicative of an unfavourable placental environment are associated with preterm labor per se and not restricted to preterm birth.

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Altered immune phenotype and DNA methylation in panic disorder

Clinical Epigenetics ◽

10.1186/s13148-020-00972-9 ◽

2020 ◽

Vol 12 (1) ◽

Author(s):

Curtis L. Petersen ◽

Ji-Qing Chen ◽

Lucas A. Salas ◽

Brock C. Christensen

Keyword(s):

Dna Methylation ◽

Panic Disorder ◽

Methylation Status ◽

Methylation Data ◽

Cell Type ◽

Repeat Elements ◽

Study Approach ◽

Immune Alterations ◽

Dna Elements ◽

Repetitive Dna Elements

Abstract Background Multiple studies have related psychiatric disorders and immune alterations. Panic disorder (PD) has been linked with changes in leukocytes distributions in several small studies using different methods for immune characterization. Additionally, alterations in the methylation of repetitive DNA elements, such as LINE-1, have been associated with mental disorders. Here, we use peripheral blood DNA methylation data from two studies and an updated DNA methylation deconvolution library to investigate the relation of leukocyte proportions and methylation status of repetitive elements in 133 patients with panic disorder compared with 118 controls. Methods and results We used DNA methylation data to deconvolute leukocyte cell-type proportions and to infer LINE-1 element methylation comparing PD cases and controls. We also identified differentially methylated CpGs associated with PD using an epigenome-wide association study approach (EWAS), with models adjusting for sex, age, and cell-type proportions. Individuals with PD had a lower proportion of CD8T cells (OR: 0.86, 95% CI: 0.78–0.96, P-adj = 0.030) when adjusting for age, sex, and study compared with controls. Also, PD cases had significantly lower LINE-1 repetitive element methylation than controls (P < 0.001). The EWAS identified 61 differentially methylated CpGs (58 hypo- and 3 hypermethylated) in PD (Bonferroni adjusted P < 1.33 × 10–7). Conclusions These results suggest that those with panic disorder have changes to their immune system and dysregulation of repeat elements relative to controls.

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Pharmacokinetics of Prophylactic Cefazolin in Parturients Undergoing Cesarean Delivery

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.02613-13 ◽

2014 ◽

Vol 58 (6) ◽

pp. 3504-3513 ◽

Cited By ~ 18

Author(s):

Mohammed H. Elkomy ◽

Pervez Sultan ◽

David R. Drover ◽

Ekaterina Epshtein ◽

Jeffery L. Galinkin ◽

...

Keyword(s):

Cord Blood ◽

Pregnant Women ◽

Cesarean Delivery ◽

Plasma Concentrations ◽

Maternal Blood ◽

Blood Samples ◽

Elective Cesarean ◽

Neonatal Blood ◽

The Impact ◽

Maternal Administration

ABSTRACTThe objectives of this work were (i) to characterize the pharmacokinetics of cefazolin in pregnant women undergoing elective cesarean delivery and in their neonates; (ii) to assess cefazolin transplacental transmission; (iii) to evaluate the dosing and timing of preoperative, prophylactic administration of cefazolin to pregnant women; and (iv) to investigate the impact of maternal dosing on therapeutic duration and exposure in newborns. Twenty women received 1 g of cefazolin preoperatively. Plasma concentrations of total cefazolin were analyzed from maternal blood samples taken before, during, and after delivery; umbilical cord blood samples obtained at delivery; and neonatal blood samples collected 24 h after birth. The distribution volume of cefazolin was 9.44 liters/h. The values for pre- and postdelivery clearance were 7.18 and 4.12 liters/h, respectively. Computer simulations revealed that the probability of maintaining free cefazolin concentrations in plasma above 8 mg/liter during scheduled caesarean surgery was <50% in the cord blood when cefazolin was administered in doses of <2 g or when it was administered <1 h before delivery. Therapeutic concentrations of cefazolin persisted in neonates >5 h after birth. Cefazolin clearance increases during pregnancy, and larger doses are recommended for surgical prophylaxis in pregnant women to obtain the same antibacterial effect as in nonpregnant patients. Cefazolin has a longer half-life in neonates than in adults. Maternal administration of up to 2 g of cefazolin is effective and produces exposure within clinically approved limits in neonates.

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