Maternal adversity, inflammation, and neurodevelopment: how intergenerational processes perpetuate disadvantage in a low-resource setting

• Grant number: 19/21612-0
• Support Opportunities: Research Projects - Thematic Grants
• Duration: February 01, 2020 - January 31, 2026
• Field of knowledge: Health Sciences - Medicine - Psychiatry
• Convênio/Acordo: National Institutes of Health (NIH)
• Principal Investigator: Andrea Parolin Jackowski
• Grantee: Andrea Parolin Jackowski
• Principal researcher abroad: Cristiane Seixas Duarte
• Institution abroad: Columbia University in the City of New York, United States
• Principal researcher abroad: Jonathan Posner
• Institution abroad: Columbia University in the City of New York, United States
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
• Pesquisadores principais:( Atuais ): Ivaldo da Silva ; Jair de Jesus Mari
• Pesquisadores principais:( Anteriores ): Síntia Iole Nogueira Belangero
• Associated researchers: Ana Carolina Coelho Milani ; Andrea de Abreu Feijó de Mello ; Nitamar Abdala ; Síntia Iole Nogueira Belangero
• Associated grant(s): 24/02709-1 - iPSC as a model for investigating the impact of childhood adverse experiences on neurodevelopment in different ethnic backgrounds, AP.R SPRINT
• Associated scholarship(s): 24/07936-6 - The impact of maternal childhood adversities of the dynamics of parenting: a study on the mother and infant relationship at 14 months, BP.IC; 24/07961-0 - The effects of maternal childhood adversities in the development and quality of mother infant interaction at 14 months, BP.IC; 24/07551-7 - The impact of maternal childhood adversities on postpartum depression, breastfeeding and offspring development in the first year of life, BP.IC; + associated scholarships 24/07591-9 - The impact of maternal childhood adversities on maternal nutrition during the gestacional period and on the brain volume of the offspring, BP.IC; 24/05837-0 - The differential impact of maternal childhood adversities on the infant cognitive development, BP.TT; 23/11206-0 - The relationship between maternal stress caused by exposure to adverse childhood experiences and infant developmental milestones, BP.TT; 23/11204-8 - The differential impact between the types of maternal childhood adversities on the newborn cognitive and socioemotional development, BP.TT; 23/11221-0 - Maternal childhood adversities and their impact on the global development of the newborn, BP.TT; 23/01245-9 - The impact of maternal care on cortisol levels and on the offspring brain's volume whose mothers were victims of childhood adversities, BP.IC; 23/01277-8 - Maternal childhood adversities and the environment impacting the offspring cognitive and socio emotional development, BP.TT; 22/10662-0 - Introduction to scientific research: molecular technical training and its applications, BP.TT; 22/04559-1 - The impact of maternal adverse childhood experiences on offspring neurodevelopment, BP.IC; 22/04483-5 - The relationship between maternal stress caused by exposure to adverse childhood experiences and infant developmental milestones, BP.TT; 22/04519-0 - The relationship between maternal stress caused by exposure to adverse childhood experiences and the infant cognitive development, BP.TT; 22/04518-3 - The impact of maternal exposure to childhood adverse events on neonatal cortisol levels, BP.IC; 21/08576-5 - Can maternal stress caused by violence prior to pregnancy change baby's development?, BP.TT; 21/09748-4 - Can maternal stress caused by violence prior to pregnancy change the offspring cognitive development process?, BP.TT; 21/10019-7 - Can maternal stress caused by violence prior to pregnancy and the family environment alter the baby's cognitive development process?, BP.TT; 21/03943-0 - Adverse experiences and family functioning in childhood in a population of pregnant women from basic health units (UBS) in Guarulhos - São Paulo, BP.TT; 21/04819-0 - The intergerational impact of maternal exposure to childhood adversities on child cerebral development: regulation and functioning of the hpa axis as a resilience marker, BP.PD; 20/15286-0 - The possible association between maternal early life adversities, cortisol levels and the sex of the neonate, BP.IC; 20/15407-2 - Types of adverse experiences in childhood most frequent in a population of pregnant women using a Basic health Unit (UBS) in Guarulhos - São Paulo, BP.TT; 20/13568-9 - Introduction to scientific research: training on molecular techniques and their application, BP.TT; 20/15046-0 - The impact of the early life maternal exposure to adversities on the offspring brain development, BP.IC; 20/11246-4 - The frequency of adverse childhood experiences in a population of pregnant women from a basic health unit (UBS) in Guarulhos - São Paulo, BP.TT - associated scholarships

Abstract

Adverse childhood experiences (ACEs) - which includes physical/sexual abuse, neglect or parental mental illness - confer risk for psychiatric dysfunction not only to those directly exposed, but also to the next generation. However, mechanisms underlying these ACE-related intergenerational effects are unclear, significantly limiting a unique prevention opportunity. Our study aims to examine mechanisms by which maternal ACEs influence offspring neurodevelopment, with special focus on prenatal inflammation. Toward this end, we will enroll, in the Brazilian Universal Health Care system (SUS), pregnant women with (n=290) and without (n=290) a history of substantial ACEs and follow their offspring over the first two years of life focused on the neurodevelopment of cognitive control, a cornerstone in the future development of impulsive behaviors. First, we will start by testing associations between maternal ACEs and offspring brain-behavior development using infant MRI and behavioral assessments of cognitive control at 12 and 24 months. Second, we will examine mechanisms underlying these associations, focusing on the role of prenatal inflammation and the placenta using techniques to examine DNA epigenetics and RNA sequencing, while also taking into account genetic influences. As suggested by preclinical research, we hypothesize differential effects of prenatal inflammation in male vs. female pregnancies. In addition, we will explore modifiable post-natal factors and their influence on offspring neurodevelopment, monitoring parental depressive/mood symptoms and conducting two in-home assessments of the family. Revealing mechanisms of intergenerational transmission of adversity, our study will set the stage for high-impact preventive research. We will establish research infrastructure within a Sao Paulo primary care clinic network in a high-risk, low-resource community where preventive effects can have their most substantial impact. (AU)