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Home    Association of maternal 25(OH)D levels and metabolic profile in early pregnancy, with child cardiometabolic traits and neurodevelopment at preschool age: the "Rhea" pregnancy cohort in Crete, Greece  

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Identifier 000411419
Title Association of maternal 25(OH)D levels and metabolic profile in early pregnancy, with child cardiometabolic traits and neurodevelopment at preschool age: the "Rhea" pregnancy cohort in Crete, Greece
Alternative Title Προοπτική μελέτη του ρόλου της 25(ΟΗ) βιτD και παραγόντων του μεταβολικού συνδρόμου στο 1ο τρίμηνο της κύησης στην σωματική ανάπτυξη και νευροανάπτυξη παιδιών προσχολικής ηλικίας-Μελέτη Μητέρας Παιδιού Κρήτης, Μελέτη ΡΕΑ
Author Δαράκη, Βασιλική
Thesis advisor Χατζή, Λήδα
Reviewer Παπαβασιλείου, Στάθης
Κογιεβίνας, Μανόλης
Λιονής, Χρήστος
Γερμανάκης, Ιωάννης
Σίμος, Παναγιώτης
Τσατσάνης, Χρήστος
Abstract Introduction: Most organs and structures of the developing fetus are formed in the first months after conception. Therefore, early pregnancy is highly recognized as a time period with significant susceptibility to an adverse intrauterine environment. Beyond nutrition and other environmental risk factors, maternal pre-pregnancy obesity has been associated with increased risk of offspring obesity, adverse lipid profile and impaired glucose tolerance as well as neurodevelopmental disorders in childhood and adulthood. However, little is known about the potential impact of other parameters of the metabolic syndrome in early pregnancy on metabolic programming and neurodevelopment in the offspring. Additionally, maternal vitamin D levels are considered an essential biological factor for intrauterine skeletal growth and muscle development, but limited data exist so far on the potential impact of circulating vitamin D on offspring adiposity and mental development. We aimed to investigate in greater detail the effect of metabolic dysregulation and maternal 25(OH)D levels in early pregnancy with multiple offspring metabolic and neuropsychological outcomes at 4 years of age, in a prospective pregnancy cohort in Crete, Greece. Specific Objectives: 1) To investigate the impact of components of metabolic syndrome in early pregnancy on offspring cardiometabolic traits at 4 years of age. 2) To evaluate the role of components of metabolic syndrome in early pregnancy in psychomotor development, and behavioral difficulties at 4 years of age. 3) To investigate the association of 25(OH)D levels in early pregnancy on offspring cardiometabolic traits at preschool age. 4) To examine the impact of 25(OH)D levels in early pregnancy on cognitive and psychomotor development at preschool age. Methods: Our study population was part of the “Rhea” study, a prospective pregnancy cohort, at the prefecture of Heraklion, Crete, Greece. Pregnant women were recruited at the time of the first ultrasound examination, during the twelve-month period from February 2007 until February 2008. Women were contacted again at various times during pregnancy, at birth, and for child’s follow-up at 9th, 18th months, and at 4 and 6 years of age. Face-to face completed questionnaires together with self-administered questionnaires and medical records were used to obtain information on dietary, environmental, and psychosocial exposures during pregnancy and early childhood. Maternal pre-pregnancy BMI was calculated by maternal height, measured at the first prenatal visit, and pre-pregnancy weight, as reported at the first ultrasound visit. At the first prenatal visit trained examiners measured maternal blood pressure levels, and collected maternal serum samples for maternal glucose, lipid and 25(OH)D measurements. At 4 years of age data on child anthropometry, blood pressure measures, and serum samples for offspring lipid measurements were collected by specially trained research assistants, according to standard operating procedures. Αdditionally, at 6 years follow up offspring body composition was estimated, by a bioelectric impedance analysis (BIA). Moreover, children’s cognitive and motor function at 4 years of age was evaluated by two trained psychologists through the McCarthy Scales of Children Abilities. Behavioral difficulties were assessed by Strengths and Difficulties Questionnaire and Attention Deficit Hyperactivity Disorder Test, completed by mothers. Adjusted associations were obtained via multivariable linear and logistic regression analyses. Results: 1) In the analysis of the relationship between components of metabolic syndrome in early pregnancy and cardiometabolic traits at preschool age, we found that maternal overweight/obesity pre-pregnancy was associated with increased risk of offspring overweight/obesity, central adiposity, and greater fat mass at 4 years of age, predominantly in girls. In addition, an increase of 40mg/dl in fasting serum cholesterol levels in early pregnancy was also associated with increased risk of overweight/obesity and fat mass in preschoolers. The associations remained the same after adjustment for several maternal and child characteristics, including maternal BMI. Seemingly a significant positive association was observed between higher levels of maternal diastolic blood pressure and adiposity measures at 4 years of age. 2) Among maternal metabolic diseases examined, only maternal overweight/obesity pre-pregnancy was associated with a significant score reduction in perceptual performance, quantitative ability, general cognitive function, and executive functions at 4years of age. In addition maternal overweight/obesity pre-pregnancy was associated with significant increment in behavioral problems and ADHD-like symptoms at preschool age. The observed associations remained significant after adjustment for several confounders, including paternal BMI. 3) In our analysis for the impact of maternal 25(OH)D status on offspring health outcomes at preschool age, about two-thirds of participating women suffered from vitamin D deficiency in the first half of pregnancy. Offspring of mothers with 25(OH)D levels in the lower tertile had significantly increased BMI SD score, central adiposity and body fat percentage at 4 years of age, compared to offspring of mothers with higher 25(OH)D levels. 4) In contrast increased maternal 25(OH)D levels in early pregnancy seemed to protect from behavioral problems in early childhood, as offspring of women with 25(OH)D levels in the high tertile had significantly decreased hyperactivity/impulsivity and total ADHD-like symptoms, as well as decreased total behavioral difficulties at 4 years of age, compared to offspring of women with 25(OH)D levels in the low tertile. Τhe observed associations remained the same after adjustment for several confounders and maternal BMI, and were more pronounced in girls than in boys. Conclusions: In summary, findings in the present thesis support the view that maternal metabolic dysregulation and vitamin D status in early pregnancy may have an important impact on offspring adiposity measures and neurodevelopmental outcomes in early childhood, independently of sociodemographic and family parameters. Our results may have important public health implications, as the examined exposures are modifiable risk factors and may be prevented with appropriate awareness and guidance. Further follow-up of this cohort will allow to determine whether our findings persist at later ages.
Language English
Subject Obesity
Issue date 2017-12-12
Collection   School/Department--School of Medicine--Department of Medicine--Doctoral theses
  Type of Work--Doctoral theses
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