Epigenome Wide Association and Stochastic Epigenetic Mutation Analysis on Cord Blood of Preterm Birth

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Abstract

Preterm birth (PTB) can be defined as the endpoint of a complex process that could be influenced by maternal and environmental factors. Epigenetics recently emerged as an interesting field of investigation since it represents an important mechanism of regulation. This study evaluates epigenetic impact of preterm birth on DNA methylation. Genome-wide DNAm was measured using the Illumina 450K array in cord blood samples obtained from 72 full term and 18 preterm newborns. Lymphocyte composition was calculated based on specific epigenetic markers that are present on the 450k array. Differential methylation analysis was performed both at site and region level; moreover, stochastic epigenetic mutations (SEMs) were also evaluated. The study showed significant differences in blood cell composition between the two groups. Moreover, after multiple testing correction, statistically significant differences in DNA methylation levels emerged between the two groups both at site and region levels. Results obtained were compared to those reported by previous EWAS, leading to a list of more consistent genes associated with PTB. Finally, the SEMs analysis revealed that the burden of SEMs resulted significantly higher in the preterm group. In conclusion, PTB resulted associated to specific epigenetic signatures that involve immune system. Moreover, SEMs analysis revealed an increased epigenetic drift at birth in the preterm group.

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Preterm birth and the metabolic syndrome in adult life: a systematic review and meta-analysis.

Matthew J. Hyde, Chris Gale, Neena Modi … (2013)

Preterm birth is associated with features of the metabolic syndrome in later life. We performed a systematic review and meta-analysis of studies reporting markers of the metabolic syndrome in adults born preterm. Reports of metabolic syndrome-associated features in adults (≥18 years of age) born at <37-week gestational age and at term (37- to 42-week gestational age) were included. Outcomes assessed were BMI, waist-hip ratio, percentage fat mass, systolic (SBP) and diastolic (DBP) blood pressure, 24-hour ambulatory SBP and DBP, flow-mediated dilatation, intima-media thickness, and fasting glucose, insulin, and lipid profiles. Twenty-seven studies, comprising a combined total of 17,030 preterm and 295,261 term-born adults, were included. In adults, preterm birth was associated with significantly higher SBP (mean difference, 4.2 mm Hg; 95% confidence interval [CI], 2.8 to 5.7; P < .001), DBP (mean difference, 2.6 mm Hg; 95% CI, 1.2 to 4.0; P < .001), 24-hour ambulatory SBP (mean difference, 3.1 mm Hg; 95% CI, 0.3 to 6.0; P = .03), and low-density lipoprotein (mean difference, 0.14 mmol/L; 95% CI, 0.05 to 0.21; P = .01). The preterm-term differences for women was greater than the preterm-term difference in men by 2.9 mm Hg for SBP (95% CI [1.1 to 4.6], P = .004) and 1.6 mm Hg for DBP (95% CI [0.3 to 2.9], P = .02). For the majority of outcome measures associated with the metabolic syndrome, we found no difference between preterm and term-born adults. Increased plasma low-density lipoprotein in young adults born preterm may represent a greater risk for atherosclerosis and cardiovascular disease in later life. Preterm birth is associated with higher blood pressure in adult life, with women appearing to be at greater risk than men.

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The immune consequences of preterm birth

Jacqueline Melville, Timothy Moss (2013)

Preterm birth occurs in 11% of live births globally and accounts for 35% of all newborn deaths. Preterm newborns have immature immune systems, with reduced innate and adaptive immunity; their immune systems may be further compromised by various factors associated with preterm birth. The immune systems of preterm infants have a smaller pool of monocytes and neutrophils, impaired ability of these cells to kill pathogens, and lower production of cytokines which limits T cell activation and reduces the ability to fight bacteria and detect viruses in cells, compared to term infants. Intrauterine inflammation is a major contributor to preterm birth, and causes premature immune activation and cytokine production. This can induce immune tolerance leading to reduced newborn immune function. Intrauterine inflammation is associated with an increased risk of early-onset sepsis and likely has long-term adverse immune consequences. Requisite medical interventions further impact on immune development and function. Antenatal corticosteroid treatment to prevent newborn respiratory disease is routine but may be immunosuppressive, and has been associated with febrile responses, reductions in lymphocyte proliferation and cytokine production, and increased risk of infection. Invasive medical procedures result in an increased risk of late-onset sepsis. Respiratory support can cause chronic inflammatory lung disease associated with increased risk of long-term morbidity. Colonization of the infant by microorganisms at birth is a significant contributor to the establishment of the microbiome. Caesarean section affects infant colonization, potentially contributing to lifelong immune function and well-being. Several factors associated with preterm birth alter immune function. A better understanding of perinatal modification of the preterm immune system will allow for the refinement of care to minimize lifelong adverse immune consequences.

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Social adversity and epigenetic aging: a multi-cohort study on socioeconomic differences in peripheral blood DNA methylation

Giovanni Fiorito, Silvia Polidoro, Pierre-Antoine Dugué … (2017)

Low socioeconomic status (SES) is associated with earlier onset of age-related chronic conditions and reduced life-expectancy, but the underlying biomolecular mechanisms remain unclear. Evidence of DNA-methylation differences by SES suggests a possible association of SES with epigenetic age acceleration (AA). We investigated the association of SES with AA in more than 5,000 individuals belonging to three independent prospective cohorts from Italy, Australia, and Ireland. Low SES was associated with greater AA (β = 0.99 years; 95% CI 0.39,1.59; p = 0.002; comparing extreme categories). The results were consistent across different SES indicators. The associations were only partially modulated by the unhealthy lifestyle habits of individuals with lower SES. Individuals who experienced life-course SES improvement had intermediate AA compared to extreme SES categories, suggesting reversibility of the effect and supporting the relative importance of the early childhood social environment. Socioeconomic adversity is associated with accelerated epigenetic aging, implicating biomolecular mechanisms that may link SES to age-related diseases and longevity.

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Journal

Journal ID (nlm-ta): Int J Mol Sci

Journal ID (iso-abbrev): Int J Mol Sci

Journal ID (publisher-id): ijms

Title: International Journal of Molecular Sciences

Publisher: MDPI

ISSN (Electronic): 1422-0067

Publication date (Electronic): 17 July 2020

Publication date Collection: July 2020

Volume: 21

Issue: 14

Electronic Location Identifier: 5044

Affiliations

[1 ]Department of Brain and Behavioral Sciences, University of Pavia, 27100 Pavia, Italy; elena.spada01@ 123456universitadipavia.it (E.S.); luigi.corsaro01@ 123456universitadipavia.it (L.C.); teresa.fazia01@ 123456ateneopv.it (T.F.); luiber04@ 123456unipv.it (L.B.)

[2 ]Bioinformatics and Statistical Genomics Unit, Istituto Auxologico Italiano IRCCS, Cusano Milanino, 20095 Milano, Italy; luciano.calza@ 123456gmail.com

[3 ]Molecular Biology Laboratory, Istituto Auxologico Italiano IRCCS, Cusano Milanino, 20095 Milano, Italy; m.mencarelli@ 123456auxologico.it (M.M.); a.diblasio@ 123456auxologico.it (A.M.D.B.)

[4 ]Department of Biomedical Science for the Health, University of Milan, Macedonio Melloni Hospital, 20129 Milan, Italy; giuliazangheri@ 123456hotmail.com (G.Z.); michele.vignali@ 123456unimi.it (M.V.)

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[* ]Correspondence: davide.gentilini@ 123456unipv.it ; Tel.: +39-0382987541

Author information

Luciano Calzari https://orcid.org/0000-0003-4283-0988

Teresa Fazia https://orcid.org/0000-0002-9577-8450

Luisa Bernardinelli https://orcid.org/0000-0002-7551-6664

Michele Vignali https://orcid.org/0000-0002-9806-3741

Article

Publisher ID: ijms-21-05044

DOI: 10.3390/ijms21145044

PMC ID: 7403978

PubMed ID: 32708910

SO-VID: 66c8912f-ac58-46f6-b846-2fe4b816f3fa

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Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

Epigenome Wide Association and Stochastic Epigenetic Mutation Analysis on Cord Blood of Preterm Birth

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Higher order chromatin architecture

Most cited references 29

Preterm birth and the metabolic syndrome in adult life: a systematic review and meta-analysis.

The immune consequences of preterm birth

Social adversity and epigenetic aging: a multi-cohort study on socioeconomic differences in peripheral blood DNA methylation

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