Background: Birth weight and rapid weight gain during early childhood have been associated with childhood overweight and cardiometabolic diseases such as cardiovascular diseases and type 2 diabetes in adulthood. However, evidence of the relative importance of birth fat mass (FM), birth fat-free mass (FFM), and their accretion in early childhood on later adiposity and cardiometabolic health is limited. Furthermore, little is known about how associations of growth in early childhood with body composition, and cardiometabolic markers are tracking throughout childhood. Despite an increasing burden of childhood overweight and cardiometabolic diseases in sub-Saharan African countries, there is limited evidence from longitudinal studies on how birth size and early childhood growth are related to adiposity and cardiometabolic risk in later childhood. Objective: The overall objective of this PhD thesis was to examine associations of weight and body composition at birth and early childhood growth from 0-5 years with anthropometry, body composition, abdominal fat, and cardiometabolic markers at age 10 years. Methods: This thesis is based on data from the Ethiopian infant Anthropometry and Body Composition (iABC) birth cohort study. Body composition from birth to 10 years of age was assessed using air-displacement plethysmography. The exposure variables included in the thesis were weight, FM, and FFM at birth (Paper I), previously identified body mass index (BMI) trajectories from 0-5 years (Paper II), as well as FM and FFM accretion in selected periods from 0-5 years (0-3, 3-6, 6-48, and 48-60 months) (Paper III). Linear spline mixed-effects modeling was applied to estimate FM and FFM from 0-5 years (Paper III). Outcomes were obtained from 355 children who attended the 10-year follow-up and included anthropometry (height, waist
circumference, and BMI), body composition (fat mass index [FMI] and fat-free mass index [FFMI]), abdominal subcutaneous- and visceral fat, cardiometabolic markers including blood pressure (systolic and diastolic), markers of glucose homeostasis (glucose, insulin, C-peptide, and homeostasis model assessment of insulin resistance [HOMA-IR]), and lipid profile (total-, LDL-, HDL-cholesterol, and triglycerides). Associations between exposure variables and the 10-year outcomes were assessed using multiple linear regression analysis. Results: At 10 years, the mean ( SD) age of the children was 9.8 (1.0) years, mean height z-scoreand BMI z-score were -0.76 (0.94) and -0.77 (1.15), respectively. Higher birth weight and FFM were associated with greater height, FFMI, and higher insulin, C-peptide, and HOMA-IR, whereas higher birth FM was associated with greater FMI and abdominal subcutaneous fat, but not visceral fat (Paper I). FM accretion from 0-3 months and 3-6 months, but not FFM, was linked to higher blood pressure and glucose concentrations. Furthermore, FM and FFM accretion between 6-48 months predicted higher insulin and HOMA-IR, whereas FFM accretion during the same period was associated with lower total and LDL cholesterol concentrations (Paper III). Children with rapid growth to high BMI trajectories had greater waist circumference, and those with slow to high BMI trajectories had higher FM and abdominal subcutaneous fat, whereas children with stable low BMI had lower FFMI compared to those with normal BMI trajectories (Paper II). Additionally, children with slow growth to high BMI trajectories showed higher insulin and HOMA-IR, whereas those with rapid BMI trajectories showed higher C-peptide and lower total cholesterol concentrations at 10 years of age. Conclusion: Overall, based on the children included in this cohort, Ethiopian children were on average shorter and thinner compared with standard reference and showed lower FM and FFM than UK children at 10 years of age. In this cohort, prenatal environment, as indicated by proxy measures of birth weight and birth body composition and early childhood growth trajectories, and FM and FFM accretions were associated with adiposity, body composition, and cardiometabolic
markers in later childhood. Children with higher FFM accretion in early childhood may have a lower risk of dyslipidemia later in life. Conversely, those with higher FM accretion and who experienced rapid or slow growth to high BMI growth patterns in early childhood might have an increased risk of adiposity and increased cardiometabolic markers later in life, given that these children are exposed to an obesogenic environment and have sedentary lifestyles.