Obesity rates in Ireland have increased dramatically over the past few decades, especially in childhood. The National Children’s Survey in 2005 found that, depending on the method used to define obesity, 4.1 to 11% of boys were obese and 9.3 to 16.3% of girls.¹ In 2011, the Growing Up in Ireland Study² showed that 19% of nine-year-olds were overweight with 7% obese. Girls are more likely to be defined as overweight or obese than boys, with a total of 30% of girls and 22% of boys found to be overweight or obese.² Depending on the definition used, there has been a two to four-fold increase in child obesity in Ireland since 1990.¹

Children who become overweight often go on to become overweight or obese adults.^3,4,5 Obesity is not only an adverse condition in itself, but is a prelude to a number of diseases later in life including diabetes mellitus, metabolic syndrome and cardiovascular disease.³ Treatment of overweight and obesity is notoriously difficult and often unsuccessful.⁶ For this reason, public health efforts to prevent obesity have received increased focus worldwide.⁶ There has been a particular focus on prevention of obesity in early childhood and infancy. 

A meta-analysis of prospective observational studies following children from birth to two years found maternal overweight, high infant birthweight and rapid weight gain during the first 12 months of life to be strongly associated with childhood overweight⁷. Several other studies have found similar results^{8, 9, 10} and there is now an evidence-based consensus that obesity may be programmed prenatally and during early infancy³ and that intervention at this early age may help to prevent later obesity and overweight. However, research into intervention to prevent obesity during this key period is rare and shows mixed outcomes and there is insufficient evidence to identify the key areas to target³. This short review focuses on some of the research into the metabolic programming of obesity through rapid growth in the first two years of life.

Programming

Programming refers to the concept that an insult or stimulus applied at a critical or sensitive period may have long-term lifetime effects on the structure or function of an organism.¹¹ Programming effects in animals have been seen in research since the 1960s.¹¹ Nutrition in early life in animals has been shown to affect, in adulthood, blood lipids, blood pressure, body fatness, behaviour, learning and longevity.¹¹ Programming studies in humans tend to be observational which creates difficulties in proving causation or to form the basis of clinical practice. Intervention studies on potential programming are limited but do suggest that, in particular, rapid postnatal growth in humans may increase later cardiovascular risk, insulin resistance and obesity.^{7, 12, 13, 14, 15}

Rapid early weight gain

Rapid early weight gain has been consistently shown to be a risk factor for later obesity.^{4, 10, 16, 17, 18} In a meta-analysis, Druet et al¹⁷ showed that an increase of one SD in weight Z-score in the first year of life is associated with a two-fold risk of childhood obesity and a 23% higher risk of obesity in adulthood. Absolute weight gain in infants over six months is correlated with overweight at age four years and with BMI, fat mass and metabolic risk score at 17 years.^{19, 20} Studies suggest that the first few weeks and months of life are particularly associated with later weight status⁶. The effect of weight gain in the first three years of life also had a stronger impact on metabolic disturbances at 17 years than did weight gain between the ages of three and six years, suggesting that early infancy is a crucial window of metabolic programming.¹⁹ Rapid weight gain in the first two years is linked to a range of late-onset adverse outcomes including high blood pressure,²¹ increased body fat deposition,²² unfavourable lipoprotein profiles²³ and diabetes.⁷

What affects early growth?

It has become well accepted that the preconception health of the mother as well as the in utero environment programs the infant metabolic profile including later obesity risk²⁴. High birthweight and high weight gain in the first two years of life are associated with increased risk of later obesity.²⁵ Both in utero and in early life, infants organ systems still maintain considerable plasticity for adaptation to nutritional and environmental exposures⁶ and may be influenced by feeding choices. However, the precise mechanisms driving the correlation between excess weight gain in the first six months of life and later obesity remains unknown.⁶

Early protein hypothesis

One possible mechanism of metabolic programming is represented by the ‘early protein hypothesis’. This hypothesis comes from the observation that, compared to breastfed infants, formula fed infants have greater body weight gains in infancy.^{26, 27,28,29,30} This difference in weight gain may be linked to differences in protein content and type between breast milk and formula milk. Protein per kilogram of body weight is 55-80% higher in formula milk than breast milk.³¹ It was proposed that a higher protein intake may stimulate secretion of insulin-like growth factor I (IGF-I) which can lead to accelerated growth and increased adipose tissue ^{31, 32,33,34}. A positive association between protein and early growth has been seen in some but not all studies^35,36,37 however, this is an area of active research and there is a growing body of evidence that protein intakes in early infancy may impact later obesity. 

In 2009, the European Childhood Obesity Program (CHOP) study³¹ carried out a multi-centre, double-blind intervention trial. A total of 636 infants were randomly assigned to receive infant and follow-on formulas with a lower or higher content of cows milk protein during the first year of life. Their growth pattern was compared with that of breast fed infants. They found that a higher protein content of infant formula was associated with higher growth. 

Although weight was higher in the higher protein group, there were no significant differences in length, suggesting that the additional weight observed was due to a difference in body fat or a difference in adiposity. In a follow up study in the same cohort, Weber et al³⁸ found that the children fed the higher protein infant formula had a significantly higher BMI at six years of age compared to the children who had received the lower protein formula. In general, studies of total energy, carbohydrate and fat intake in the first two years of life do not show the same later associations with obesity. ^31,39

The protein content of formula milks has traditionally been higher than that of breastmilk.⁴⁰ Among other reasons, this is largely due to the lower digestibility of cow’s milk protein, limiting the supply of essential amino acids.⁴⁰ Legislation also sets the minimum and maximum protein contents of formula milk. Growing evidence of the possible link between higher protein intakes in infancy and obesity has recently led to EFSA recommending a reduction in the permitted amount of protein in infant formula from 3.0g per 100kcal to 2.5g per 100kcal.³³

Although higher protein intakes in early life, from birth to two years are associated with increased weight gain and later obesity, there are many other factors which may play a role. Maternal increased BMI, smoking and circulating triglycerides are also associated with rapid postnatal growth and may represent a ‘double-hit’ in programming effects in their offspring.⁷ More research is needed into the factors that affect obesity programming and into the specific underlying mechanisms. Although evidence is gathering that higher protein intakes in the early years may be significant, there are no scientific data available as yet to establish a precise cut off value for the maximum protein content in formula milk.³³

Conclusion

Obesity rates continue to climb with Ireland expected to have the highest obesity prevalence in Europe by 2030.⁴¹ Early intervention represents one area for prevention of obesity and intervention in infancy is easier because dietary intake is homogenous and many common childhood feeding issues have not yet manifested.⁶ The levels of protein supplied to infants both before and during complementary feeding may be a key factor in determining growth and future obesity, but there are many other factors that can affect both rapid growth in infants and future obesity risk.

References

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