Early-life nutrition and obesity risk
Authors:   , Kouwenhoven Stefanie Maria Petronella 
Published: April 2023

SUMMARY OF THE RESULTS
Part 1: Early nutrition and its effect on later health:
current evidence and recommendations
In Chapter 2 we summarized current standards, recommendations, guidelines, and regulations on nutrition and its effect on later metabolic health in healthy children aged 1 to 3 years in a systematic review. We found the strongest and most consistent evidence for a protective, long-term effect of early nutrition was documented for
breastfeeding. In Chapter 3 we explored within a systematic review whether nutrition and supplements in lactating women are of influence on metabolic programming of the offspring. No recent guidelines or recommendations were found. The lack of literature and guidelines related to maternal diet during lactation and its effect on offspring’s highlights the need for further research regarding this topic. In Chapter 4 we performed a systematic review of systematic reviews on the effects of nutritional interventions or exposures in healthy children on the subsequent risk of obesity. We found that there is no strong evidence that nutritional interventions or exposures in children aged up to 3 years consistently reduces the risk of increased adiposity. However, a consistent association between breastfeeding and a modest reduction in the risk of later overweight and obesity in childhood and adulthood was found. Furthermore, lowering the protein content of infant formula is a promising intervention to reduce the risk of later overweight and obesity in children.

Part 2: Early-life protein intake and childhood obesity
In Chapter 5 we investigated current evidence on the effects of infant formulas and follow-on formulas with different protein concentrations on infants’ and children’s body composition and later risk of obesity in a systematic review. The main conclusion is that more studies assessing the effects of low-protein infant formula on long-term health are needed. In Chapter 6 and Chapter 7 we studied the effects of a modified low-protein infant formula on both short-term and long-term growth and body composition within a multicenter double-blind randomized controlled trial (the ProtEUs trial). We have found that the use of an infant formula with a reduced protein content of 20% was safe and supports adequate growth and body composition development until the age 6 months (Chapter 6). Up until the age of 2, no differences in growth or body composition were found between the intervention and control groups, except for fat-free mass index at age 4 months, which was significantly lower in the modified low-protein group after adjustment for potential confounders (Chapter 7). In Chapter 8 we analysed metabolic and hormonal blood markers in study participants of the ProtEUs trial at the age of 4 months. We have found that a reduced protein intake during the first months of life did not affect glucose homeostasis or the IGF system in formula-fed infants at the age of 4 months. Next, we found that formula-fed infants had lower insulin sensitivity compared to breast-fed infants. Long-lasting associations were found between all metabolic and hormonal blood markers and growth and body composition except for IGF-1.

Part 3: body composition techniques
In Chapter 9 we showed the obtained fat mass percentage predicted by means of SFT was significantly different from that measured with ADP in healthy, term-born infants during the first 6 months of life and that there is poor agreement between ADP and SFTs for estimating fat mass in infancy and early childhood. In Chapter 10 we described different applications of stable isotopes in nutritional research during infancy and early childhood in both breast-fed and formula-fed infants.

CONCLUSIONS
In Chapter 11 the results of our studies in context of the available literature and the implications for future research are discussed.