| CTRI Number |
CTRI/2018/10/015951 [Registered on: 09/10/2018] Trial Registered Prospectively |
| Last Modified On: |
01/07/2019 |
| Post Graduate Thesis |
No |
| Type of Trial |
Observational |
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Type of Study
|
Cohort Study |
| Study Design |
Other |
|
Public Title of Study
|
Brain performance in children born to mothers with diabetes in pregnancy. |
|
Scientific Title of Study
|
Cognitive achievement in offspring of diabetic mothers. |
| Trial Acronym |
|
|
Secondary IDs if Any
|
| Secondary ID |
Identifier |
| NIL |
NIL |
|
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Details of Principal Investigator or overall Trial Coordinator (multi-center study)
|
| Name |
Dr Chittaranjan S Yajnik |
| Designation |
Director |
| Affiliation |
Diabetes Unit, KEM Hospital Research Centre |
| Address |
Diabetes Unit KEM Hospital Research Centre 6th Floor Banoo Coyaji Building Rasta Peth Pune
Pune
MAHARASHTRA
411011
India |
| Phone |
02026061958 |
| Fax |
|
| Email |
csyainik@gmail.com |
|
Details of Contact Person
Scientific Query
|
| Name |
Dr Chittaranjan S Yajnik |
| Designation |
Director |
| Affiliation |
Diabetes Unit, KEM Hospital Research Centre |
| Address |
Diabetes Unit KEM Hospital Research Centre 6th Floor Banoo Coyaji Building Rasta Peth Pune
Pune
MAHARASHTRA
411011
India |
| Phone |
02026061958 |
| Fax |
|
| Email |
csyainik@gmail.com |
|
Details of Contact Person
Public Query
|
| Name |
Dr Ranjana Mundhe |
| Designation |
Member Secretary, Ethics Committee |
| Affiliation |
KEM Hospital Research Centre |
| Address |
KEM Hospital Research Centre 3rd Floor TDH Buildig
Sardar Moodliyar Road
Rasta peth Pune
Pune
MAHARASHTRA
411011
India |
| Phone |
02066037335 |
| Fax |
|
| Email |
ethics@kemhrcpune.org |
|
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Source of Monetary or Material Support
|
|
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Primary Sponsor
|
| Name |
Diabetes Unit |
| Address |
Diabetes Unit KEM Hospital Research Centre 6th Floor Banoo Coyaji Building Rasta Peth Pune |
| Type of Sponsor |
Research institution and hospital |
|
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Details of Secondary Sponsor
|
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Countries of Recruitment
|
India |
|
Sites of Study
|
| No of Sites = 1 |
| Name of Principal
Investigator |
Name of Site |
Site Address |
Phone/Fax/Email |
| Dr Chittaranjan S Yajnik |
Diabetes Unit |
KEM Hospital Research Centre 6th Floor Banoo Coyaji Building Rasta Peth Pune
Pune
MAHARASHTRA |
02026061958
csyainik@gmail.com |
|
Details of Ethics Committee
Modification(s)
|
| No of Ethics Committees= 1 |
| Name of Committee |
Approval Status |
| KEM Hospital Research Centre Ethics Committee |
Approved |
|
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Regulatory Clearance Status from DCGI
|
|
Health Condition / Problems Studied
Modification(s)
|
| Health Type |
Condition |
| Healthy Human Volunteers |
Our study participants are :
1. neonate : all are healthy.Therefore, no ICD-10 code.
2. Mothers : with diabetes during pregnancy (ICD-10 code : O24.4) and without diabetes during pregnancy (No ICD-10 code). |
|
Intervention / Comparator Agent
Modification(s)
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Inclusion Criteria
|
| Age From |
2.00 Year(s) |
| Age To |
30.00 Year(s) |
| Gender |
Both |
| Details |
Offspring of diabetic and non-diabetic mothers without any medical conditions |
|
| ExclusionCriteria |
|
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Method of Generating Random Sequence
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Not Applicable |
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Method of Concealment
|
Not Applicable |
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Blinding/Masking
|
Not Applicable |
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Primary Outcome
|
| Outcome |
TimePoints |
| The study will give cross sectional assessment of cognitive achievement in relation to maternal hyperglycemia during pregnancy in offspring of diabetic mothers. |
Cross sectional assessments performed in four age groups namely 2 years, 4 years, 12 years and 18 years and above. |
|
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Secondary Outcome
|
| Outcome |
TimePoints |
| The study will yield information regarding the effect of adiposity and glycemia on cognitive achievement in offspring of diabetic mothers in comparison with offspring of non-diabetic mothers. |
Cross sectional assessments performed in four age groups namely 2 years, 4 years, 12 years and 18 years and above. |
|
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Target Sample Size
|
Total Sample Size="300"
Sample Size from India="300"
Final Enrollment numbers achieved (Total)= "Applicable only for Completed/Terminated trials"
Final Enrollment numbers achieved (India)="Applicable only for Completed/Terminated trials" |
|
Phase of Trial
|
N/A |
|
Date of First Enrollment (India)
|
01/01/2019 |
| Date of Study Completion (India) |
Applicable only for Completed/Terminated trials |
| Date of First Enrollment (Global) |
Date Missing |
| Date of Study Completion (Global) |
Applicable only for Completed/Terminated trials |
|
Estimated Duration of Trial
|
Years="3"
Months="0"
Days="0" |
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Recruitment Status of Trial (Global)
|
Not Applicable |
| Recruitment Status of Trial (India) |
Not Yet Recruiting |
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Publication Details
|
No publications yet |
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Individual Participant Data (IPD) Sharing Statement
|
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
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Brief Summary
|
Background:
Diabetes Mellitus makes a significant contribution to the burden of disease in India with more than 71milllion patients in 2015. India also has one of the highest prevalence of common mental disorders in adults (10-15%) (Poongothai et al 2009). Hence diabetes and neuropsychiatric conditions together forms a huge burden of non-communicable disorders in our population. Indians develop diabetes at a younger age and at a lower BMI compared to Europeans (Yajnik 2001). This contributes to high prevalence of diabetes during pregnancy in Indian mothers in both rural and urban population (10-20%). (Hirst, 2012, Seshiah, 2008). Intra-uterine exposure to hyperglycemia, hyperinsulinemia and pro-inflammatory mediators can affect fetal hippocampal development and impair memory function (Rao et al 2018). Diabetes during pregnancy is also associated with perinatal and neonatal complications including neural tube defects, other congenital abnormalities, premature deliveries, perinatal asphyxia and cerebral palsy (Parnell et al 2018). It is now increasingly realised that an important determinant of health in adulthood is adverse intrauterine exposures (fetal programming). The rapid rate of brain development during fetal and other critical period of growth makes it particularly vulnerable to insults like maternal diabetes. These can impact long term cognitive outcomes which in turn reflect in the developmental potential of the individual and human capital (Sally Grantham-McGregor 2007). Cohort studies from Western population demonstrate adverse neurocognitive functioning in Offspring of Diabetic Mothers (ODM). There is a dearth of studies from India. Only one study from Mysore Parthenon Cohort has examined a small sample of ODM and reported that ODM have better cognitive function compared to Offspring of Non Diabetic Mothers (ONDM) (Veena et al 2010). Studies from high income countries focus on maternal obesity and diabetes which cause fetal over nutrition (“macrosomic†babies). In contrast, a large proportion of Indian mothers and young children still face undernutrition and Indian babies are the smallest in the world. It will be important to understand the influence of maternal diabetes on offspring brain development and its effects on neurocognitive achivements and human potential because they might be very different than those in the well-nourished population of the developed countries.
Previous studies have reported performance on standardized neuropsychological batteries as measures of cognitive outcomes in ODM. The validity of these measurements is strengthened when correlated with a brain functional connectivity measure. Functional Near Infrared Spectroscopy (fNIRS) represents a breakthrough in techniques used for brain function assessment. This tool has been considered promising for the evaluation of children’s cerebral cortical function (Aslin et al 2015). However, these may not necessarily reflect hard real-world outcomes in terms of cognitive achievement. Scholastic performance, temperamental traits, presence of behavioral disorders (ADHD, autistic spectrum disorders), employment and earning potential are important outcomes contributing to human capital. No study till date has comprehensively examined multiple domains of cognitive achievement along with a brain functional connectivity measure in ODM.
The Diabetes Unit, KEM Hospital Research Center, Pune is a DBT Center of Excellence in fetal programming. It has done pioneering work in understanding intrauterine influences on fetal growth and development and long-term cardio-metabolic outcomes. It has an enviable bio-bank dating back 3 decades and 3 generations. It has vast experience in running prospective birth cohort studies and has been following up its flagship cohort the Pune Maternal Nutrition Study(PMNS) for 25 years with follow up rate of 90%. At the Unit, we have also maintained a registry of more than 1000 diabetic pregnancies and a biobank of maternal and cord blood samples. Two hundred of these offspring (aged 2-26 years) were followed up for cardio metabolic risk factors in a recent study. In addition, as part of a DBT grant (InDiaGDM study) we enrolled 152 diabetic pregnancies and 234 non-diabetic pregnancies to measure epigenetic markers of maternal diabetes in the cord blood. A substantial clinical, phenotypic, biochemical and nutritional information was recorded. A biobank is available. These babies will also be enrolled in this study.
Unit has experience in performing neurocognitive assessments in young children, adolescents and young adults in their cohorts, and has recently acquired expertise in performing brain functional neuroimaging (fMRI) to study structural functional connectivity in young adults of PMNS cohort.
In this proposal, we bring together our expertise in the field of pregnancy diabetes, fetal programming and neurocognition to study cognitive achievement and its functional neural correlates in a large sample of ODM. The outcomes from this study can help understand effect of maternal diabetes on neurocognitive development in Indian scenario where maternal undernutrition is common and gestational diabetes is escalating rapidly.
Key Question: Does maternal diabetes influence cognitive development of the offspring? Objectives: 1. To examine cognitive achievements (neurocognitive performance, scholastic achievement, temperament, behavioral disorders) in ODM (children, adolescents and young adults of Type 1, Type 2 and GDM mothers) as compared to ONDM.
2. To examine functional neural correlates of cognitive performance using fNIRS.
3. To examine the mediating and modifying effects of obesity, adiposity and glycemia on cognitive achievement among ODM and ONDM.
Hypothesis: Null hypothesis:
Children of diabetic mothers will have similar cognitive achievements compared to those of non-diabetic mothers.
Methods: Setting: A cohort of offspring born in diabetic pregnancies (ODM) and non-diabetic pregnancies (ONDM) in KEM Hospital Pune (1986 to 2015). Subjects: Out of ~1000 ODMs born in diabetes clinic patients we expect to study one in three offspring. From the InDiaGDM(2014-2017) study we expect to follow more than 50% offspring. Around ~300 ONDMs have also been recruited as part of ongoing studies in the unit. Additional age and gender matched ONDM will be recruited as required. Appropriate ethics approval and participant assent, consent and parental consent will be obtained. Assessments: Exposures: Systematic assessments of the exposures (Maternal glycemic status during pregnancy, antenatal and perinatal complications, Birth weight, head circumference at birth) have been performed in the cohort. This data of recruited subjects will be extracted from available records. Outcomes: Following Measurements will be performed in the ODM and ONDM based on their age at assessment.
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