Ignite Creation Date:
2024-10-26 @ 3:41 PM
Last Modification Date:
2024-10-26 @ 3:41 PM
Study NCT ID:
NCT06614413
Status:
NOT_YET_RECRUITING
Last Update Posted:
None
First Post:
2024-09-19
Brief Title:
Intervention Based on the Mediterranean Diet During Pregnancy and the First Two Years for the Improvement of Neurological Development
Sponsor:
None
Organization:
None
Study Overview
Official Title:
Randomized Controlled Clinical Trial Dietetic-nutritional Intervention Based on the Mediterranean Diet During Pregnancy and the First Two Years First Thousand Days for the Improvement of Neurological Development
Status:
NOT_YET_RECRUITING
Status Verified Date:
2024-09
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
No
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
CONMED
Brief Summary:
The main objective is to evaluate the effect of the Mediterranean diet during pregnancy and the first two years of the childampampamp39s life on the childampampamp39s neurodevelopment and behavior externalizing and internalizing disorders measured at one and a half and two years Secondary objectives are to evaluate the effect of the Mediterranean diet on body composition at two years of age in infants densitometry and of the mother at 3 months postpartum the incidence of allergic disease in infants the fetal and infant s growth and metabolic risk in the mother during pregnancy and in the boygirl at two years fasting glucose insulin HOMA LDL and HDL cholesterol and micronutrient status iron calcium phosphorus magnesium sodium potassium chloride selenium zinc and LCPUFAs
Randomized controlled clinical trial with a 11 ratio parallel and open label Group 1 Mother-child binomial with nutritional intervention Group 2 Mother-child binomial as a control group with follow-up without intervention
Assuming a loss of 25 10 at follow-up 15 failure of nutritional intervention we would need a sample size of 267 patients per group 1 Evaluation of neurodevelopment using the Bayleys scale version -III at 2 years of age 2
Behavioral assessment CBCL at 15 and two years and BRIEF-P at two years
Randomized controlled clinical trial with a 11 ratio parallel and open label Group 1 Mother-child binomial with nutritional intervention Group 2 Mother-child binomial as a control group with follow-up without intervention
Assuming a loss of 25 10 at follow-up 15 failure of nutritional intervention we would need a sample size of 267 patients per group 1 Evaluation of neurodevelopment using the Bayleys scale version -III at 2 years of age 2
Behavioral assessment CBCL at 15 and two years and BRIEF-P at two years
Detailed Description:
It will be registered in ClinicalTrialsgov Randomization will be carried out in blocks of 50 patients the last of 34 for having a total of 534 patients
using the ampamp34sampleampamp34 function of the statistical program R version 402 R Core Team 2020
Study subjects
All adult pregnant women who attend the routine first trimester visit from 4 weeks 0 days of gestation up to 14 weeks 6 days of gestation will be candidates to participate in the study
The study will be carried out at the La Paz University Hospital and in associated health centers
Estimation of sample size
1 Using the cognitive development score of the Bayleys III test at 2 years A sample size of 200 patients per group reaches a power of 80 to reject the null hypothesis of equality of means when the difference in population means is μ1 - μ2 1236 - 1186 50 with a standard deviation of 178 for both groups JAMA Netw Open 2023 and with a significance level alpha of 005 using a two-sample t test of equal variances
2 Using the socioemotional score of the Bayleys III test A sample size of 200 patients per group for the diet and control group reaches a power of 80 to reject the null hypothesis of equality of means when the difference in population means is μ1 - μ2 1086 - 1034 52 with a standard deviation of 185 for both groups JAMA Netw Open 2023 and with a significance level alpha of 005 using a two-way t test samples of equal variances
Assuming a loss of 25 10 at follow-up 15 failure of nutritional intervention we would need a sample size of 267 patients per group
The sample size estimate is smaller using CBCL with two repeated measures for the outcome variablesThe number of women recruited with a statistical power of 08 and an alpha value of 05 should be 82 infants per group Assuming losses of 25 a total of 107 per group
In order to objectively evaluate adherence to the MEDITERRANEAN diet MD the following will be used
Quantification of total phenolic compounds CFT in urine samples The total phenolic compounds will be determined in urine samples For the determination of total phenolic compounds in urine a procedure will be followed Spectrophotometric method using the Folin-Ciocalteu reagent described and validated by Medina-Remón et al We will perform a solid phase pre-extraction using OASIS 30 mg MAX 96-well plates to remove interferences with the Folin-Ciocalteu reagent For the determination of CFT the gallic acid will be used as a reference Creatinine will be determined using a method previously described Jaffé M et al and adapted for plates of 96 wells by Medina-Remón et al A calibration curve will be prepared for creatinine CFTs will be normalized by creatinine and will be expressed as mg equivalents of gallic acidg of creatinine
Magnetic resonance analysis of metabolic fingerprints and biomarkers of specific food intake and food groups precise measurement developed and validated at Imperial College London doi101016S2213-85871630419-3 101038s43016-020-0093-y
Study variables
1 Bayleys scale version III deriving the following four scales raw and typical scalar derived scores a cognitive b language receptive and expressive c motor fine and gross and d socioemotional
2 Evaluation of behavior externalizing problems in the child attention deficit aggressiveness and internalizing disorders anxiety depression through validated parent surveys For this they will be used
Child Behavior Checklist CBCL parents will answer this questionnaire
BRIEF-P Behavior Rating Inventory for Executive Function-Preschool which is an instrument designed to evaluate executive function EF of infants as an endophenotypic indicator of externalizing problems after two years From this test the following three indices will be extracted
Inhibitory self-control index
Flexibility Index
Emergent metacognition index A psychologist accredited for Bayleys III will carry out the neurodevelopmental evaluation and the questionnaires will be evaluated as well as the Bayleys test blind to the childampamp39s group
3 Evaluation of secondary objectives influence of MD
31 Micronutrient status in the child They are related to the nutritional status of infants and may have a significant impact on the development and health of the nervous system Blood determinations of
Omega-3 fatty acids especially docosahexaenoic acid DHA
Iron
Vitamin D and retinol transport protein
Calcium phosphorus magnesium selenium and zinc 32 Additionally blood samples will be used for proteomics and evaluation of epigenetic changes the latter also in the father
33 Body composition the measurement of body composition will be carried out using DEXA X-ray absorptiometry dual energy This very low dose X-ray technique determines body composition considering 3 components lean tissue fat and bone The values obtained allow the calculation of fat mass indices IMG and lean IMM as indicators of nutritional status Mazess RB et al 1990 The densitometry will acquire software in the GE IDXA Lunar Densitometer enCORE v17 installed in the Nuclear Medicine Service from the La Paz University Hospital 34 Oxidative damage to proteins lipids and DNA in urine 35 Composition of breast milk given that it has been observed that dietary intake can modify the composition of breast milk BM milk samples will be collected from mothers during the lactation period at 3 months postpartum
36 Microbiota To know the relationship that MD adherence has with changes in the microbiota of mothers and infants analysis of feces milk and vaginal exudate will be performed in the mother and feces in the child for measurement of microbiota and analysis of short-chain fatty acids in feces
Data collection
In the mother
1 Sociodemographic data of the mother age highest level of education achieved employment situation and status socioeconomic monthly net salary of the family unit country of birth street of residence to estimate minimum average income and environmental pollution
2 Obstetric history gestational diabetes weight gain first second and third trimester diseases associated with pregnancy
3 Maternal prenatal history body mass index pregestational diabetes
4 During pregnancy Fasting glucoseinsulin HOMA blood pressure anemia in mother maternal medication
5 Data on mothersamp39 physical activity practice in the third trimester of pregnancy through Pregnancy Physical Activity Questionnaire PPAQ
6 Type of delivery
7 Postpartum Abdominal waist measurement and body composition fat mass and lean mass at 3 months delivery
8 Type of breastfeeding
9 Toxic habits smoker before during pregnancy and breastfeeding Ingestion of alcohol or other toxic substances before during pregnancy and breastfeeding
In the infant-toddler
1 Sex weight length and head circumference at birth 3 9 18 and 24 months and dietary diary at 6 12 18 and 24 months of age
2 Incidence of allergic disease Diagnoses of atopic dermatitis asthma recurrent bronchospasm and presence of food allergies at 6 12 18 and 24 months
3 Quality of life at two years old as reported by parents using the TAPQOL questionnaire
4 Micronutrient values
5 Body composition at two years measured by densitometry
6 Use of screens evaluated using the SCREENQ a questionnaire completed by parents
7 Health assessment including events and medications
8 Number of siblings and position 1st 2nd
9 Exposure to green areas All questionnaires will be used in their Spanish version
Statistical analysis The statistical study will be carried out at the end of the study by intention to treat Good adhesion is defined by protocol such as improvement in three points in the 17-food questionnaire in mothers As the main variable is in toddlers we will consider good adherence to the DM in these according to the questionnaire score KIDMED at 24 months 8 good adherence 4-7 intermediate adhesion 3 low adhesion As possible confounding variables the effect of breastfeeding defined as exclusive 6 months of age mixed lt 6 months of breastfeeding with the use of formula or artificial breastfeeding the sex of the child and the socioeconomic level of the families defined as the net monthly income of the family unit lt1300 1300 - 1900 1900 - 2550 2550 - 3550 3550 - 4500 gt4500
The description of the qualitative data will be done in the form of absolute frequencies and percentages and the data quantitative using mean and standard deviation or median and interquartile range depending on the distribution of this data
The normality of the continuous variables will be studied using the Kolmogorov Smirnov test
For the comparison between the diet groups and the qualitative variables the Pearson Chi-Square test will be used
For the target variables measured after two years that show differences according to the diet groups generalized linear models to adjust the effect of diet for the variables considered to be confounding described previously All statistical tests will be considered bilateral and as significant values those p lower 005
using the ampamp34sampleampamp34 function of the statistical program R version 402 R Core Team 2020
Study subjects
All adult pregnant women who attend the routine first trimester visit from 4 weeks 0 days of gestation up to 14 weeks 6 days of gestation will be candidates to participate in the study
The study will be carried out at the La Paz University Hospital and in associated health centers
Estimation of sample size
1 Using the cognitive development score of the Bayleys III test at 2 years A sample size of 200 patients per group reaches a power of 80 to reject the null hypothesis of equality of means when the difference in population means is μ1 - μ2 1236 - 1186 50 with a standard deviation of 178 for both groups JAMA Netw Open 2023 and with a significance level alpha of 005 using a two-sample t test of equal variances
2 Using the socioemotional score of the Bayleys III test A sample size of 200 patients per group for the diet and control group reaches a power of 80 to reject the null hypothesis of equality of means when the difference in population means is μ1 - μ2 1086 - 1034 52 with a standard deviation of 185 for both groups JAMA Netw Open 2023 and with a significance level alpha of 005 using a two-way t test samples of equal variances
Assuming a loss of 25 10 at follow-up 15 failure of nutritional intervention we would need a sample size of 267 patients per group
The sample size estimate is smaller using CBCL with two repeated measures for the outcome variablesThe number of women recruited with a statistical power of 08 and an alpha value of 05 should be 82 infants per group Assuming losses of 25 a total of 107 per group
In order to objectively evaluate adherence to the MEDITERRANEAN diet MD the following will be used
Quantification of total phenolic compounds CFT in urine samples The total phenolic compounds will be determined in urine samples For the determination of total phenolic compounds in urine a procedure will be followed Spectrophotometric method using the Folin-Ciocalteu reagent described and validated by Medina-Remón et al We will perform a solid phase pre-extraction using OASIS 30 mg MAX 96-well plates to remove interferences with the Folin-Ciocalteu reagent For the determination of CFT the gallic acid will be used as a reference Creatinine will be determined using a method previously described Jaffé M et al and adapted for plates of 96 wells by Medina-Remón et al A calibration curve will be prepared for creatinine CFTs will be normalized by creatinine and will be expressed as mg equivalents of gallic acidg of creatinine
Magnetic resonance analysis of metabolic fingerprints and biomarkers of specific food intake and food groups precise measurement developed and validated at Imperial College London doi101016S2213-85871630419-3 101038s43016-020-0093-y
Study variables
1 Bayleys scale version III deriving the following four scales raw and typical scalar derived scores a cognitive b language receptive and expressive c motor fine and gross and d socioemotional
2 Evaluation of behavior externalizing problems in the child attention deficit aggressiveness and internalizing disorders anxiety depression through validated parent surveys For this they will be used
Child Behavior Checklist CBCL parents will answer this questionnaire
BRIEF-P Behavior Rating Inventory for Executive Function-Preschool which is an instrument designed to evaluate executive function EF of infants as an endophenotypic indicator of externalizing problems after two years From this test the following three indices will be extracted
Inhibitory self-control index
Flexibility Index
Emergent metacognition index A psychologist accredited for Bayleys III will carry out the neurodevelopmental evaluation and the questionnaires will be evaluated as well as the Bayleys test blind to the childampamp39s group
3 Evaluation of secondary objectives influence of MD
31 Micronutrient status in the child They are related to the nutritional status of infants and may have a significant impact on the development and health of the nervous system Blood determinations of
Omega-3 fatty acids especially docosahexaenoic acid DHA
Iron
Vitamin D and retinol transport protein
Calcium phosphorus magnesium selenium and zinc 32 Additionally blood samples will be used for proteomics and evaluation of epigenetic changes the latter also in the father
33 Body composition the measurement of body composition will be carried out using DEXA X-ray absorptiometry dual energy This very low dose X-ray technique determines body composition considering 3 components lean tissue fat and bone The values obtained allow the calculation of fat mass indices IMG and lean IMM as indicators of nutritional status Mazess RB et al 1990 The densitometry will acquire software in the GE IDXA Lunar Densitometer enCORE v17 installed in the Nuclear Medicine Service from the La Paz University Hospital 34 Oxidative damage to proteins lipids and DNA in urine 35 Composition of breast milk given that it has been observed that dietary intake can modify the composition of breast milk BM milk samples will be collected from mothers during the lactation period at 3 months postpartum
36 Microbiota To know the relationship that MD adherence has with changes in the microbiota of mothers and infants analysis of feces milk and vaginal exudate will be performed in the mother and feces in the child for measurement of microbiota and analysis of short-chain fatty acids in feces
Data collection
In the mother
1 Sociodemographic data of the mother age highest level of education achieved employment situation and status socioeconomic monthly net salary of the family unit country of birth street of residence to estimate minimum average income and environmental pollution
2 Obstetric history gestational diabetes weight gain first second and third trimester diseases associated with pregnancy
3 Maternal prenatal history body mass index pregestational diabetes
4 During pregnancy Fasting glucoseinsulin HOMA blood pressure anemia in mother maternal medication
5 Data on mothersamp39 physical activity practice in the third trimester of pregnancy through Pregnancy Physical Activity Questionnaire PPAQ
6 Type of delivery
7 Postpartum Abdominal waist measurement and body composition fat mass and lean mass at 3 months delivery
8 Type of breastfeeding
9 Toxic habits smoker before during pregnancy and breastfeeding Ingestion of alcohol or other toxic substances before during pregnancy and breastfeeding
In the infant-toddler
1 Sex weight length and head circumference at birth 3 9 18 and 24 months and dietary diary at 6 12 18 and 24 months of age
2 Incidence of allergic disease Diagnoses of atopic dermatitis asthma recurrent bronchospasm and presence of food allergies at 6 12 18 and 24 months
3 Quality of life at two years old as reported by parents using the TAPQOL questionnaire
4 Micronutrient values
5 Body composition at two years measured by densitometry
6 Use of screens evaluated using the SCREENQ a questionnaire completed by parents
7 Health assessment including events and medications
8 Number of siblings and position 1st 2nd
9 Exposure to green areas All questionnaires will be used in their Spanish version
Statistical analysis The statistical study will be carried out at the end of the study by intention to treat Good adhesion is defined by protocol such as improvement in three points in the 17-food questionnaire in mothers As the main variable is in toddlers we will consider good adherence to the DM in these according to the questionnaire score KIDMED at 24 months 8 good adherence 4-7 intermediate adhesion 3 low adhesion As possible confounding variables the effect of breastfeeding defined as exclusive 6 months of age mixed lt 6 months of breastfeeding with the use of formula or artificial breastfeeding the sex of the child and the socioeconomic level of the families defined as the net monthly income of the family unit lt1300 1300 - 1900 1900 - 2550 2550 - 3550 3550 - 4500 gt4500
The description of the qualitative data will be done in the form of absolute frequencies and percentages and the data quantitative using mean and standard deviation or median and interquartile range depending on the distribution of this data
The normality of the continuous variables will be studied using the Kolmogorov Smirnov test
For the comparison between the diet groups and the qualitative variables the Pearson Chi-Square test will be used
For the target variables measured after two years that show differences according to the diet groups generalized linear models to adjust the effect of diet for the variables considered to be confounding described previously All statistical tests will be considered bilateral and as significant values those p lower 005
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None