Maternal Adversity, Vulnerability and Neurodevelopment

Maternal Adversity Vulnerability and Neurodevelopment (MAVAN) project is a prospective community-based, pregnancy and birth cohort of Canadian mother-child dyads. The main objective of MAVAN project is to examine the pre- and postnatal influences, and their interaction, in determining individual differences in children development. The MAVAN project is designed to examine the consequences of fetal adversity as a function of the quality of the postnatal environment, focusing on mother-infant interactions.

In 2003 the Canadian Institutes of Health Research (CIHR) funded an ambitious and internationally unique study on the development of individual differences in vulnerability for mental illness. Increasing evidence indicates that many forms of mental illness as well as diabetes and cardiovascular disease are best considered as developmental disorders where vulnerability emerges as a function of genetic and epigenetic events. Frank pathology then develops as a function of the continuous interaction between underlying vulnerability and prevailing environmental triggers. The critical question is that of understanding the mechanisms by which specific forms of gene x environment interactions in perinatal life define the level of vulnerability/resistance to illness.

Maternal adversity during fetal life including maternal stress (as well as depression), low social support, poor maternal nutrition, and tobacco/alcohol consumption predict both preterm labour and intrauterine growth restriction. These birth outcomes, in turn, represent major epidemiological risk factors for heart disease, diabetes, and depression in adulthood, and neurodevelopmental impairments in children. Postnatal maternal adversity compromises maternal care/behaviour and infant development, and predicts increased risk for obesity, heart disease, attentional deficit disorders (ADD), drug abuse, and depression. Despite the enormous potential for the interaction of prenatal and postnatal influences, research has largely been restricted to the effects of events occurring during only one developmental period which, among other things, ignores the potential importance of 'protective' factors operating at later stages in life. Moreover, the underlying mechanisms by which perinatal adversity might directly affect neurocognitive development have been very poorly studied.

The investigators proposed an innovative research program that focuses on child development using a longitudinal, within-subject design examining neural and cognitive/emotional outcomes as a function of genomic and epigenomic factors. These studies focus on 500 mother-infant dyads drawn from two human studies (Montreal \& Hamilton). Assessment of maternal wellbeing and infant development (cognition, socio-emotional development, temperament, and brain structure) trajectories are undertaken from mid-pregnancy until 10 years of age. Genomic and epigenomic approaches were used to assess genetic vulnerability in these populations using a GWAS approach. This represents the first longitudinal study linking neurocognitive/behavioural function with structural neurodevelopment through neuroimaging and genetic vulnerability in humans, in the presence or absence of maternal adversity. The ability to identify postnatal events that serve to reverse a condition of vulnerability has enormous implications for the development of prevention /intervention programs reducing the future rates of a broad spectrum of chronic illnesses.

Eligibility Criteria:
Inclusion Criteria:

* Pregnant women recruited when they attending antenatal care clinics at the time of routine ultrasound or through advertisements at hospitals (usually at 13 to 20 weeks' gestation). Women were included in the study if they were 18 years of age or older, and fluent in either English or French. Only babies born at 37 weeks or later and above 2000 g were included in the MAVAN cohort.

Exclusion Criteria:

* Exclusion criteria included serious obstetric complications during the pregnancy or delivery of the child, extremely low birth weight, prematurity (less than 37 weeks of gestation), or any congenital diseases.