Adult phenotype of preterm birth at very low birth weight : brain, bone and fat - a sibling study

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Sammanfattning

Being born preterm (< 37 gestational weeks) and especially preterm with very low birth weight (< 1500 grams) has been shown to associate with adverse health outcomes in adolescence and adulthood: higher blood pressure, elevated glucose levels, and lower bone mineral density. Being born very preterm at very low birth weight has been associated with smaller brain volumes. It is still unclear, however, how the extreme stress of preterm birth manifests in adulthood. Nearly all studies have been conducted with unrelated controls, leaving room for residual confounding that a sibling comparison may address. In my dissertational thesis I investigate how adults born preterm at very low birth weight differ from their term born siblings in regard to brain, bone, and abdominal adipose tissue pools. In addition to this, I aim to identify epigenetic imprints of preterm birth from adult leukocyte DNA from individuals born preterm at very low birth weight, which could reflect a permanent change in gene activity regulation. I discovered that adults born at very low birth weight have more incidental findings than their term siblings in brain MRI, smaller total brain volume, less gray matter, smaller basal ganglia and larger ventricles than their siblings. Contrary to earlier studies, there was no difference in white matter volume. I discovered that adults born preterm at very low birth weight have a lower bone mineral density in the femoral neck, and additionally whole body bone mineral content was lower in those born at very low birth weight. The differences between groups, however, attenuated after taking body mass index and height into account in statistical modelling. Regarding fat outcomes, no differences in adipose tissue volumes or hepatic fat were observed. There was, however, less unsaturation in magnetic resonance spectroscopy of subcutaneous abdominal adipose tissue, which may be related to reported differences in resting state energy expenditure or fatty acid metabolism. I discovered differences in the methylation of several genes and further aimed to validate these findings in independent cohorts. By combining results from said cohorts, I discovered five sites in the epigenome that seem to be associated with both birth weight and being born preterm at very low birth weight. Being born preterm, very preterm or with a very low birth weight is a major factor contributing to adult health, which, based on my dissertational thesis and sibling comparison, has lasting effects well into adulthood. In particular, my thesis contributes to the understanding of brain volume differences and high prevalence of incidental findings as well as bone and adipose tissue differences and similarities between adults born at very low birth weight and term siblings.
Originalspråkengelska
Handledare
  • Kajantie, Eero, Handledare
  • Lundbom, Nina, Handledare
  • Lundbom, Jesper, Handledare
UtgivningsortHelsinki
Förlag
Tryckta ISBN978-951-51-9028-4
Elektroniska ISBN978-951-51-9029-1
StatusPublicerad - 2023
MoE-publikationstypG5 Doktorsavhandling (artikel)

Bibliografisk information

M1 - 116 s. + liitteet

Vetenskapsgrenar

  • 3123 Kvinno- och barnsjukdomar

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