Biological determinants linking infant weight gain and child obesity: current knowledge and future directions

Abstract

Childhood obesity rates have reached epidemic proportions. Excessive weight gain in infancy is associated with persistence of elevated weight status and later obesity. In this review, we make the case that weight gain in the first 6 mo is especially predictive of later obesity risk due to the metabolic programming that can occur early postpartum. The current state of knowledge regarding the biological determinants of excess infant weight gain is reviewed, with particular focus on infant feeding choice. Potential mechanisms by which different feeding approaches may program the metabolic profile of the infant, causing the link between early weight gain and later obesity are proposed. These mechanisms are likely highly complex and involve synergistic interactions between endocrine effects and factors that alter the inflammatory and oxidative stress status of the infant. Gaps in current knowledge are highlighted. These include a lack of data describing 1) what type of infant body fat distribution may impart risk and 2) how maternal metabolic dysfunction (obesity and/or diabetes) may affect milk composition and exert downstream effects on infant metabolism. Improved understanding and management of these early postnatal determinants of childhood obesity may have great impact on reducing its prevalence.

Figure 1

Infant weight gain in the first 6 mo is associated with increased odds of overweight at 18–24 mo. Infants born in Denver, Colorado, between 1999 and 2004 (N = 15,552) were followed through the first 2 y of life. All infants were born at term (≥37 wk and <42 wk gestation) and had a birth weight >2.5 kg; 2636 infants had a birth weight <3.0 kg, and 1234 infants had a birth weight >4.0 kg. Weight gain was monitored bimonthly and weight for age Z-scores (WAZ) generated from the 2006 WHO growth curves. Logistic regression was used to generate the OR of overweight (achieving a weight-for-length ≥95th percentile) at 18–24 mo based on birth weight and gaining ≥0.5 WAZ units between 0 and 2, 2 and 4, or 4 and 6 mo. Birth weight ≥3.0 and ≤4.0 kg (N = 11,682) was used as the reference group, as indicated by the dashed line. Error bars represent 95% CI. The OR attributed to each category (birth weight <3.0 kg or >4.0 kg or gaining ≥0.5 WAZ units at any time point) was significant (P < 0.0001). *ΔWAZ controlled for birth weight. **OR of overweight at 18–24 mo associated with gaining ≥0.5 WAZ between 2 and 4 mo was significantly larger than the OR associated with gaining ≥0.5 WAZ between 0 and 2 or 4 and 6 mo (P < 0.0001).

Figure 2

Potential biological mechanisms whereby maternal phenotype/behavior may indirectly affect infant metabolic phenotype via alterations in human milk (HM). Shown is a conceptual diagram of potential biological mechanisms by which maternal phenotype may affect infant metabolic phenotype via alterations in HM, affecting weight gain and obesity risk. All infant outcomes listed in the right-hand column may individually or in combination predispose the infant to obesity and metabolic dysfunction later in childhood and adulthood. Solid black lines represent relationships that have been suggested by published data (from animal models and human studies). Dashed gray lines represent hypothesized relationships postulated here. ¹Incorporating total fat intake, saturated fat intake, and fatty acid composition of diet, including the n-6:n-3 ratio of dietary fatty acids. ²Inflammatory load incorporates the cumulative effect of both pro- and anti-inflammatory cytokines and other factors of HM. ³Oxidative load incorporates the cumulative effect of both oxidants and the antioxidant capacity of HM. *The cycle of metabolic syndrome in which increased inflammation, and oxidative stress mutually stimulate and respond to malprogrammed adipocytes.