Prenatal Lead and Depression Exposures Jointly Influence Birth Outcomes and NR3C1 DNA Methylation

Many gestational exposures influence birth outcomes, yet the joint contribution of toxicant and psychosocial factors is understudied. Moreover, associated gestational epigenetic mechanisms are unknown. Lead (Pb) and depression independently influence birth outcomes and offspring NR3C1 (glucocorticoid receptor) DNA methylation. We hypothesized that gestational Pb and depression would jointly influence birth outcomes and NR3C1 methylation. Pregnancy exposure information, DNA methylation, and birth outcome data were collected prospectively from n = 272 mother–infant pairs. Factor analysis was used to reduce the dimensionality of NR3C1. Multivariable linear regressions tested for interaction effects between gestational Pb and depression exposures with birth outcomes and NR3C1. Interaction effects indicated that higher levels of Pb and depression jointly contributed to earlier gestations, smaller infant size at birth, and asymmetric fetal growth. Pb and depression were also jointly associated with the two primary factor scores explaining the most variability in NR3C1 methylation; NR3C1 scores were associated with some infant outcomes, including gestational age and asymmetric fetal growth. Pb and depression can cumulatively influence birth outcomes and epigenetic mechanisms, which may lay the foundation for later health risk. As toxicants and social adversities commonly co-occur, research should consider the life course consequences of these interconnected exposures.

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Association between maternal cannabis use and birth outcomes: an observational study

BMC Pregnancy and Childbirth ◽

10.1186/s12884-020-03371-3 ◽

2020 ◽

Vol 20 (1) ◽

Author(s):

Camilla A. Michalski ◽

Rayjean J. Hung ◽

Ryan A. Seeto ◽

Cindy-Lee Dennis ◽

Jennifer D. Brooks ◽

...

Keyword(s):

Birth Outcomes ◽

Gestational Age ◽

Birth Outcome ◽

Pain Medication ◽

Outcome Data ◽

Cannabis Use ◽

Factors Associated ◽

Cannabis Consumption ◽

Pregnancy Status ◽

Multivariable Adjustment

Abstract Background As cannabis consumption is increasing globally, including among pregnant women, there is a critical need to understand the effects of cannabis on fetal development and birth outcomes. We had two objectives: to determine 1) the factors associated with self-reported cannabis use in the pre/early-pregnancy period, and 2) whether cannabis use is associated with low birth weight, preterm birth, or small size for gestational age (GA) infants. Methods Maternal questionnaire and birth outcome data was gathered from 2229 women and 1778 singleton infants in the Ontario Birth Study, a hospital-based prospective cohort study (2013–2019). Women self-reported cannabis use within 3 months of learning their pregnancy status. Multivariable linear and logistic regression was conducted to 1) identify factors associated with cannabis use, and 2) determine the associations between cannabis use with the selected birth outcomes. Results Cannabis use increased in the cohort over time. Women who reported cannabis use (N = 216) were more likely to be younger and more likely to use alcohol, tobacco, and prescription pain medication, although most did not. These women had infants born at lower average birth weights and had 2.0 times the odds of being small for GA (95% confidence interval: 1.3, 3.3) after multivariable adjustment for socioeconomic factors and other substance use. Conclusion Our results suggest that women who use cannabis around the time of conception have higher odds of having infants that are small for gestational age. Targeted clinical messaging may be most applicable to women actively trying to conceive.

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Prenatal maternal stress and birth outcomes in rural Ghana: sex-specific associations

BMC Pregnancy and Childbirth ◽

10.1186/s12884-019-2535-9 ◽

2019 ◽

Vol 19 (1) ◽

Cited By ~ 1

Author(s):

Kenneth Ayuurebobi Ae-Ngibise ◽

Blair J. Wylie ◽

Ellen Boamah-Kaali ◽

Darby W. Jack ◽

Felix Boakye Oppong ◽

...

Keyword(s):

Birth Weight ◽

Birth Outcomes ◽

Fetal Growth ◽

Head Circumference ◽

Maternal Stress ◽

Birth Outcome ◽

Sub Saharan Africa ◽

Adverse Birth Outcome ◽

Prenatal Maternal Stress ◽

Rural Ghana

Abstract Background In developed countries, prenatal maternal stress has been associated with poor fetal growth, however this has not been evaluated in rural sub-Saharan Africa. We evaluated the effect of prenatal maternal stress on fetal growth and birth outcomes in rural Ghana. Methods Leveraging a prospective, rural Ghanaian birth cohort, we ascertained prenatal maternal negative life events, categorized scores as 0-2 (low stress; referent), 3-5 (moderate), and > 5 (high) among 353 pregnant women in the Kintampo North Municipality and Kintampo South District located within the middle belt of Ghana. We employed linear regression to determine associations between prenatal maternal stress and infant birth weight, head circumference, and length. We additionally examined associations between prenatal maternal stress and adverse birth outcome, including low birth weight, small for gestational age, or stillbirth. Effect modification by infant sex was examined. Results In all children, high prenatal maternal stress was associated with reduced birth length (β = − 0.91, p = 0.04; p-value for trend = 0.04). Among girls, moderate and high prenatal maternal stress was associated with reduced birth weight (β = − 0.16, p = 0.02; β = − 0.18, p = 0.04 respectively; p-value for trend = 0.04) and head circumference (β = − 0.66, p = 0.05; β = − 1.02, p = 0.01 respectively; p-value for trend = 0.01). In girls, high prenatal stress increased odds of any adverse birth outcome (OR 2.41, 95% CI 1.01-5.75; p for interaction = 0.04). Sex-specific analyses did not demonstrate significant effects in boys. Conclusions All infants, but especially girls, were vulnerable to effects of prenatal maternal stress on birth outcomes. Understanding risk factors for impaired fetal growth may help develop preventative public health strategies. Trial registration NCT01335490 (prospective registration). Date of Registration: April 14, 2011. Status of Registration: Completed.

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Placental DNA methylation signatures of maternal smoking during pregnancy and potential impacts on fetal growth

10.1101/663567 ◽

2019 ◽

Cited By ~ 3

Author(s):

Todd M. Everson ◽

Marta Vives-Usano ◽

Emie Seyve ◽

Andres Cardenas ◽

Marina Lacasaña ◽

...

Keyword(s):

Dna Methylation ◽

Birth Outcomes ◽

Fetal Growth ◽

Maternal Smoking ◽

Meta Analysis ◽

Growth Factor Signaling ◽

Hormone Activity ◽

Smoking During Pregnancy ◽

Placental Function ◽

Maternal Smoking During Pregnancy

AbstractMaternal smoking during pregnancy (MSDP) contributes to poor birth outcomes, in part through disrupted placental functions, which may be reflected in the placental epigenome. We meta-analyzed the associations between MSDP and placental DNA methylation (DNAm) and between DNAm and birth outcomes within the Pregnancy And Childhood Epigenetics (PACE) consortium (7 studies, N=1700, 344 with any MSDP). We identified 1224 CpGs that were associated with MSDP, of which 341 associated with birth outcomes and 141 associated with gene expression. Only 6 of these CpGs were consistent with the findings from a prior meta-analysis of cord blood DNAm, demonstrating substantial tissue-specific responses to MSDP. The placental MSDP associated CpGs were enriched for growth-factor signaling, hormone activity, inflammation, and vascularization, which play important roles in placental function. We demonstrate links between placental DNAm, MSDP and poor birth outcomes, which may better inform the mechanisms through which MSDP impacts placental function and fetal growth.

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Potential Economic Impact of a Coordinated Home Visitation Program

Californian Journal of Health Promotion ◽

10.32398/cjhp.v14i2.1870 ◽

2016 ◽

Vol 14 (2) ◽

pp. 01-13 ◽

Cited By ~ 1

Author(s):

Yuqing Guo ◽

Jung-Ah Lee ◽

Julie Rousseau ◽

Pamela Pimentel ◽

Yvette Bojorquez ◽

...

Keyword(s):

Birth Outcomes ◽

Orange County ◽

Birth Outcome ◽

Cost Savings ◽

Preterm Births ◽

Social Background ◽

Home Visitation ◽

Outcome Data ◽

Potential Cost ◽

Home Visitation Program

Background and Purpose Evidence about the efficacy of healthy pregnancy home visitation programs is needed in California’s underserved Hispanic population, where preterm birth rates are higher than nonHispanic Whites. This study describes birth outcome data in a sample of families participating in the MOMS Orange County home visitation program. Methods: A descriptive comparative design was used. Birth outcome data for 1,102 women who participated in MOMS Orange County and had a live birth in 2010 were compared with data from the county of Orange (N = 38, 237) and the state of California (N = 509, 979) for the same time period, derived from county and state birth and death reports. Measures included social background, birth outcomes, and potential cost savings. Results: Although MOMS program mothers were less educated and had a higher level of poverty compared to both county and state samples, they had significantly fewer preterm births compared with the countywide and statewide samples. It was estimated that the provision of a home visitation program both countywide and statewide would result in a potential cost saving that $1.1 and $ 2.1 million, respectively. Conclusion: This coordinated prenatal program may improve birth outcomes among communities of impoverished women at potentially reduced costs.

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Maternal vitamin B12 status in early pregnancy and its association with birth outcomes in Canadian mother–newborn Dyads

British Journal Of Nutrition ◽

10.1017/s0007114521000581 ◽

2021 ◽

pp. 1-9 ◽

Cited By ~ 1

Author(s):

Amy Tan ◽

Graham Sinclair ◽

Andre Mattman ◽

Hilary D. Vallance ◽

Yvonne Lamers

Keyword(s):

Birth Weight ◽

Birth Outcomes ◽

Early Pregnancy ◽

Screening Program ◽

Birth Outcome ◽

Secondary Analysis ◽

Outcome Data ◽

Maternal Serum ◽

Cognitive Outcomes ◽

Serum Samples

Abstract Vitamin B12 (B12) is a co-enzyme essential for fetal growth and development. Lower maternal B12 status has been associated with preterm birth (<37 gestational weeks) and low birth weight (<2500 g), which are linked to morbidity and mortality across the lifespan. In Canada, 17–25 % of women in early pregnancy had a serum total B12 concentration <148 pmol/l and maternal total B12 concentration decreased throughout pregnancy. This study aimed to determine the association between maternal B12 status and birth outcomes in Canadian mother–newborn dyads. A secondary analysis of 709 mother–newborn dyads in British Columbia (BC), Canada, was conducted. Bio-banked first- (n 656) and second-trimester (n 709) maternal serum samples of apparently healthy South Asian (50 %) and European (50 %) women from the BC Prenatal Genetic Screening Program were quantified for B12 biomarkers (total B12, holotranscobalamin (holoTC), methylmalonic acid (MMA) and total homocysteine (tHcy)). Obstetric history and birth outcome data were obtained from the BC Perinatal Data Registry. All associations were determined using multiple linear regression. Maternal serum total B12, holoTC, MMA and tHcy had a mean weekly decrease of 3·64 pmol/l, 1·04 pmol/l, 1·44 nmol/l and 0·104 μmol/l, respectively (P < 0·001). Despite a total B12 concentration <148 pmol/l among 20–25 % of the women, maternal B12 biomarker concentrations were not associated with birth weight z-score, head circumference z-score and gestational age at birth (P > 0·05). Additional research in women at high risk of adverse birth outcomes and the association between maternal B12 status and functional, for example, cognitive, outcomes is needed.

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Placental DNA methylation signatures of maternal smoking during pregnancy and potential impacts on fetal growth

Nature Communications ◽

10.1038/s41467-021-24558-y ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Todd M. Everson ◽

Marta Vives-Usano ◽

Emie Seyve ◽

Andres Cardenas ◽

Marina Lacasaña ◽

...

Keyword(s):

Dna Methylation ◽

Birth Outcomes ◽

Fetal Growth ◽

Maternal Smoking ◽

Meta Analysis ◽

Growth Factor Signaling ◽

Environmental Response ◽

Smoking During Pregnancy ◽

Placental Function ◽

Maternal Smoking During Pregnancy

AbstractMaternal smoking during pregnancy (MSDP) contributes to poor birth outcomes, in part through disrupted placental functions, which may be reflected in the placental epigenome. Here we present a meta-analysis of the associations between MSDP and placental DNA methylation (DNAm) and between DNAm and birth outcomes within the Pregnancy And Childhood Epigenetics (PACE) consortium (N = 1700, 344 with MSDP). We identify 443 CpGs that are associated with MSDP, of which 142 associated with birth outcomes, 40 associated with gene expression, and 13 CpGs are associated with all three. Only two CpGs have consistent associations from a prior meta-analysis of cord blood DNAm, demonstrating substantial tissue-specific responses to MSDP. The placental MSDP-associated CpGs are enriched for environmental response genes, growth-factor signaling, and inflammation, which play important roles in placental function. We demonstrate links between placental DNAm, MSDP and poor birth outcomes, which may better inform the mechanisms through which MSDP impacts placental function and fetal growth.

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Biomarkers of maternal environmental enteric dysfunction are associated with shorter gestation and reduced length in newborn infants in Uganda

American Journal of Clinical Nutrition ◽

10.1093/ajcn/nqy176 ◽

2018 ◽

Vol 108 (4) ◽

pp. 889-896 ◽

Cited By ~ 4

Author(s):

Jacqueline M Lauer ◽

Christopher P Duggan ◽

Lynne M Ausman ◽

Jeffrey K Griffiths ◽

Patrick Webb ◽

...

Keyword(s):

Birth Outcomes ◽

Birth Outcome ◽

Newborn Infants ◽

Outcome Data ◽

Adverse Birth Outcomes ◽

Z Score ◽

Linear Regression Models ◽

Environmental Enteric Dysfunction ◽

Immunoglobin G

Abstract Background Adverse birth outcomes, including preterm birth and stunting at birth, have long-term health implications. The relation between adverse birth outcomes and chronic, asymptomatic gastrointestinal inflammation (environmental enteric dysfunction—EED) is poorly understood. Objective We aimed to examine the relation between maternal EED and adverse birth outcomes in a sample of pregnant Ugandan women and their newborn infants. Design We conducted a prospective cohort study in Mukono, Uganda. A total of 258 pregnant women were enrolled at their first prenatal visit (∼18 weeks of gestation). EED was measured by urinary lactulose:mannitol (L:M) ratio and serum concentrations of antibodies to the bacterial components flagellin and LPS. Covariates were obtained from survey data collected at 2 time points. Associations were assessed through the use of unadjusted and adjusted simple linear regression models. Results Complete birth outcome data were recorded for 220 infants within 48 h of delivery. Mean ± SD gestational age was 39.7 ± 2.1 wk, and 7% were born preterm. Mean ± SD length and length-for-age z score (LAZ) at birth were 48.1 ± 3.2 cm and −0.44 ± 1.07, respectively. L:M ratio was not associated with any birth outcome. In adjusted models, higher concentrations of natural log-transformed anti-flagellin immunoglobin G (IgG) and anti-LPS IgG were significantly associated with shorter length of gestation (β: −0.89 wk; 95% CI: −1.77, −0.01 wk, and β: −1.01 wk; 95% CI: −1.87, −0.17 wk, respectively) and with reduced length (β: −0.80 cm; 95% CI: −1.55, −0.05 cm, and β: −0.79 cm; 95% CI: −1.54, −0.04 cm, respectively) and LAZ at birth (β −0.44 z score; 95% CI: −0.83, −0.05, and β: −0.40 z score; 95% CI: −0.79, −0.01, respectively). Conclusion Maternal anti-flagellin and anti-LPS IgG concentrations in pregnancy, but not L:M ratio, were associated with shorter gestation and reduced infant length at birth. Further research on the relation between maternal EED and birth outcomes is warranted.

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Epigenetic Mechanisms of Maternal Dietary Protein and Amino Acids Affecting Growth and Development of Offspring

Current Protein and Peptide Science ◽

10.2174/1389203720666190125110150 ◽

2019 ◽

Vol 20 (7) ◽

pp. 727-735 ◽

Cited By ~ 2

Author(s):

Yi Wu ◽

Zhibin Cheng ◽

Yueyu Bai ◽

Xi Ma

Keyword(s):

Amino Acids ◽

Dna Methylation ◽

Dietary Protein ◽

Growth And Development ◽

Later Life ◽

Biological Macromolecules ◽

Epigenetic Mechanisms ◽

Maternal Circulation ◽

Energy Processing ◽

Living Organisms

Nutrients can regulate metabolic activities of living organisms through epigenetic mechanisms, including DNA methylation, histone modification, and RNA regulation. Since the nutrients required for early embryos and postpartum lactation are derived in whole or in part from maternal and lactating nutrition, the maternal nutritional level affects the growth and development of fetus and creates a profound relationship between disease development and early environmental exposure in the offspring’s later life. Protein is one of the most important biological macromolecules, involved in almost every process of life, such as information transmission, energy processing and material metabolism. Maternal protein intake levels may affect the integrity of the fetal genome and alter DNA methylation and gene expression. Most amino acids are supplied to the fetus from the maternal circulation through active transport of placenta. Some amino acids, such as methionine, as dietary methyl donor, play an important role in DNA methylation and body’s one-carbon metabolism. The purpose of this review is to describe effects of maternal dietary protein and amino acid intake on fetal and neonatal growth and development through epigenetic mechanisms, with examples in humans and animals.

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Epigenetics, Nutrition, Disease and Drug Development

Current Drug Discovery Technologies ◽

10.2174/1570163815666180419154954 ◽

2019 ◽

Vol 16 (4) ◽

pp. 386-391 ◽

Cited By ~ 1

Author(s):

Kenneth Lundstrom

Keyword(s):

Dna Methylation ◽

Drug Discovery ◽

Rna Interference ◽

Nutritional Requirements ◽

Signal Pathways ◽

Disease Development ◽

Epigenetic Mechanisms ◽

Epigenetic Changes ◽

Health And Disease ◽

Novel Drug

Epigenetic mechanisms comprising of DNA methylation, histone modifications and gene silencing by RNA interference have been strongly linked to the development and progression of various diseases. These findings have triggered research on epigenetic functions and signal pathways as targets for novel drug discovery. Dietary intake has also presented significant influence on human health and disease development and nutritional modifications have proven important in prevention, but also the treatment of disease. Moreover, a strong link between nutrition and epigenetic changes has been established. Therefore, in attempts to develop novel safer and more efficacious drugs, both nutritional requirements and epigenetic mechanisms need to be addressed.

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New Aspects of the Epigenetics of Pancreatic Carcinogenesis

Epigenomes ◽

10.3390/epigenomes4030018 ◽

2020 ◽

Vol 4 (3) ◽

pp. 18

Author(s):

Murat Toruner ◽

Martin E. Fernandez-Zapico ◽

Christopher L. Pin

Keyword(s):

Pancreatic Cancer ◽

Dna Methylation ◽

Survival Rate ◽

Epigenetic Mechanisms ◽

Therapeutic Approaches ◽

Cancer Epigenetics ◽

Pancreatic Carcinogenesis ◽

New Therapeutic Approaches ◽

Environmental Events ◽

Underlying Pathogenesis

Pancreatic cancer remains among the deadliest forms of cancer with a 5 year survival rate less than 10%. With increasing numbers being observed, there is an urgent need to elucidate the pathogenesis of pancreatic cancer. While both contribute to disease progression, neither genetic nor environmental factors completely explain susceptibility or pathogenesis. Defining the links between genetic and environmental events represents an opportunity to understand the pathogenesis of pancreatic cancer. Epigenetics, the study of mitotically heritable changes in genome function without a change in nucleotide sequence, is an emerging field of research in pancreatic cancer. The main epigenetic mechanisms include DNA methylation, histone modifications and RNA interference, all of which are altered by changes to the environment. Epigenetic mechanisms are being investigated to clarify the underlying pathogenesis of pancreatic cancer including an increasing number of studies examining the role as possible diagnostic and prognostic biomarkers. These mechanisms also provide targets for promising new therapeutic approaches for this devastating malignancy.

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