Objectives: To investigate the preventive potential of the Developmental Origins of Health and Disease (DOHaD) hypothesis as it pertains to emotion dysregulation and psychopathology by: i) elucidating the impact of modifiable perinatal risk factors, and ii) examining whether a postnatal intervention can improve infant emotion regulation. Methods: Studies 1 and 2 used data from the Canadian Healthy Infant Longitudinal Development (CHILD) cohort and the Maternal-Infant Research on Environmental Chemicals (MIREC) cohort to examine if modifiable perinatal risk factors (including prenatal diet quality) confounded the link between prenatal metabolic complications and offspring psychopathology. Study 3 used MIREC data to examine if prenatal diet quality was linked to a biomarker of emotion regulation in infants (autonomic nervous system (ANS) function). Studies 4 and 5 used data from 40 infants of mothers diagnosed with postpartum depression (PPD) and 40 healthy control infants matched on infant age sex and socioeconomic status. These studies examined if infant emotion regulation (Study 4) and mother-infant physiological synchrony (a marker of dyadic emotion regulation-Study 5) improved following maternal cognitive behavioral therapy (CBT) for PPD. Results: In Studies 1 and 2, prenatal diet quality accounted for significant variance in the links between prenatal metabolic complications and offspring psychopathology. In Study 3, poor prenatal diet quality was associated with adverse ANS development in offspring. In Studies 4 and 5, infants exhibited more adaptive emotion regulation and mother-infant synchrony improved following maternal receipt of CBT for PPD. v Conclusions: Elucidating the impact of modifiable perinatal risk factors on offspring psychopathology provides meaningful targets for intervention, and postnatal interventions may improve offspring emotion regulation and could reduce the risk of psychopathology. This work highlights the importance of the perinatal period as a time during which modifiable risk factors can be identified and intervened upon to reduce mental disorder risk across the lifespan. / Dissertation / Doctor of Philosophy (PhD) / Healthy brain development is important for health and success in life. However, risk factors such as the mother’s poor physical and mental health during pregnancy and in the first postnatal year can increase the risk of emotion and behaviour problems in offspring. Therefore, the objectives of this thesis were to i) identify links between modifiable pre and postnatal risk factors and poorer offspring brain development and ii) determine if intervening on one of these risk factors might improve offspring brain development. Results from this thesis show that an unhealthy maternal diet in pregnancy was linked to more offspring emotion, behaviour, and brain development problems and that treating postpartum depression in mothers may improve offspring brain development. This work suggests that identifying and intervening on modifiable risk factors is important to improve early brain development and may prevent the development of mental disorders later in life.

<div>The first 1000 days of life, from conception until the child’s second birthday, constitute a critical window for child growth and development. During infancy and early childhood, significant and rapid physical changes occur, including increases in weight, height, and brain size and organ development accompanied by cognitive and psychomotor development. Adequate infant feeding, including breastfeeding and complementary feeding, that meets the infants’ energy and nutrient requirements can help protect against growth faltering, infant and child morbidity and mortality, and delayed mental and motor development. Adequate nutrition during this critical period can also protect against adverse health outcomes and chronic diseases later in life according to the hypothesis of developmental origins of health and disease.</div><div><br></div><div>A web of factors that are country- and culture- specific influence infant feeding practices and child growth. Further, the microbiome has been suggested as a strong potential player in the association between infant nutrition and child growth. Therefore, the overarching theme of the current dissertation is to investigate hypotheses that can provide evidence to inform the paradigm linking socio-demographic, maternal, and child determinants including prenatal intake to infant feeding, the breast milk and infant gut microbiome, and child growth within the first 1000 days of life. Specifically, aims one and two examine the socio-demographic, maternal, and child determinants of child growth and breastfeeding in a cross-sectional survey of mother-child dyads in Lebanon, a middle-income country undergoing nutrition transition in the Middle East. The third aim focuses on the CHILD cohort study, a multi-center longitudinal prospective birth cohort study, to examine the associations between prenatal diet and supplement intake and the breast milk microbiome. Finally, the fourth aim is to review the evidence for the potential of the infant gut microbiome as a promising target linking complementary feeding to child undernutrition in low- and middle- income countries (LMIC) with the highest burden of undernutrition.</div><div><br></div><div>The results for aim one revealed sex-specific determinants of child growth in Lebanon. The determinants examined through a hierarchical conceptual framework included: maternal and paternal education among boys and crowding index among girls at the distal sociodemographic level, and maternal obesity among girls at the intermediate maternal level. The proximal child determinants included birth length, number of children in the household and breastfeeding duration among girls, birthweight among boys and child’s age among boys and girls.</div><div><br></div><div>In the analysis for aim two, breastfeeding practices were suboptimal in Lebanon as less than half (41.5%) of the infants were exclusively breastfed during the 40-day rest period and 12.3% were exclusively breastfed during the 6-month duration recommended by the World Health Organization. Higher socioeconomic status, as reflected by a larger number of cars owned, and C-section delivery were consistently inversely associated with lower odds of exclusive breastfeeding for 40 days and 6 months. Belonging to a family with more children was associated with higher odds of exclusive breastfeeding for 40 days; while maternal overweight and obesity were associated with lower odds of exclusive breastfeeding for 6 months.</div><div><br></div><div>Findings from aim three suggested that prenatal supplement use, but not prenatal dietary quality and patterns, modulate the breast milk microbiota composition in the CHILD cohort in Canada. This project was exploratory and utilized one of the largest birth cohort studies with available breast milk microbiome data. Specifically, use of vitamin C and D supplements plus multivitamins during any trimester in pregnancy was consistently associated with milk microbial diversity and genus composition before and after adjustment for socio-demographic, maternal, and child covariates. Use of other supplements such as fish oil, folate, and calcium was less consistently associated with the breast milk microbiome.</div><div>The fourth aim of the review chapter focused on the infant gut microbiome. The effects of complementary feeding on the infant gut microbiome are less commonly studied than those of breastfeeding, with most research conducted in high-income countries but not LMIC. In contrast, associations between inadequate complementary feeding and undernutrition have been examined in LMIC where undernutrition is most prevalent. Further, a disrupted gut microbiota has been associated with child undernutrition. Indeed, animal studies have suggested a causal association although the direction of the causality is not clear and is potentially bi-directional depending on genetic and environmental conditions. In light of the current state of knowledge described in our review supporting the potential of the gut microbiota as a key player in the relation between complementary feeding and undernutrition, the development of microbiota-directed interventions during the complementary period offers a promising route for undernutrition management.</div><div><br></div><div>Findings from the studies presented in this dissertation highlight several culture-specific determinants of child growth and breastfeeding in Lebanon. The findings also highlight the need for future research using longitudinal prospective cohorts, intervention trails and animal models to provide evidence for the proposed links to enhance the understanding of the paradigm. Such a holistic view of the determinants of and pathways between infant feeding and child growth are of great public health significance to improve the health of children throughout their lives.</div>