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      Is the risk of low birth weight or preterm labor greater when maternal stress is experienced during pregnancy? A systematic review and meta-analysis of cohort studies

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          Abstract

          Antenatal stress is linked to fetal risks that increase the chances of neonatal complications and reduction of child cognitive ability. Therefore, we aimed to evaluate if maternal stress affects fetal, neonatal or child development. The following databases were searched: MEDLINE (1966 to May 2016), Embase (1980 to May 2016), LILACS (1982 to May 2016) and CENTRAL (1972 to May 2016). Observational studies published in English and Portuguese were included whether there was any relationship between fetal and neonatal outcome, such as birth weight, preterm labor, child development with pregnant women that were subjected to any stress type during at least one month of follow-up. Two independent reviewers screened eligible articles, extracted data and assessed the risk of bias. Thus, 8 cohort studies with about 8,271 pregnant women and 1,081,151 children proved eligible. Results suggested a significant association between antenatal stress exposure and increasing rates of low birth weight (Odds ratio (OR) 1.68 [95% Confidential Interval (CI) 1.19, 2.38]). However, there was no statistically significance difference between non-exposed and exposed groups related to preterm labor (OR 1.98 [95% CI 0.91 to 4.31]; I2 = 68%, p = 0.04). Although, results were inconsistent with primary analysis suggesting a significant association between antenatal stress exposure and the occurrence of higher rates of preterm birth (OR 1.42 [95% CI 1.05 to 1.91]; I2 = 68%, p = 0.04) in the sensitivity analysis. Furthermore, the current review has suggested that stress perceived during antenatal negatively influences fetal life and child development. Yet, further studies are necessary with adequate sample size and longer follow-up time to confirm our findings.

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          Newcastle-Ottawa Scale: comparing reviewers’ to authors’ assessments

          Background Lack of appropriate reporting of methodological details has previously been shown to distort risk of bias assessments in randomized controlled trials. The same might be true for observational studies. The goal of this study was to compare the Newcastle-Ottawa Scale (NOS) assessment for risk of bias between reviewers and authors of cohort studies included in a published systematic review on risk factors for severe outcomes in patients infected with influenza. Methods Cohort studies included in the systematic review and published between 2008–2011 were included. The corresponding or first authors completed a survey covering all NOS items. Results were compared with the NOS assessment applied by reviewers of the systematic review. Inter-rater reliability was calculated using kappa (K) statistics. Results Authors of 65/182 (36%) studies completed the survey. The overall NOS score was significantly higher (p < 0.001) in the reviewers’ assessment (median = 6; interquartile range [IQR] 6–6) compared with those by authors (median = 5, IQR 4–6). Inter-rater reliability by item ranged from slight (K = 0.15, 95% confidence interval [CI] = −0.19, 0.48) to poor (K = −0.06, 95% CI = −0.22, 0.10). Reliability for the overall score was poor (K = −0.004, 95% CI = −0.11, 0.11). Conclusions Differences in assessment and low agreement between reviewers and authors suggest the need to contact authors for information not published in studies when applying the NOS in systematic reviews.
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            Prenatal exposure to maternal depression, neonatal methylation of human glucocorticoid receptor gene (NR3C1) and infant cortisol stress responses.

            In animal models, variations in early maternal care are associated with differences in hypothalamic-pituitary-adrenal(HPA) stress response in the offspring, mediated via changes in the epigenetic regulation of glucocorticoid receptor (GR) gene (Nr3c1) expression. To study this in humans, relationships between prenatal exposure to maternal mood and the methylation status of a CpG-rich region in the promoter and exon 1F of the human GR gene (NR3C1) in newborns and HPA stress reactivity at age three months were examined. Prenatal exposure to increased third trimester maternal depressed/anxious mood was associated with increased methylation of NR3C1 at a predicted NGFI-A binding site. Increased NR3C1 methylation at this site was also associated with increased salivary cortisol stress responses at 3 months, controlling for prenatal SRI exposure, postnatal age and pre and postnatal maternal mood. The methylation status of a CpG-rich region of the NR3C1 gene, including exon 1F, in genomic DNA from cord blood mononuclear cells was quantified by bisulfite pyrosequencing in infants of depressed mothers treated with a serotonin reuptake inhibitor antidepressant (SRI) (n = 33), infants of depressed nontreated mothers (n = 13) and infants of non depressed/non treated mothers (n = 36). To study the functional implications of the newborn methylation status of NR3C1 in newborns, HPA function was assessed at three months using salivary cortisol obtained before and following a non noxious stressor and at a late afternoon basal time. Methylation status of the human NR3C1 gene in newborns is sensitive to prenatal maternal mood and may offer a potential epigenetic process that links antenatal maternal mood and altered HPA stress reactivity during infancy.
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              Developmental origins of health and disease: brief history of the approach and current focus on epigenetic mechanisms.

              "Barker's hypothesis" emerged almost 25 years ago from epidemiological studies of birth and death records that revealed a high geographic correlation between rates of infant mortality and certain classes of later adult deaths as well as an association between birthweight and rates of adult death from ischemic heart disease. These observations led to a theory that undernutrition during gestation was an important early origin of adult cardiac and metabolic disorders due to fetal programming that permanently shaped the body's structure, function, and metabolism and contributed to adult disease. This theory stimulated interest in the fetal origins of adult disorders, which expanded and coalesced approximately 5 years ago with the formation of an international society for developmental origins of health and disease (DOHaD). Here we review a few examples of the many emergent themes of the DOHaD approach, including theoretical advances related to predictive adaptive responses of the fetus to a broad range of environmental cues, empirical observations of effects of overnutrition and stress during pregnancy on outcomes in childhood and adulthood, and potential epigenetic mechanisms that may underlie these observations and theory. Next, we discuss the relevance of the DOHaD approach to reproductive medicine. Finally, we consider the next steps that might be taken to apply, evaluate, and extend the DOHaD approach. Thieme Medical Publishers.
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                Author and article information

                Contributors
                Role: ConceptualizationRole: Data curationRole: Formal analysisRole: Funding acquisitionRole: InvestigationRole: MethodologyRole: Project administrationRole: ResourcesRole: SoftwareRole: SupervisionRole: ValidationRole: VisualizationRole: Writing – original draftRole: Writing – review & editing
                Role: Formal analysisRole: MethodologyRole: ResourcesRole: SoftwareRole: Validation
                Role: Data curationRole: Formal analysisRole: Funding acquisitionRole: VisualizationRole: Writing – original draftRole: Writing – review & editing
                Role: Formal analysisRole: Funding acquisitionRole: ResourcesRole: SoftwareRole: VisualizationRole: Writing – original draft
                Role: MethodologyRole: Project administrationRole: ResourcesRole: SoftwareRole: Supervision
                Role: Data curationRole: Formal analysisRole: Funding acquisitionRole: Writing – original draftRole: Writing – review & editing
                Role: ConceptualizationRole: Data curationRole: Funding acquisitionRole: Project administrationRole: VisualizationRole: Writing – original draftRole: Writing – review & editing
                Role: ConceptualizationRole: Data curationRole: Formal analysisRole: Funding acquisitionRole: InvestigationRole: MethodologyRole: Project administrationRole: ResourcesRole: SoftwareRole: SupervisionRole: ValidationRole: VisualizationRole: Writing – original draftRole: Writing – review & editing
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                26 July 2018
                2018
                : 13
                : 7
                Affiliations
                [1 ] Nursing Department, Botucatu Medical School, UNESP–Univ Estadual Paulista, Botucatu, Brazil
                [2 ] Institute of Science and Technology, Department of Biosciences and Oral Diagnosis, UNESP, São José dos Campos, Brazil
                [3 ] Nursing Department of Gynecology and Obstetrics, Universidade Estadual Paulista (Unesp) Botucatu Medical School, UNESP, Botucatu, Brazil
                [4 ] Municipal Authority of Botucatu, São Paulo, Brazil
                [5 ] Minas Gerais Medical School, UFMG -Univ Federal de Minas Gerais, Belo Horizonte, Brazil
                [6 ] Department of Collective Health, Botucatu Medical School, Botucatu, São Paulo, Brazil
                University of Washington, UNITED STATES
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Article
                PONE-D-17-26827
                10.1371/journal.pone.0200594
                6061976
                30048456
                eeb18a4c-7c72-49e3-9cda-197928f8e2a5
                © 2018 Lima et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                Page count
                Figures: 4, Tables: 4, Pages: 15
                Product
                Funding
                Funded by: funder-id http://dx.doi.org/10.13039/501100003593, Conselho Nacional de Desenvolvimento Científico e Tecnológico;
                Award ID: 310953/2015-4
                Award Recipient :
                Regina El Dib received a scholarship from the Brazilian National Research Council (CNPq 310953/2015-4). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Research Article
                Medicine and Health Sciences
                Mental Health and Psychiatry
                Neuropsychiatric Disorders
                Anxiety Disorders
                Post-Traumatic Stress Disorder
                Medicine and Health Sciences
                Mental Health and Psychiatry
                Neuroses
                Anxiety Disorders
                Post-Traumatic Stress Disorder
                Physical Sciences
                Physics
                Classical Mechanics
                Mechanical Stress
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                Psychological Stress
                Biology and Life Sciences
                Psychology
                Psychological Stress
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                Pregnancy
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                Research and Analysis Methods
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