In examining maternal depression, placental 11 beta-HSD2 mRNA expression and offspring cortisol regulation as a potential fetal programming pathway in relation to later child emotional disorders,... Show moreIn examining maternal depression, placental 11 beta-HSD2 mRNA expression and offspring cortisol regulation as a potential fetal programming pathway in relation to later child emotional disorders, it has become clear that sex differences may be important to consider. This study reports on data obtained from 209 participants in the Mercy Pregnancy and Emotional Wellbeing Study (MPEWS) recruited before 20 weeks of pregnancy. Maternal depressive disorders were diagnosed using the SCID-IV and maternal childhood trauma using the Childhood Trauma Questionnaire. Placental 11 beta-HSD2 mRNA was measured using qRT-PCR. For assessment of stressinduced cortisol reactivity, salivary cortisol samples were taken at 12 months of age. At 4 years of age, measurement of Childhood Emotional Disorders (depression and anxiety) was based on maternal report using the Preschool Age Psychiatric Assessment (PAPA) and internalizing symptoms using the Child Behavior Checklist (CBCL). Maternal depression in pregnancy and postpartum, and infant cortisol reactivity, was associated with internalizing symptoms for females only. For female offspring only, increased 12-month cortisol reactivity was also associated with increased emotional disorders at 4 years of age; however, there was no association with placental 11 beta-HSD2 mRNA expression. In females only, the combination of lower placental 11 beta-HSD2 mRNA expression and higher cortisol reactivity at 12 months of age predicted increased internalising problems. These findings suggest there may be sex differences in prenatal predictors and pathways for early childhood depression and anxiety symptoms and disorder. Show less
Current prenatal diagnostics is mainly based on obtaining fetal DNA through invasive procedures such as chorionic villi sampling (CVS) or amniocentesis. These procedures are associated with a small... Show moreCurrent prenatal diagnostics is mainly based on obtaining fetal DNA through invasive procedures such as chorionic villi sampling (CVS) or amniocentesis. These procedures are associated with a small, but significant risk of fetal loss. The discovery of the presence of cell-free fetal DNA (cffDNA) in maternal plasma opened possibilities for less of noninvasive alternative procedures. CffDNA is comprised of small fragments of fetal extracellular DNA derived from placental cells that go into apoptosis and can be detected already early in gestation. However, the majority of total cell-free DNA in maternal plasma is of maternal origin and the fetal contribution in the first trimester is relatively small. In this thesis, we describe novel applications and approaches for the use of cffDNA in noninvasive prenatal testing and diagnostics for a wide variaty of genetics defects such as fetal trisomy 21 (Down syndrome), hereditary breast cancer mutation detection and noninvasive detection of the expanded CAG repeat in Huntington disease. Show less
