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In-Utero and early life origins of adiposity in infants born to obese mothers

Student thesis: Doctoral ThesisDoctor of Philosophy

Experimental animal models and observational studies suggest that maternal obesity in pregnancy influences the development of obesity in early infancy. As the trajectory of later adiposity is thought to be determined in early life; an understanding of potential contributing factors and associative mechanisms are essential to inform targeted interventions.
The analyses reported in this thesis have sought to address these associations in mothers and their offspring from the UK Pregnancies Better Eating and Physical Activity Trial (UPBEAT), a randomised controlled trial of a behavioural intervention (diet and physical activity) in obese pregnant women. As the trial, did not show a reduction in the primary outcomes; incidence of gestational diabetes and delivery of a large for gestational age neonate, the dataset was treated as a cohort.
Modifiable maternal risk factors including early pregnancy measures of maternal adiposity, were linearly associated with neonatal adiposity. An independent association with maternal birthweight and neonatal adiposity was also identified. Mode of early infant feeding (breast, formula and mixed feeding) and measures of general appetite influenced measures of infant growth and body composition at 6 months in offspring born to obese women from the UPBEAT cohort; providing evidence of a potential target for intervention within a sensitive window of opportunity.
To address mechanistic pathways underpinning the associations between in-utero exposures and offspring adiposity, assessment of the cord blood metabolic profile was undertaken including measurement of candidate biomarkers and metabolome. A novel relationship between cord lysophosphatidylcholine with neonatal and infant anthropometry was identified, which was associated with maternal fasting glucose in late second trimester.
Maternal fasting glucose in late second trimester was also found to partially mediate the effect of maternal parity and early pregnancy adiposity with neonatal adiposity.
The UPBEAT intervention was associated with a reduction in a measure of offspring central adiposity, which was mediated through changes in antenatal diet and gestational weight gain instigated by the intervention. This provides evidence, within a randomised control trial setting that a behavioural intervention may potentially reduce offspring adiposity.
Original languageEnglish
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Award date2017

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