The Maternal Nutritional Buffering Model: an evolutionary framework for pregnancy nutritional intervention

Abstract

Evidence that fetal nutrition influences adult health has heightened interest in nutritional interventions targeting pregnancy. However, as is true for other placental mammals, human females have evolved mechanisms that help buffer the fetus against short-term fluctuations in maternal diet and energy status. In this review, we first discuss the evolution of increasingly elaborate vertebrate strategies of buffering offspring from environmental fluctuations during development, including the important innovation of the eutherian placenta. We then present the Maternal Nutritional Buffering Model, which argues that, in contrast to many micronutrients that must be derived from dietary sources, the effects of short-term changes in maternal macronutrient intake during pregnancy, whether due to a deficit or supplementation, will be minimized by internal buffering mechanisms that work to ensure a stable supply of essential resources. In contrast to the minimal effects of brief macronutrient supplementation, there is growing evidence that sustained improvements in early life and adult pre-pregnancy nutrition could improve birth outcomes in offspring. Building on these and other observations, we propose that strategies to improve fetal macronutrient delivery will be most effective if they modify the pregnancy metabolism of mothers by targeting nutrition prior to conception and even during early development, as a complement to the conventional focus on bolstering macronutrient intake during pregnancy itself. Our model leads to the prediction that birth weight will be more strongly influenced by the mother's chronic pre-pregnancy nutrition than by pregnancy diet, and highlights the need for policy solutions aimed at optimizing future, intergenerational health outcomes. Lay summary: We propose that strategies to improve fetal macronutrient delivery will be most effective if they modify the pregnancy metabolism of mothers by targeting nutrition prior to conception and even during early development, as a complement to the conventional focus on bolstering macronutrient intake during pregnancy itself.

Keywords: DOHaD; birth outcomes; fetal programming; placenta; pregnancy; supplementation.

Figure 1.

Evolutionary innovations in maternal buffering of offspring rearing environment. Dates (mya, million years ago) represent minimum fossil-based estimate for last common ancestor for each branching point [based on 126]. Giving birth to live young (viviparity) has evolved independently more than 100 times among marsupials, eutherian mammals, reptiles and even some species of fish, pointing to the evolutionary advantages of this strategy. Of the various reproductive strategies, the eutherian mammalian profile of internal fertilization, having a true placenta, and giving birth to live young that subsist on breast milk provides many opportunities for maternal biology to buffer environmental fluctuations and also to modify offspring development

Figure 2.

Pathways linking maternal intake of a nutrient or compound with fetal exposure to that compound. (A) Essential nutrient—a beneficial resource that the body is not capable of adequately synthesizing de novo. Delivery of adequate levels of the resource to the fetus is contingent upon dietary intake and the size of the mother’s bodily stores. (B) Major macronutrients—internal availability is homeostatically regulated by dietary intake, mobilizing tissue stores and through de novo synthesis from precursors. In light of these redundant sources, nutrient delivery to the fetus is often unrelated to the mother’s current dietary intake. Maternal regulatory set points that govern nutrient transfer to the fetus may be more effective targets for intervention

Figure 3.

Redundant sources of glucose within the mother’s body. Glucose levels rise after consuming a meal. During a fast, circulating glucose is first maintained by mobilizing the body’s modest glycogen stores, which are sufficient to meet glucose needs for several hours. After glycogen stores are depleted, glucose is produced from mobilized amino acids (protein) and glycerol (fats). During prolonged fasts, peripheral tissues use fatty acids for energy and become insulin resistant, conserving glucose for obligate glucose-using functions and tissues. Although the brain generally only uses glucose, during starvation it may also use ketone bodies derived from mobilized fatty acids as an alternative fuel source. The shift to a predominant focus on fat metabolism with prolonged energy deficits reduces glucose requirements and thereby minimizes the need to catabolise protein in tissues and organs to provide substrate for glucose production