Telomere length is associated with growth in children in rural Bangladesh

Abstract

Background: Previously, we demonstrated that a water, sanitation, handwashing, and nutritional intervention improved linear growth and was unexpectedly associated with shortened childhood telomere length (TL) (Lin et al., 2017). Here, we assessed the association between TL and growth.

Methods: We measured relative TL in whole blood from 713 children. We reported differences between the 10th percentile and 90th percentile of TL or change in TL distribution using generalized additive models, adjusted for potential confounders.

Results: In cross-sectional analyses, long TL was associated with a higher length-for-age Z score at age 1 year (0.23 SD adjusted difference in length-for-age Z score [95% CI 0.05, 0.42; FDR-corrected p-value = 0.01]). TL was not associated with other outcomes.

Conclusions: Consistent with the metabolic telomere attrition hypothesis, our previous trial findings support an adaptive role for telomere attrition, whereby active TL regulation is employed as a strategy to address 'emergency states' with increased energy requirements such as rapid growth during the first year of life. Although short periods of active telomere attrition may be essential to promote growth, this study suggests that a longer overall initial TL setting in the first 2 years of life could signal increased resilience against future telomere erosion events and healthy growth trajectories.

Funding: Funded by the Bill and Melinda Gates Foundation.

Clinical trial number: NCT01590095.

Keywords: child; developmental origins of health; disease; epidemiology; global health; growth; human; low-income; pediatric population; telomere length.

Figure 1.. Diagram of participants at each phase of the telomere length and growth substudy within the WASH Benefits trial.

Figure 2.. Adjusted association between telomere length and growth.

Adjusted differences in mean anthropometry Z score between 10th and 90th percentile of telomere measure. LAZ = length-for-age Z score; WAZ = weight-for-age Z score; WLZ = weight-for-length Z score; HCZ = head circumference-for-age Z score.

Figure 2—figure supplement 1.. Association between telomere length at Year 1 and concurrent and subsequent growth.

Spline curves of telomere length at Year 1 and anthropometric Z scores at Years 1 and 2, change in anthropometric Z scores, and growth velocity. T/S Ratio = unit for relative telomere length; LAZ = length-for-age Z score; WAZ = weight-for-age Z score; WLZ = weight-for-length Z score; HCZ = head circumference-for-age Z score.

Figure 2—figure supplement 2.. Association between telomere length at Year 2 and concurrent growth.

Spline curves of telomere length at Year 2 and anthropometric Z scores at Year 2. T/S ratio = unit for relative telomere length; LAZ = length-for-age Z score; WAZ = weight-for-age Z score; WLZ = weight-for-length Z score; HCZ = head circumference-for-age Z score.

Figure 2—figure supplement 3.. Association between change in telomere length between Years 1 and 2 and growth.

Spline curves of change in telomere length between Years 1 and 2 and anthropometric Z scores at Year 2, change in anthropometric Z scores, and growth velocity. T/S ratio = unit for relative telomere length; LAZ = length-for-age Z score; WAZ = weight-for-age Z score; WLZ = weight-for-length Z score; HCZ = head circumference-for-age Z score.

Figure 3.. Regression to the mean assessment: association between telomere length at Year 1 and change in telomere length between Years 1 and 2.

T/S ratio = unit for relative telomere length.

Figure 3—figure supplement 1.. Regression to the mean comparison of unadjusted association between change in telomere length and growth.

Unadjusted differences in mean anthropometry Z score between 10th and 90th percentile of change in telomere length between Years 1 and 2. Unadjusted associations corrected for the regression to the mean (RTM) effect using the equation in Verhulst et al., 2013. LAZ = length-for-age Z score; WAZ = weight-for-age Z score; WLZ = weight-for-length Z score; HCZ = head circumference-for-age Z score.

Figure 3—figure supplement 2.. Regression to the mean comparison of adjusted association between change in telomere length and growth.

Adjusted differences in mean anthropometry Z score between 10th and 90th percentile of change in telomere length between Years 1 and 2. Adjusted associations corrected for the regression to the mean (RTM) effect using the equation in Verhulst et al., 2013. LAZ = length-for-age Z score; WAZ = weight-for-age Z score; WLZ = weight-for-length Z score; HCZ = head circumference-for-age Z score. Adjusted for pre-specified covariates: Child age, child sex, birth order, prior child length and weight measurements from Year 1 (included in Year 2 outcomes only), season of measurement, time between anthropometry measurements (included in growth velocity and change in growth measurements between Year 1 and Year 2 outcomes only), caregiver-reported diarrhoea, mother’s age, mother’s height, mother’s education level, mother’s Center for Epidemiologic Studies Depression Scale Revised (CESD-R) score, mother’s Perceived Stress Scale score, mother’s lifetime exposure to physical, sexual, and emotional intimate partner violence, household food insecurity, number of children <18 years in the household, number of individuals living in the compound, distance in minutes to the primary water source, household floor materials, household wall materials, household electricity, and household assets (wardrobe, table, chair, clock, khat, chouki, radio, television, refrigerator, bicycle, motorcycle, sewing machine, mobile phone, cattle, goats, and chickens), and treatment arm (control or N + WSH) (Supplementary file 1a).