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Jessica Wilson

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Instituteof Medicine (US) Committee on Nutritional Status During Pregnancy and Lactation. Nutrition During Pregnancy: Part I Weight Gain: Part II Nutrient Supplements. Washington (DC): National Academies Press (US); 1990.

Protein is a macronutrient of major importance in human nutrition. Plant and animal proteins are composed of more than 20 individual amino acids. Within the body, amino acids are used for a wide variety of structural proteins and enzymes; and they serve as a source of energy, carbon, and nitrogen.


Protein has an energy value of approximately 5.5 kcal/g. Of this, approximately 4 kcal/g is used during metabolism; the unmetabolized portion is excreted as urea and other compounds. For meeting metabolic needs and promoting satisfactory rates of protein synthesis, the diet must provide amino acids of adequate quality and quantity.


Amino acids and nitrogen are available to mammals through degradation of proteins and other nitrogenous compounds. Mammals can synthesize nonessential amino acids de novo, if energy and suitable forms of carbon and nitrogen are available. Thus, net requirements for nonessential amino acids can be met both by dietary protein and by endogenous synthesis of amino acids. Ordinarily, the following amino acids are considered to be essential amino acids, because they cannot be synthesized by mammals: histidine, isoleucine, leucine, lysine, methionine + cystine, phenylalanine + tyrosine, threonine, tryptophan, and valine (NRC, 1989). Thus, these must be provided in adequate amounts by the diet. Other amino acids, such as arginine and taurine, may functionally appear to be essential during fetal and infant development in some species (Gaull, 1983; Sturman, 1986; Visek, 1986), because the metabolic pathways have not yet fully developed to adult levels and because the amount needed to cover growth and net new protein accretion is high. Developmental immaturity of biochemical pathways may also limit conversion of pairs of metabolically related essential amino acids, such as conversion of phenylalanine to tyrosine.


In postnatal life, ingested protein is hydrolyzed to amino acids, which are absorbed and carried via the portal system to the liver. The amino acids then enter the systemic circulation and are distributed throughout the body. The liver is an especially active site for synthesis of protein from amino acids. Since considerable reutilization of amino acids occurs, there is synthesis and degradation of more protein daily than has been ingested.


Pregnancy complicates the already complex metabolism of amino acids. Expansion of blood volume and growth of the maternal tissues require substantial amounts of protein (Table 19-1). Growth of the fetus and placenta also places protein demands on the pregnant woman. Thus, additional protein is essential for the maintenance of a successful pregnancy. However, a review of the processes controlling these changes in maternal protein metabolism is beyond the scope of this chapter.


Maternal protein restriction, alone and in combination with energy restriction, results in consistently decreased fetal growth in many species (Fattetr et al., 1984; Hill, 1984; Lederman and Rosso, 1980; Pond et al, 1988; Rosso, 1977a,b, 1980; Rosso and Streeter, 1979). These models demonstrate not only decreased body weight and growth but also decreased numbers of cells and a variety of biochemical changes. A particular concern is that the developing fetus may or may not adequately compensate for some of the effects of maternal protein deprivation, and effects may even span generations.


The fetus receives a continuous stream of amino acids from the mother via placenta (Battaglia, 1986); the amino acids cross the placenta by a complex series of transport systems, probably including both active and facilitated transport systems. Transport systems may differ on the maternal and fetal sides of the placenta, and different classes of amino acids are transported by different placental systems (Battaglia, 1986; Eaton and Yudilevitch, 1981; Lemons and Schreiner, 1983; Schneider et al., 1979; Smith, 1986; Yudilevitch and Sweiry, 1985). Amino acid concentrations are typically somewhat higher in the fetus than in the mother (Cetin et al., 1988; Soltesz et al., 1985; Yudilevitch and Sweiry, 1985). Moreover, the placenta is very active metabolically, and in laboratory animals, it plays an important role in nitrogen metabolism (Meschia et al., 1980). Because of the complexity of the transport processes and placental metabolism, it is difficult to predict the effect of altered maternal protein intake on fetal amino acid metabolism, both in terms of the total quantitative amino acid flux and in terms of relative changes in the fluxes of individual amino acids.


The fetus must handle rapid entry of both exogenous and endogenous amino acids, and it must provide for the rapid accretion of new protein (Battaglia, 1986). Studies in the unstressed fetal lamb have shown rapid turnovers of leucine and lysine in amounts several fold higher than umbilical uptakes of the amino acids from the placenta (Battaglia. 1986). More recently, turnover measurements of the nonessential amino acid glycine have suggested the interconversion of glycine and serine in the fetal liver (Marconi et al., 1989). The sheep fetus also appears to catabolize amino acids to urea at a rapid rate (Lemons et al., 1976).


Several investigators have studied the effect of direct amino acid infusion in experimentally induced growth retardation in fetal animals (Charlton and Johengen, 1985; Fattetr et al., 1984; Mulvihill et al., 1985). These studies have demonstrated at least partial restitution of birth weight with direct nutritional supplementation. However, there is no evidence that amino acid supplementation of normally grown fetuses significantly increases birth weights above those achieved by controls.


Information regarding total protein requirements during pregnancy has been provided through the factorial approach, balance studies, turnover studies, and epidemiologic surveys (see Chapter 12). As noted above, there are theoretical and experimental differences of opinion regarding requirements for protein and amino acids.


Nitrogen is found in many compounds other than protein. Nucleic acids and polyamines are two such compounds that may be of particular relevance to the growing fetus. In detailed studies of the chemical composition of the guinea pig fetus, approximately 20% of the nitrogen content was found in compounds other than protein (Sparks et al., 1985). If this is also true of the human fetus, its protein content and requirements may be lower than current estimates.


Turnover studies have indicated that protein turnover increases early and remains elevated throughout pregnancy (de Benoist et al., 1985; Fitch and King, 1987; Jackson, 1987). Some investigators have expressed technical concerns about using turnover measurements to estimate protein requirements during pregnancy (Fitch and King, 1987). All human studies to date have used nonessential amino acids to measure the turnover of protein in pregnant women, further complicating the interpretation of these data.


The deposition of protein is not necessarily linear throughout pregnancy. Early during pregnancy, the fetal component is minimal, whereas the requirement for maternal volume expansion and tissue growth may be substantial. Late in pregnancy, the fetus may account for the major increase in protein needs. The additional requirement averaged over gestation appears to be roughly 3 to 4 g of protein per day. If it is assumed that there is a 15% variation in birth weight and that dietary protein is converted at 70% efficiency, the requirement for protein would be an additional 6.0 g/day averaged over pregnancy, but the demand is highest (10.7 g/day) in the last trimester (NRC, 1989). On the basis of these and other considerations, a maternal protein intake of 10 g/day over the Recommended Dietary Allowance (RDA) for protein (i.e., a total of 60 g/day) is recommended throughout pregnancy. This subcommittee notes that most foods that are good sources of protein (e.g., grains, flesh foods, milk, cheese, and dried peas and beans) are also good sources of many other nutrients and thus their use should be encouraged as part of a balanced diet during pregnancy.


As discussed in Chapter 13, usual protein intakes by pregnant women in the United States range from 75 to 110 g/day. The estimated average intakes of protein by low-income women enrolled in the Supplemental Food Program for Women, Infants, and Children (WIC) were higher than the 1980 RDA of 74 g/day, even before participation in the program (Rush et al., 1988). However, inadequate energy intake may contribute to protein deficiency if there is compensatory catabolism of protein and amino acids to meet energy needs. Thus, the adequacy of dietary protein must be considered in the context of total nutrient intake.


Deficiency of protein is difficult to asses, both because of protein's dynamic and complex metabolism and because protein deficiency is generally associated with deficiencies of other nutrients and energy. Classic signs of protein deficiency include poor growth, muscular weakness, poor hair growth, and low serum albumin, which result in edema. Classic protein deficiency is rare in the general U.S. population, occurring primarily in people with serious illness or injury rather than as a result of poor dietary intake. However, protein-energy malnutrition is relatively common in other areas of the world, especially among children, and it is associated with decreased birth weight. It is difficult, however, to isolate the effect of protein malnutrition from that of energy intake.


The results of most laboratory tests used to assess protein deficiency show changes during pregnancy. With the increase in plasma volume, there is a decreased concentration of albumin and certain other blood constituents. However, some blood proteins, especially those whose levels are influenced by astrogen, increase during pregnancy. Urea nitrogen and alpha amino nitrogen levels decrease.

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