Cord Blood Telomere Length Research Articles

Association Between Prenatal Exposure to Organochlorine Pesticides and Telomere Length in Neonatal Cord Blood

Objectives: Environmental exposure may affect the telomere length (TL) of newborns, which is considered as an early biomarker indicating susceptibility for later life diseases. However, the effects of prenatal organochlorine pesticide (OCP) exposure on newborn TL remain unclear. This study aimed to investigate the association between prenatal exposure levels of OCPs during pregnancy and TL in neonatal cord blood. Methods: A total of 168 mother–infant pairs from a birth cohort in Wuhan, China, were included this study. The concentrations of hexachlorocyclohexanes (HCHs, including β-HCH, α-HCH, and γ-HCH), p,p’-dichlorodiphenyltrichloroethane (p,p’-DDT) and its metabolites (p,p’-dichlorodiphenyldichloroethane, p,p’-DDD; p,p’-dichlorodiphenyldichloroethylene, p,p’-DDE) were measured in cord blood. The associations between the OCPs and the TL in newborns were analyzed by a generalized linear regression model. Stratified analyses by newborn sex, maternal gestational weight gain, and pregnancy body mass index (BMI) were performed to evaluate if the associations were modified by these factors. Results: The detection rates of various OCPs ranged from 50.9% to 100.0%. The median concentration of p,p’-DDE was the highest (33.90 ng/g lipid), followed by β-HCH (8.67 ng/g lipid), and the median concentrations of the other OCPs were between 0.12 and 0.33 ng/g lipid. Among the all newborns, a two-fold increase in the γ-HCH concentration in the cord blood was significantly associated with a 0.024 (95% CI: −0.041, −0.007) decrease in the TL. After stratification by newborn sex, the inverse association between γ-HCH and the TL was only statistically significant in boys, but not in girls (P for interaction <0.05). In addition, after stratification by pre-pregnancy BMI, β-HCH and p,p’-DDT concentrations were significantly associated with a decreased TL in the overweight pre-pregnancy BMI group [−0.111 (95% CI: −0.203, −0.018) and −0.036 (95% CI: −0.049, −0.023), respectively]. Conclusions: Prenatal exposure to OCPs during pregnancy was associated with a decreased neonatal telomere length, which may be affected by the newborn sex and pre-pregnancy BMI. These findings may provide new insights into the mechanisms underlying OCP-induced adverse health effects.

Sex-specific effects of maternal blood pressure on newborn telomere length: A prospective study.

To investigate the relationship between maternal blood pressure (BP) and neonatal cord blood telomere length (TL) during pregnancy, and to clarify the sensitive period. We conducted a prospective cohort study with 621 mother-newborn pairs from the Guangxi Zhuang Birth Cohort (GZBC) in China. Multiple informant models, restricted cubic spline regression (RCS) models, and quantile regression models were conducted to analyze the correlation between maternal BP and neonatal TL. Maternal diastolic blood pressure (DBP) was inversely related to neonatal cord blood TL in the second trimester (P = 0.015) and the third trimester (P = 0.011). There was a male-specific relationship between maternal BP and neonatal TL. A 1 mmHg increment in maternal systolic blood pressure (SBP) and DBP during the second trimester was related with 0.42% (95% CI: -0.80%, -0.04%) and 0.61% (95% CI: -1.13%, -0.09%) shorter TL in male newborns, respectively. Per unit increase of maternal DBP during the third trimester was related with 0.54% (95% CI: -1.03%, -0.05%) shorter TL in male newborns. Pregnant women with hypertensive disease of pregnancy (HDP) had male offspring with shorter TL (P = 0.003). However, no significant relationships were found in female newborns (P = 0.570). Maternal BP during pregnancy is inversely correlated with male neonatal TL and the second and third trimesters are sensitive windows.

Association between rare earth element exposure during pregnancy and newborn telomere length.

Telomere length (TL) is considered a marker of biological aging and lifetime health, and some epidemiological studies report that the environmental exposures may influence TL at birth. We aimed to investigate the associations between prenatal rare earth elements (REE) exposure and newborn TL. A total of 587 mother-newborn pairs were recruited during 2013 to 2015 in Wuhan, China. Maternal urinary concentrations of REE collected during three trimesters were measured by inductively coupled plasma mass spectrometry. Quantitative real-time polymerase chain reaction was used to measure relative cord blood TL. The trimester-specific associations between prenatal REE exposure and cord blood TL were evaluated using multiple informant models. Weighted quantile sum regression was used to estimate the mixture effect of urinary REE on cord blood TL. After adjustment for potential confounders, per doubling of urinary REE (Dy, Yb, Pr, Nd, and Tm) concentrations (μg/g creatinine) during the second trimester was respectively associated with 1.94% (95% CI 0.19%, 3.72%), 2.10% (95% CI 0.31%, 3.92%), 2.11% (95% CI 0.35%, 3.89%), 2.08% (95% CI 0.01%, 4.20%), and 1.38% (95% CI 0.09%, 2.70%) increase in cord blood TL. Furthermore, exposure to the mixture of REE during the second trimester was also significantly associated with increased cord blood TL (percent change 1.20%, 95% CI 0.30%, 2.11%). However, these associations were not statistically significant in the first and third trimesters. This study provides new evidence on the potential effect of prenatal REE exposure on the initial (newborn) setting of offspring's telomere biology. Further epidemiological studies are warranted to confirm our findings.

Placental and Umbilical Cord Blood Oxidative Stress Level and Telomere Homeostasis in Early Onset Severe Preeclampsia.

Although the etiopathogenesis of preeclampsia (PE) is unknown, evidence suggests that it may be associated with increased oxidative stress. Studies have shown that oxidative stress can affect DNA fragments called telomeres. However, the interactions of PE, oxidative stress, and telomere length are not clearly known. This study aims to evaluate the oxidative/anti-oxidative stress balance in the placenta and umbilical cord and examine the effect of oxidative stress on telomeres. Cord blood and placental samples were collected from 27 pregnant women with severe PE (280/7-336/7 gestational weeks) and 53 healthy pregnant women. Telomere length (TL) was measured by real-time PCR in the cord blood and placenta tissue. Total antioxidant status (TAS) and total oxidant status (TOS) levels were measured in the cord blood and placenta tissue using a colorimetric method. No significant differences were found between groups regarding age, BMI, gravida, parity, and newborn gender (p>0.05). Cord blood and placental TL of PE patients were significantly shorter than the control group, while cord blood and placental TAS and TOS levels were higher (p<0.05). The results of a multivariate logistic regression analysis showed that the level of placental TOS in PE patients (OR=1.212, 95% CI=1.068-1.375) was an independent risk factor affecting PE. This study found that oxidative stress is an independent risk factor in the development of PE and shortens TL in both placental and umbilical cord blood. Future research on telomere homeostasis may offer a new perspective for the treatment of PE.

Genetic regulation of newborn telomere length is mediated and modified by DNA methylation.

Telomere length at birth determines later life telomere length and potentially predicts ageing-related diseases. However, the genetic and epigenetic settings of telomere length in newborns have not been analyzed. In addition, no study yet has reported how the interplay between genetic variants and genome-wide cytosine methylation explains the variation in early-life telomere length. In this study based on 281 mother-newborn pairs from the ENVIRONAGE birth cohort, telomere length and whole-genome DNA methylation were assessed in cord blood and 26 candidate single nucleotide polymorphism related to ageing or telomere length were genotyped. We identified three genetic variants associated with cord blood telomere length and 57 cis methylation quantitative trait loci (cis-mQTLs) of which 22 mQTLs confirmed previous findings and 35 were newly identified. Five SNPs were found to have significant indirect effects on cord blood telomere length via the mediating CpGs. The association between rs911874 (SOD2) and newborn telomere length was modified by nearby DNA methylation indicated by a significant statistical interaction. Our results suggest that DNA methylation in cis might have a mediation or modification effect on the genetic difference in newborn telomere length. This novel approach warrants future follow-up studies that are needed to further confirm and extend these findings.

Ambient exposure and fetal black carbon load in association with telomere length in cord blood

Background: Ambient particulate matter (PM) is an important factor that is associated with telomere length (TL) at birth. A recent study has shown that translocation of black carbon (BC), one of the most toxic components of PM, towards the fetus is possible, but it is not yet linked to biological outcomes. In this study, we investigated whether 1) ambient BC is associated with cord blood TL, 2) fetal BC load relates to ambient BC exposure and 3) fetal BC load is related to newborn TL. Methods: In 247 mother-newborn pairs from the ENVIRONAGE (Environmental Influence On Early Ageing) study, which is a population-based birth cohort study located in Limburg, Belgium, maternal residential exposure to BC during pregnancy was estimated using a spatial-temporal interpolation model. BC particles were detected in cord blood by the generation of white-light under femtosecond pulsed laser illumination. Cord blood TL was measured using qPCR. We applied Pearson correlations and distributed lag models to associate BC exposure with cord blood TL. Results: An IQR increment (0.85 µg/m3) in ambient BC was associated with a -12% (95% CI: −21% to −2.8%) decrease and a 20% (95% CI: 7.6% to 34%) increase in cord blood TL during the second and third trimester of pregnancy respectively. Secondly, fetal BC load showed the highest correlation with ambient BC during trimester 3 (r=0.28, p&amp;#x3c;0.0001). Thirdly, fetal BC load was positively correlated with TL in cord blood (r=0.15, p=0.023). Conclusion: Our findings show that mothers with a higher exposure to ambient BC had more BC particles in cord blood. The positive correlation between both ambient and fetal BC exposure during trimester 3 and cord blood TL may suggest the possibility of an acute protective response, but additional studies are needed to investigate the underlying mechanisms. Keywords: Telomere Length, Particulate Matter, Black Carbon, Ageing

Maternal Serum Vitamin E Levels and its Association with Cord Blood Telomere Length and Mitochondrial DNA Copy Number in Preterm Premature Rupture of Membranes.

Oxidative stress is one of the pathophysiological factors of pPROM and Vit. E being antioxidant may have preventive role. Study was conducted to estimate maternal serum vitamin E levels and cord blood oxidative stress markers in pPROM cases. This was a case-control study including 40 pPROM cases and 40 controls. Maternal serum vitamin E levels were measured at recruitment. Cord blood was collected at delivery for estimation of telomere length and mtDNA copy number as oxidative stress markers. Levels were compared using student's t test or Mann Whitney test. For correlation Pearson coefficient was used. Maternal serum vitamin E levels were normal in pPROM cases. Cord blood telomere length was more in pPROM than controls (428.99 ± 290.65 vs 322.35 ± 180.33) (p value 0.05). Cord blood mtDNA copy number was more in pPROM than controls (516.46 ± 443.55 vs 384.77 ± 328.27) (p value 0.13) though it was not significant. mtDNA copy number had negative correlation with Vit. E levels but it was statistically not significant (p value 0.49). There was no association of vitamin E levels with telomere length (p value 0.95). pPROM was not associated with vitamin E deficiency. There was insignificant oxidative stress in cord blood as measured by mtDNA copy number but cord blood telomere length measurement did not detect any oxidative stress in pPPROM cases.

Interrelationships and determinants of aging biomarkers in cord blood

BackgroundIncreasing evidence supports the concept of prenatal programming as an early factor in the aging process. DNA methylation age (DNAm age), global genome-wide DNA methylation (global methylation), telomere length (TL), and mitochondrial DNA content (mtDNA content) have independently been shown to be markers of aging, but their interrelationship and determinants at birth remain uncertain.MethodsWe assessed the inter-correlation between the aging biomarkers DNAm age, global methylation, TL and mtDNA content using Pearson's correlation in 190 cord blood samples of the ENVIRONAGE birth cohort. TL and mtDNA content was measured via qPCR, while the DNA methylome was determined using the human 450K methylation Illumina microarray. Subsequently, DNAm age was calculated according to Horvath's epigenetic clock, and mean global, promoter, gene-body, and intergenic DNA methylation were determined. Path analysis, a form of structural equation modeling, was performed to disentangle the complex causal relationships among the aging biomarkers and their potential determinants.ResultsDNAm age was inversely correlated with global methylation (r = -0.64, p < 0.001) and mtDNA content (r = − 0.16, p = 0.027). Cord blood TL was correlated with mtDNA content (r = 0.26, p < 0.001) but not with global methylation or DNAm age. Path analysis showed the strongest effect for global methylation on DNAm age with a decrease of 0.64 standard deviations (SD) in DNAm age for each SD (0.01%) increase in global methylation (p < 0.001). Among the applied covariates, newborn sex and season of delivery were the strongest determinants of aging biomarkers.ConclusionsWe provide insight into molecular aging signatures at the start of life, including their interrelations and determinants, showing that cord blood DNAm age is inversely associated with global methylation and mtDNA content but not with newborn telomere length. Our findings demonstrate that cord blood TL and DNAm age relate to different pathways/mechanisms of biological aging and can be influenced by environmental factors already at the start of life. These findings are relevant for understanding fetal programming and for the early prevention of noncommunicable diseases.Graphical

Association of Newborn Telomere Length With Blood Pressure in Childhood

Adult telomere length (TL) is a biological marker of aging associated with vascular health. TL at birth is associated with later life TL and may contain early biological information of later life cardiovascular health and disease. To evaluate whether newborn TL is associated with early life blood pressure differences in childhood. This cohort study was part of the ENVIRONAGE (Environmental Influence on Aging in Early Life) study, a birth cohort of Belgian mother-child pairs with recruitment at birth and a median follow-up of 4.5 years conducted between October 2014 and July 2021. Participants included for analysis provided full data for evaluation at follow-up visit. Data analysis was conducted between August and September 2021. Cord blood and placental average relative TL were measured at birth using quantitative polymerase chain reaction (qPCR). Systolic, diastolic, and mean arterial pressure (MAP) were evaluated at follow-up. High childhood blood pressure (standardized for child age, sex, and height) was defined following the 2017 American Academy of Pediatrics guidelines. Multivariable adjusted linear and logistic regression models were used to associate newborn TL and blood pressure indicators in childhood. This study included 485 newborn children (52.8% girls) with a mean (SD) age of 4.6 (0.4) years at the follow-up visit. Newborn TL was associated with lower blood pressure in childhood. A 1-IQR increase in cord blood TL was associated with a -1.54 mm Hg (95% CI, -2.36 to -0.72 mm Hg) lower diastolic blood pressure and -1.18 mm Hg (95% CI, -1.89 to -0.46 mm Hg) lower MAP. No association was observed with systolic blood pressure. Furthermore, a 1-IQR increase in cord blood TL was associated with lower odds of having high blood pressure at the age of 4 to 6 years (adjusted OR, 0.72; 95% CI, 0.53 to 0.98). In placenta, a 1-IQR increase in TL was associated with a -0.96 mm Hg (95% CI, -1.72 to -0.21 mm Hg) lower diastolic, -0.88 mm Hg (95% CI, -1.54 to -0.22 mm Hg) lower MAP, and a lower adjusted OR of 0.69 (95% CI, 0.52 to 0.92) for having a high blood pressure in childhood. In this prospective birth cohort study, variation in early life blood pressure at school-age was associated with TL at birth. Cardiovascular health may to some extent be programmed at birth, and these results suggest that TL entails a biological mechanism in this programming.

Ambient ozone exposure during pregnancy and telomere length in newborns: a prospective investigation in Wuhan, China

Recent studies suggest that environmental exposures, including air pollution, may influence initial (newborn) telomere length (TL), which has important implications for lifetime health. However, the effect of prenatal ozone exposure on newborn TL is unclear. This study aimed to examine the association of ozone exposure during pregnancy with newborn TL. We used data from a birth cohort study of 762 mother-newborn pairs performed in Wuhan, China, during 2013-2015. Land-use regression models were used to assess prenatal ozone exposure. Newborn TL was quantified in cord blood by qPCR assay. We applied multiple informant model to explore the relationship of prenatal ozone exposure with newborn TL. After adjustment for potential confounders, an interquartile range (IQR) increase in ozone exposure during the 2nd trimester, 3rd trimester, and whole pregnancy were associated with 6.00% (95% confidence interval [CI]: 1.59%, 10.62%), 12.64% (95% CI: 7.52%, 18.00%), and 7.10% (95% CI: 4.09%, 10.20%) longer cord blood TL, respectively. In contrast, an IQR increase in ozone exposure during the 1st trimester was associated with a 8.39% (95% CI: - 12.90%, - 3.65%) shorter cord blood TL. In multipollutant models, consistent associations were observed between ozone exposures during the 2nd trimester and whole pregnancy and cord blood TL, but not significant for the 1st and 3rd trimesters. In conclusion, our findings suggest positive associations of ozone exposure during the 2nd trimester, 3rd trimester, and whole pregnancy with newborn TL and a negative association during the 1st trimester. This study provides new evidence in humans for a potential "programming" mechanism linking maternal ozone exposure to the initial (newborn) setting of offspring's telomere biology.

The telomere-mitochondrial axis of aging in newborns.

Aging starts at the beginning of life as evidenced by high variability in telomere length (TL) and mitochondrial DNA content (mtDNAc) at birth. Whether p53 and PGC-1α are connected to these age-related markers in early life is unclear. In this study, we hypothesized that these hallmarks of aging are associated at birth.In 613 newborns from the ENVIRONAGE birth cohort, p53 and PGC-1α protein levels were measured in cord plasma, while TL and mtDNAc were measured in both cord blood and placental tissue. Cord blood methylation data of genes corresponding to the measured protein levels were available from the Human MethylationEPIC 850K BeadChip array. Pearson correlations and linear regression models were applied while accounting for selected covariates. In cord, a 10% increase in TL was associated with 5.22% (95% CI: 3.26 to 7.22; p < 0.0001) higher mtDNAc and −2.66% (95% CI: –5.04 to −0.23%; p = 0.032) lower p53 plasma level. In placenta, a 10% increase in TL was associated with 5.46% (95% CI: 3.82 to 7.13%; p < 0.0001) higher mtDNAc and −2.42% (95% CI: −4.29 to −0.52; p = 0.0098) lower p53 plasma level. Methylation level of TP53 was correlated with TL and mtDNAc in cord blood and with cord plasma p53 level.Our study suggests that p53 may be an important factor both at the protein and methylation level for the telomere-mitochondrial axis of aging at birth.

Prenatal exposure to PM10 and changes in DNA methylation and telomere length in cord blood

BackgroundAir pollution exposure in pregnancy can cause molecular level alterations that might influence later disease susceptibility. ObjectivesWe investigated DNA methylation (DNAm) and telomere length (TL) in the cord blood in relation to gestational PM10 exposure and explored potential gestational windows of susceptibility. MethodsCord blood epigenome-wide DNAm (N = 384) and TL (N = 500) were measured in children of the Italian birth cohort Piccolipiù, using the Infinium Methylation EPIC BeadChip and qPCR, respectively. PM10 daily exposure levels, based on maternal residential address, were estimated for different gestational periods using models based on satellite data. Epigenome-wide analysis to identify differentially methylated probes (DMPs) and regions (DMRs) was conducted, followed by a pathway analysis and replication analysis in an second Piccolipiù dataset. Distributed lag models (DLMs) using weekly exposures were used to study the association of PM10 exposure across pregnancy with telomere length, as well as with the DMPs that showed robust associations. ResultsGestational PM10 exposure was associated with the DNA methylation of more than 250 unique DMPs, most of them identified in early gestation, and 1 DMR. Out of 151 DMPs available in the replication dataset, ten DMPs showed robust associations: eight were associated with exposure during early gestation and 2 with exposure during the whole pregnancy. These exposure windows were supported by the DLM analysis. The PM10 exposure between 15th and 20th gestational week seem to be associated with shorter telomeres at birth, while exposure between 24th and 29th was associated with longer telomeres. DiscussionThe early pregnancy period is a potential critical window during which PM10 exposure can influence cord blood DNA methylation. The results from the TL analysis were consistent with previous findings and merit further exploration in future studies. The study underlines the importance of considering gestational windows outside of the predefined trimesters that may not always overlap with biologically relevant windows of exposure.

Prenatal lead exposure, telomere length in cord blood, and DNA methylation age in the PROGRESS prenatal cohort

BackgroundLead is a ubiquitous pollutant with deleterious effects on human health and remains a major current public health concern in developing countries. This heavy metal may interfere with nucleic acids via oxidative stress or epigenetic changes that affect biological markers of aging, e.g., telomere length and DNA methylation (DNAm). Telomere shortening associates with biological age in newborns, and DNA methylation at specific CpG sites can be used to calculate “epigenetic clocks". ObjectiveThe aim of this study was to examine the associations of prenatal lead exposures with telomere length and DNA-methylation-based predictors of age in cord blood. DesignThe study included 507 mother–child pairs from the Programming Research in Obesity, Growth, Environment and Social Stressors (PROGRESS) study, a birth cohort in Mexico City. Maternal blood (second trimester, third trimester and at delivery) and bone lead levels (one month postpartum) were measured using inductively coupled plasma-mass spectrometry and X-ray fluorescence, respectively. Cord blood leukocyte telomere length was measured using quantitative PCR and apparent age by DNA methylation biomarkers, i.e., Horvath's DNA methylation age and the Knight's predictor of gestational age. ResultsAverage maternal age was 28.5 ± 5.5 years, and 51.5% reported low socioeconomic status. Children's mean telomere length was 1.2 ± 1.3 relative units, and mean DNA methylation ages using the Horvath's and Knight's clocks were −2.6 ± 0.1 years and 37.9 ± 1.4 weeks (mean ± SD), respectively. No significant associations were found between maternal blood and bone lead concentrations with telomere length and DNAm age in newborns. ConclusionWe found no associations of prenatal lead exposure with telomere length and DNA methylation age biomarkers.

Prospective Associations of Early Pregnancy Metal Mixtures with Mitochondria DNA Copy Number and Telomere Length in Maternal and Cord Blood.

Background:Metal exposure during pregnancy influences maternal and child health. Oxidative stress and inflammation may mediate adverse effects of heavy metals, whereas essential metals may act as antioxidants. Mitochondrial DNA is a prime target for metal-induced oxidative damage. Telomere dysfunction is attributed to imbalances between reactive oxidant species and antioxidants.Objectives:We evaluated individual and joint associations of prenatal metals with mitochondrial DNA copy number (mtDNAcn) and telomere length (TL) in maternal and cord blood as biomarkers of inflammation and oxidative stress.Methods:We measured six nonessential metals (arsenic, barium, cadmium, cesium, lead, mercury) and four essential metals (magnesium, manganese, selenium, zinc) in first-trimester maternal red blood cells in Project Viva, a U.S. prebirth cohort. We measured relative mtDNAcn () and TL () in second-trimester maternal blood and mtDNAcn () and TL () in cord blood. We used multivariable linear regression and quantile g-computation to estimate associations between prenatal metals and the biomarkers. We used generalized additive models and Bayesian kernel machine regression to examine nonlinearity and interactions.Results:A 2-fold increase in maternal magnesium was associated with lower maternal [, 95% confidence interval (CI): , ] and cord blood (, 95% CI: , ) mtDNAcn. Lead was associated with higher maternal mtDNAcn (, 95% CI: 0.01, 0.06). Selenium was associated with longer cord blood TL (, 95% CI: 0.01 0.50). An association was observed between the nonessential metal mixture and higher maternal mtDNAcn (, 95% CI: 0.01, 0.07). There was a nonlinear relationship between cord blood mtDNAcn and magnesium; maternal mtDNAcn and barium, lead, and mercury; and maternal TL and barium.Discussion:Maternal exposure to metals such as lead, magnesium, and selenium was associated with mtDNAcn and TL in maternal second trimester and cord blood. Future work will evaluate whether these biomarkers are associated with child health. https://doi.org/10.1289/EHP9294

Pre-conception and Prenatal Exposure to Ambient PM2.5 with Newborn Telomere Length in Cord Blood

BACKGROUND AND AIM: Telomere length (TL) at birth determines TL in a later life and has been linked to midlife risk of cardiovascular disease, but its own determinants remain unclear. We aim to examine the association and to identify the sensitive window of pre-conception and prenatal exposures to fine particulate matter (PM2.5) with cord blood TL in a heavily air-polluted area in China. METHODS: In 2017, 107 pregnant women admitted for delivery at Anzhen Hospital in Beijing, China, were interviewed for demographics, addresses, and lifestyle factors. Weekly levels of ambient PM2.5 exposure from the three months before pregnancy to the end of pregnancy were estimated from a validated spatiotemporal model. PM2.5 exposure levels based on home and work addresses were combined by work routines. Cord blood leukocyte TL was measured using quantitative polymerase chain reaction. We used distributed lag models (DLMs) to analyze the association and to identify the sensitive window of ambient PM2.5 exposure with cord blood TL with adjusting for potential confounders. DLM analyses were also conducted in stratified subsamples by newborn sex. RESULTS:PM2.5 levels (median: 85 μg/m3) in the three months before LMP was positively (r=0.16) correlated with cord blood TL, while PM2.5 levels (median 78 μg/m3) in the whole pregnancy was inversely (r=-0.15) correlated with cord blood TL, although none of the correlation was significant (P0.05). From DLM, we found PM2.5 exposure was significantly associated with cord blood TL in three sensitive windows: 6-12 weeks before pregnancy (positive association), 6-18 weeks during pregnancy (inverse association), and 39-40 weeks during pregnancy (inverse association). These associations were more evident in female than male newborns. CONCLUSIONS:Preconception and prenatal exposure to ambient PM2.5 exposure may shorten cord blood TL, especially for female fetuses. Future studies with larger sample size are needed to replicate our findings. KEYWORDS: Particulate matter, Birth outcomes, Environmental epidemiology, Modeling

Prenatal exposure to PM10 and changes in DNA methylation and telomere length in cord blood

BACKGROUND AND AIM: Air pollution exposure in pregnancy can cause molecular level alterations associated with later disease susceptibility. We aimed to investigate changes in two molecular marker types, DNA methylation and telomere length, in cord blood in relation to gestational PM10 exposure and to explore potential gestational windows of susceptibility. METHODS: Cord blood epigenome-wide DNA methylation (N=384) and telomere length (N=500) were measured in children of the Italian birth cohort Piccolipiù using the Infinium Methylation EPIC BeadChip (Illumina) and qPCR, respectively. PM10 exposure levels were estimated for different gestational periods based on maternal residential address, using advanced methods based on satellite data. Lag distributed models using weekly exposures were used to further confirm the identified exposure windows. RESULTS:PM10 exposure during the first gestational weeks was associated with DNA methylation of more than 100 unique CpGs, mapped to genes with relevant functions in cell replication, differentiation and response to environmental stressors. We were able to test half of the CpGs in an independent sample from the same cohort and six CpGs showed robust associations. PM10 exposure during mid and later pregnancy was associated with shorter and longer telomeres, respectively. CONCLUSIONS:The first weeks of pregnancy seems to be a particularly important PM10 exposure window for DNA methylation that should be accounted for in future analyses, while exposure to PM10 in mid and late pregnancy might be important for telomere length. DNA methylation and telomere length are fundamental regulators of cellular processes during early life, and their alterations could have major implications for later disease susceptibility. KEYWORDS: Environmental epidemiology, Particulate matter, Epigenomics, Telomere length

Prenatal lead exposure, telomere length in cord blood and DNA methylation age in the PROGRESS cohort

BACKGROUND AND AIM: Lead is a ubiquitous pollutant with deleterious effects on human health and remains as a major current public health concern in countries in development. Telomere length shortening has been related with aging in newborns. DNA methylation levels with specific CpG sites could be used as

Maternal Vitamin D and Newborn Telomere Length.

Nutrition is important during pregnancy for offspring health. Gestational vitamin D intake may prevent several adverse outcomes and might have an influence on offspring telomere length (TL). In this study, we want to assess the association between maternal vitamin D intake during pregnancy and newborn TL, as reflected by cord blood TL. We studied mother–child pairs enrolled in the Maternal Nutrition and Offspring’s Epigenome (MANOE) cohort, Leuven, Belgium. To calculate the dietary vitamin D intake, 108 women were asked to keep track of their diet using the seven-day estimated diet record (EDR) method. TL was assessed in 108 cord blood using a quantitative real-time PCR method. In each trimester of pregnancy, maternal serum 25-hydroxyvitamin D (25-OHD) concentration was measured. We observed a positive association (β = 0.009, p-value = 0.036) between newborn average relative TL and maternal vitamin D intake (diet + supplement) during the first trimester. In contrast, we found no association between average relative TL of the newborn and mean maternal serum 25-OHD concentrations during pregnancy. To conclude, vitamin D intake (diet + supplements), specifically during the first trimester of pregnancy, is an important factor associated with TL at birth.

Different epigenetic signatures of newborn telomere length and telomere attrition rate in early life.

Telomere length (TL) and telomere shortening are biological indicators of aging, and epigenetic associates have been found for TL in adults. However, the role of epigenetic signatures in setting newborn TL and early life telomere dynamics is unknown. In the present study, based on 247 participating newborns from the ENVIRONAGE birth cohort, whole-genome DNA methylation, profiled on the Illumina MethylationEPIC BeadChip microarray, and TL were measured in cord blood. In a follow-up visit at a mean age of 4.58 years, leukocyte TL was evaluated. We combined an epigenome-wide association study and a statistical learning method with re-sampling to select CpGs and their two-way interactions to model baseline (cord blood) TL and early-life telomere attrition rate, where distinct epigenetic signatures were identified for the two outcomes. In addition, a stronger epigenetic regulation was suggested in setting newborn TL than that of telomere dynamics in early life: 47 CpGs and 7 between-CpG interactions explained 76% of the variance in baseline TLs, while 72% of the total variance in telomere attrition rate was explained by 31 CpGs and 5 interactions. Functional enrichment analysis based on the selected CpGs in the two models revealed GLUT4 translocation and immune cell signaling pathways, respectively. These CpGs and interactions, as well as the cellular pathways, are potential novel targets of further investigation of telomere biology and aging.

Effects of prenatal exposure to bisphenols on newborn leucocyte telomere length: a prospective birth cohort study in China.

Telomere length (TL) at birth is related to diseases that may arise in the future and long-term health. Bisphenols exhibit toxic effects and can cross the placenta barrier. However, the effects of prenatal exposure to bisphenols on newborn TL remain unknown. We aimed to explore the effects of prenatal exposure to bisphenols (i.e., bisphenol A [BPA], bisphenol B [BPB], bisphenol F [BPF], bisphenol S [BPS] and tetrabromobisphenol A [TBBPA]) on relative TL in newborns. A total of 801 mother-infant pairs were extracted from the Guangxi Zhuang Birth Cohort. The relationship between bisphenol levels in maternal serum and relative TL in cord blood was examined by generalized linear models and restricted cubic spline (RCS) models. After adjusting for confounders, we observed a 3.19% (95% CI: -6.08%, -0.21%; P = 0.037) reduction in relative cord blood TL among mothers ≥ 28 years old, with each onefold increase in BPS. However, in each onefold increase of TBBPA, we observed a 3.31% (95% CI: 0.67%, 6.01%; P = 0.014) increase in relative cord blood TL among mothers < 28 years old. The adjusted RCS models revealed similar results (P overall < 0.05, P non-linear >0.05). This study was the first to establish a positive association between serum TBBPA levels and relative TL in newborns born to young mothers. However, BPS levels were inversely correlated with TL in fetus born to old mothers. The results suggested that the fetus of old pregnant women may be more sensitive to BPS exposure. Moreover, BPS exposure early in life may accelerate aging or increase the risk of developing BPS-related diseases in later life.