B4103 - Quantifying the multi-system impact of antenatal maternal wellbeing across generations - 01/08/2022

B number: 
Principal applicant name: 
Kieran O'Donnell | Yale University
Adelaide Feibel, Anna Lahdepuro, Adam Lombroso, Hung Pham, Dr. Vivette Glover, Dr. Thomas O'Connor, Dr. Marius Lahti, Dr. Katri Räikkönen
Title of project: 
Quantifying the multi-system impact of antenatal maternal wellbeing across generations
Proposal summary: 

Maternal antenatal anxiety, depression, and stress increase the risk for socioemotional and behavioral problems in childhood, effects which persist into early adulthood (O’Donnell et. al, 2014; Pearson et. al, 2013; Robinson et. al, 2008). These findings are consistent with the fetal origins of mental health hypothesis, which posits that exposures in utero contribute to individual differences in mental health outcomes across the lifespan (O’Donnell, Meaney, 2017).

While the association between antenatal maternal wellbeing and child development is well-established, much less is known about the multi-generational impact of antenatal maternal wellbeing on child health and development. Existing findings from multigenerational studies focus on birth weight (Lahti-Pulkkinen et. al, 2018; Drake et. al, 2015), and antenatal lead (Sen et. al, 2015) or diethylstilbestrol exposure (Kioumourtzoglou et. al, 2018)​​. Interestingly, mouse models have shown the multi-generational effects of stress or dietary manipulations on molecular characteristics of the offspring across multiple generations (Ward et. al, 2013; Radford et. al, 2014; Jawaid, Roszkowski, Mansuy, 2018).

In this proposal, we examine multi-generational effects of maternal well-being (encompassing mental and physical health) in an index pregnancy across 2 or more generations. Our analysis framework will consider important confounds including maternal and child genetic variation and will examine candidate biological processes for the transmission of risk e.g. variation in DNA methylation.

Impact of research: 
The association between maternal wellbeing during pregnancy and subsequent health outcomes in future generations has important clinical implications. Currently, most interventions related to maternal mental health are targeted at mothers after they give birth due to increased awareness surrounding postpartum depression. However, evidence of a negative effect of antenatal maternal distress across multiple generations on health outcomes would further underline the need to start mental health interventions earlier during pregnancy.
Date proposal received: 
Thursday, 21 July, 2022
Date proposal approved: 
Monday, 1 August, 2022
Developmental biology, Developmental disorders - autism, Learning difficulty, Mental health, Pregnancy - e.g. reproductive health, postnatal depression, birth outcomes, etc., GWAS, Statistical methods, Ageing, Biological samples -e.g. blood, cell lines, saliva, etc., Offspring, Birth outcomes, Development, Epigenetics, Genetic epidemiology, Genetics, Genomics, Genome wide association study, Hormones - cortisol, IGF, thyroid