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Interactive Research School For Health Affairs (IRSHA), Pune

Mother and Child Health

Dr. Sadhana Joshi

The theme of my research is mother and child health which addresses the importance of maternal nutrition, with special reference to micronutrients and risk of developing metabolic/neurodevelopmental disorders in childhood and later life. My main focus is on maternal omega-3 fatty acids, folic acid and vitamin B12 since these micronutrients are the key constituents of one carbon metabolism which influence DNA and chromatin methylation patterns. A disturbed one carbon metabolism due to maternal micronutrient imbalance may lead to altered epigenetic programming in the fetus with implications for non-communicable diseases in later life.

At IRSHA I initiated the work on mother and child health in collaboration with the clinicians from Bharati Hospital on pregnancy related disorders (preeclampsia, preterm labor). The incidence of these pregnancy complications are alarmingly increasing in developing countries like India making it an important health issue. However, the mechanisms responsible for the pathogenesis of these complications have not been completely understood. Animal models are also used to validate the mechanisms of interactions of micronutrients during pregnancy and their role in fetal programming for adult diseases.

Current Research projects

  • Regional differences in neurotrophin regulation of vascularization in preeclamptic placentae

    Funded by Indian Council of Medical Research, Government of India

    Preeclampsia (PE), characterized by new-onset hypertension, proteinuria and vascular dysfunction is a major cause of maternal and fetal morbidity and mortality. During pregnancy, matrix metalloproteinases (MMPs) play an important role in angiogenesis, trophoblastic invasion and vascular remodelling. Recent studies suggest that neurotrophins play an important role during implantation and placental development and may also be involved in the regulation of angiogenesis and placental MMPs. It is likely that the placental architecture, oxygen availability and oxidative stress indices vary across the placenta and may lead to regional differences in expression of neurotrophins and hence MMPs and angiogenic factors. This study for the first time examine regional differences in the placental levels and gene expression of neurotrophins, MMPs and angiogenic factors in preeclampsia which may influence placental and fetal development.

  • Disturbed Maternal 1-Carbon Cycle in Preeclampsia Increases Risk for Cardiometabolic Variables in Children

    Funded by Department of Biotechnology, Government of India

    Micronutrients like vitamin B12 folate and docosahexaenoic acid (DHA) are key constituents of 1-carbon cycle that influence DNA and chromatin methylation patterns which may have implications in fetal programming. Influences of maternal nutrition on epigenetic programming are most important during prenatal and early postnatal development, when epigenetic mechanisms undergo establishment and maturation. Disruption of normal gene-specific methylation patterns by perturbations in maternal nutrition may affect pregnancy outcome which may have long term implications in the offspring.

  • Maternal micronutrient status, inflammatory markers and risk for non-communicable diseases in the offspring in a preeclamptic rat model

    Funded by Department Biotechnology, Government of India

    Pre-eclampsia (PE) is a hypertensive multisystem disorder resulting in maternal and fetal mortality and morbidity and complicates almost 10% of all pregnancies. The pathophysiology of PE is not clearly understood, although it is believed to be of placental origin. Further, the role of maternal nutrition in influencing the risk of developing preeclampsia is unclear. Studies examining the effect of individual supplementation of omega-3 fatty acids, folic acid and vitamin B12 in reducing the risk of PE are few and these findings are inconsistent.

  • Multigenerational effects of vitamin B12 deficiency/ supplementation on brain development and metabolic syndrome variables in a rat model.

    Funded by Department of Science and Technology, India

    Maternal nutrition is an important determinant of fetal growth and development. Micronutrient deficiencies are common in developing countries and associated with poor pregnancy outcome. Indians have a low vitamin B12 and omega-3 fatty acid status and are at increased risk for non communicable diseases (NCDs). Nutrient fortification/ supplementation is recommended to improve the pregnancy outcome and reduce the burden of non-communicable diseases. There is a need to examine the safety and long term effects of fortification.

Publications: (International: 94; National: 6)

PhDs awarded: 10

Current Team

Post Doctoral Fellows

  • Deepali Sundrani
  • Nisha Wadhwani

Technical asstt.

  • Kamini Dangat: Research Assistant
  • Hemlata Pisal: Research Assistant
  • Vidya Patil: Technical Assistant
  • Vrushali Kadam: Technical Assistant (Nutrition)
  • Shruti Koparkar: Technical Assistant (Psychology)
  • Karuna Randhir: Technical Assistant (Statistics)
  • Mayur Swami: Project Assistant II
  • Yasmin Aktar: Project Assistant II
  • Sandhya Kadam: Project Assistant II
  • Anjali Jadhav: Project Assistant II

Students

  • Harsha Chopra
  • Amrita Khaire (ICMR-SRF)
  • Richa Rathod (ICMR-SRF)
  • Nisha Kemse (Co-Guide)
  • Vinita Khot (ICMR-SRF) (Co-Guide)
  • Akriti Sahay (DST INSPIRE-SRF) (Co-Guide)
  • Pranita A (Co-Guide)
  • Anindita Nandi (UGC - JRF)
  • Vidya Patil
  • Vaishali Kasture (DST INSPIRE-JRF)

Dr. Preeti Chavan Gautam

The focus of this research programme is

  • Understanding the placental mechanisms involved in uptake, metabolism and transfer of nutrients from the mother to the fetus.
  • Understanding the role of growth factors in regulating cell survival, growth and apoptosis in the placenta and its effect on feto-placental growth and development.
  • Studies on the role of maternal nutrition/stress on placental mechanisms leading to adverse pregnancy outcomes like recurring pregnancy loss, preterm birth and preeclampsia.

Research projects:

Extramural

  • Title: Epigenetic regulation of matrix metalloproteinases in preterm placenta.

    Funded by: Dept. of Science and Technology

    Role: Principal Investigator

    Duration: Feb 2012-15

    Status: completed

    This study showed an imbalance in matrix metalloproteinases (MMP-1, -2, -3,-9) and their tissue inhibitors (TIMP-1, TIMP-2) which possibly favors premature upregulation of matrix metalloproteinases leading to extracellular remodeling in the placenta thereby leading to preterm delivery. Further, we have reported differential effect of mode of delivery (vaginal Vs caesarean) on MMP levels in preterm placenta for the first time.

  • Title: Regional differences in neurotrophin regulation of vascularization in preeclamptic placentae

    Funded by:Indian Council for Medical Research

    Role: Co-Investigator

    Duration: 2015-17

    Status: On-going

  • Title: Exploring the efficacy of omega 3 fatty acid supplementation to a maternal high fat diet deficient in vitamin B12 in ameliorating the risk for impaired brain development and metabolic syndrome in the offspring.

    Funded by: Indian Council for Medical Research

    Role:Co-Investigator

    Duration: 2013-16

    Status: On-going

Intramural:

  • Title:Regional Fatty acid Metabolism and Transport in Preeclampsia Placentae
  • Title: Comparison of placental pro-NGF and p75NTR levels in term and preterm pregnancies

Dr. Anvita Kale

Neurodevelopmental disorders impair growth and development of the brain in the womb (Reynolds et al., 1999). These disorders affect approximately 12% of the global burden of disease (Reddy et al., 2013) and associated with cognitive impairment (Anjos et al., 2013). The neurodevelopmental disorders include attention deficit hyperactivity disorder (ADHD), autism (ASD), schizophrenia and dyslexia. Nutrition is one of the factors influencing the neurodevelopmental outcome. Our group will focus on the role of omega-3 fatty acids and explore the possible mechanisms through which omega 3 fatty acids may influence brain growth and development in these neurodevelopmental disorders.

The emerging role of gestational factors especially micronutrients like folic acid, vitamin B12 and omega-3 fatty acids in shaping the brain and on the influence of these intrauterine experiences on later development of neurodevelopmental disorders is my focus area of research. The nine months of intrauterine development and the first three years of postnatal life are critical for periods of development. Further, the importance of these nutrients arises from the fact that an Indian population has a low consumption of omega-3 fatty acids and is known to be deficient in Vitamin B12. Currently due to Westernisation there is also an increased consumption of a high fat diet. Further, there is a rise in burden of mental disorders in developing coutries and a need to explore the underlying mechanisms.

Current Research projects

Exploring the efficacy of Omega 3 fatty acid supplementation to a maternal high fat diet deficient in Vitamin B12 in Ameliorating the risk for impaired brain development and metabolic syndrome in the offspring funded by Indian Council for Medical Research (ICMR), India.(Dec 2013-Nov-2016).

India is currently facing an epidemic of diabetes, obesity and cardiovascular diseases. Human and animal studies have demonstrated that maternal nutrition plays a key role in determining the risk for these diseases. Increased consumption of high fat and low omega 3 fatty acids are reported in Indians (Gupta et al, 2010). Indian diets mainly being vegetarian in nature are also deficient in vitamin B12 and omega 3 fatty acids especially docosahexaenoic acid (DHA). A series of our studies in humans have highlighted the importance of omega 3 fatty acids in determining pregnancy outcome (Mehendale et al., 2008; Kilari et al., 2009; Dangat et al., 2010; Kulkarni et al., 2011; Dhobale et al., 2011). We have reported the beneficial effects of maternal omega 3 fatty acid supplementation to a micronutrient imbalanced diet on brain development (Sable et al., 2011, 2012; Roy et al., 2012) and placental global methylation levels (Kulkarni et al., 2011). Our earlier studies have shown that Folate, vitamin B12 and DHA are all interlinked in the one carbon metabolism and any imbalance leads to methyl group deficiency which can down regulate the expression of transcription factors like sterol regulatory elementbinding protein (SREBP) and PPAR. Since DHA is a ligand for these transcription factors it may help in ameliorating the negative effects (Wadhwani et al., 2012). However, there are no studies which have examined the effect of omega 3 fatty acid supplementation to maternal high fat diet deficient in vitamin B12 on fetal brain development and metabolic syndrome in the offspring. The present proposal therefore aims to evaluate these effects using an animal model.

Publications

  • 28 + 1 book chapter

Current Team

  • Ms. Surabhi Dalvi(Technical Assistant)

Dr. Anitha Kilari

Her research program mainly focuses on ‘Health of Women’ from reproductive age to post menopause. Women with history of pregnancy complications like preeclampsia (PE) are at high risk for cardio-metabolic disorders in later life. Higher prevalence of non-communicable diseases is leading to > half of the 800,000 annual CVD deaths in women occur prematurely in India. Evidences suggest that adverse pregnancies such as PE, intrauterine growth restriction and preterm deliveries (PTD) have been associated with a 50-300% increased risk of cardiovascular diseases (CVD) and CVD-related mortality (Robbins et al., 2014; Fraser et al., 2012; Smith et al., 2009). The physiological demands of pregnancy on the maternal cardiovascular system can catapult women into a metabolic syndrome that predisposes to atherosclerosis in later life. Retrospective studies have reported the associations between cardio-metabolic risk and history of preeclampsia. However, no prospective studies have explored the associations between biochemical changes during delivery in adverse pregnancy conditions (PE / PTD) and cardio-metabolic disorders (CMD) in women at later life. Therefore, there is a need to study the associations between cardio-metabolic risk factors in women with their previous pregnancy biochemical parameters.

Research Projects:

Title: Evaluation of Cardio-metabolic Risk in Women with a History of Preeclampsia
Funding Agency: Bharati Vidyapeeth Deemed University, Pune

Role: Principal Investigator
Status: Just initiated

Title: Disturbed Maternal 1-Carbon Cycle in Preeclampsia Increases Risk for Cardiometabolic Variables in Children
Funding Agency: Department of Biotechnology (DBT), New Delhi, India
Role: Co-investigator
Status: On-going
Duration: May 2015 to June 2018

Title: Role of long chain polyunsaturated fatty acids, neurotrophins and vascular endothelial growth factor in mothers with pre-eclampsia and their association with infant growth

Funding Agency: Indian Council for Medical Research, New Delhi,
Role: Co-investigator
Status: Completed
Duration: 2010-2012

Key findings of the project

Increases milk DHA levels inspite of lower plasma DHA levels in women with preeclampsia till 3 months of lactation. Milk linoleic and a linolenic Acids were increased while arachidonic and docosahexaenoic acids were gradually decreased from day 3 to 6 months of lactation. Breast milk NGF levels significantly increased while BDNF levels decreased from day 3 to 6 months in both controls and preeclamspsia (PE) groups At 6 mo, breast milk long chain fatty acids like DHA and AA were associated with baby weight.

Symposium

2nd David Barker Memorial Symposium on Developmental Origins of Health and Disease (DOHaD) on Saturday 18th February 2017

CME by Ministry of AYUSH

CME on Basic Research Techniques for Ayurvedic PG Teachers Contact: Dr. Supriya Bhalerao - 27th February to 4th March 2017

World Obesity Day

On occasion of World Obesity Day, a workshop on Anthropometric assessment was organized by Obesity Research Lab, IRSHA on 13th October 2016. Dr. Sanjay Juvekar and Dr. Hemangi Lubree from Vadu Rural Health Program (VRHP), an initiative of KEM Hospital delivered a lecture on basic techniques of anthropometry followed by demonstration of the anthropometry assessment on volunteers by their team.

National Ayurveda Day

Ministry of AYUSH has declared Dhanateras to be celebrated as National Ayurveda Day. Prof. M S Baghel (Ex- Chairman, Ayurveda Chair University of Debrecan, Hungary) was the special invitee for the auspicious day. He threw light over the Ayurveda concepts of Diabetes, its consequences and its management. A lecture was delivered by Dr. Jyoti Shirodkar (Ayurvedic Diabetologist, Asso. Prof. Dept of Dravyaguna, TAMV) based on the theme Prevention and Control of diabetes using Ayurveda.

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