Associate Professor, PhD, Consultant
Christina Anne Vinter
Department of Gynecology and Obstetrics SDCO - Steno Diabetes Center Odense OUH - Odense University Hospital Department of Clinical Research, University of Southern Denmark, SDU.
| Projekt styring | ||
| Projekt status | Open | |
| Data indsamlingsdatoer | ||
| Start | 17.10.2023 | |
| Slut | 01.03.2033 | |
LiPO Teen (the Lifestyle in Pregnancy and Offspring Teenagers): Identification of modifiable risk factors for childhood obesity - a follow-up of a randomized controlled trial.
Short summary
Background It is increasingly recognized that the adverse health consequences of female obesity expand across generations and childhood obesity is one of the most serious public health challenges of the 21st century. Both high maternal BMI and excessive gestational weight gain (GWG) have been recognized as significant and independent predictors of both future child and adult obesity. Aims 1.To evaluate the effect of lifestyle intervention during pregnancy on offspring body composition measur
Rationale
To evaluate long-term effects of lifestyle intervention in obese pregnant women on the mothers and their 14-year-old teenage offspring. The study is a follow-up of a Randomized Controlled Trial (RCT) performed in 2007-10 - the "Lifestyle in Pregnancy" LiP study. The primary study was accepted by local ethics committee of the Region of Southern Denmark in 2007 (S-20070058) and registered at clinicaltrials.gov as NCT00530439 before inclusion of participants. The LiP study included 360 pregnant women with BMI ≥30 kg/m2 from Odense University Hospital and Aarhus University Hospital. The women were randomized to intervention with low-calorie diet and physical activity from gestational age 10-14 in pregnancy and until delivery - or to a standard care control group. The objective of the LiPO-Teen project is to perform a clinical follow-up study of the eligible 301 mothers who completed the trial until delivery with a liveborn child, and their 14 year-old offspring. The overall ambition is to understand whether lifestyle intervention in pregnancy prevents obesity and its complications across generations, with a specific focus on modifiable factors. Hypotheses The aims are to test the following hypotheses: Teenage outcomes Lifestyle intervention during pregnancy in obese women is associated with lower fat mass, higher lean body mass and better cardio-metabolic health in the 14-year-old offspring compared with offspring from the control group. Poor maternal mental health during pregnancy and postpartum predicts the risk of high fat mass in 14 year old offspring. Lifestyle intervention during pregnancy in obese women is associated with specific circulating biomarkers and epigenetic changes in the 14-year-old offspring. Psychosocial and mental factors, family dynamics and health literacy are associated with the risk of obesity in 14-year-old offspring. Maternal outcomes Lifestyle intervention during pregnancy in obese women is associated with lower fat mass and BMI, improved cardio-metabolic health and lifestyle 14 years after pregnancy compared with the control group. Breastfeeding intensity and duration is associated with lower fat mass and improved cardio-metabolic health in the women 14 years after pregnancy. Poor maternal mental health during pregnancy and postpartum predicts the risk of high fat mass 14 years after pregnancy. Primary aim: To evaluate the effect of lifestyle intervention during pregnancy on offspring body composition measured by DEXA scanning in 14-year-old offspring. Secondary aims: To explore the effect of lifestyle intervention during pregnancy on obesity related dysmetabolic traits in mothers and 14-year-old offspring. To obtain insights into putative causal factors of overweight and obesity in children, by investigating the following: Association between lifestyle, metabolic and inflammatory markers in pregnancy, breastfeeding intensity and dysmetabolic traits in mothers and teenagers 14 years after pregnancy Epigenetic changes in the offspring 14 years after intervention during pregnancy Associations between maternal mental health during pregnancy and postpartum and the long term risk of maternal and offspring obesity Mental health and health literacy in mother and offspring 14 years after pregnancy and the risk of obesity in mothers and offspring
Description of the cohort
Former participants (mothers) of the LiP study and their offspring, now aged 14 years, will be re-invited to participate in the follow-up study. Therefore using the existing inclusion criteria as has already been selected at the baseline study in 2007-2010. The only exclusion criteria is if mother or child is no longer alive.
Data and biological material
Anthropometrics Height, weight, waist-, hip- and abdominal circumference. Skinfolds. X X Body composition Assessed by Dual-Energy X-ray Absorptiometry (DEXA). Hologic Horizon, serie number: 301872M. Fat mass, lean mass and bone density will be calculated. Bioimpedance measurements X X Blood pressure and heart rate Standardized measurement in sitting position. X X Fasting blood samples: X X 7 Glucose, HbA1c, lipids (total cholesterol, HDL, LDL, triglyceride), electrolytes, leukocytes, kidney function (e-GFR), liver enzymes will be analysed immediately. For full use of the test tube kits, blood samples will be stored at -80°C until the end of study, and then be analysed for: - Advanced metabolic and inflammatory biomarkers (e.g insulin, c-peptide, leptin, adiponectin, hsCRP, IL6, ferritin, CD163) - Proteomics - Micronutrient's status (e.g. vitamin D, selenium, zinc.) - Sex hormones (e.g. estradiol, testosterone) - Epigenetic examinations (The epigenetic profile of DNA samples extracted from whole blood will be characterized by Genome-wide DNA methylation using Infinium MethylationEPIC v2.0 Kit. Principle component and hierarchical clustering analyses will be used to identify associations between methylation patterns and a range of clinical characteristics, biomarkers as well as gene expression levels (RNAseq). Storage will take place at SDCO OUH and analyses performed in close collaboration with professor Charlotte Ling at Lund University, Sweden. In relation to the epigenetic analysis planned in the study, these include only targeted analyses using standard array platforms. We will not be applying comprehensive genetic analysis such as whole genome sequencing, and we do therefore not consider the analysis to provide any secondary findings of importance. The genetic and epigenetic findings will be described as overall and not for the individual participant) - circulating mRNA Research biobank: A research biobank will be established for all blood samples that are collected from the study. All blood samples are designated with a code that cannot be directly referred to the individual. We expect that all analyses have been performed within ten years, and that the project is completed before September 1st 2032. When all the planned analyses have been performed, eventual blood sample residues will be stored in a biobank for future research. Biological material can only be used in a new research project with permission from the Regional Committee on Health Research Ethics Denmark for the Southern Region. The samples will generally only be used after obtaining new consent from the participant, but the Committee may dispense with this. X X Continuous glucose monitoring (CGM, DEXCOM G6Pro): 10 days recording of fasting glucose and postprandial glucose values. Glucose variability will be assessed using a device, which performs repeated glucose measurements in the skin providing insights into glucose fluctuations throughout the day and night. X X Physical activity (PA) 8 Pattern and level of PA and sleep will be measured 7 days (24/7) monitored by activity tracker on the wrist (Actigraph GT3X+). The submaximal performance- based test "the Danish step test" will be used for estimation of maximal oxygen uptake. The test has been cross validated against a VO2 max test with a moderate to high correlation. PA level will also be evaluated by a questionnaire (IPAQ). X X Diet Diet intake will be assessed by a validated 360-item Food Frequency questionnaire (FFQ). It can be filled in electronically and is now also validated for teenagers X X Pubertal staging According to the classifications of Marshall and Tanner(19). In girls, breast development and development of pubic hair is assessed. In boys, the growth of testicles and the development of pubic hair is assessed. During the examination, the child's clothes is lifted up, but the child will not be asked to take off the clothes X Mental health and health literacy A self-administrated questionnaire is under development for women and offspring, respectively. The questions will be answered before, and during the visits, participants will be provided an IPad to answer the questionnaire. The questionnaire has an overall focus on mental health, psychosocial behavior and health literacy. They questionnaire will include scales from the below brutto list, which is at the moment in expert review. Questionnaires WHO-5 (Well-being index) SF-36 (The Short Form 36 Health Survey questionnaire) SF12 (The Short Form 12 Health Survey questionnaire) Three Item loneliness Scale (T-ILS), SSI-B (Stigmatizing Situations Inventory), Brief HLQ (Health literacy among adults) HLSAC (Health literacy for School-Age Children) SDQ (Strenght and difficulty questionnaire) PSS (Percieved stress scale) GAD7 (Anxiety/Depression concerns during the past two weeks) Mood and feelings questionnaire (MFQ) Pittsbrug Sleep Quality Index (PSQI)/Karolinska Sleep Quest The Warwick-Edinburgh Mental Wellbeing Scales (WEMWBS) short form Eating Disorder Inventory 3.0 (EDI-3), SCOO The multidimensional Scale of Perceived Social Support (MSPSS) Family assesment device (FAD) KIDSCREEN-10 Development and Well-Being Assessment (DAWBA), selected scales Qualitative interviews A subgroup of 15-20 mothers will be invited to qualitative interviews about mental health, well-being and quality of life. The interviews will follow international standards of ethically correct interview practice.
Collaborating researchers and departments
SDCC Herlev
Publications associated with the project