Table: Determinants or risk factors for development of childhood obesity or increased adiposity

  Association potentially modifiable Type of evidence
Genetic variation
Rare single gene defects in which obesity is the specific abnormality - eg, those related to the leptin signalling pathway (figure 1) No, apart from leptin replacement in the few leptindeficient individuals Basic science studies, case series, family linkage, and genetic association studies
Obesity is a manifestation of several genetic syndromes (figure 2); Prader-Willi syndrome is associated with hyperghrelinaemia, but the mechanism of hyperphagia remains unclear;12,13 animal models of ciliopathies (Bardet-Biedl and Alström syndromes) have defects in leptin pathway signalling;14,15 haploinsufficiency of BDNF, a downstream mediator of leptin action, is associated with hyperphagia and obesity in children with WAGR syndrome No Genetic association studies
Genome-wide association studies have identified several common genetic variants associated with high adiposity and obesity, each with weak effects No Genome-wide association studies
The mechanism whereby in-utero factors can produce heritable changes in adiposity has been suggested to be due to DNA methylation or histone modification of DNA in gene regulatory regions; however, evidence in man is scarce Possibly; in animals, maternal consumption of folate, methionine, and vitamin B12 during pregnancy can affect DNA methylation in offspring Non-systematic review of evidence (largely from basic science and animal studies)
Endocrine disease
Classically, hypothyroidism, growth hormone deficiency or resistance, and cortisol excess; PCOS is a consequence of but also possible contributor to obesity; obesity associated with pseudohypoparathyroidism (caused by Gas inactivating mutation) might be due to defective signalling at G-protein coupled receptors, including the melanocortin receptor of the leptin pathway Some-eg, thyroxine and growth-hormone replacement, surgical treatment of Cushing syndrome; for PCOS, oral contraceptives, anti-androgens, and insulin sensitisers have been used, but long-term large RCTs in adolescents are scarce Non-systematic review of evidence (basic science, epidemiology, clinical)
CNS pathology
Congenital or acquired hypothalamic abnormalities have been associated with a severe form of obesity in children and adolescents Possibly, but still under investigation; hyperinsulinaemia due to increased vagal tone has been postulated as a contributing factor, prompting studies using octreotide, which prevented further weight gain in a small RCT, but long-term large RCTs are needed Non-systematic review of evidence (basic science, epidemiology, clinical)
Intrauterine exposure to gestational diabetes
In populations at high risk of obesity and diabetes (eg, Pima Indians), exposure to gestational diabetes is associated with increased risk of childhood and early adult obesity in offspring; evidence for similar associations in other populations is poor Yes Review of observational studies in Pima Indians;24 prospective cohorts in other populations25 (and other studies cited in this reference)
Intrauterine exposure to high maternal adiposity
Investigators comparing obesity in children whose mothers had undergone bariatric surgery for extreme morbid obesity showed that siblings born before surgery (when mother was very obese) were more obese than were siblings born after weight loss in response to surgery; evidence that less extreme variation in maternal adiposity affects offspring obesity is scarce Yes Within sibling comparisons,26 prospective cohort studies,24,27 and mendelian randomisation study
High birthweight is associated with increased offspring fat and lean mass; small-for-gestational age babies who show catch-up growth might be at risk of childhood obesity, but this finding could simply show increased growth resulting in larger size Safe means of modification of birthweight to improve health are unknown Prospective cohort studies
BMI rebound
Early age at BMI rebound is associated with greater risk of obesity, but this finding could be a statistical artifact No, since can only be established retrospectively in individuals Non-systematic review of largely prospective cohort studies
Breastfeeding is unlikely to be causally protective against childhood obesity Yes Systematic review of prospective cohort studies, RCT
High-quality prospective evidence is sparse; available evidence suggests that high energy intake in early infancy and high consumption of sweetened drinks in childhood are prospectively associated with raised childhood obesity risk; absence of evidence for other dietary characteristics could be attributable to poor study design and dificulties of accurate assessment of diet in children Yes Non-systematic review of observational studies
Energy expenditure
Low levels of physical activity are associated with high childhood obesity risk Yes Systematic review of observational studies
Television viewing
Large number of hours spent viewing are associated with raised childhood obesity risk Yes Systematic review of observational and experimental studies
Short sleep duration in infancy and childhood is associated with raised childhood obesity risk Possibly Prospective cohort study
Microbial infection
Potential role of microbial infection (eg, adenovirus Ad-36) and composition of gut flora (eg, ratio of Firmicutes to Bacteroidetes spp) in the pathogenesis of obesity; however, epidemiological evidence in the non-selected general population is scarce Yes Cross-sectional studies
Cranial irradiation or surgery causing hypothalamic damage; psychotropic drugs (eg, olanzapine and risperidone), chemotherapeutics (eg, treatment of acute lymphocytic leukaemia even without cranial irradiation), and hormonal contraception (eg, depot medroxyprogesterone acetate) have been associated with increased weight gain in children and adolescents Depends on disease or treatment and risk-benefit considerations Non-systematic review of evidence (basic science, epidemiology, clinical) and prospective cohort studies
Ethnic origin
Some ethnic groups - "eg, Hispanic and south Asian - "seem to be more likely to become obese; at a specific BMI, children and infants of south Asian origin have higher adiposity than do their counterparts No Cross-sectional studies
Country of birth
Children from countries with low and middle incomes tend to be stunted and underweight, but with sufficient nutrition gain healthy weight, and with overnutrition are prone to obesity No Cross-sectional and ecological studies
Urban versus rural residence
Children in urban areas are more likely to be obese than are those in rural areas in many countries, including those with high and low-middle incomes Unlikely to be able to change where families live, but might be able to modify underlying reasons for association Cross-sectional studies
Socioeconomic position
In high-income countries, generations born before the 1950s and 1960s did not show socioeconomic differentials in adiposity or obesity in childhood (though do as adults); some evidence exists that in contemporary populations, children in lowest socioeconomic groups in high-income countries have raised obesity rates Yes, with major political and cultural changes; might be able to modify underlying reasons for association Prospective two-generational cohort study
This table has been modified and updated from reference 4. *We cite the most recent systematic review of the highest level of evidence for most risk factors, rather than providing a comprehensive list of all papers for every risk factor, which would be beyond the scope of this Seminar. BDNF=brain-derived neurotrophic factor. WAGR=Wilms tumour, aniridia, genitourinary anomalies, mental retardation. PCOS=polycystic ovary syndrome. RCT=randomised controlled trial. BMI=body-mass index.
Table: Determinants or risk factors for development of childhood obesity or increased adiposity