Timing of the Infancy-Childhood Growth Transition in Rural Gambia

Abstract

The Karlberg model of human growth describes the infancy, childhood, and puberty (ICP) stages as continuous and overlapping, and defined by transitions driven by sequential additional effects of several endocrine factors that shape the growth trajectory and resultant adult size. Previous research has suggested that a delayed transition from the infancy to the childhood growth stage contributes to sub-optimal growth outcomes. A new method developed to analyze the structure of centile crossing in early life has emerged as a potential tool for identifying the infancy-childhood transition (ICT), through quantifying patterns of adjacent monthly weight-forage z-score (WAZ) deviation correlations. Using this method, the infancy-childhood transition was identified as taking place at around 12 months of age in two cohorts of UK infants. Here, we apply this method to data collected as part of a longitudinal growth study in rural Gambia [the Hormonal and Epigenetic Regulators of Growth, or HERO-G study, N = 212 (F = 99, M = 113)], in order to identify the ICT and assess whether timing of this transition differs across groups based on sex or birth seasonality. We calculated Pearson correlation coefficients for adjacent monthly WAZ score deviations. Based on the patterns of change in the correlation structure over time, our results suggest that the infancy-childhood transition occurs at around 9 months of age in rural Gambian infants. This points to an accelerated ICT compared to UK infants, rather than a delayed ICT. A comparatively later transition, seen in UK infants, allows maximal extension of the high rates of growth during the infancy stage; an earlier transition as seen in Gambian infants cuts short this period of rapid growth, potentially impacting on growth outcomes in childhood while diverting energy into other processes critical to responses to acute infectious challenges. Growth in later developmental stages in this population offers an extended window for catch-up.

Identification of methylation changes associated with positive and negative growth deviance in Gambian infants using a targeted methyl sequencing approach of genomic DNA

“…Thus, any continued challenges (such as those provoked by under nutrition and infection) to homeostasis during the development period may trigger epigenetic programming and shift the timing and duration of these periods of growth. The study reported by Bernstein et al (91) has revealed an accelerated transition to a childhood pattern of growth in Gambian compared to UK infants. A later transition, observed in UK infants, extends the high growth rate experienced during the infancy stage.…”

A Novel method for the identification and quantification of weight faltering

“…If the global issue of stunting is to be addressed, its dynamic causes must be identified and explored. From a mechanistic perspective, it is clear that repeated rounds of growth faltering (e.g., resulting from high morbidity, undernutrition, repeated seasonal pressures, or other adverse conditions) could potentially (a) deplete resources available to support growth (Stearns, 1989), and (b) signal a “high risk” environment to the developing individual, potentially impacting growth patterns and health in both the short‐ and long‐term (Bernstein et al, 2020; Gluckman et al, 2005). Close analysis of the dynamics of faltering episodes as presented here can help tease apart the causes and consequences of faltering, shed light on how those episodes contribute to the broader state of faltering from a “potential” trajectory identified by prior methods, and may provide valuable insight regarding the efficacy of interventions designed to improve growth and growth outcomes.…”

Family Size and the Age at Infancy-Childhood Transition Determine a Child’s Compromised Growth in Large Families

“…In the present analysis, it was impossible to determine the ICT for almost a quarter (161/657) of the study children. Recently it was proposed to use the infancy-childhood transition of weight for age z-score, based on the Widdowson and Cambridge Infant Growth Study (CIGS) (30,31), however this model requires validation and endocrine and evolutionary collateral.…”