Caesarean section delivery and childhood obesity

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Masukume, Gwinyai
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University College Cork
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Background and aims: Caesarean section (CS) birth, in particular elective/planned CS, has been found to be associated with an increased risk of childhood obesity. Various mechanisms that differ by birth mode, including differences in the vaginal and faecal microflora and stress hormone concentration have been suggested to underpin this association. The literature describing this association, often derived from non-nationally representative cohorts has been inconsistent, limited by small sample size, often unable to distinguish between elective and emergency CS, have publication bias favouring positive effects and often unable to adjust for key confounders like maternal pre-pregnancy body mass index (BMI). Given the rising global use of CS with some countries having CS rates above 50%, the aim of this thesis was to critically evaluate the association between CS birth and childhood obesity and to use three large contemporary nationally representative prospective longitudinal cohort studies and one smaller cohort, with detailed phenotypic data, to investigate this association. Structure and methods: The existing published literature relating to CS birth and childhood obesity was critically evaluated and synthesised to identify major conceptual themes and research gaps (Chapter 1). Chapter 2 details and justifies the thesis’ methodological approach. The following four longitudinal birth cohort studies were utilised: Screening for Pregnancy Endpoints (SCOPE) and Babies After SCOPE: Evaluating the Longitudinal Impact on Neurological and Nutritional Endpoints (BASELINE); Growing Up in Ireland (GUI); Growing Up in New Zealand (GUiNZ) and the Millennium Cohort Study (MCS) cohorts. In order to facilitate comparison between different cohorts (Chapters 3 through to 7), children were classified, on the basis of their BMI, as obese, overweight, normal or underweight according to the sex and age specific International Obesity Task Force criteria. A range of statistical analytic approaches including linear, multinomial and mixed-effects regression were employed. Multiple imputation was used to handle substantial missing data. In addition to our primary outcome BMI, which was modeled as continuous or categorical variable, the association between our exposure CS birth and BF% was investigated in cohorts that had this data available. Where the sample size permitted, the association between CS birth and transition into or out of obesity was examined. The overall results in the context of the published literature were discussed including limitations and strengths and future research directions (Chapter 7). Results: SCOPE-BASELINE cohorts: At two months of age, children born by CS, had a similar BF% to those born vaginally. At age six months, children born by CS had a significantly higher BMI, adjusted mean difference=0.24; 95% confidence interval (CI) 0.06 to 0.41, but this did not persist into future childhood, at age five years. There was no evidence to support an association between mode of delivery and long-term risk of obesity in the child. GUI cohort: We found insufficient evidence to support a relationship between elective CS and childhood obesity at age three and five years. An increased risk of obesity in children born by emergency CS, adjusted relative risk ratio (aRRR) = 1.56; [95% CI 1.20 to 2.03], but not elective, suggests that the influence of vaginal microflora in developing childhood obesity was minimal. The association with emergency CS was likely due to its indications. GUiNZ cohort: Planned CS was an independent predictor of obesity in early childhood at age two years aRRR=1.59; [95% CI 1.09 to 2.33] but this association was not apparent by four and a half years This suggests that birth mode is associated with early growth, at least in the short term. This association occurred during a critical phase of human development, the first two years of life. Given the developmental origins of health and disease hypothesis this may lead to long-term detrimental cardiometabolic changes. MCS cohort: Infants born by planned CS did not have a significantly higher BMI at ages three, five, seven, eleven and fourteen years adjusted mean difference=0.00; [95% CI -0.10 to 0.10], or BF% at ages seven 0.13; [95% CI -0.23; 0.49] and fourteen compared to those born by normal VD. This may suggest that the association, described in the literature, could be due to the indications/reasons for CS birth or residual confounding. Conclusions: The hallmark finding of the thesis was an association between CS birth in general, elective CS in particular, and childhood obesity during the first two years of life. This association had dissipated by age three through to fourteen. Whether this association remerges in adulthood or is a risk factor for cardiometabolic disease is an area for future research. The association observed with emergency CS is possibly due to confounding by the underlying reasons for CS, confounding by indication. There is potential to improve consistency and robustness in this research field by better and standardised definition particularly of the exposure, CS birth. Better consistency in the timing of obesity assessment is also warranted.
Caesarean section , Ireland , New Zealand , United Kingdom , Body composition , Body fat , Obesity , Childhood , Microbiota , Overweight , Vaginal microflora
Masukume, G. 2020. Caesarean section delivery and childhood obesity. PhD Thesis, University College Cork.
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