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Ketone Body Metabolism in the Neonate

Acknowledgments The authors are most grateful to previous edition contributors to this chapter, including Paul S. Thornton, whose leadership and input on the chapter’s themes and data (particularly within the tables) were invaluable. Introduction The metabolism of ketone bodies is evolutionarily conserved among all the domains of life on Earth. In mammals, ketone bodies are predominantly synthesized in the liver from acetyl coenzyme A (CoA) derived…

Lipids as an Energy Source for the Premature and Term Neonate

Acknowledgments The authors thank Dr. Peter Dodds for editing and linguistic revision of the manuscript. Preparation of this chapter was carried out in part with grants from the Universidad San Pablo—CEU, the Fundación Ramón Areces (CIVP16A1835) of Spain, and the Spanish Ministry of Science and Innovation (SAF2012-39273). Introduction In utero, the fetus receives a continuous supply of substrates for growth and oxidative metabolism, and produces large…

Brown Adipose Tissue: Development and Function

Introduction Mammals such as humans are exposed to their greatest temperature-related shock at birth. Coming from a protected and thermoneutral environment, the newborn infant is suddenly exposed to “cool” surroundings, where survival depends on self-generation of sufficient heat to keep warm. The development of the ability to regulate body temperature regardless of the temperature of the surroundings (and through this to ensure that activity of the…

Maternal-Fetal Transfer of Lipid Metabolites

Acknowledgments The authors thank pp-science-editing.com for editing and linguistic revision of the manuscript. Preparation of this chapter was carried out in part with grants from the Universidad CEU—San Pablo, and the Ministerio de Economía y Competitividad (SAF2015-70747-R) of Spain. CIBEROBN is an initiative of the Instituto de Salud Carlos III (ISCIII), Spain. Introduction Changes in maternal lipid metabolism during gestation control the availability of lipid metabolites…

Vitamin K Metabolism in the Fetus and Neonate

Introduction In his classic studies in the 1930s, Henrik Dam identified vitamin K as an essential fat-soluble antihemorrhagic factor. Later studies pinpointed the bleeding disorder caused by a dietary deficiency of vitamin K to a lack of four coagulation proteins, namely prothrombin (factor II) and factors VII, IX, and X, all of which are synthesized in the liver. Descriptions of a bleeding syndrome in newborns that…

Vitamin E Nutrition in Pregnancy and the Newborn Infant

Introduction Vitamin E, a micronutrient with antioxidant functions, has important actions in both intrauterine and postnatal life. Even in pregnant women with adequate vitamin stores, it seems that there is a transplacental barrier that limits its transfer to the fetus. Thus, physiologic concentrations of vitamin E are lower at birth, which makes newborns (especially premature infants) more susceptible to development of vitamin E deficiency (VED). This…

Vitamin A Metabolism in the Fetus and Neonate

Introduction Vitamin A (retinol) is an essential nutrient for all vertebrates. It was discovered in 1913 as an ether-soluble fraction present in certain fats and tissues, such as butter and egg yolk, that young rats required for growth and survival. Early in the history of vitamin A research, investigators demonstrated some of the fundamental properties of vitamin A, namely its indispensability for proper vision, immunity, reproduction,…

Zinc in the Fetus and Neonate

Introduction In a remarkably short time, the general perception of zinc has progressed from that of a rather obscure essential trace mineral of doubtful significance for human health to that of a micronutrient of exceptional biologic and public health importance. This is most evident in relation to early development, both prenatal and postnatal. Space allotted to an overview of trace minerals other than iron and zinc…

Fetal and Neonatal Calcium, Phosphorus, and Magnesium Homeostasis

Introduction Calcium, phosphorus, and magnesium are essential minerals that function in their physiologically active ionic forms in a wide range of cellular processes, and as key components of the bone mineral matrix. In utero, calcium, phosphorus, and magnesium are readily transferred from maternal to fetal circulations, and fetal mineral stores are predominantly accrued in the third trimester. In the postnatal period, the newborn must rapidly adapt…

Fetal and Neonatal Iron Metabolism

Acknowledgments Preparation of this chapter was supported by grants from the National Institutes of Health (NICHD) and the Scottish Government (Rural and Environmental Scientific and Analytical services, RESAS). Introduction Iron is the fourth most abundant element and constitutes approximately 0.0075% of human body composition. It is a cofactor in some of the most basic biologic reactions, yet its beneficial effects are tempered by the fact that…

Physiology of Lactation

Functional Anatomy of the Breast The human female breast is composed of a tubuloalveolar parenchyma embedded in a connective and adipose tissue stroma. The glandular component of the mature breast is composed of radially organized lobes, each connected to the nipple by a single milk duct. Each lobe is composed of multiple lobules containing the alveolar structures responsible for milk production and an associated network of…

Human Milk Composition and Function in the Infant

Introduction Lactation is the defining characteristic of “mammal” and has enabled the wide distribution of more than the 4000 species. The evolution of a large brain that consumes approximately 23% of resting energy has given humankind a significant competitive intellectual advantage over all other mammals. Unlike other mammals, most brain growth in humans occurs after birth and is facilitated by the nutrients present in human milk…

Endocrine Factors Affecting Neonatal Growth

Introduction Growth reflects a complex interaction of genetic, epigenetic, endocrine, and nutritional factors that regulate cell division, differentiation, and function (see Meler et al. for a recent compilation of genetic and epigenetic conditions leading to fetal growth restriction). Various phases of growth appear “programmed” to occur within specific time intervals. If missed, growth may not be fully recoverable. Ever-increasing evidence indicates that the pattern and rapidity of…

Placental and Fetal Circulatory and Metabolic Changes Accompanying Fetal Growth Restriction

Introduction During fetal life, factors associated with maternal, placental, and fetal environments interact to ensure optimal fetal metabolism and growth. However, in 3% to 7% of pregnancies these interactions become suboptimal and growth of the fetus does not align with its in utero genetic growth potential, resulting in a reduced growth trajectory and the outcome at birth often termed fetal growth restriction (FGR) . To ensure…

Drug Transfer During Breastfeeding

Introduction Since the early 2000s, researchers and clinicians have greatly expanded the knowledge base of drug entry kinetics as they relate to human milk. Most of the physiochemical properties that affect a drug’s transfer into milk are well known and understood today. , For the busy clinician, the National Institutes of Health and others have published reference works that consolidate the evidence supporting the relative safety…

Drug Distribution in Fetal Life

Introduction Drug distribution and clearance determine the concentration of drug that will be attained at the site of drug action. Drug targets include cell surface receptors, intracellular receptors, enzymes, transcriptional mechanisms, ion channels, and molecular transport systems. These targets may be within the circulatory system, in well-perfused tissues, in less well-perfused tissues, or behind specialized endothelial or epithelial barriers. The fetus lies behind one of these…

Pharmacogenomics

Introduction Pharmacogenetic variants are DNA variants that influence the metabolism and elimination or the action of medications. Research in pharmacogenetics seeks to understand how these variants influence variability in medication response. For the perinatal pharmacologist, genetic variations that affect drug disposition in the fetus, the mother, and the neonate must be considered as one of many sets of variables, along with developmental changes in fetal and…

The Physiology of Placental Drug Disposition

Introduction: From a Passive Filter Barrier Concept to an Active Drug Handling Organ When deconstructed to its basic structure, the placenta is an active (“drug handling”) barrier between two separated systems (maternal, fetal) with placental drug disposition driven by differences in concentration-time profiles between both systems, and the maternal and fetal blood flow to and from the filter. This setting is somewhat similar to hemodialysis or…

Principles of Pharmacokinetics

Introduction Pharmacokinetics describes the absorption, distribution, metabolism, and excretion of drugs. The pharmacokinetic parameters of a drug are used to characterize the drug concentrations reached within the body after a dose and the changes in those concentrations over time. Clinical pharmacokinetics is the discipline that applies pharmacokinetic principles to individualize dosage regimens, optimize the therapeutic effects of a medication, and minimize the chances of an adverse…

Basic Pharmacologic Principles

Introduction Pharmacology is a science concerned with the interaction of substances (e.g., drugs) with cells, tissues, and organisms. The in vivo efficacy of a drug is guided by two principles of pharmacology, namely pharmacokinetics and pharmacodynamics. Pharmacokinetics deals with the processes of drug concentration in the tissue compartments and therefore involves absorption, distribution, biotransformation, and excretion. Pharmacodynamics applies to the study of mechanisms of action of drugs.…