Stress During Pregnancy and Epigenetic Modifications to Offspring DNA: A Systematic Review of Associations and Implications for Preterm Birth.
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ABSTRACT:
SUBMITTER: Nowak AL
PROVIDER: S-EPMC7185032 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Maternal plasma samples collected longitudinally from pregnant women were profiled using SomaLogic aptamer-based assays in women with normal pregnancy and those who delivered preterm. DiagnosisGA is the gestational age at diagnosis with any disease indicated by the Group variable, and it is set to NA for normal pregnancies. In the Group variable, sPTD stands for spontaneous preterm delivery, and PPROM for preterm premature rupture of membranes. Additional longitudinal samples of the controls, including the two samples included herein, are also available and described in PMID: 28738067.
2021-05-24 | GSE150167 | GEO
Project description:Preterm birth (PTB) is a major public health challenge, and novel, sensitive approaches to predict PTB are still evolving. Epigenomic markers are being explored as biomarkers of PTB because of their molecular stability compared to gene expression. This approach is also relatively new compared to gene-based diagnostics, which relies on mutations or single nucleotide polymorphisms. The fundamental principle of epigenome diagnostics is that epigenetic reprogramming in the target tissue (e.g. placental tissue) might be captured by more accessible surrogate tissue (e.g. blood) using biochemical epigenome assays on circulating DNA that incorporate methylation, histone modifications, nucleosome positioning, and/or chromatin accessibility. Epigenomic-based biomarkers may hold great potential for early identification of the majority of PTBs that are not associated with genetic variants or mutations. In this review, we discuss recent advances made in the development of epigenome assays focusing on its potential exploration for association and prediction of PTB. We also summarize population-level cohort studies conducted in the USA and globally that provide opportunities for genetic and epigenetic marker development for PTB. In addition, we summarize publicly available epigenome resources and published PTB studies. We particularly focus on ongoing genome-wide DNA methylation and epigenome-wide association studies. Finally, we review the limitations of current research, the importance of establishing a comprehensive biobank, and possible directions for future studies in identifying effective epigenome biomarkers to enhance health outcomes for pregnant women at risk of PTB and their infants.
| S-EPMC7293830 | biostudies-literature
Project description:IntroductionOvert thyroid disease in pregnancy is associated with numerous maternal and neonatal complications including preterm birth. Less is known about the contribution of trimester-specific subclinical alterations in individual thyroid hormones, especially in late gestation, on the risk of preterm birth. Herein, we examined the associations between subclinical changes in maternal thyroid hormone concentrations (TSH, total T3, free and total T4), measured at multiple time points in pregnancy, and the odds of preterm birth in pregnant women without clinical thyroid disease.Participants and methodsData were obtained from pregnant women participating in a nested case-control study of preterm birth within on ongoing birth cohort study at Brigham and Women's Hospital in Boston, MA (N = 439; 116 cases and 323 controls). We measured thyroid hormones in plasma collected at up to four time points in pregnancy (median = 10, 18, 26, and 35 weeks). We used multivariate logistic regression models stratified by study visit of sample collection to examine associations. To reveal potential biological pathways, we also explored these relationships by obstetric presentation of preterm birth (e.g., spontaneous preterm delivery) that have been previously hypothesized to share common underlying mechanisms.ResultsIn samples collected at median 10 and 26 weeks of gestation, we found inverse associations between FT4 and the odds of overall preterm birth (odds ratio [OR] = 0.57, 95% confidence interval (CI) = 0.33, 1.00; and OR = 0.53, 95% CI = 0.34, 0.84, respectively). Positive associations were detected for total T3 at these same time points (OR = 2.52, 95% CI = 1.20, 5.31; and OR = 3.40, 95% CI = 1.56, 7.40, respectively). These effect estimates were stronger for spontaneous preterm birth.ConclusionsOur results suggest that subclinical alterations in individual maternal thyroid hormones may influence the risk of preterm birth, and the strength of these associations vary by gestational age.
| S-EPMC5217954 | biostudies-literature
Project description:Twin pregnancies are associated with a three-fold greater perinatal mortality than singleton pregnancies. Prematurity is a main contributor, with 50% of twin pregnancies delivering before 37 weeks and 10% delivering before 32 weeks of gestation.The aetiology of preterm delivery in twin pregnancies is likely multifactorial and different from that of singletons.Cervical cerclage reduces preterm birth rates in singletons but has mixed results in twins with some studies showing harm.The use of progesterone to prevent preterm birth in singletons has conflicting results and has not been proven to prevent preterm birth in twins. Studies continue to determine whether the cervical pessary is effective in preventing preterm birth in multiple pregnancies.There is a paucity of data available on the prevention of preterm birth in triplets/higher order multiples but similar principles to twin pregnancy apply.To review the burden of preterm birth in multiple pregnancy.To understand the methods available for preventing preterm birth in multiple pregnancies and the evidence surrounding the use of each one.To be aware of the use of the Arabin pessary.
| S-EPMC6034359 | biostudies-other
Project description:BACKGROUND:Preterm birth is a disease of multifactorial etiologies that has environmental, social, and maternal health components. Individual studies have shown that exposure to arsenic contaminated drinking water, child marriage, and low maternal weight gain during pregnancy contribute to preterm birth. These factors are highly prevalent and often co-exist in Bangladesh, a country in South Asia with one of the world's highest prevalences of preterm birth. OBJECTIVE:To evaluate the individual and interactive effects of prenatal arsenic exposure, child marriage, and pregnancy weight gain on preterm birth in a prospective birth cohort in Bangladesh. METHODS:During 2008-2011, we recruited 1613 pregnant women aged ?18years at ?16weeks of gestation and followed them until 1-month post-partum. We measured total arsenic in drinking water (n=1184) and in maternal toenails (n=1115) collected at enrollment and ?1-month post-partum, respectively using inductively coupled plasma mass spectrometry. Child marriage (<18years old) was defined using self-report, and 2nd and 3rd trimester pregnancy weight gain was calculated using monthly records. Gestational age was determined at enrollment by ultrasound. RESULTS:In multivariate adjusted Poisson regression models, the risk ratios (RR) for preterm birth were 1.12 (95% CI: 1.07-1.18) for a unit change in natural log water arsenic exposure, 2.28 (95% CI: 1.76-2.95) for child marriage, and 0.64 (95% CI: 0.42-0.97) for a pound per week increase in maternal weight during the 2nd and 3rd trimesters. In stratified analysis by child marriage, pregnancy weight gain was inversely associated with preterm birth among women with a history of child marriage (RR=0.58; 95% CI: 0.37-0.92), but not among women with no history of child marriage (RR=86; 95% CI: 0.37-2.01). Mediation analysis revealed that both arsenic exposure and child marriage had small but significant associations with preterm birth via lowering pregnancy weight gain. Similar associations were observed when arsenic exposure was assessed using maternal toenail arsenic concentrations. CONCLUSIONS:Reducing arsenic exposure and ending child marriage could reduce the risk of preterm birth in Bangladesh. Furthermore, enhancing nutritional support to ensure adequate weight gain during pregnancy may provide additional benefits especially for women with a history of child marriage.
| S-EPMC6530570 | biostudies-literature
Project description:IntroductionAt the maternal-fetal interface in pregnancy, stress during pregnancy can lead to an increased vulnerability to later psychopathology of the fetus. Potential mediators of this association have scarcely been studied and may include early alterations of fetal brain-derived neurotrophic factor (BDNF). Amniotic fluid is of particular interest for effects on fetal endocrine alterations, as the assessment in amniotic fluid allows for measurements over a time integral. This study hypothesized that maternal psychometrics, socioeconomic status and glucocorticoids are related to BDNF levels in amniotic fluid at birth. The association of fetal BDNF with newborn anthropometrics was tested.MethodsWomen near term who underwent elective cesarean section and their newborns were investigated (n = 37). Maternal psychometrics, socioeconomic status and glucocorticoids (the sum of cortisol and cortisone) in amniotic fluid at birth were analyzed for an association with fetal BDNF in amniotic fluid at birth. Newborn anthropometrics were assessed by length, weight, head circumference and gestational age at birth.ResultsIn bivariate analysis, maternal psychometrics and socioeconomic status were not related to fetal BDNF in amniotic fluid at birth. The sum of cortisol and cortisone related to increased fetal BDNF in amniotic fluid at birth (r = 0.745, p < 0.001). BDNF in amniotic fluid was associated negatively with fetal birth weight per gestational age (r = -0.519, p < 0.001), length per gestational age (r = -0.374, p = 0.023), head circumference per gestational age (r = -0.508, p = 0.001), but not with gestational age at birth. In multiple regression analysis, the sum of cortisol and cortisone (p < 0.001) and birth weight per gestational age (p = 0.012) related to higher fetal BDNF levels in amniotic fluid at birth (R2 = 0.740, p < 0.001) when controlling for fetal sex and maternal age. Head circumference per gestational age predicted fetal BDNF with borderline significance (p = 0.058) when controlling for confounders.ConclusionGlucocorticoids in amniotic fluid were positively associated with high fetal BDNF at birth, which may be an adaptive fetal response. Maternal psychological variables and socioeconomic status did not link to fetal BDNF. Birth weight and head circumference per gestational age were inversely associated with fetal BDNF at birth, which may represent a compensatory upregulation of BDNF in fetuses with low anthropometrics. Longitudinal studies are needed to assess the role of stress during pregnancy on later offspring development. The analysis of additional fetal growth factors and inflammation upon maternal stress in further biomaterials such as the placenta is warranted, to understand mechanistic alterations of how maternal stress links to fetal development and an increased vulnerability for psychopathology.
| S-EPMC11294724 | biostudies-literature
Project description:Most studies linking maternal diet with offspring adiposity have focused on single nutrients or foods, but a dietary pattern approach is more representative of the overall diet. We thus aimed to investigate the relations between maternal dietary patterns and offspring adiposity in a multi-ethnic Asian mother-offspring cohort in Singapore. We derived maternal dietary patterns using maternal dietary intake information at 26-28 weeks of gestation, of which associations with offspring body mass index (BMI), abdominal circumference (AC), subscapular skinfold (SS), and triceps skinfold (TS) were assessed using longitudinal data analysis (linear mixed effects (LME)) and multiple linear regression at ages 0, 3, 6, 9, 12, 15, 18, 24, 36, 48, and 54 months. Three dietary patterns were derived: (1) vegetables-fruit-and-white rice (VFR); (2) seafood-and-noodles (SfN); and (3) pasta-cheese-and-bread (PCB). In the LME model adjusting for potential confounders, each standard deviation (SD) increase in maternal VFR pattern score was associated with 0.09 mm lower offspring TS. Individual time-point analysis additionally revealed that higher VFR score was generally associated with lower postnatal offspring BMI z-score, TS, SS, and sum of skinfolds (SS + TS) at ages 18 months and older. Maternal adherence to a dietary pattern characterized by higher intakes of fruit and vegetables and lower intakes of fast food was associated with lower offspring adiposity.
| S-EPMC5295046 | biostudies-literature
Project description:BackgroundPreterm birth is a leading cause of perinatal mortality and long-term health consequences. Epigenetic mechanisms may have been at play in preterm birth survivors, and these could be persistent and detrimental to health later in life.MethodsWe performed a genome-wide DNA methylation profiling in adult twins of premature birth to identify genomic regions under differential epigenetic regulation in 144 twins with a median age of 33 years (age range 30-36).ResultsAssociation analysis detected three genomic regions annotated to the SDHAP3, TAGLN3 and GSTT1 genes on chromosomes 5, 3 and 22 (FWER: 0.01, 0.02 and 0.04) respectively. These genes display strong involvement in neurodevelopmental disorders, cancer susceptibility and premature delivery. The three identified significant regions were successfully replicated in an independent sample of twins of even older age (median age 66, range 56-80) with similar regulatory patterns and nominal p values < 5.05e-04. Biological pathway analysis detected five significantly enriched pathways all explicitly involved in immune responses.ConclusionWe have found novel evidence associating premature delivery with epigenetic modification of important genes/pathways and revealed that preterm birth, as an early life event, could be related to differential methylation regulation patterns observable in adults and even at high ages which could potentially mediate susceptibility to age-related diseases and adult health.
| S-EPMC6020425 | biostudies-literature
Project description:Prenatal antidepressant exposure has been associated with adverse outcomes. Previous studies, however, may not have adequately accounted for confounding.To evaluate alternative hypotheses for associations between first-trimester antidepressant exposure and birth and neurodevelopmental problems.This retrospective cohort study included Swedish offspring born between 1996 and 2012 and followed up through 2013 or censored by death or emigration. Analyses controlling for pregnancy, maternal and paternal covariates, as well as sibling comparisons, timing of exposure comparisons, and paternal comparisons, were used to examine the associations.Maternal self-reported first-trimester antidepressant use and first-trimester antidepressant dispensations.Preterm birth (<37 gestational weeks), small for gestational age (birth weight <2 SDs below the mean for gestational age), and first inpatient or outpatient clinical diagnosis of autism spectrum disorder and attention-deficit/hyperactivity disorder in offspring.Among 1?580?629 offspring (mean gestational age, 279 days; 48.6% female; 1.4% [n?=?22?544] with maternal first-trimester self-reported antidepressant use) born to 943?776 mothers (mean age at childbirth, 30 years), 6.98% of exposed vs 4.78% of unexposed offspring were preterm, 2.54% of exposed vs 2.19% of unexposed were small for gestational age, 5.28% of exposed vs 2.14% of unexposed were diagnosed with autism spectrum disorder by age 15 years, and 12.63% of exposed vs 5.46% of unexposed were diagnosed with attention-deficit/hyperactivity disorder by age 15 years. At the population level, first-trimester exposure was associated with all outcomes compared with unexposed offspring (preterm birth odds ratio [OR], 1.47 [95% CI, 1.40-1.55]; small for gestational age OR, 1.15 [95% CI, 1.06-1.25]; autism spectrum disorder hazard ratio [HR], 2.02 [95% CI, 1.80-2.26]; attention-deficit/hyperactivity disorder HR, 2.21 [95% CI, 2.04-2.39]). However, in models that compared siblings while adjusting for pregnancy, maternal, and paternal traits, first-trimester antidepressant exposure was associated with preterm birth (OR, 1.34 [95% CI, 1.18-1.52]) but not with small for gestational age (OR, 1.01 [95% CI, 0.81-1.25]), autism spectrum disorder (HR, 0.83 [95% CI, 0.62-1.13]), or attention-deficit/hyperactivity disorder (HR, 0.99 [95% CI, 0.79-1.25]). Results from analyses assessing associations with maternal dispensations before pregnancy and with paternal first-trimester dispensations were consistent with findings from the sibling comparisons.Among offspring born in Sweden, after accounting for confounding factors, first-trimester exposure to antidepressants, compared with no exposure, was associated with a small increased risk of preterm birth but no increased risk of small for gestational age, autism spectrum disorder, or attention-deficit/hyperactivity disorder.
| S-EPMC5875187 | biostudies-literature
Project description:ObjectiveTo assess whether exposure to high temperatures in pregnancy is associated with increased risk for preterm birth, low birth weight, and stillbirth.DesignSystematic review and random effects meta-analysis.Data sourcesMedline and Web of Science searched up to September 2018, updated in August 2019.Eligibility criteria for selecting studiesClinical studies on associations between high environmental temperatures, and preterm birth, birth weight, and stillbirths.Results14 880 records and 175 full text articles were screened. 70 studies were included, set in 27 countries, seven of which were countries with low or middle income. In 40 of 47 studies, preterm births were more common at higher than lower temperatures. Exposures were classified as heatwaves, 1°C increments, and temperature threshold cutoff points. In random effects meta-analysis, odds of a preterm birth rose 1.05-fold (95% confidence interval 1.03 to 1.07) per 1°C increase in temperature and 1.16-fold (1.10 to 1.23) during heatwaves. Higher temperature was associated with reduced birth weight in 18 of 28 studies, with considerable statistical heterogeneity. Eight studies on stillbirths all showed associations between temperature and stillbirth, with stillbirths increasing 1.05-fold (1.01 to 1.08) per 1°C rise in temperature. Associations between temperature and outcomes were largest among women in lower socioeconomic groups and at age extremes. The multiple temperature metrics and lag analyses limited comparison between studies and settings.ConclusionsAlthough summary effect sizes are relatively small, heat exposures are common and the outcomes are important determinants of population health. Linkages between socioeconomic status and study outcomes suggest that risks might be largest in low and middle income countries. Temperature rises with global warming could have major implications for child health.Systematic review registrationPROSPERO CRD 42019140136 and CRD 42018118113.
| S-EPMC7610201 | biostudies-literature