Developmental Origins of Mental Health Disorders

NCT03096028 | Completed DMC

• 1 other identifier: kemhrc/adhoc27
• Study Type: observational
• Target: 386
• Locations: 1 country
• Sites: 1

Brief Summary

Common mental disorders (CMD) such as Depression, contributes significantly to the global burden of disease. Fetal exposure to adverse intrauterine environment mediated by life course factors can enhance risk of non-communicable disease in later life. Maternal micronutrients such as Vitamin B12 and folate play an important role in early fetal development through their effect on one carbon metabolism. Vitamin B12 deficiency is common in Indian women; however guidelines recommend only iron, folic acid supplementation during pregnancy. This study aims to investigate effects of maternal B12, folate during pregnancy on mental health and neurocognitive outcomes in offspring during adulthood. The Pune Maternal Nutrition Study(PMNS) birth-cohort(n=762) was established in 1993 at the Diabetes Unit of KEM Hospital Pune with well characterized serial data and archived biological samples. The subjects of the cohort are now in age range of 20-22 years and this provides an opportunity to examine the proposed objectives. Key objectives: To examine the specific association between maternal vitaminB12, folate, homocysteine levels at 18 \& 28 weeks of gestation and risk for CMD, neurocognitive outcomes. Examine the causality of this association by Mendelian randomisation using genetic determinants of vitamin B12 and homocysteine. Design and analysis: Consenting members of the birth cohort of PMNS (n=690) will be recruited after ethics approval. Following cross-sectional outcome measures will be measured Neurocognitive functions: using standardized neuropsychological battery Brain imaging for Structural and functional magnetic resonance imaging (MRI). Temperament-character dimensions (TCI):140 item short TCI-R. Structured clinical interview for CMD, Diet, physical activity, High-risk behaviors, Early life stress. Serum Brain Derived Neurotrophic factor (BDNF), Insulin like growth factor (IGF-1) from serum archived at 6,12 \& 18 years. Longitudinal methods and multivariate regression analysis would be used to investigate the hypothesized associations. Path analysis will be used to generate pathways of evolution of the abnormalities. Causality of the associations will be assessed by Mendelian randomization analysis (triangulation and instrumental variable analysis) using maternal genetic determinants of vitamin B12 and homocysteine

Conditions

Neurodevelopmental Disorders

Keywords

maternal nutrition; neurocognitive development; brain volume

Outcome Measures

Primary Outcomes (1)

• Prevalence of common mental disorders in members of the PMNS cohort Assessed on Mini Neuropsychiatric interview 6.0

  Odds ratios for prevalence of common mental disorders will be computed

  outcome assessed at 22 years from primary exposure

Secondary Outcomes (3)

• Neurocognitive functioning as assessed by performance on a standardized neuropsychological test battery

  outcome assessed at 22 years from primary exposure

• Temperament and character dimensions as assessed on the Temperament and character inventory - R 140

  outcome assessed at 22 years from primary exposure

• Brain volumes on structural and functional connectivity using resting stated Magnetic resonance imaging

  outcome assessed at 22 years from primary exposure

Study Arms (1)

PMNS cohort

The Pune Maternal Nutrition Study (PMNS) is a preconceptional birth cohort established in 1993 at Diabetes unit KEM hospital research center, Pune. 700 offsprings of the cohort are being followed every 6 years. Maternal vitamin B12 folate level during pregnancy were measured at 18 \& 28 weeks.

Other: maternal vitamin B12 folate level during pregnancy

Interventions

maternal vitamin B12 folate level during pregnancy OTHER

Maternal Vitamin B12 and folate level at 18\&28 weeks of pregnancy is the primary exposure of interest

PMNS cohort

Eligibility Criteria

• Age: 20 Years - 23 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)
• Sampling Method: Non-Probability Sample

Study Population

700 male and female adult members of the Pune Maternal Nutrition Study birth cohort

You may qualify if:

• male or female adult member of the PMNS cohort
• Availability of data on maternal vitamin B12 and folate levels during 18\&28 weeks of pregnancy for the subject
• Subject should have completed longitudinal assessments at 6, 12 and 18 years of age

You may not qualify if:

• Pregnancy
• Contraindications for MRI such as metallic orthopedic or dental implants, claustrophobia.

Sponsors & Collaborators

• Kem Hospital, Pune, India: lead

Study Sites (1)

KEM Hospital Research Center

Pune, Maharashtra, 411011, India

Location

Related Publications (1)

• Behere RV, Deshpande G, Bandyopadhyay SK, Yajnik C. Maternal vitamin B12, folate during pregnancy and neurocognitive outcomes in young adults of the Pune Maternal Nutrition Study (PMNS) prospective birth cohort: study protocol. BMJ Open. 2021 Sep 22;11(9):e046242. doi: 10.1136/bmjopen-2020-046242.

  PMID: 34551940 DERIVED

Related Links

• Official webpage of diabetes unit KEM hospital research center Pune

MeSH Terms

Conditions

Neurodevelopmental Disorders

Condition Hierarchy (Ancestors)

Mental Disorders

Study Officials

• Rishikesh V Behere, MD

  Wellcome trust/DBT India Alliance Intermediate Fellow

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: March 20, 2017
• First Posted: March 30, 2017
• Study Start: May 14, 2018
• Primary Completion: February 20, 2020
• Study Completion: February 20, 2020
• Last Updated: February 21, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will not share

Locations

IN (1)