Associations between maternal prenatal stress, methylation changes in IGF1 and IGF2, and birth weight

Maternal stress has been linked to low birth weight in newborns. One potential pathway involves epigenetic changes at candidate genes that may mediate the effects of prenatal maternal stress on birth weight. This relationship has been documented in stress-related genes, such as NR3C1. There is less literature exploring the effect of stress on growth-related genes. IGF1 and IGF2 have been implicated in fetal growth and development, though via different mechanisms as IGF2 is under imprinting control. In this study, we tested for associations between prenatal stress, methylation of IGF1 and IGF2, and birth weight. A total of 24 mother–newborn dyads in the Democratic Republic of Congo were enrolled. Ethnographic interviews were conducted with mothers at delivery to gather culturally relevant war-related and chronic stressors. DNA methylation data were generated from maternal venous, cord blood and placental tissue samples. Multivariate regressions were used to test for associations between stress measures, DNA methylation and birth weight in each of the three tissue types. We found an association between IGF2 methylation in maternal blood and birth weight. Previous literature on the relationship between IGF2 methylation and birth weight has focused on methylation at known differentially methylated regions in cord blood or placental samples. Our findings indicate there may be links between the maternal epigenome and low birth weight that rely on mechanisms outside known imprinting pathways. It thus may be important to consider the effect of maternal exposures and epigenetic profiles on birth weight even in the setting of maternally imprinted genes such as IGF2.

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Prenatal Bisphenol a Exposure, DNA Methylation, and Low Birth Weight: A Pilot Study in Taiwan

International Journal of Environmental Research and Public Health ◽

10.3390/ijerph18116144 ◽

2021 ◽

Vol 18 (11) ◽

pp. 6144

Author(s):

Yu-Fang Huang ◽

Chia-Huang Chang ◽

Pei-Jung Chen ◽

I-Hsuan Lin ◽

Yen-An Tsai ◽

...

Keyword(s):

Dna Methylation ◽

Birth Weight ◽

Low Birth Weight ◽

Bisphenol A ◽

Cord Blood ◽

Developmental Disorders ◽

Metabolic Diseases ◽

System Development ◽

Maternal Blood ◽

Blood Samples

Prenatal exposure to bisphenol A (BPA) may increase the risk of abnormal birth outcomes, and DNA methylation might mediate these adverse effects. This study aimed to investigate the effects of maternal BPA exposure on maternal and fetal DNA methylation levels and explore whether epigenetic changes are related to the associations between BPA and low birth weight. We collected urine and blood samples originating from 162 mother-infant pairs in a Taiwanese cohort study. We measured DNA methylation using the Illumina Infinium HumanMethylation 450 BeadChip in 34 maternal blood samples with high and low BPA levels based on the 75th percentile level (9.5 μg/g creatinine). Eighty-seven CpGs with the most differentially methylated probes possibly interacting with BPA exposure or birth weight were selected using two multiple regression models. Ingenuity pathway analysis (IPA) was utilized to narrow down 18 candidate CpGs related to disease categories, including developmental disorders, skeletal and muscular disorders, skeletal and muscular system development, metabolic diseases, and lipid metabolism. We then validated these genes by pyrosequencing, and 8 CpGs met the primer design score requirements in 82 cord blood samples. The associations among low birth weight, BPA exposure, and DNA methylation were analyzed. Exposure to BPA was associated with low birth weight. Analysis of the epigenome-wide findings did not show significant associations between BPA and DNA methylation in cord blood of the 8 CpGs. However, the adjusted odds ratio for the dehydrogenase/reductase member 9 (DHRS9) gene, at the 2nd CG site, in the hypermethylated group was significantly associated with low birth weight. These results support a role of BPA, and possibly DHRS9 methylation, in fetal growth. However, additional studies with larger sample sizes are warranted.

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Tissue differences in DNA methylation changes at AHRR in full term low birth weight in maternal blood, placenta and cord blood in Chinese

Placenta ◽

10.1016/j.placenta.2017.02.017 ◽

2017 ◽

Vol 52 ◽

pp. 49-57 ◽

Cited By ~ 7

Author(s):

Fu-Ying Tian ◽

Marie-France Hivert ◽

Xiaozhong Wen ◽

Chuanbo Xie ◽

Zhongzheng Niu ◽

...

Keyword(s):

Dna Methylation ◽

Birth Weight ◽

Low Birth Weight ◽

Cord Blood ◽

Maternal Blood ◽

Full Term ◽

Tissue Differences

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Antioxidant Levels in Cord Blood of Term Low Birth Weight Neonates Requiring Delivery Room Resuscitation

Journal of Neonatology ◽

10.1177/0973217921991402 ◽

2021 ◽

pp. 097321792199140

Author(s):

Rimjhim Sonowal ◽

Anamika Jain ◽

V. Bhargava ◽

H.D. Khanna ◽

Ashok Kumar

Keyword(s):

Birth Weight ◽

Low Birth Weight ◽

Vitamin A ◽

Cord Blood ◽

Serum Levels ◽

Study Groups ◽

Delivery Room ◽

Normal Birth Weight ◽

Normal Birth ◽

Major Congenital Malformations

Objective: The objective of this study was to evaluate the serum levels of various antioxidants, namely, vitamin A and E, superoxide dismutase (SOD), catalase, and glutathione peroxidase (GPx) in the cord blood of term low birth weight (LBW) neonates who required delivery room resuscitation (DRR). Materials and Methods: This case control study included 37 term LBW neonates who needed DRR as cases and 44 term neonates as controls (15 term LBW and 29 term normal birth weight) who did not require resuscitation at birth. Neonates suffering from major congenital malformations, infection, or hemolytic disease were excluded. Standard methods were used to measure the levels of vitamin A, vitamin E, SOD, catalase, and GPx levels in the cord blood. Results: Vitamin A and E levels were significantly low in cases compared to term LBW controls as well as term normal birth weight controls. Levels of SOD, GPx, and catalase were comparable in different study groups. Conclusion: Our study shows that term LBW neonates requiring DRR had significantly low levels of vitamin A and E in their cord blood. This might compromise their ability to tolerate oxidative stress during DRR.

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Maternal and cord blood metal concentrations and low birth weight—a case-control study

American Journal of Clinical Nutrition ◽

10.1093/ajcn/31.7.1181 ◽

1978 ◽

Vol 31 (7) ◽

pp. 1181-1187 ◽

Cited By ~ 24

Author(s):

J D Bogden ◽

I S Thind ◽

D B Louria ◽

H Caterini

Keyword(s):

Birth Weight ◽

Low Birth Weight ◽

Cord Blood ◽

Case Control Study ◽

Case Control ◽

Metal Concentrations ◽

Control Study

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1400 Nosocomial Infection and Cd4+ Lymphocytes in Very Low Birth Weight (VLBW) Infants' Cord Blood

Pediatric Research ◽

10.1203/00006450-201011001-01400 ◽

2010 ◽

Vol 68 ◽

pp. 692-692

Author(s):

E Zamora ◽

Sanchez M Luna ◽

E Maderuelo ◽

S Villar ◽

B Alonso ◽

...

Keyword(s):

Birth Weight ◽

Low Birth Weight ◽

Nosocomial Infection ◽

Cord Blood ◽

Very Low Birth Weight ◽

Vlbw Infants ◽

Cd4 Lymphocytes

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Antibiotic Concentration in Maternal Blood, Cord Blood and Placental Tissue in Women with Chorioamnionitis

Gynecologic and Obstetric Investigation ◽

10.1159/000294878 ◽

1992 ◽

Vol 33 (3) ◽

pp. 185-186 ◽

Cited By ~ 13

Author(s):

Mark C. Maberry ◽

Kenneth J. Trimmer ◽

Roger E. Bawdon ◽

Sorab Sobhi ◽

Jody B. Dax ◽

...

Keyword(s):

Cord Blood ◽

Placental Tissue ◽

Maternal Blood ◽

Antibiotic Concentration

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Effects of Maternal Blood Levels of One‐carbon Nutrients on Global DNA Methylation and Demethylation in Cord Blood Lymphocytes

The FASEB Journal ◽

10.1096/fasebj.29.1_supplement.749.6 ◽

2015 ◽

Vol 29 (S1) ◽

Author(s):

Lesley Plumptre ◽

Stephanie Tammen ◽

Shannon Masih ◽

Carly Visentin ◽

Anna Ly ◽

...

Keyword(s):

Dna Methylation ◽

Cord Blood ◽

Maternal Blood ◽

Blood Levels ◽

Global Dna Methylation ◽

Blood Lymphocytes ◽

Cord Blood Lymphocytes

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Autism-Associated DNA Methylation at Birth From Multiple Tissues Is Enriched for Autism Genes in the Early Autism Risk Longitudinal Investigation

Frontiers in Molecular Neuroscience ◽

10.3389/fnmol.2021.775390 ◽

2021 ◽

Vol 14 ◽

Author(s):

Kelly M. Bakulski ◽

John F. Dou ◽

Jason I. Feinberg ◽

Max T. Aung ◽

Christine Ladd-Acosta ◽

...

Keyword(s):

Dna Methylation ◽

Cord Blood ◽

Late Pregnancy ◽

Maternal Blood ◽

Autism Spectrum ◽

Epigenetic Mark ◽

Global Methylation ◽

Risk Genes ◽

Longitudinal Investigation ◽

Research Initiative

Background: Pregnancy measures of DNA methylation, an epigenetic mark, may be associated with autism spectrum disorder (ASD) development in children. Few ASD studies have considered prospective designs with DNA methylation measured in multiple tissues and tested overlap with ASD genetic risk loci.Objectives: To estimate associations between DNA methylation in maternal blood, cord blood, and placenta and later diagnosis of ASD, and to evaluate enrichment of ASD-associated DNA methylation for known ASD-associated genes.Methods: In the Early Autism Risk Longitudinal Investigation (EARLI), an ASD-enriched risk birth cohort, genome-scale maternal blood (early n = 140 and late n = 75 pregnancy), infant cord blood (n = 133), and placenta (maternal n = 106 and fetal n = 107 compartments) DNA methylation was assessed on the Illumina 450k HumanMethylation array and compared to ASD diagnosis at 36 months of age. Differences in site-specific and global methylation were tested with ASD, as well as enrichment of single site associations for ASD risk genes (n = 881) from the Simons Foundation Autism Research Initiative (SFARI) database.Results: No individual DNA methylation site was associated with ASD at genome-wide significance, however, individual DNA methylation sites nominally associated with ASD (P < 0.05) in each tissue were highly enriched for SFARI genes (cord blood P = 7.9 × 10–29, maternal blood early pregnancy P = 6.1 × 10–27, maternal blood late pregnancy P = 2.8 × 10–16, maternal placenta P = 5.6 × 10–15, fetal placenta P = 1.3 × 10–20). DNA methylation sites nominally associated with ASD across all five tissues overlapped at 144 (29.5%) SFARI genes.Conclusion: DNA methylation sites nominally associated with later ASD diagnosis in multiple tissues were enriched for ASD risk genes. Our multi-tissue study demonstrates the utility of examining DNA methylation prior to ASD diagnosis.

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Is low birth weight a risk indicator for congenital cytomegalovirus infection?

The Journal of Infection in Developing Countries ◽

10.3855/jidc.539 ◽

2009 ◽

Vol 4 (01) ◽

pp. 044-047 ◽

Cited By ~ 4

Author(s):

Zakyieh Al-Hareth ◽

Fawza Monem ◽

Nagwa Abdel Megiud

Keyword(s):

Birth Weight ◽

Low Birth Weight ◽

Cord Blood ◽

Umbilical Cord ◽

Umbilical Cord Blood ◽

Head Circumference ◽

Cytomegalovirus Infection ◽

Congenital Infection ◽

Congenital Cytomegalovirus Infection ◽

Congenital Cytomegalovirus

Background: Congenital cytomegalovirus infection is currently the leading cause of congenital infection in 0.2-2.2% of live births worldwide leading to variable serious sequalae. The aim of the study was to determine if low birth weight is an indicator of CMV congenital infection evidenced by detecting CMV-DNA in umbilical cord blood at the time of delivery. Methodology: CMV-IgG and IgM antibodies and CMV-DNAemia were assessed in umbilical cord blood of two hundreds newborns, one hundred of whom had birth weight ≤ 2700 gram and/or head circumference ≤ 32 cm. Results: CMV-IgM was not detected, while CMV-IgG was positive in 80-90% of the two hundreds tested newborns. CMV-DNA was detected in four out of the 200 newborns. One of them was over the adopted weight limit (> 2700 gram). Conclusions: CMV-IgM and IgG antibodies assessment was not a potential discriminative test to identify congenitally infected newborns. In addition, low birth weight and small head circumference at birth failed to predict congenital CMV infection. CMV-DNA detection in umbilical cord blood at the time of delivery using real-time PCR of all newborns is recommended as decisive, rapid and non-invasive test.

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