Our study confirms that BW in isolation would minimally affect the metabolic abnormalities related to NCD in children. Consequently, children with optimum body composition (children belonging to middle BW and BMI tertiles) were found to be metabolically healthier, denoting the role of BW on subsequent metabolic derangements. However, more importantly and contrary to the Barker hypothesis, the study further shows that, if a child is born with a lower BW but is able to maintain an optimum BMI, he too is protected from adverse metabolic derangements. This is in contrast to children born with a lower BW, followed by a higher weight gain during childhood (those belonging to lower BW and higher BMI tertiles) showing the worst metabolic outcomes. This highly suggests that BW is not the only risk factor that determines a poorer metabolic profile in children, but the weight gain during the first few years of life that has a greater contribution.
According to studies, changes in BP appear to track down from a younger age. The 1970 British birth cohort showed an inverse relationship between SBP at 10 years of age and BW [12]. When the cohort was stratified by BW and current weight tertiles, the highest mean SBP was observed among those belonging to the lowest BW and highest weight tertiles, while the lowest mean SBP was seen in the highest BW and lowest bodyweight tertiles. In comparison, the best mean SBP and DBP observed in our study were among children belonging to the middle BW and lowest BMI tertiles.
In the same British study, when children were stratified by prematurity, no difference in BP was observed [12], highlighting the greater role played by BW and subsequent weight gain in the BP of later life. Furthermore, Barker and co-workers in their 1946 British birth cohort at 36 years of age showed an inverse relationship of SBP with mothers’ height, which could be considered as an indirect measure of uterine size that may contribute to birth size. This association, derived independent of maturity, led the authors to conclude that intrauterine environment influences the BP in adult life. As per this study, the control of NCDs could even be a generation long process, where a healthy girl child with good uterine size would give birth to a well-grown healthy baby.
With regards to RBG, a significant relationship was established with BW and BMI tertiles in our study. In contrast, FBG failed to show a relationship, highlighting its poor applicability as a routine screening test to detect impaired glycaemic control. In a previous study, we showed that fasting and 2-hour post glucose serum insulin levels as well as insulin resistance measured using HOMA-IR have a strong relationship with lower BW and higher current BMI [13].
Hales and co-workers studying a group of 59–70 year old men from Hertfordshire, UK showed that adults of both low BMI with poor prenatal growth helped in protecting against dysglycaemia [14]. A similar relationship was noted in relation to the current size of adults, where 2-hour plasma glucose was lower in men having both lower weight at one year and lower BMI as adults (6.6 mmol/L), compared to those with lower weight at one year but higher BMI as adults (7.7 mmol/l). The lowest 2-hour glucose was seen in those having higher BW and lower BMI as adults (5.8 mmol/L). Plasma 32–33 split pro-insulin concentration also showed a similar distribution. This denotes that weight at one year in combination with later growth is a better predictor of adverse health outcomes in later life than early weight alone.
Interestingly, a study involving 16–19 year old children in India, which reports a higher incidence of low BW, did not show significant associations between BW and metabolic derangements during late adolescence [2, 15]. However, a higher risk for coronary heart disease (CHD) and DM was seen in low BW children who were better nourished at the time than their counterparts. This study further reiterates the role played by catch-up growth.
It is shown that children with catch-up growth have a greater risk of dying from CHD later in life. According to Helsinki study, there was a 14% (95% CI = 8–19%, p < 0.0001) increase in this risk for each unit increase of ponderal index (kg/m3) at birth and a 22% (95% CI = 10–36%, p = 0.001) increase for each unit increase of BMI at 11 years of age [16]. The highest death rates were seen in children who were thin at birth but had catch-up growth to reach normal BMI at 7 years [16]. Similarly, Harvard growth study showed the effect of high BMI at childhood on CHD in later life, which was independent of adult BMI [15]. In comparison, our data also showed that low BW children achieving a higher BMI in early life would have an adverse metabolic profile. As to the cause underlying this, accumulation of fat was strongly implicated.
Reports suggest that foetal nutrition, as denoted by BW, may have an inverse programing effect on abdominal adiposity in later life, which could contribute to the development of insulin resistance [6]. This indicates that one’s body composition during foetal and early life is associated with adult disease risk [17]. Two primary mechanisms have been identified [17]. One is that poor foetal and infant growth could constrain on the development of lean body mass, thus reducing the metabolic capacity which is not able to tolerate a calorie-rich diet. The other mechanism is rapid growth in infancy and excess weight gain disproportionately diverts energy to abdominal adipose tissue, thus increasing the metabolic load.
It is shown that rapid weight gain during infancy in SGA children is associated with increased fat mass rather than lean mass [6, 18]. Early catch-up growth after SGA birth rather than SGA itself has been noted as a CVD risk factor in later life [19]. However, the tendency of SGA children to assimilate intra-abdominal fat is not yet clear; whether due to low BW itself, rapid postnatal catch-up growth or a combination of both [6, 20]. During recovery from wasting or protein-energy malnutrition in children and adults, fat mass is shown to accumulate much faster than the muscle mass. This phenomenon could partly explain the adverse outcomes in SGA children during catch-up growth [6]. Therefore, although catch-up growth explicitly confers several benefits in relation to improved neurodevelopment, enhanced immune function and achieving adult height, there are certain adverse metabolic consequences as well, such as the insulin resistance, metabolic syndrome, DM, CVD, increased fat mass and obesity. As such, it is imperative that early feeding of SGA children requires close growth monitoring. In this regard, growth of SGA children should be monitored monthly in the first two years, with close attention paid to any upward crossing of SD lines (WHO growth references).
This paper highlights several implications for improving the clinical practice related to children in early life, especially in developing countries where poor prenatal growth of a child is still a grave issue. In such clinical settings, measures should be in place to prevent excess weight gain in SGA children. To this end, length/height of a baby, which is usually parallel to weight gain, should be assessed at 3–6 month intervals up to two years, so that growth could be evaluated with the use of length/height for weight charts. If practically possible, regular assessment of catch-up fat is necessary. Further, larger cohort studies are needed from developing countries to understand the best possible trajectory of growth based on anthropometry with the metabolically favourable body composition to prevent complications of SGA infants.