Examining the essentiality of maternal choline intake during early infant development

• Author / Creator

  Lewis, Erin D

• Choline is an essential micronutrient with increased requirements during pregnancy and lactation due to a high demand by the developing fetus and infant. Animal studies have demonstrated that choline is essential for brain development, and as a component of all cell membranes it is hypothesized that choline is also required during the postnatal period for the rapidly developing immune system. Choline is not routinely consumed in supplements; therefore, food is the primary exogenous source. Despite the reliance on dietary sources, there is little research on the amount and forms of choline in the maternal diet, and the role of maternal choline intake on infant health outcomes. Therefore, the objective of this thesis was to describe pre- and early postnatal maternal choline intake and examine the consequences of consuming low dietary choline, and the differential effects of form, on offspring immune development. A comprehensive choline database was created to estimate dietary choline, and included the choline composition of meat and pulses commercially available in Alberta. Interview and online 24-h dietary intake recalls were collected at each trimester of pregnancy and 3 months postpartum from women in the Alberta Pregnancy Outcomes and Nutrition (APrON) study using two different methods. It was found that only 23% and 10% of women met recommendations for choline during pregnancy and 3-months postpartum, respectively. Phosphatidylcholine (PC) and free choline were the forms of choline consumed in the highest proportions. Only energy-adjusted estimates of total choline had strong correlation and good agreement between the 24-h recall methods, and were comparable between methods when categorizing low choline intake. In a parallel set of animal experiments, we sought to understand the consequences of not consuming sufficient amounts of choline during lactation and the effect of meeting choline recommendations through different forms on offspring immune development. Lactating rats were fed diets containing varying forms and amounts of choline and the offspring immune development investigated by identifying changes in the types of immune cells and response to ex vivo immune challenges. A maternal diet devoid of choline during the suckling period resulted in lower body weight, lymphopenia and lower percentage of major T cell phenotypes (CD3+, CD4+, CD8+) (all P<0.05), compared to maternal diet sufficient in choline (1g choline as free choline/kg diet). Choline-devoid offspring had lower production of cytokines IL-1β and IFN-γ following ex vivo mitogen stimulation. The long-term consequences of a lower supply of choline during this critical period of development resulted in a lower expansion of the CD4+ population and a lower ability to produce IL-6 in offspring at 10 weeks of age, even after choline was fed in the weaning diet (P<0.05). There was no difference in offspring growth when dams were fed choline as PC compared to free choline. However, feeding PC resulted in lower proportion of cells involved in antigen presentation and higher cytokine production following immune challenge (IL-2, IL-6, IFN- γ and TNF-α) (all P<0.05). In a cell culture model using isolated splenocytes, lysoPC was shown to increase T cell activation and T cell proliferation (IL-2 production). PC pups appeared more efficient at mounting a response to antigens and developmentally more mature compared to pups from free choline-fed dams and increasing the supply of PC, or lysoPC, may be responsible for these effects. Overall, we concluded that maternal dietary choline intake is low during pregnancy and early postpartum, and choline is essential in the maternal diet to support offspring growth and immune system development. Furthermore, the forms of choline in the maternal diet differentially affect immune system development, with choline in the form of PC improving development of the offspring’s T and B cells.

• Subjects / Keywords

  • Choline
  • Dietary intake
  • Immune development
  • Nutrition
  • Phosphatidylcholine

• Graduation date

  Fall 2016

• Type of Item

  Thesis

• Degree

  Doctor of Philosophy

• DOI

  https://doi.org/10.7939/R3K06XB5G

• License

  This thesis is made available by the University of Alberta Libraries with permission of the copyright owner solely for non-commercial purposes. This thesis, or any portion thereof, may not otherwise be copied or reproduced without the written consent of the copyright owner, except to the extent permitted by Canadian copyright law.