Growth and metabolic outcomes in children born preterm :the Growmore study

Abstract

Background: The Growmore Study was an observational cohort study of adolescents born preterm, in Newcastle-upon-Tyne. The cohort were born between 1993 and 1998: mean gestation at birth was 31 weeks (range 24+5d to 36+2d) and birthweight 1392g (690-2200g). Individuals were originally recruited into one of two randomised, controlled trials (‘growth’, n=113; and ‘protein’, n=134). As separate groups they were followed up at intervals, undergoing assessment of growth and development. From 247 children originally recruited, 220 completed assessments to 24 months of age. At age 10 underwent cognitive assessment. Between 9 and 13 years old, the two cohorts were amalgamated to a single cohort and underwent further auxological and metabolic testing (n=153/247) including DEXA scan (n=109) and bloods (n=139). The current study revisited the cohort, aged between 12 and 18 years old. Aims: The study aimed to explore relationships between: growth in early life; body fat deposition; mitochondrial oxidative capacity; and quantitatively assessed diet and activity in ex-preterms. Methods: 60 of the 235 traceable members of the original cohort were recruited into this study. They underwent multimodal assessment, including: auxological measures; body composition measurement by air-displacement plethysmography and skinfold thickness; magnetic resonance spectroscopy (MRS), using a 3-Tesla scanner, custom-built coils and a tailored scanning routine to quantify skeletal muscle mitochondrial oxidative capacity, lipid content of the liver, and fat-containing tissue at the L2/3 vertebral level; a standard OGTT (bloods taken at 0 and 120minutes); and serum insulin, glucose, lipid profile, liver function and Vitamin D measurement. Dietary intake was assessed using a computer-based recall diary and physical activity by wearing of accelerometers. Data was analysed by using a variety of statistical methods including comparative, correlation and regression analysis. Results: The 60 adolescents recruited for this study had a mean gestation at birth of 31 weeks (range 26+1d to 34+4d) with birthweight of 1370g (range 840-1870g). Their mean age at study was 15.5 years and M:F ratio was 1:1.4. Analysis showed they were not significantly different from their peers at the previous cohort assessment and both of the two original RCTs were almost equally represented (‘growth’: ‘protein’ = 1:1.07). The current study showed that amongst this cohort subgroup, vitamin D status iii correlated with time of year (p=0.046) and current weight SDS (p= 0.039). Skeletal muscle oxidative function was significantly related to vitamin D status (p=0.021) and gestational age at birth (p=0.005); combined r2:0.31; p=0.002). Earlier gestational age (GA) at birth and lower serum vitamin D was associated with reduced oxidative capacity. Physical activity was not associated with oxidative capacity. Visceral adipose tissue (VAT), circulating triglyceride (TG) and waist circumference were strongly associated with hepatic lipid content (all p<0.001); dietary intake was not. VAT and TG were highly significant when the model was adjusted for Tanner Stage (r2: 0.4; p=0.0002). GA and birthweight were not related to hepatic lipid deposition. Insulin sensitivity by two different measures was predicted by triglyceride levels (p<0.001), light activity (P<0.05) and vitamin D levels (p<0.05). Conclusion: Environment and early life both have an influence on adolescent physiology. The strength of association between vitamin D and muscle oxidative capacity has been observed in other conditions, but the contribution of gestation at birth in those born preterm is a novel finding. This may reflect either a variance in muscle fibre type or mitochondrial density directly related to developmental arrest or delay as a result of preterm birth. Vitamin D status also influences insulin sensitivity, as seen in other populations: Vitamin D status is an obvious target for dietary advice. Absence of an association between gestation and adiposity, and correlation between VAT and hepatic lipid deposition suggests that there are opportunities for children born preterm to improve their health in adolescence, and by implication, their future adult health.