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Title: Stress and glucocorticoid treatment during pregnancy, early growth and metabolic outcomes in childhood
Author: Ali Khan, Anokhi
ISNI:       0000 0004 5922 7066
Awarding Body: Imperial College London
Current Institution: Imperial College London
Date of Award: 2014
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Background: Variation in birth size has been linked to increased risk of a number of disorders later in life, including cardiovascular and metabolic disorders. However, less is known about other parameters of birth size, beyond birth weight, on later health. Moreover, the impact of the biological markers of stress, i.e. glucocorticoids, on various parameters of birth size remains understudied as well as their impact on later metabolic outcomes. Aims and objectives: The aim of this study was to examine the influence of the HPA axis on birth size (birth weight, ponderal index, birth length, head circumference) and subsequent metabolic health in adolescence. The main predictor being exposure to glucocorticoids either administered clinically or inferred as a result of maternal social stress. The genetic environment interplay of birth weight lowering alleles near LEKR and CCNL1 and in ADCY5 was also examined. Methods: Data came from the Northern Finland Birth Cohort (NFBC1986), and the National Finnish Medical Birth Registry (MBR) 2006-2010. Glucocorticoid treatment (sGC) to mature foetal lung in threatened preterm birth, social stress measures, and birth outcomes were obtained from medical records and via maternal report (in NFBC1986) during pregnancy. Data on NFBC1986 children at 16 years included anthropometry, blood pressure, blood sample for DNA, and metabolic outcomes. Results: The systematic literature review showed a dearth of information on the association of sGC on birth size, with the larger studies reporting smaller birth size in infants exposed to sGC. The NFBC1986 cohort showed only 17% (n=58) preterm infants had received sGC due to threatened preterm birth, with an association with smaller birth length of -0.18cm(95%CI -0.26, -0.10), but a larger birth weight of 116g(95%CI 98.9, 133.1) and head circumference of 0.75cm(95%CI 0.7, 0.81). In contrast, in the MBR (5090 exposed subjects) sGC treatment was consistently associated with lower birth weight of -207g(95%CI -220, -195), birth length of -1.26cm(95%CI -1.31, -1.20), head circumference of -0.94cm(95%CI -0.98, -0.90), and ponderal index of -0.91 (95%CI-1.02, -0.81). Maternal social stress during pregnancy and risk allele near LEKR and CCNL1 each was associated with smaller birth size. The association with stress was magnified with lower birth weight of -118g(95%CI -156, -79), birth length of -0.30cm(95%CI -0.46, -0.14), head circumference of -0.23cm(-0.35, -0.11), and ponderal index of -0.47(95%CI -0.67, -0.26) in the presence of risk allele. No robust association was found between maternal social stress during pregnancy and metabolic syndrome at 16 years. There was an association with more adverse lipid profile in particular with apolipoprotein B/A ratio (1.92% increase, 95%CI 0.34, 3.52, by maternal exposure to social stress). Conclusion: Stress and exposure to sGC during pregnancy in addition to genetic risk are related to smaller birth size. In the NFBC1986 there was no evidence of longer term impact of in utero stress exposure on metabolic syndrome in adolescence, though there was a poorer lipid profile noted. To better understand the degree to which the HPA axis plays in foetal programming, maternal and foetal cortisol levels during pregnancy would be beneficial.
Supervisor: Jarvelin, Marjo-Riitta ; Rodriguez, Alina Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available