Infant Formula Protein Content And Childhood Obesity
Child growth and obesity risk is affected by infant feeding. In this study, we assessed the effect of protein intake in infancy on the body mass index, obesity and adiposity rebound of children aged up to 11 years. Healthy infants from five European countries who were born at term were enrolled in a randomized, double blind trial. 16 examinations were carried out during follow-up visits for a duration of 11 years. 1090 Infants were fed with formula and randomized to isoenergetic formula which contained either a lower or higher protein content still within the recommended range stipulated by the European Union Legislation in 2001. 588 children that were breastfed were included as the reference group.
Body mass index (BMI) trajectories and adiposity rebound were evaluated using a generalized additive mixed model in a total of 917 children, with the 11-year follow up period being carried out on 712 children.
Body mass index (BMI) trajectories were notably higher in the group of infants taking high protein content formula compared to the low protein formula group. Adiposity rebound and body mass index (BMI) varied significantly between the high protein formula group and the low protein formula group. The high protein formula group was seen to have a higher risk of being overweight at age 11 compared to the lower protein formula group.
There was no significant difference in the timing of adiposity rebound in both formula groups, however, an early adiposity rebound before 4 years of age resulted in childhood obesity at 11 years.
Feeding infants with formula containing low protein content was seen to reduce body mass index trajectories and helps the child attain similar adiposity rebound and body mass index as breastfed infants compared to infant formula with high protein content.
Childhood obesity is a condition where a child weighs more than the normal reference values for their age or has excessive body fat to an extent that it has detrimental effects on health and wellbeing.
Over the years, obesity has been quantified or diagnosed using body mass index, with values greater than or equal to 30 kg/m2 or the 95th percentile. Childhood obesity is a serious concern in public health and obese children have a higher risk of becoming obese adults. Obese children who do not end up becoming obese adults still have a high risk of coming down with cardiovascular disease and type 2 diabetes mellitus. The 19% to 25% prevalence of obesity in European regions is still notably high despite the stabilized prevalence of obesity and overweight in children aged 2 to 13 years from 1999 to 2016 in most European countries.
Early prevention of obesity and overweight is vital in curbing this problem. Increased obesity risk has been shown to be associated with some critical growth phases or periods in childhood. Early weight gain may lead to a peak of first adiposity at the 1 year old and adiposity rebound between the ages of 2 and years which is a rise in BMI after its physiological drop at 2 years. These two points have been hypothesized to be vital risk predictors for becoming obese or overweight based on their intensity and timing, that is, the body mass index values at adiposity peak and adiposity rebound.
A lower risk of childhood obesity in several observational studies has been linked with breastfeeding when compared to formula feeding. The lower protein content of breastmilk compared to formula is seen to be the reason for this. Hypothesis called the “early protein hypothesis” proposed that a higher intake of protein in infancy leads to an enhanced or increased adipogenic activity due to increases in the levels of insulin and insulin-like-growth factor-1. Protein supply in infancy was demonstrated to have an effect on early weight gain in interventional trials that compared infant formulas with different protein contents. Infant formulas with low protein content were seen to cause a significantly lower body mass index score at 2 years of age compared to the infant formula with high protein content.
In a previous study, we noted a significant impact of protein supply in infancy on the prevalence of body fatness and obesity by 6 years of age. However, there is not enough evidence from controlled interventional trials on the likelihood of long-term effects of infant nutrition on the timing and intensity of the body mass index during adiposity rebound and in later childhood. The results obtained from observational cohort studies are not consistent.
Children in the randomized, double-blind outpatient trial who were given dietary intervention (i.e infant formula with lower versus higher protein content) during infancy were followed up for 11 years and their timing of adiposity rebound, BMI at adiposity rebound, BMI trajectories and obesity or overweight risk at 11 years of age was evaluated. It was hypothesized that the early dietary intervention with infant formula containing low protein content in infancy lowered the BMI trajectories to levels similar to infants that were breastfed, lowered the risk of obesity and overweight at 8 and 11 years of age and led to variations in the timing of adiposity and BMI score at adiposity rebound.
This outpatient study was a randomized, double blind, controlled interventional trial carried out in multiple centers. This trial enrolled a total of 1678 healthy infants born at term with adequate birth weight and gestational age in Germany (Munich, Nuremberg), Poland (Warsaw), Belgium (Brussels, Liège) and Italy (Milano). The study’s details, conduct and design has been published previously. The study was carried out in accordance with the Declaration of Helsinki and the local ethical committees of all participating centers reviewed the study.
Formula fed infants were randomized by the first two months of life to infant formula and follow-on formula containing high protein content (3.2 g/dl in follow-on, 1.6 g/dl in infant) or low protein content (2.05 g/dl in follow-on, 1.25 g/dl in infant) which is provided during the period of infancy. Infants who were compliant were given the study formula for a minimum of 90% of their total feeds. The selected protein levels were maintained within the recommended range provided by the European Union Legislation. The fat contents were adjusted to achieve the isoenergetic infant formulas in the two randomized groups.
Infants who were exclusively breastfed for a minimum duration of 3 months were enrolled into the study as a reference group.
Study personnel who were repeatedly trained carried out anthropometric measurements in accordance with carefully drafted standard operating procedures during follow-up visits at 3 months, 6 months, 1 year and 2 years and thereafter biannually until 6 years, then at 7 years, 8 years and 11 years. These measurements include skinfold thickness, height and weight. Fat mass index(using the slaughter equation for skinfolds) and body mass index were also calculated. Obesity and overweight were classified using the body mass index cutoffs of the International Obesity Task Force.
A comparison was made using a generalized additive mixed model (GAMM) with thin plate regression spline for age, basis dimension, slope and random intercept for age feeding group between the BMI trajectories from the age of one to 11 among the higher protein content formula group, lower protein content formula group and infants who were breastfed.
Linear regression models were used to evaluate the association between infant feeding (High protein formula, Low protein formula and Breastmilk) and the continuous outcomes (such as BMI at adiposity rebound and age at adiposity rebound).
Quantities and stratified sample means of body mass index and fat mass index were plotted for visualization.
1066 out of 1678 infants participated in anthropometric measurements at one year. 917 out of the 1066 were included for assessment of adiposity rebound. 712 out of the total 1678 infants included in the study participated in regular follow-up for a period of 11 years.
Mothers in the breastfed group had a lower rate of smoking during pregnancy, higher educational level and lower cesarean section rates compared to the high protein and low protein infant formula group. There were no differences at randomization in the infant formula groups.
At the end of infancy (i.e the interventional period), a significantly higher BMI was noted in the high protein formula group compared to the low protein formula group and the breastfed group. At 2 years of age, the BMI of the high protein infant formula group is still notably higher than that of the low protein infant formula group. The differences in BMI steadily increases by the age of 2 to 8 years as the high protein infant formula group has the highest projected BMI trajectories while the breastfed group has the least predicted BMI trajectories.
There were no observable differences in the adiposity rebound timing between the high protein infant formula group and the low protein infant formula group. Both the high protein infant formula group and the low protein infant formula group showed an age of adiposity rebound to be 9 months earlier than that for the breastfed group.
The high protein infant formula group was seen to have a higher risk of obesity and overweight at ages 8 and 11 compared to the low protein infant formula group and breastfed infants. Notably, 94% of children who were obese at 8 years and 96% of children who were obese at 11 years were seen to be early rebounders, having attained adiposity rebound before 3.5 years. All children who had obesity attained adiposity rebound younger than 4 years. No child at ages 8 and 11 who attained adiposity rebound late (i.e after 5 years) was considered to have obesity.
This study demonstrated the long-term effect of infant feeding on BMI trajectories. High protein infant formulas such as those containing cow’s milk were seen to induce higher rates of early weight gain, adiposity peak, increased adiposity rebound and higher body mass index at adiposity rebound compared to low protein infant formulas.
Providing low protein infant formulas to infants results in a lowered BMI trajectory evolution from 3 months of life to 11 years of age compared to the regular high protein infant formulas.
Breastfeeding and the use of low protein infant formula in the first year of life led to a significantly lower body mass index and adiposity rebound in children up to 11 years. It is thus concluded by this study that excess protein intake in infancy should be avoided as this can further lower the childhood obesity burden.
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