Dataset Information

Maternal pro-inflammatory state during pregnancy and newborn leukocyte telomere length: A prospective investigation.

ABSTRACT:

Introduction

Telomere biology plays a fundamental role in maintaining the integrity of the genome and cell, and shortened telomeres have been linked to several age-related diseases. The initial (newborn) telomere length (TL) represents a critically important feature of the telomere biology system. Exposure to a variety of adverse prenatal conditions such as maternal stress, suboptimal diet, obesity, and obstetric complications, is associated with shorter offspring TL at birth and in adult life. Many, if not all, of these exposures are believed to have an inflammatory component. In this context, stress-related immunological processes during pregnancy may constitute a potential additional biological pathway because they can affect telomere length and telomerase activity via transcriptions factors such as cyclic adenosine monophosphate-dependent transcription factor (ATF7) and nuclear factor-kappa B (NF-?B). Thus, in the present study we examined the hypothesis that maternal pro-inflammatory state across pregnancy, operationalized as the balance between tumor necrosis factor (TNF)-?, a major pro-inflammatory cytokine, and interleukin-10 (IL-10), the major anti-inflammatory cytokine, is associated with newborn leukocyte telomere length (LTL) at birth.

Methods and materials

Participants were healthy women (N?=?112) recruited in early pregnancy. Concentrations of TNF- ? and IL-10 were quantified in early, mid and late pregnancy from maternal blood samples. Telomere length was assessed in newborn blood samples soon after birth.

Results

After adjusting for maternal age, maternal pre-pregnancy BMI, birth weight percentile, and infant sex, a higher mean TNF-?/IL-10 ratio across pregnancy was significantly associated with shorter newborn TL (??=?-.205, p?=?.030). Newborn TL was, on average, 10% shorter in offspring of women in the upper compared to lower quartile of the TNF-?/IL-10 ratio during pregnancy.

Discussion

These findings provide new evidence in humans for a potential "programming" mechanism linking maternal systemic pro-inflammatory processes during pregnancy with the initial (newborn) setting of her offspring's telomere system.

SUBMITTER: Lazarides C

PROVIDER: S-EPMC7954441 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature

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Project description:Newborn telomere length is a potential biomarker of the effects of maternal-fetal processes on offspring long-term health. A number of maternal psychosocial and environmental factors in pregnancy (e.g., stress, health, socioeconomic status) have been associated with shortened telomere length at birth. The physiological mechanisms responsible for potential effects of maternal factors on newborn telomere length have yet to be identified. Indirect evidence suggests that disruptions in maternal hypothalamic-pituitary-adrenal (HPA) axis functioning in pregnancy may be involved. Studies are needed that test whether maternal HPA axis functioning in pregnancy is associated with newborn telomere length. This study examined whether maternal HPA axis functioning across pregnancy, reflected in hair cortisol collected within one week after delivery, predicted newborn telomere length assessed from leukocyte cord blood collected at birth among 93 sociodemographically diverse mother-infant dyads. We further tested whether associations between maternal hair cortisol and newborn telomere length differed by infant sex, given documented sex differences in prenatal environmental exposure effects on offspring health, patterns of cortisol exposure during gestation, and telomere biology across the lifespan. In a multi-group structural equation modeling analysis that accounted for cortisol exposures across trimesters, maternal cortisol levels in pregnancy were not associated with newborn telomere length in the sample as a whole. However, significant sex differences emerged, with a significant positive association among females and a lack of a significant association among males. In addition, analyses revealed that cortisol levels were higher across trimesters among mothers of male infants than mothers of female infants. The results suggest that functioning of the maternal HPA axis in pregnancy may differ by fetal sex and have sex-specific effects on newborn telomere biology. These findings have implications for understanding the mechanisms by which maternal psychosocial and environmental exposures influence newborn telomere length and for elucidating mechanisms contributing to sex disparities in health.

Project description:IntroductionTelomeres protect the ends of chromosomes, and shorter leukocyte telomeres are associated with major group diseases. Maternal psychological stress may be related to the shortening of telomeres in infants. This systematic review and meta-analysis set out to consolidate the varying effect sizes found in studies of maternal psychological stress and telomere length (TL) in newborns and identify moderators of the relationship between stress during pregnancy and newborn TL.MethodsOur systematic review was registered in Prospero. Six databases (PubMed, Scopus, Embase, PsycINFO, Web of Science, and CINAHL Complete) were searched for records in English from inception to February 10, 2023. Observational studies were included that measured the relationship of psychological stress of the mother during pregnancy on the TL of the newborn. The Newcastle-Ottawa quality assessment scale was used to assess the quality of the included studies. A random-effect model was selected. Statistical analysis performed by Stata software version 17.ResultsEight studies were included for qualitative and four for quantitative analysis. There was an inverse statistically significant relationship between maternal stress and newborn TL; A one score increase in maternal psychological stress resulted in a 0.04 decrease in the TL of the newborn (B = -0.04, 95% CI = [-0.08, 0.00], p = 0.05). Selectivity analysis showed that the pooled effect size was sensitive to one study; After removing this study, the pooled effect size remained significant (B = -0.06, 95% CI = [-0. 10, -0.02], p < 0.001).ConclusionPhysiological and environmental factors can significantly affect the TL of newborns. Our results support a significant impact of maternal psychological stress on the TL of a newborn. This association demonstrates the significance of stress in influencing the telomere length, which can be a contributing factor in the infant's future. Therefore, recognizing this association is crucial for understanding and addressing potential health risks and necessitates the need for additional future studies to validate our findings.

Project description:There is growing interest in elucidating the determinants of newborn telomere length, given its potential as a biomarker of lifetime disease risk affected by prenatal exposures. There is limited evidence that increased maternal stress during pregnancy predicts shorter newborn telomere length. However, the few studies published to date have been conducted primarily with small samples utilizing inconsistent definitions of maternal stress. Moreover, the potential influence of fetal sex as a moderator of maternal stress effects on newborn telomere length has been largely ignored despite compelling evidence of likely impact. In a prospective cohort study of pregnant women seeking routine prenatal care, we tested whether a range of maternal measures of stressor exposures, subjective feelings of stress, and mental health (depression, anxiety) were associated with newborn telomere length assessed from cord blood among 146 pregnant women and their newborn infants. We further examined whether the pattern of associations differed by infant sex. Sociodemographic and maternal and newborn health indicators were considered as potential covariates. When examined within the whole sample, none of the maternal psychosocial measures were associated with newborn telomere length. Among potential covariates, maternal history of smoking and preeclampsia in a previous pregnancy were negatively associated with newborn telomere length. In adjusted linear regression analyses that considered potential sex-specific effects, maternal depression, general anxiety, and pregnancy-specific anxiety symptoms were positively associated with newborn telomere length among males. Overall, the findings provide some evidence for an association between maternal psychosocial wellbeing in pregnancy and newborn telomere length in males, although in the opposite direction than previously reported. Maternal smoking and obstetric history prior to conception may be associated with shorter offspring telomere length.

Project description:Little research has examined determinants of newborn telomere length, a potential biomarker of lifetime disease risk impacted by prenatal exposures. No study has examined whether maternal exposures in childhood influence newborn telomere length or whether there are sex differences in the maternal factors that influence newborn telomere length. We tested whether a range of maternal risk and protective factors in childhood and pregnancy were associated with newborn telomere length among 151 sociodemographically diverse mother-infant dyads. We further examined whether the pattern of associations differed by infant sex. Newborn telomere length was assessed from cord blood collected at birth. Risk/protective factors included maternal health (smoking, body mass index), socioeconomic status (education, income), stress exposures, and mental health (depressive and posttraumatic stress disorder symptoms) in pregnancy as well as maternal experiences of abuse (physical, emotional, sexual) and familial emotional support in childhood. When examined within the whole sample, only maternal smoking in pregnancy and familial emotional support in childhood emerged as significant predictors of newborn telomere length. Male and female newborns differed in their pattern of associations between the predictors and telomere length. Among males, maternal smoking, higher body mass index, and elevated depressive symptoms in pregnancy and maternal sexual abuse in childhood were associated with shorter newborn telomere length; higher maternal educational attainment and household income in pregnancy and greater maternal familial emotional support in childhood were associated with longer newborn telomere length. Together, these factors accounted for 34% of the variance in male newborn telomere length. None of the risk/protective factors were associated with female newborn telomere length. The results suggest that male fetuses are particularly susceptible to maternal exposure effects on newborn telomere length. These findings have implications for elucidating mechanisms contributing to sex disparities in health.

Project description:Study questionIs preconception leukocyte telomere length associated with fecundability, pregnancy loss and live birth among women attempting natural conception with a history of 1-2 prior pregnancy losses?Summary answerPreconception leukocyte telomere length is not associated with fecundability, pregnancy loss or live birth.What is known alreadyAs women increasingly delay childbearing, accessible preconception biomarkers to predict pregnancy outcomes among women seeking natural conception could improve preconception counseling. Findings of small case-control or cross-sectional studies suggest that telomere attrition is associated with adverse pregnancy outcomes among women undergoing fertility treatment, but prospective studies in non-clinical populations are lacking.Study design, size, durationParticipants included 1228 women aged 18-40 years with a history of 1-2 prior pregnancy losses who were recruited at four university medical centers (2006-2012).Participants/materials, setting, methodsPreconception leukocyte telomere length was measured at baseline using PCR and reported as a ratio (T/S) in relation to population-specific standard reference DNA. Women were followed for up to six cycles while attempting to conceive. Associations of telomere length with fecundability, live birth and pregnancy loss were estimated using discrete Cox proportional hazards models and log-binomial models.Main results and the role of chanceAfter adjustment for age, BMI, smoking and other factors, preconception telomere length was not associated with fecundability (Q4 vs Q1 FOR = 1.00; 95% CI = 0.79, 1.27), live birth (Q4 vs Q1 RR = 1.00; 95% CI = 0.85, 1.19), or pregnancy loss (Q4 vs Q1 RR = 1.12; 95% CI = 0.78, 1.62).Limitations, reasons for cautionTelomere length was measured in leukocytes, which is an accessible tissue in women attempting natural conception but may not reflect telomere length in oocytes. Most women were younger than 35 years, limiting our ability to evaluate associations among older women. Participants had a history of 1-2 prior pregnancy losses; therefore, our findings may not be widely generalizable.Wider implications of the findingsDespite prior research suggesting that telomere length may be associated with pregnancy outcomes among women seeking fertility treatment, our findings suggest that leukocyte telomere length is not a suitable biomarker of pregnancy establishment or maintenance among women attempting natural conception.Study funding/competing interest(s)This research was supported by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development (National Institutes of Health, Bethesda, MD, USA; contract numbers HHSN267200603423, HHSN267200603424 and HHSN267200603426). The authors have no conflicts of interest to disclose.Trial registration numberThe trial was registered with ClinicalTrials.gov, number NCT00467363.