Nutritional Requirements

Early nutrition critically influences growth, neurodevelopment and morbidity among infants born of very low birth weight (VLBW), but current one-size-fits-all feeding regimes do not optimally support these vulnerable infants. There is increasing interest in "precision nutrition" approaches, but it is unclear which Human Milk (HM) components require personalized adjustment of doses. Previous efforts have focused on macronutrients, but HM also contains essential micronutrients as well as non-nutrient bioactive components that shape the gut microbiome. Further, it is unclear if or how parental factors (e.g. body mass index, diet) and infant factors (e.g. genetics, gut microbiota, sex, acuity) influence relationships between early nutrition and growth, neurodevelopment and morbidity. Understanding these complex relationships is paramount to developing effective personalized HM feeding strategies for VLBW infants. This is the overarching goal of the proposed Optimizing Nutrition and Milk (Opti-NuM) Project. The Opti-NuM Project brings together two established research platforms with complementary expertise and resources: 1) the MaxiMoM Program\* with its clinically embedded translational neonatal feeding trial network in Toronto (Dr. Deborah O'Connor, Dr. Sharon Unger) and 2) the International Milk Composition (IMiC) Consortium, a world-renowned multidisciplinary network of HM researchers and data scientists collaborating to understand how the myriad of HM components contribute "as a whole" to infant growth and development, using systems biology and machine learning approaches. Members of the IMiC Corsortium that will work with on this study are located at the University of Manitoba (Dr. Meghan Azad), University of California (Dr. Lars Bode) and Stanford (Dr. Nima Aghaeepour).

Iodine as an essential trace element for human, both excessive and insufficient intake would be harmful for human health. As susceptible population, children will be more sensitive to adverse effects caused by inadequate intake of iodine since they are at the peak of growth and development. Meanwhile, there are few direct evidence to establish dietary intakes levels of iodine for 3-6 years old pre-school children.

In order to solve the bottleneck problems of"zero balance displacement"and"large variation of breastmilk"in the study of iodine EAR of pregnant women, lactating women and infants, firstly, this study intends to clarify the rate of metabolism and distribution of iodine during pregnancy by 125I tracer, SPECT/CT in vivo small animal imaging and γ counting study. Then, the iodine balance study in rats was conducted to verify the degree of "zero balance value displacement"caused by the difference of iodine absorption and store in different organs and tissues under different iodine exposure levels, so as to determine the iodine selection conditions of subjects in the population experiment. To determine the EAR of pregnant women by optimizing the population iodine balance experiment. Secondly, we proposed to study the regulatory mechanism of NIS and Pendrin in the mammary gland of lactating rats under different iodine nutrition levels to clarify the range of breastmilk iodine compensation. Mammary cell experiments intend to clarify the mutual regulations of iodine nutrition, oestrogen, and NIS and Pendrin. Based on the results of animal and cellular experiments, and the effect of genetic, oestrogen and iodine status were considered, a cross-sectional study of lactating women was conducted to determine the normal reference range of breastmilk iodine after screening out the people with abnormal indicators. This study will solve the bottleneck problems and difficulties in the iodine RNI research for pregnant women, lactating women and infants, found the iodine nutritional compensatory mechanism under special physiology, and provide the scientific basis for obtaining the accurate EAR basic data and the revision of iodine DRIs.