Prenatal Programming of Childhood Obesity and Cardio Metabolic Disorders

Prenatal Programming of Childhood Obesity and Cardio Metabolic Disorders - Role of Maternal Obesity, Pregnancy Complications, and Maternal-fetal Metabolome

This is a prospective 11-17 -years follow-up of two existing pregnancy cohort (PREDO) and prevention (RADIEL) studies. The main objective is to investigate the associations between maternal overweight, obesity, hypertensive disorders in pregnancy, gestational diabetes, and maternal-fetal metabolome, child's birth outcomes, and overweight and obesity and cardio metabolic health outcomes in childhood and adolescence. During this follow-up study, the mothers and their 11-17-year-old children are invited for a study visit and their cardio metabolic health is studied by many different methods.

The study comprises two Finnish pregnancy cohort /prevention studies, in which mother-child pairs have already been followed from early pregnancy until the threshold of adolescence. During this project period the follow-up of PREDO and RADIEL mothers and children will be extended until 11-17 and 11-14 years of age, respectively. This adolescence follow-up will include detailed measurements of overweight/obesity, body composition, and cardiovascular and metabolic health as well as lifestyle factors.

Research methods:

1. Maternal cardiometabolic conditions during pregnancy (data available): is defined by maternal pre-pregnancy BMI extracted from the Medical Birth; gestational weight gain calculated from maternal weight at childbirth derived from antenatal cards; blood pressure and proteinuria from antenatal cards, and results of 2-h oral glucose tolerance test and diagnoses of gestational diabetes and hypertensive disorders (chronic hypertension, gestational hypertension, preeclampsia) extracted from medical records and verified by an expert jury comprising two medical doctors and a research nurse with expertise in obstetrics.

2. Maternal and fetal metabolome (data available): is quantified by using high-throughput proton nuclear magnetic resonance (NMR) metabolomics platform (Nightingale Health Ltd, Helsinki, Finland). In total 220 metabolites were quantified covering multiple metabolic pathways, including lipoprotein lipids and subclasses, apolipoproteins, fatty and amino acids, ketone bodies, glycolysis and gluconeogenesis-related metabolites, fluid balance and inflammation.

3. Child's overweight/obesity and cardiometabolic health in childhood (data available): Child's weight and height have been derived from the child health center registry with data available from birth to 7-11 years in PREDO and from birth to 5 years in RADIEL. The 24-h ambulatory blood pressure data are available in the PREDO study from the child follow-up at age 7-11 years, and in the RADIEL study from the 5-year follow-up visit.

4. Child's overweight/obesity and cardiometabolic health in adolescence (11-17yrs): (data entry and quality control 1/22-6/24) will include

   • Body weight, height, blood pressure, pulse
   • Tanner stage
   • Body fat percentage (bioimpedance, InBody)
   • Digital questionnaires: Background, and Assessment of the psychological development of the child: Child Behavior Checklist for Ages 6-18 (CBCL), Strengths and Difficulties Questionnaire (SDQ), and Sleep Disturbance Scale for Children (SDSC) substance abuse, Level of Puberty (Tanner scale), Food frequency questionnaire (FFQ)
   • ActiGraph (acceleration sensor), assessment of physical activity and sleep for 7 days
   • Blood samples for analyses of: glucose and insulin metabolism, vitamin D, Calcium, Phosphate, AFOS and PTH, blood samples for assessment of lipidomics and metabonomics, DNA-sample (blood and buccal) and samples for adipocytokines and inflammation marker assessment
   • Endothelial function and pulse wave velocity (PWV) will be assessed
   • An epigenome-wide association study (EWAS) will be performed in the offspring according to maternal obesity and GDM status.
   • Continuous glucose monitoring (CGM, Dexcom G6, Dexcom®, USA) will be assessed in a subpopulation of 150 children, aged 11-14 yrs: 50 overweight/obese and 50 normal weight children from high-risk pregnancies (RADIEL) and 50 normal weight controls form normal pregnancies (PREDO).

5. The following maternal data will be collected 11-17 years post partum (data entry and quality control 1/22-6/24):

   • Blood pressure, pulse, weight, height, BMI, waist and hip circumference
   • Body fat percentage (bioimpedance, InBody).
   • Laboratory tests: OGTT, insulin, glucose, HbA1c, ALAT, lipids, TSH, free T4, DNA sample (blood)
   • DNA sample from buccal mucosa
   • Spare blood for future analyses (metabonomics and lipidonomics studies, inflammatory markers incl, P-hCRP, P-IL-6, adiponectin, TNFa)
   • Digital questionnaires: background, diet (FFQ) and physical activity, psychological questionnaires: Center of Epidemiological Studies Depression Scale (CES-D), Beck Anxiety Inventory II (BDI-II), Pittsburgh Sleep Quality Index (PSQI), Cohen Perceived Stress Scale (PSS5), PANAS-10 (Positive and negative affect schedule), VAS Social Support (Visual Analogue Scale for Social Support), and STAI state (Spielberger State-Trait-Anxiety-Inventory-state version
   • food frequency questionnaire (FFQ)
   • ActiGraph (acceleration sensor), assessment of physical activity and sleep for 7 days
   • Endothelial function and pulse wave velocity (PWV)

6. National registries and patient records on the course of pregnancy, the growth and development of the child and related diseases or their risk factors

Inclusion Criteria:

• all mothers participated originally in the PREDO or the RADIEL studies during pregnancy and with delivery during this index pregnancy

Exclusion Criteria:

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