Background: Maternal stress during utero has been shown to have negative health consequences on the offspring, including low birth weight and increased risk of adult disease. Variation in breastmilk may act as an environmental cue of maternal stress and continue to program the infant during early life. This research aimed to explore the role of breastmilk on developmental programming of the infant. Specifically, to examine how breastmilk may act as a medium for the exposure of stress between the mother and the offspring, and see if variation in insulin like growth factor-1 (IGF-1) a potential mechanism for the relationship. Methods: Survey-interviews, anthropometrics of the mother and offspring (height and weight), and breastmilk samples were collected for 31 breastfeeding mother-offspring pairs in the Tampa Bay area. Breastmilk was analyzed for IGF-1 and fat content. Maternal stress was measured through the PSS-10 and two self-reported ten-point stress scales. Offspring length for age and weight for age Z-scores were calculated using LMS equation. Results: PPS-10 score was negatively correlated with child length for age and weight for age Z-scores. Child length for age and weight for age Z-scores were also negatively correlated with the breastmilk fat variables (creamatocrit percent, fat g/dL, and kcal/dL). No relationships were found between breastmilk IGF-1 and offspring length for age, weight for age, or maternal stress. Conclusions: Results indicate that maternal stress may negatively impact offspring growth. However, more research is necessary to better understand if or how breastmilk fat may act as a mechanism to mediate offspring growth due to maternal stress. This sample had low levels and prevalence of detectable IGF-1, which likely contributed to the lack of statistical relationships. Further research using lower dilutions and larger samples sizes is necessary to better explore the potential role of breastmilk IGF-1 on offspring growth and/or its relationship to maternal stress.

Maternal obesity has significant consequences on the lifelong health of the developing child and rising global incidences make it one of the most common comorbidities during pregnancy. Offspring of obese mothers are at an increased risk of hospitalization for respiratory infections throughout childhood, which predispose these children to non-communicable respiratory diseases in later life. Animal models of maternal high fat diet (mHFD) feeding have observed common inflammatory outcomes with obesogenic models, but the effect on offspring varies with timing of the nutritional challenge and diet composition across studies. These studies demonstrate significant alterations to circulating and lung specific immune cells but the sequence of events that link maternal diet to these fetal outcomes are unclear, nor have they been tested in the context of a bacterial respiratory infection. Streptococcus pneumonaie is the most common causative pathogen of bacterial pneumonia and meningitis, making it of high clinical relevance. We aimed to investigate the effect of a mHFD (45% kcal from fat) during gestation and lactation, on offspring outcome and recovery from Streptococcus pneumoniae infection. Immunophenotyping, both before and after infection, revealed a hypo-inflammatory phenotype in circulating monocytes of the mHFD offspring with a decreased capacity to both initiate and terminate inflammatory responses. These offspring had significantly higher bacterial counts in lung tissues during infection and sustained cellular inflammation in survivors. In this thesis, we present foundational work on the detrimental influence of excess maternal nutrition on offspring immune function and infection outcomes, which may be involved in susceptibility to inflammatory and chronic disease in later life. A better understanding of this deep and lasting influence of the maternal environment will allow us to target preconception health as a form of harm reduction, informing stake holders and institutions to direct efforts towards DOHaD knowledge translation. / Thesis / Master of Science (MSc)

<p>Emerging evidence indicates that in utero exposure to vitamin D metabolites may influence fetal and neonatal bone development. Bone accretion in prenatal and early postnatal life may impact peak bone mass achieved in early adolescence; and peak bone mass is a well-established predictor of osteoporosis risk in later life. <strong>Hypothesis</strong>: We hypothesized that offspring of mothers with higher serum vitamin D status during pregnancy will have higher whole body BMC z-score and bone size at 3 years of age, after adjustment for confounders. <strong>Methods</strong>: In a prospective, longitudinal study, 372 mothers with singleton birth were recruited during pregnancy, and maternal blood samples were obtained during the third trimester. Child bone outcome measures at 3 years of age included: whole body BMC, femoral and humeral lengths by DXA. We controlled for other relevant factors such as maternal nutrition, pre-pregnancy BMI, physical activity during pregnancy, maternal BMD, as well as the child’s nutrition at 6 months and 3 years, and the child’s physical activity. <strong>Results & Discussion</strong>: Maternal vitamin D status during pregnancy did not predict whole body BMC z-score of the child at 3 years of age. Over 92% of Canadian women in our sample were vitamin D sufficient with mean intakes of 435 IU/day from food and supplements and mean serum 25OHD of 111.2 nM. Further, data indicate a potential negative effect on offspring bone size at maternal serum 25OHD concentrations that exceed the upper limit suggested by the most recent DRI report (>125 nM), at which adverse health effects may occur. Our findings may differ from previous studies in the United Kingdom, India and Finland that found a positive relationship between maternal vitamin D status and child bone outcomes due to the high frequency of our mothers that had optimal vitamin D status. In addition, we adjusted for most of the key covariates that were not adjusted for in previous studies, which may contribute to the different findings compared to previous investigations.</p> / Master of Science (MSc)