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Correlation of cord blood telomere length with birth weight.

ABSTRACT: Intrauterine growth restriction affects 3% of newborns; and the lightest 10% of whom are classified as small for gestational age (SGA). These low-birth weight newborns are at increased risk of neonatal morbidity such as hypoxia and hypoglycaemia. In later life, they are at higher risk of several age-related diseases such as cardiovascular and metabolic disorders and dementia. As having short telomeres is also associated with these diseases, we tested if these newborns might already start with shorter telomeres at birth.Relative telomere lengths were determined using quantitative real-time PCR in cord blood samples from 195 newborns of Chinese ancestry. Based on the telomere length normalised to a single copy gene and a reference DNA sample as internal control, we found statistically significant correlations between relative telomere length and both unadjusted and gestational age-adjusted birth weight, with the lighter newborns having shorter telomeres. The SGA birth weight group comprising the bottom 10% of the samples also had the shortest telomeres compared to the medium and heaviest birth weight groups.Our results indicate that there is reduction of cord blood telomere length for newborns with lower birth weight.

SUBMITTER: Lee SP

PROVIDER: S-EPMC5591543 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature

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Correlation of cord blood telomere length with birth weight.

Lee Siew-Peng SP Hande Prakash P Yeo George Sh GS Tan Ene-Choo EC

BMC research notes 20170908 1

<h4>Background</h4>Intrauterine growth restriction affects 3% of newborns; and the lightest 10% of whom are classified as small for gestational age (SGA). These low-birth weight newborns are at increased risk of neonatal morbidity such as hypoxia and hypoglycaemia. In later life, they are at higher risk of several age-related diseases such as cardiovascular and metabolic disorders and dementia. As having short telomeres is also associated with these diseases, we tested if these newborns might al ...[more]

PMID: 28886728

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Project description:BackgroundThe uterine environment may be important for the chromosomal telomere length (TL) at birth, which, in turn, influences disease susceptibility throughout life. However, little is known about the importance of specific nutritional factors.ObjectivesWe assessed the impact of multiple maternal nutritional factors on TL in placenta and cord blood.MethodsIn a population-based mother-child cohort in northwestern Argentina, we measured maternal weight, BMI, body fat percentage (BFP), and several nutrients [selenium, magnesium, calcium, zinc, manganese, iodine, vitamin B-12, folate, 25-hydroxycholecalciferol (25(OH)D3)], hemoglobin, and homocysteine in maternal whole blood, serum, plasma, or urine during pregnancy (mean gestational week 27). We measured the relative TL (rTL) in placenta (n = 99) and cord blood (n = 98) at delivery by real-time PCR. Associations were evaluated by multivariable-adjusted linear regression.ResultsThe women's prepregnancy BMI (kg/m2; mean ± SD: 23.7 ± 4.1), body weight (55.4 ± 9.9 kg), and BFP (29.9 ± 5.5%), but not height (153 ± 5.3 cm), were inversely associated with placental rTL (P < 0.01 for all), with ?0.5 SD shorter rTL for an IQR increase in prepregnancy body weight, BMI, or BFP. Also, impedance-based BFP, but not lean body mass, in the third trimester was associated with shorter placental rTL. In addition, serum vitamin B-12 (232 ± 96 pmol/L) in pregnancy (P = 0.038), but not folate or homocysteine, was associated with shorter placental rTL (0.2 SD for an IQR increase). In contrast, plasma 25(OH)D3 (46 ± 15 nmol/L) was positively associated with placental rTL (P < 0.01), which increased by 0.4 SD for an IQR increase in 25(OH)D3. No clear associations of the studied maternal nutritional factors were found with cord blood rTL.ConclusionsMaternal BMI, BFP, and vitamin B-12 were positively associated, whereas 25(OH)D3 was inversely associated, with placental TL. No association was observed with cord blood TL. Future studies should elucidate the role of placental TL for child health.

Project description:BackgroundEnvironmental exposures including air pollutants, toxic metals, and psychosocial stress have been associated with shorter telomere length (TL) in newborns. These exposures have in turn been linked to an enhanced inflammatory immune response. Increased inflammation during pregnancy may be a central biological pathway linking environmental factors with reduced TL at birth. Approaches that more comprehensively characterize the prenatal inflammatory milieu rather than targeting specific individual cytokines in relation to newborn TL may better elucidate inflammatory mechanisms.MethodsAnalyses included 129 mother-child dyads enrolled in the PRogramming of Intergenerational Stress Mechanisms (PRISM) pregnancy cohort. We measured 92 inflammation related proteins during pregnancy in maternal serum using the Olink protein array and quantified cord blood relative leukocyte TL (rLTL) via qPCR. We leveraged a tree-based machine learning algorithm to select the most important inflammatory related proteins jointly associated with rLTL. We then evaluated the combined association between the selected proteins with rLTL using Bayesian Weighted Quantile Sum (BWQS) Regression. Analyses were adjusted for gestational week of serum collection, maternal race/ethnicity, age, and education, and fetal sex. We evaluated major biological function of the identified proteins by using the UniProtKB, a centralized repository of curated functional information.ResultsThree proteins were negatively and linearly associated with rLTL (CASP8 β: -0.22 p = 0.008, BNGF β: -0.43 p = 0.033, TRANCE β: 0.38 p = 0.004). Results from BWQS regression showed a significant overall decrease in rLTL (β: -0.26 95%CrI: -0.43, -0.07) per quartile increase of the mixture, with CASP8 contributing the greatest weight (CASP8 50%; BNGF 27%, and TRANCE 23%). The identified proteins were involved in the regulation of apoptotic processes and cell proliferation.ConclusionsThis proteomics approach identifies novel maternal prenatal inflammatory protein biomarkers associated with shortened rLTL in newborns.

Project description:IntroductionIn utero particulate matter exposure produces oxidative stress that impacts cellular processes that include telomere biology. Newborn telomere length is likely critical to an individual's telomere biology; reduction in this initial telomere setting may signal increased susceptibility to adverse outcomes later in life. We examined associations between prenatal particulate matter with diameter ≤2.5 µm (PM2.5) and relative leukocyte telomere length (LTL) measured in cord blood using a data-driven approach to characterize sensitive windows of prenatal PM2.5 effects and explore sex differences.MethodsWomen who were residents of Mexico City and affiliated with the Mexican Social Security System were recruited during pregnancy (n = 423 for analyses). Mothers' prenatal exposure to PM2.5 was estimated based on residence during pregnancy using a validated satellite-based spatio-temporally resolved prediction model. Leukocyte DNA was extracted from cord blood obtained at delivery. Duplex quantitative polymerase chain reaction was used to compare the relative amplification of the telomere repeat copy number to single gene (albumin) copy number. A distributed lag model incorporating weekly averages for PM2.5 over gestation was used in order to explore sensitive windows. Sex-specific associations were examined using Bayesian distributed lag interaction models.ResultsIn models that included child's sex, mother's age at delivery, prenatal environmental tobacco smoke exposure, pre-pregnancy BMI, gestational age, birth season and assay batch, we found significant associations between higher PM2.5 exposure during early pregnancy (4-9 weeks) and shorter LTL in cord blood. We also identified two more windows at 14-19 and 34-36 weeks in which increased PM2.5 exposure was associated with longer LTL. In stratified analyses, the mean and cumulative associations between PM2.5 and shortened LTL were stronger in girls when compared to boys.ConclusionsIncreased PM2.5 during specific prenatal windows was associated with shorter LTL and longer LTL. PM2.5 was more strongly associated with shortened LTL in girls when compared to boys. Understanding sex and temporal differences in response to air pollution may provide unique insight into mechanisms.

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Correlation of cord blood telomere length with birth weight.

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Correlation of cord blood telomere length with birth weight.

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