Josef Ressel Centre Perinatal Programming

Childhood Obesity Clinical Trial

— JRP  

Official title:

Josef Ressel Centre for the Investigation of Early Life Metabolic Programming Regarding Dispositions of Obesity

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03634930
• Other study ID #: PJM.16.001.01
• Status: Recruiting
• Start date: February 16, 2017
• Est. completion date: June 30, 2025

Study information

• Verified date: September 2023
• Source: FH Joanneum Gesellschaft mbH
• Contact: Moenie D van der Kleyn, MPH
• Phone: ++ 43 316 5453
• Email: moenie.vanderkleyn[@]fh-joanneum.at
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Background: Metabolic imprinting through early childhood nutrition seems to play an important role in the aetiology of obesity. Overweight at age two and later in life is associated with excessive weight gain as early as three months of age. Breastfeeding in the first year of life appears to be protective against obesity development.

Objective: of the "Josef Ressel Centre for Early Life Metabolic Programming of Dispositions of Obesity" is to identify maternal and infant predictors of metabolic risk of obesity. The main considerations of modifiable factors are early infant nutrition, 24-hours-drinking-volume, the velocity of infant weight gain, in relation to infant fat mass and fat free mass, to biomarker and to the nutritional status of the mother. A second focus is put on maternal feeding style, infant eating behaviour and the identification of satiety cues.

Multi-Study design: a monocentric prospective longitudinal cohort of 100 healthy, non-obese, non-smoking pregnant mothers and their term, normal birthweight, singleton babies. Mothers and exclusively breastfed versus exclusively formula fed children (at 16 weeks) will be examined at 36 weeks of pregnancy, 4 - 8 - 12 and 16 weeks of life, follow-up at 1 and 2 years of life.

Methods: four weighing protocols between 4th and 16th week of life, feeding diary, anthropometric data measurement of mother and child, child fat mass index by air displacement plethysmograph. Macronutrient and energy content of the breast milk will be analysed by MIRIS™.

Well-defined biomarkers of oxidative stress and inflammation, lipid profile, adipokines, insulin, as well as micro- und macronutrients will be analysed as meaningful indicators regarding the development of obesity and/or the metabolic syndrome in newborns. Samples, such as plasma, urine, saliva, and stool of the mothers and children will be examined with High Performance Liquid Chromatography, High Performance Gas Chromatography, Mass Spectrometry, Enzyme-Linked Immunosorbent Assay (ELISA) and more. Also questionnaires for the evaluation of the maternal milk feeding style are used as well as the Baby and Child Eating and Behaviour Questionnaire at 16 weeks, 1 and 2 years.

A semi-automatic recognition of infants' satiety cues during feeding will be performed. The recording environment includes video cameras and microphones, a pulse oximeter, etc. All signals are synchronously recorded with the aid of the hardware and software infrastructure.

Description:

Nutrition related diseases such as obesity are considered as the main health problems in the 21st century. Overweight and obesity are significant risk factors regarding the development of cardiovascular diseases, strokes, diabetes mellitus, and other non-communicable diseases. In the "Josef Ressel Centre for the Investigation of Early Life Metabolic Programming regarding Dispositions of Obesity" possible predictors towards obesity and their relationship to the volume uptake of formula are to be explored multi-dimensionally. During the first part of the project, the volume study, including a total of 66 mother-infant pairs at the 16th week of life, the overfeeding of infants will be investigated. Overfeeding of infants can be regarded in the context of the amount of food consumed, the ingredients, or in the context of satiety perception of babies by their mother. A closer inspection of the drinking volume of breast-fed infants in comparison to formula-fed ones could give an indication of how much and in what frequency infants ingest food and how the drinking volume affects the weight gain and body fat percentage. To do so, applicable anthropometric data will be collected and the measurement of body fat from mothers and infants will be carried out. Additionally, a semi-automatic detection of satiety signals during feeding will be performed. The identification of satiety signs and the reaction of the mother to those signals, in addition with the feeding style, are related to the weight of the infant and its risk of becoming obese later in life. During the second part of the research project, it will be emphasized whether a coherence exists between early infant nutrition and the manifestation of biomarkers of oxidative stress and inflammation. Thus, detailed analyses regarding macro- and micronutrients, adipokines and biomarkers of oxidative stress of mother milk and biological specimen from mothers and infants will be performed Furthermore, the microbiome of the gut of mothers and infants will be investigated. Results from bioanalytical experiments are intended to sup-port the interpretation of results from the volume study to perceive a deep understanding of the metabolic programming phenomenon of infants at the molecular level.

The five main areas of investigation are:

1. 24-hours-drinking-volume: Background: beyond the quality of nutrition during neonatal life, also the quantity in terms of overfeeding plays a critical role in the development of obesity. Objective: to derive evidence on the drinking volume of exclusively breastfed versus exclusively formula fed children, applying strictly the WHO definitions of exclusivity. Secondary objective is the integration of body composition and growth velocity, which may contribute to insights on critical time slots for programming overweight. Methods: weighing protocol, feeding diary, anthropometric data measurement of mother and child, child fat mass index by air displacement plethysmograph PeaPod™ and BodPod™ of the company Cosmed™. The macronutrient and energy content of the breast milk will be also analyzed by MIRIS™.

2. Nutritional Status of Mother and Child:

Background: evidence suggests that programming may be induced by even mild intrauterine poor nutrition and may confer an increased risk of obesity, without neonates exhibiting birth weights below or above what is considered to be normal. Objectives: both maternal over- and undernutrition, seen as excess energy intake and/or deficiencies of micro- and macronutrients during (late) pregnancy, may increase infant fat mass. Methods: maternal food frequency questionnaire is adapted for pregnancy, an infant food frequency questionnaire is developed for the time span up to two years.

3. Maternal Feeding Style and Child Eating Behaviour:

Background: a strong maternal control of eating habits is associated with obesity in childhood. Objectives: a prospective investigation of associations between infant eating behaviour and weight gain to gather evidence on the time of establishment and the causal role of infant eating behaviours in weight gain and BMI at two years. Methods: also questionnaires for the evaluation of the maternal milk feeding style are used as well as the Baby and Child Eating and Behaviour Questionnaire at 16 weeks, 1 and at 2 years.

4. Infant Satiety Cues:

Background: there is an increasing probability that bottle feeding habits, like encouraging the infants to drink the whole content of the bottle, develops overfeeding habits and causes a lower feeling of satiety. Objective: the identification of satiety cues may directly contribute to an objective method to assess satiety. Methods: a semi-automatic recognition of infants' satiety cues during feeding will be performed. The recording environment includes video cameras and microphones, a pulse oximeter, etc. All signals are synchronously recorded with the aid of the hardware and software infrastructure (Noldus-Observer- XT™, Noldus-Media-Recorder™).

5. Biomarker:

Background and Objectives: well-defined biomarkers of oxidative stress and inflammation, lipid profile, ghrelin, leptin, adipokines insulin, as well as micro- und macronutrients will be analysed as meaningful indicators regarding the development of obesity and/or the metabolic syndrome in newborns. Methods: samples, such as plasma, urine, saliva, and stool of the mothers and children will be examined with High Performance Liquid Chromatography, High Performance Gas Chromatography, Mass Spectrometry, Enzyme-Linked Immunosorbent Assay (ELISA) and more.

.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 100
• Est. completion date: June 30, 2025
• Est. primary completion date: December 31, 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 50 Years

Eligibility

Inclusion Criteria:

1. Pregnancy or mother in puerperium

2. Delivery of baby at 37+0 to 41+6 gestational age

3. Legal age (18 years old), age limit 50 years

4. Written consent of test person after having been informed

5. BMI = 18.5 kg/m² to < 30 kg/m²

6. Negative result of oGTT (oral glucose tolerance test) during pregnancy

7. Birth weight of baby 2.5-4.5 kg

8. Non-smoker since knowledge of pregnancy

9. Very good knowledge of German language and Caucasian

10. Exclusive breastfeeding or exclusive formula feeding at MR 2 (4th week of life)

Exclusion Criteria:

1. Birth before 37+0 week of pregnancy (WoP) or after the 41+6 WoP

2. Multiple pregnancy

3. Children with serious congenital malformations of

• Nervous system

• Mouth, throat, neck

• Circulation system

• Respiratory tract

• Gastrointestinal tract

• Urogenital tract

• Chromosomal aberrations

4. Diseases or hospitalization or intensive medical care of child during neonatal period

5. Hereditary metabolic diseases of child

• Hereditary disorders of fat metabolism (MCHAD: Medium Chain Acyl-CoA Dehydrogenase Deficiency, LCHAD: Long Chain Acyl-CoA Dehydrogenase Deficiency, VLCHAD: Very Long Chain Acyl-CoA Dehydrogenase Deficiency)

• Hereditary disorders of amino acid metabolism (PKU: Phenylketonuria)

• Hereditary disorders of carbohydrate metabolism (Glycogenosis, Galactosemia, Hereditary fructose intolerance, Diabetes mellitus Type 1)

6. Drug (tobacco) abuse

7. Mental illnesses that have to be treated with medicaments

8. Metabolic or autoimmune diseases of mother

9. Complications at birth (blood loss > 1000 ml or eclampsia)

10. Pre-conceptional diabetes (type 1 or 2)

11. Celiac disease and/or wheat protein allergy of mother

12. Breast surgery and/or hypomastia

13. Mixed feeding at MR 2 (4th week of life)

Related Conditions & MeSH terms

• Childhood Obesity
• Obesity
• Pediatric Obesity

Intervention

Behavioral:
• observation
Observation of growth, infant bodycomposition, 24h-drinkingvolume

Locations

Country	Name	City	State
Austria	FH Joanneum, university of applied sciences	Graz	Styria

Sponsors (3)

Lead Sponsor	Collaborator
Moenie van der Kleyn	Christian Doppler Forschungsgesellschaft, Milupa GmbH

Country where clinical trial is conducted

Austria, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Infant satiety cues of breast- and formula fed children	In order to identify satiety cues (as for example swallowing, sucking, relaxation, release of nipple) four video and two audio streams together with the physiological signals (Respiration frequency, Muscle activity (by electromyography) and Pulse and oxygen saturation) will be synchronously recorded with the aid of the IT infrastructure (Noldus-Observer-XT™, Noldus-Media-Recorder™, BIOPAC™ and NONIN-Biosignal-Amplifier-Systems™). The coding of the data will be performed offline by means of manual coding by at least two trained individuals. The classification of events that are required to detect satiety cues (sucking rhythm, sucking breaks, duration, etc.) is based on a coding scheme to be defined. Also analysing body movements based on BAP™ (Body Action and Posture Coding System; Dael, Mortillaro & Scherer, 2012) will be used to categorize breast and bottle fed infants' behaviour. The conformity of the coders will be reviewed by Cohen's Kappa.	at 8 weeks of life
Other	Changes in fecal microbial profile	DNA is extracted from both maternal and infant stool samples using the Magnapure Bacterial DNA Kit following the recommended procedures on a Hamilton Starlet workstation. DNA concentration is measured by Picogreen fluorescence. Analysis of fecal microbial profile using 16s rRNA sequencing.	Changes from 36 week of pregnancy to 8, 16 weeks of life, to 1 and 2 years
Other	Changes in eicosanoids profiles	Oxidative stress biomarker like Eicosanoids, 8-hydroxy-2-deoxy guanosine (8-OH-dG) will be measured by high pressure liquid chromatography-mass spectrometry (HPLC-MS) in maternal plasma, breast milk and urine as well as in infant plasma and urine. Concentration of carbonyl proteins in breast milk and in plasma of mothers and infants will be determiated by enzyme-linked immunosorbent assay (ELISA).	Change from 36 week of pregnancy to 8, 16 weeks of life, to 1 and 2 years
Other	Changes in satiety hormones profiles	Concentrations of Leptin, Ghrelin and Irisin will be determined using enzyme-linked immunosorbent assay (ELISA) in breast milk, maternal and infant serum. Salvia samples of mothers and infants will be subjected to cortisol quantification using enzyme-linked immunosorbent assay (ELISA).	Change from 36 week of pregnancy to 8, 16 weeks of life, to 1 and 2 years
Other	Changes in hormone profiles	The changes in hormone profiles will be monitored by measuring (Thyroid-stimulating hormone (TSH), triiodothyronine (T3) thyroxine (T4) furthermore Dehydroepiandrosterone sulfate (DHEA-S), Insulin and C-peptide using enzymeimmunoassyay (EIA) by Abbott Architect i2000SR.	Change from 36 week of pregnancy to 8, 16 weeks of life, to 1 and 2 years
Other	Changes in C-reactive protein	Biomarker of inflammation will be examinated by measuring C-reactive protein (CRP) in serum or plasma using photometrics on Cobas-c111 (Roche).	Change from 36 week of pregnancy to 8, 16 weeks of life, to 1 and 2 years
Other	Changes in the trace elements levels	Changes in the trace elements levels (e.g. zinc, selenium, iodine) in maternal plasma and breast milk and in infant plasma will be determinated by tandem mass spectrometry (ICP-MS/MS).	Change from 36 week of pregnancy to 8, 16 weeks of life, to 1 and 2 years
Primary	Changes in 24 hours drinking volume of milk intake	24 hours drinking volume (milliliter) of milk intake of exclusive breast fed versus exclusive formula fed children by 24h-testweighing on an MBC-15K2DM-Infantscale (Kern).	Changes from 4 to 8 to 12 and to 16 weeks of life
Primary	Changes in Body Mass Index (BMI) child	weight in kilograms, height in meters will be combined to report BMI in (kg/m^2)	Changes from 4 to 8 to 12 and to 16 weeks of life up to 1 and 2 years
Primary	Changes in Fat Mass Index (FMI) child	weight of fat mass in kilograms, height in meters will be combined to report Fat Mass Index in kg/m^2). Fat mass will be measured by air displacement plethysmography (ADP) system using whole body densitometry to determine body composition (fat and fat-free mass) using a PEA-POD™ and BOD-POD™ (COSMED Company USA).	Changes from 8 to 16 weeks of life and 2 years
Primary	Change in energy content of mature breast milk	Change in energy content of 3 ml mature breast milk will be determined by MIRIS HMA™ Human Milk Analyzer (Miris Holding AB, Sweden) in kcal/dL. Samples will be measured twice and mean values for all measured parameters will be calculated. Milk samples are gained by use of Harmony Breast Pump kit (Medela Inc., USA) and are immediately frozen at -80 °C. The samples are collected between 9 and 11 AM from one breast simultaneously to feeding at the other breast. Foremilk and hindmilk are mixed, sample size will be at least 20 ml.	from 8 to 16 weeks of life
Primary	Duration of exclusive milk feeding	The duration of the exclusivity of human milk- or formula feeding will be determined by means of a prospective feeding diary in which frequency, volume, content, administration form and the initiation of complementary food are recorded by the mother. Precise classification by trained study staff will be according to the WHO categories "sole" (exclusive), "predominant" and "partial" breastfeeding through determination of ratio of total breast milk intake per day to total milk intake of other fluids (like formula milk, water, tea etc.) or foods.	over the period from 4 to 8 to 12 and to 16 weeks of life up to 1 and 2 years
Secondary	Change of Eating Behaviour - baby	The validated Baby Eating and Behaviour Questionnaire (BEBQ) for parent-reported psychometric measurement of the general appetite of the infant during exclusive milk or formula feeding, containing 18 items measuring 4 appetitive traits: enjoyment of food (EF), food responsiveness (FR), slowness in eating (SE) and satiety responsiveness (SR). All items are scored on a 5-point scale as never, rarely, sometimes, often and always with mean scores for each subscale ranging from 1 to 5. Higher scores indicated higher EF and FR and lower SE and SR.	from 8 to 16 weeks of life
Secondary	Change of Eating Behaviour - child	The "Child Eating and behaviour Questionnaire" (CEBQ) is same structured as the BEBQ and is containing 35 items, each rated on a five-point Likert scale that ranges from never to always. Additional to the traits of the BEBQ (Food responsiveness (FR), Enjoyment of food (EF), Satiety responsiveness (SR), Slowness in eating (SE)), four additional scales are added: Emotional over-eating (EOE), Desire to drink (DD), Emotional under-eating (EUE), and Food fussiness (FF). Subscale scores are calculated by taking the mean of the item ratings; higher scores reflect more the behaviour in question.	change from 1 year to 2 years of life
Secondary	Change in Maternal Milk Feeding Style - Infant	Infant Milk Feeding Questionnaire (IMFQ) is a standardised multidimensional questionnaire for (self-)assessment of maternal control on food intake and eating habits of the infant (= maternal feeding style). It contains 25 items for measuring maternal control behaviour in 6 categories: 1) encouraging feeding, 2) feeding to a routine, 3) limiting intake, 4) concern for weight, 5) monitoring, 6) perceived responsibility. Each item is on a five-point Likert scale that ranges from never to always or disagree, slightly disagree, neutral, slightly agree, agree. This Questionnaire was modeled on the Child Feeding Questionnaire	from 8 to 16 weeks of life
Secondary	Change in Maternal Feeding Style - Child	The Child Feeding Questionnaire (CFQ) is a standardised multidimensional questionnaire for (self-)assessment of maternal control on food intake and eating habits of the infant, with a focus on obesity proneness in children. It contains 31 items that can be classified in 7 subscales: 3 subscales that measured aspects of parental control over feeding and 4 that measured specific eating attitudes, perceived responsibility for feeding, and perceived parent weight. Responses to all items were coded on a Likert-type scale ranging from 1 (never/ in disagreement) to 5 (always/in agreement). Higher scores reflect more the behaviour in question.	From 1 year to 2 years of life
Secondary	Changes in dietary intake - maternal	assessed with the "Food frequency questionnaire", a semi-quantitative, self-reported online-questionnaire, realised with the aid of a web-based open-source software	from 36 week of pregnancy to 16 weeks, to 1 year to 2 years of life
Secondary	Change in dietary intake - infant	assessed with the "Infant food frequency questionnaire", a semi-quantitative, online-questionnaire, reported by the mother, realised with the aid of a web-based open-source software	change from 1 year to 2 years of life

External Links

•   Homepage of FH Joanneum, university of applied sciences
•   Homepage of Josef Ressel Centre for the Investigation of Early Live Metabolic Programming regarding Dispositions of Obesity