Health : Nutrition and Metabolic Adaptations in Physiological and Complicated Pregnancy: Focus on Obesity and Gestational Diabetes

Pregnancy offers a window of opportunity to program the future health of both mothers and offspring. During gestation, women experience a series of physical and metabolic modifications and adaptations, which aim to protect the fetus development and are closely related to both pre-gestational nutritional status and gestational weight gain. Moreover, pre-gestational obesity represents a challenge of treatment, and nowadays there are new evidence as regard its management, especially the adequate weight gain. Recent evidence has highlighted the determinant role of nutritional status and maternal diet on both pregnancy outcomes and long-term risk of chronic diseases, through a transgenerational flow, conceptualized by the Development Origin of Health and Diseases (Dohad) theory. In this review we will analyse the physiological and endocrine adaptation in pregnancy, and the metabolic complications, thus the focal points for nutritional and therapeutic strategies that we must early implement, virtually before conception, to safeguard the health of both mother and progeny. We will summarize the current nutritional recommendations and the use of nutraceuticals in pregnancy, with a focus on the management of pregnancy complicated by obesity and hyperglycemia, assessing the most recent evidence about the effects of ante-natal nutrition on the long-term, on either maternal health or metabolic risk of the offspring.

INRODUCTION

Pregnancy is a period of physical, hormonal and humoral changes, aimed to ensure the development and the necessary supply of nutrients to the fetus, and to prepare the maternal organism to delivery and breastfeeding. However, in the woman’s life, this biological phenomenon is considered as a window on the future health of both mother and offspring (1).

It is clear that maternal metabolic alterations, such as obesity and diabetes, have negative consequences on the offspring, for either embryonic teratogenic effect or outcomes at birth, such as mortality or pre-term birth. Moreover, there is an increasing interest in understanding the effects on long-term susceptibility of chronic-degenerative diseases.

In the 1980s, Dr. D. Barker and collaborators from the University of Southampton (UK), recovering the historical birth data in Hertfordshire (UK), introduced the pioneering concept that the origin of disease in adulthood could be strongly associated with exposure to an adverse uterine environment during pregnancy, a low birth weight and a related increase in the risk of offspring morbidity and cardiovascular mortality (2,3). This phenomenon, better known as “Barker hypothesis”, identifies a development plasticity; therefore, adverse conditions such as maternal malnutrition in early organogenesis can permanently change the structure of organs and systems, as stated by “fetal programming”.

According to a “thrifty genotype”, Barker’s hypothesis reflects a discrepancy between a uterine restriction environment and a postnatal abundance condition in the pathogenesis of obesity (4). The fetus responds to a “poor” environment with irreversible changes in its development trajectory and growth restriction (5); afterwards, in childhood or later, the organism loses the ability to adapt itself to a richer environment, and creates the basis for the development of diseases in adulthood (6).

More than 20 years earlier, N. Freikel had already proposed the key role of the uterine environment in influencing development, and hypothesized that in utero over-nutrition was decisive in the long-term.

Discussing within the context of diabetes in pregnancy, he introduced the concept of fuel-mediated teratogenesis, i.e. alterations during cell differentiation, and fetal organogenesis induced by excessive exposure to nutrients of the fetal-placental unit, which have immediate, but mostly long-term consequences on metabolic and anthropometric functions (7).

In recent years, this topic extended to the theory of “developmental origins of health and disease” (DOHaD). This definition underlines the role of both pre- and post-natal environments in shaping developmental trajectories on long-term health (8).

To date, consistent data confirm the pivotal role of maternal nutritional status and diet for the fetal epi-genotype and the resulting phenotype (9–12). Obviously, early exposure (which confers an increased risk of obesity, diabetes, and other metabolic diseases in adult life) unavoidably cause persistent changes in metabolism and neuro-endocrine functions, which leads to this susceptibility in adulthood.

Intriguingly, the relationship between nutrient intake and future health is not limited to the maternal diet during gestation, but it should be framed within a transgenerational heritage that marks the future risk of progeny. A fetus does not depend only on the mother’s diet during pregnancy, as it would be a dangerous strategy for its survival. Rather, it thrives on stored nutrients and on turnover of proteins and fats in maternal tissues, which are obviously related to maternal body composition and reflect her nutrition throughout life. A woman owns all her oocytes since she was born, therefore even before conception the quality of the female gametes will reflect the nutritional status of her mother. The critical 1000 days of development, which will determine the health for the rest of life, reflect 100 years of “nutritional flow” (13).

Specific maternal conditions during the pre- and peri-conceptional period (mostly obesity and excessive weight gain during pregnancy) are associated with Large-for-gestational-age (LGA) infants, obesity, and impaired glucose metabolism in children and subsequently with increased cardiometabolic risk in adults. Nutritional status during pregnancy cannot disregard the assessment of pre-pregnancy nutritional status.

This review will address the fascinating process that, starting from the functionality and anatomy of the placental-fetal unit, let to ensure the full-term delivery of a healthy newborn. Moreover, we will review the nutritional recommendations and the use of nutraceuticals in pregnancy, with a focus on the management of pregnancy complicated by obesity and hyperglycemia. Finally, we will focus on the most recent evidence about the effects of ante-natal nutrition on the long-term, on either maternal health or metabolic risk of the offspring.

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https://www.frontiersin.org/articles/10.3389/fendo.2020.611929/full