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19 Protein and Amino Acids 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 kcaVg. Of this, ap- proximately 4 kcaUg 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 degra- dation of proteins and other nitrogenous compounds. Mammals can syn- thesize 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 synthe- sis 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 (N RC, 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 380
PROTEIN AND AMINO ACIDS TABLE 19-1 Factorial Estimate of Protein Components of Weight Gain in a Normal Full-Term Pregnancya Component Weight, g Protein, g Fetus3,400440 Placenta650100 Amniotic fluid8003 Uterus970166 Blood1,25081 Extracellular fluid1,680135 Total8,750925 a Modified from Calloway (1974), after Hytten and Leitch (1971), with permission. 381 protein accretion is high. Developmental immaturity of biochemical path- ways 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 i amino acids. Since considerable reutilization of amino acids occurs, there is synthesis and degradation of more protein daily than has been ingested. IMPORTANCE 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 (Fattet 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.
382 DIETARY INTAKE AND NUTRIENT SUPPLEMENTS AMINO ACID UTILIZATION The fetus receives a continuous stream of amino acids from the mother via the 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 severalfold 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 infu- sion in experimentally induced growth retardation in fetal animals (Charl- ton and Johengen, 1985; Fatter et al., 1984; Mulvihill et al., 1985~. These studies have demonstrated at least partial restitution of birth weight with di- rect nutritional supplementation. However, there is no evidence that amino acid supplementation of normally grown fetuses significantly increases birth weights above those achieved by controls. ESTIMATED REQUIREMENTS 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. The results of body composition studies in human and nonhuman
PROTEIN AND AMINO ACIDS 383 species have formed the basis for estimation of protein accretion in the fems. Hytten and Leitch (1971) reviewed classic studies of human body composition (Kelly et al., 1951; Widdowson and Dickerson, 1964) and esti- mated fetal protein requirements to be approximately 440 g over the course of pregnancy and the placental protein requirement to be an additional 100 g (Bible 19-1~. Other reviewers, using much of the same published data on humans, estimated a nitrogen accumulation of 50 to 60 g for a full-term 3,300-g fetus (Sparks, 1984; Ziegler et al., 1976~. The data on which such factorial estimates are based are limited, however, and lacking in important details such as accurate gestational age. The results differ because of differ- ences in mathematical modeling and data bases (Hytten and Leitch, 1971; Sparks, 1984; Ziegler et al., 1976~. At the standard estimate of 6.25 g of protein per gram of nitrogen, this would amount to 310 to 375 g of protein per human fetus at full term somewhat lower than previous estimates. Both approaches estimating fetal amino acid and nitrogen requirements demonstrate that the fetus and placenta present a substantial demand for amino acids from the mother. 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 compo- sition 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. Using the factorial approach and assuming a 40-week gestation and a 3,300-g newborn, Hytten and Leitch (1971) estimated that 925 g is the total increment in body protein during pregnancy (Table 19-1~. More recent nitrogen balance studies (Appel and King, 1979; Johnstone et al., 1981) suggest that nitrogen retention approaches the factorial estimate, if adjustment is made for unmeasured losses. 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 tech- nical concerns about using turnover measurements to estimate protein requirements during pregnancy (Fitch and King, 1987~. All human stud- ies 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 preg- nancy. 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 ap
384 DIETARY INTAKE AND NUTRIENT SUPPLEMENTS pears 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 gJday 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. USUAL INTAKES 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. CRITERIA FOR DEFICIENCY Deficiency of protein is difficult to assess, both because of protein's dynamic and complex metabolism and because protein deficiency is gen- erally associated with deficiencies of other nutrients and energr. Classic signs of protein deficiency include poor growth, muscular weakness, poor hair growth, and low serum albumin, which may result in edema. Classic protein deficiency is rare in the general U.S. population, occurring primar- ily 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 common 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 estrogen, increase during pregnancy. Urea nitrogen and alpha amino nitrogen levels decrease.
PROTEIN AND AMINO ACIDS 385 SUPPLEMENTATION STUDIES A large body of literature documents the results of protein supplemen- tation programs during pregnancy in regions where malnutrition is found. Many of these studies are examined in Chapter 7. In Guatemala, studies were conducted to determine the effects of a protein-energy supplement and a low energy supplement on maternal and newborn outcomes among chronically malnourished rural women (Delgado et al., 1982; Lechtig et al., 1975, 1978) (see Chapter 7, Table 7-2B). In these widely cited stud- ies, investigators found minimal change in birth weight and no effect on gestational duration among women receiving either supplement. Post hoc analysis demonstrated a significant positive effect of spontaneous energy intake on birth weight and maternal weight gain regardless of the protein content of the supplement. In Colombia, investigators examined the effect of a supplement con- taining 20 g of protein and 150 kcal of energy given to poor urban women in Bogota. They found an approximately 50-g increase in birth weight in the supplemented group and no effect on gestational duration (More et al., 1979~. In Taiwan, supplementation with both protein and calories failed to statistically increase the birth weights of infants born to poor rural women (Adair and Pollitt, 1985; Adair et al., 1983; McDonald et al., 1981; Wohlleb et al., 1983~. Studies in the developed world have also demonstrated minimal changes in birth weight as a result of protein supplementation. In the United Kingdom, protein-energy supplementation of pregnant Asian wom- en in Birmingham led to significantly higher maternal weight gains than did energy supplements alone; however, only the supplement that contained vitamins in addition to protein and energy was associated with a significant increase in birth weight (Viegas et al, 1982a,b). Rush et al. (1980) found sig- nificant decreases in both gestational length and birth weight and marginally significant increases in mortality and preterm birth rate with high-densi~ protein supplementation of poor women in Harlem, New York. Adams and colleagues (1978) reported that a high-protein supplement given to women in San Francisco resulted in a 45-g decrease in birth weight, com- pared with controls, and a 140-g decrease in birth weight, compared with infants of mothers who were provided with energy supplements. Reviews of WIC have demonstrated minimal eRects of program participation on birth weight, gestational duration, or the incidence of low birth weight (Kennedy and Kotelchuck, 1984; Metcoff et al., 1985; Rush et al., 1988~.* In a comprehensive review of the literature on supplementation, Rush and colleagues (1984) reported an inverse relationship between birth weight *An average WIC package for pregnant women provides 90 to 1,000 kcal of energy and 40 to 50 g of protein daily.
386 DIETARY INTAKE AND NUTRIENT SUPPLEMENTS and protein density in supplements. An increase in prematurity has not been generally associated with supplements that provide protein-to-energy ratios comparable to those found in usual diets. ~ summarize, in many studies, protein-energy supplements have been given to pregnant women in an effort to determine the effect on maternal and fetal outcomes. In many of them, no significant changes were found in either birth weight or gestational duration; in others, small changes from a 30- to 100-g increase in birth weight were observed. The biologic importance of changes of this magnitude (1 to 3% of the full-term birth weight) is not certain. It is difficult to interpret these studies because of variations in baseline nutritional status, composition of the supplements, and other characteristics; it is particularly problematic to separate the effect of the protein from that of the energy in the supplements. RECOMMENDATIONS REGARDING SUPPLEMENTATION On the basis of the estimated additional needs for protein and energy during pregnancy and the usual intake of these nutrients from the U.S. diet, the subcommittee concludes that the additional requirement for protein during pregnancy can be met from dietary sources. Because evidence suggests possible harm from specially formulated high-protein supplements, the use of special protein powders or specially formulated high-prote~n beverages should be discouraged. CLINICAL IMPLICATIONS · A moderate increase In the use of food sources of protein, such as whole grains, milk, and legumes, as part of a balanced diet, is encouraged during pregnancy since these foods are valuable sources of other nutrients. · Assessment of adequacy of protein status is most important in women whose energy intake Is low. · Use of specially formulated protein supplements (e.g., protein pow- ders) is not recommended during pregnancy. REFERENCES Adair, US., and E. Pollitt. 1985. Outcome of maternal nutritional supplementation: a comprehensive review of the Bacon Chow study. Am. J. Clin. Nutr. 41:948-978. Adair, L.S., E. Pollitt, and W.H. Mueller. 1983. Maternal anthropometric changes during pregnancy and lactation in a rural Taiwanese population. Hum. Biol. 55:771-787. Adams, S.O., G.D. Barr, and R.L~ Huenemann. 1978. Effect of nutritional supplementation in pregnancy. I. Outcome of pregnancy. J. Am. Diet. Assoc. 72:144-147.
PROTEIN AND AMINO ACIDS 387 Appel, J., and J.C. King. 1979. Protein utilization in pregnant and non-pregnant women. Fed. Proc., Fed. Am. Soc. Exp. Biol. 38:388. Battaglia, F.C. 1986. Placental transport and utilization of amino acids and carbohydrates. Fed. Proc., Fed. Am. Soc. Exp. Biol. 45:2508-2512. Calloway, D.H. 1974. Nitrogen balance during pregnancy. Pp. 79-94 in M. Schick, ed. Nutrition and Fetal Development. John Wiley & Sons, New York. Cetin, I., NM. Marconi, P. Bozetti, L.P. Sereni, C. Corbetta, G. Pardi, and F.C. Battaglia. 1988. Umbilical amino acid concentrations in appropriate and small for gestational age infants: a biochemical difference present in utero. Am. J. Obstet. Gynecol. 158:120-126. Charlton, V., and M. Johengen. 1985. Effects of intrauterine nutritional supplementation on fetal growth retardation. Biol. Neonate 48:125-142. de Benoist, B., A.N Jackson, J. St. E. Hall, and C. Persaud. 1985. Whole-body protein turnover in Jamaican women during normal pregnancy. Hum. Nutr.: Clin. Nutr. 39C:167-179. Delgado, H.L;, V.E. Valverde, R. Martorell, and R.E. Klein. 1982. Relationship of maternal and infant nutrition to infant growth. Early Hum. Dev. 6:273-286. Eaton, B.M., and D.L~ Yudilevich. 1981. Uptake and asymmetric efflux of amino acids at maternal and fetal sides of placenta. Am. J. Physiol. 241:C106-C112. Fattet, I., F.D. Hovell, E.R. 0rskov, D.J. Kyle, K. Pennie, and R.I. Smart. 1984. Undernutrition in sheep. The effect of supplementation with protein on protein accretion. Br. J. Nutr. 52:561-574. Fitch, W.L^, and J.C. King. 1987. Protein turnover and 3-methylhistidine excretion in non-pregnant, pregnant and gestational diabetic women. Hum. Nutr.: Clin. Nutr. 41C:327-339. Gaull, G.E. 1983. Taurine in human milk: growth modulator of conditionally essential amino acid? J. Pediatr. Gastroenterol. Nutr. 2:S266-S271. Hill, D.E. 1984. Experimental alteration of fetal growth in animals. Mead Johnson Symp. Perinat. Dev. Med. 23:29-36. Hytten, F.E., and I. Leitch. 1971. The Physiology of Human Pregnancy, 2nd ed. Blackwell Scientific Publications, Oxford. 599 pp. Jackson, ~A. 1987. Measurement of protein turnover during pregnancy. Hum. Nutr.: Clin. Nutr. 41C497-498. Johnstone, F.D., D.M. Campbell, and I. MacGillivray. 1981. Nitrogen balance studies in human pregnangy. J. Nutr. 111:1884-1893. Kelly, H.J., R.E. Sloan, W. Hoffman, and C. Saunders. 1951. Accumulation of nitrogen and six minerals in the human fetus during gestation. Hun~. Biol. 23:61-74. Kennedy, E.T., and M. Kotelchuck. 1984. The effect of WIC supplemental feeding on birth weight: a case-control analysis. Am. J. Clin. Nutr. 40:579-585. Lechtig, A., J.P. Habicht, H. Delgado, R.E. Klein, C. Yarbrough, and R. Martorell. 1975. Effect of food supplementation during pregnancy on birthweight. Pediatrics 56:508-520. Lechtig, A., R. Martorell, H. Delgado, C. Yarbrough, and R.E. Klein. 1978. Food supplementation during pregnancy, maternal anthropomet~y and birth weight in a Guatemalan rural population. J. flop. Pediatrics. 24:217-222. Lederman, S.N, and P. Rosso. 1980. Effects of protein and carbohydrate supplements on fetal and maternal weight and on body composition in food-restricted rats. Am. J. Clin. Nutr. 33:1912-1916. Lemons, J.A., and R.L. Schreiner. 1983. Amino acid metabolism in the ovine fetus. Am. J. Physiol. 244:E459-E466. Lemons, J.A., E.W. Adcock III, M.D. Jones, Jr., M.A. Naughton, G. Meschia, and F.C. Battaglia. 1976. Umbilical uptake of amino acids in the unstressed fetal lamb. J. Clin. Invest. 58:1428-1434. Marconi, A.M., F.G Battaglia, G. Meschia, and J.W. Sparks. 1989. A comparison of amino acid arteriovenous differences across the liver and placenta of the fetal lamb. Am. J. Physiol. 257:E909-E915.
388 DIETARY INTAKE AND NUTRIENT SUPPLEMENTS McDonald, E.C, E. Pollitt, W. Mueller, A.M. Hsueh, and R. Sherwin. 1981. The Bacon Chow study: maternal nutritional supplementation and birth weight of offspring. Am. J. Clin. Nutr. 34:2133-2144. Meschia, G., F.C. Battaglia, W.W. Hay, and J.W. Sparks. 1980. Utilization of substrates by the ovine placenta in viva. Fed. Proc., Fed. Am. Soc. Exp. Biol. 39:245-249. Metooff, J., P. Costiloe, WM. Crosby, S. Dutta, H.H. Sandstead, D. Milne, C.E. Bodwell, and S.H. Maprs. 1985. Effect of food supplementation (WIC) during pregnancy on birth weight. Am. J. Clin. Nutr. 41:933-947. Mora, J.O., B. de Paredes, M. Wagner, Lo de Navarro, J. Suescum, N. Christiansen, and M.G. Herrera. 1979. Nutritional supplementation and the outcome of pregnancy. I. Birth weight. Am. J. Clin. Nutr. 32:455-462. Mulvihill, SJ., A. Albert, ~ Synn, and E.W. Fonkalsrud. 1985. In utero supplemental fetal feeding in an animal model: effects on fetal growth and development. Surgery 98:500-505. NRC (National Research Council). 1989. Recommended Dietary Allowances, 10th ed. Report of the Subcommittee on the Tenth Edition of the RDAs, Food and Nutrition Board, Commission on Life Sciences. National Academy Press, Washington, D.C. 284 PP. Pond, W.G., J.T. Yen, and L^H. Yen. 1988. Body weight deficit in the absence of reduction in cerebrum weight and nucleic acid content in progeny of swine restricted in protein intake during pregnancy. Proc. Soc. Exp. Biol. Med. 188:117-121. Rosso, P. 1977a. Maternal-fetal exchange during protein malnutrition in the rat. Placental transfer of ct-amino isobutyric acid. J. Nutr. 107:2002-2005. Rosso, P. 1977b. Maternal-fetal exchange during protein malnutrition in the rat. Placental transfer of glucose and a nonmetabolizable glucose analog. J. Nutr. 107:2006 2010. Rosso, P. 1980. Placental growth, development, and function in relation to maternal nutrition. Fed. Proc., Fed. Am. Soc. Exp. Biol. 39:250-254. Rosso, P., and M.R. Streeter. 1979. Effects of food or protein restriction on plasma volume expansion in pregnant rats. J. Nutr. 109:1887-1892. Rush, D., Z. Stein, and M. Susser. 1980. A randomized controlled trial of prenatal nutritional supplementation in New York City. Pediatrics 65:683-697. Rush, D., A. Kristal, C. Navarro, P. Chauhan, W. Blanc, R. Naeye, and M.W. Susser. 1984. The effects of dietary supplementation during pregnancy on placental morphology, pathology, and histomorphometIy. Am. J. Clin. Nutr. 39:863-871. Rush, D., N.L. Sloan, J. Leighton, J.M. Alvir, D.G. Ho~vitz, W.B. Seaver, G.C. Garbowski, S.S. Johnson, R.^ Kulka, M. Halt, J.W. Devore, J.T. Lynch, M.B. Woodside, and D.S. Shanklin. 1988. The National WIC Evaluation: evaluation of the Special Supplemental Food Program for Women, Infants, and Children. V. Longitudinal study of pregnant women. Am. J. Clin. Nutr. 48:439-483. Schneider, H., K.H. Mohlen, and J. Dancis. 1979. Transfer of amino acids across the in vitro perfused human placenta. Pediatr. Res. 13:236-240. Smith, C.H. 1986. Mechanisms and regulation of placental amino acid transport. Fed. Proc., Fed. Am. Soc. Exp. Biol. 45:2443-2445. Soltesz, G., D. Harris, I.Z. Mackenzie, and ~ Aynsley-Green. 1985. The metabolic and endocrine milieu of the human fetus and mother at 18-21 weeks of gestation. I. Plasma amino acid concentrations. Pediatr. Res. 19:91-93. Sparks, J.W 1984. Human intrauterine growth and nutrient accretion. Semin. Perinatol. 8:74-93. Sparks, J.W., J.R. Girard, S. Callikan, and F.C. Battaglia. 1985. Growth of fetal guinea pig: physical and chemical characteristics. Am. J. Physiol. 248:E132-E139. Sturman, J.A., AD. Gargano, J.M. Messing, and H. Imaki. 1986. Feline maternal taurine deficient: effect on mother and offspring. J. Nutr. 116:655-667. Viegas, O.A.C., P.H. Scott, TO. Cole, P. Eaton, P.G. Needham, and B.A. Wharton. 1982a. Dietary protein energy supplementation of pregnant Asian mothem at Sorrento, Birmingham. I. Unselective during second and third trimesters. Br. Med. J. 285:589- 592.
PROTEIN AND AMINO ACIDS 389 Viegas, O.A.C., PH. Soott, T.J. Cole, P. Eaton, P.G. Needham, and B.A Wharton. 1982b. Dietary protein energy supplementation of pregnant Asian mothers at Sorrento, Birmingham. II. Selective during third trimester only. Br. Med. J. 285:592-595. Visek, W3. 1986. Arginine needs, physiological state and usual diets. A reevaluation. J. Nutr. 116:36-46. W~ddowson, E.M., and J.W.T. Dickerson. 1964. Chemical composition of the body. Pp. 1-247 in CL. Comar and F. Bronner, eds. Mineral Metabolism: An Advanced Treatise. Vol. II, The Elements, Part A. Academic Press, New York. Wohlleb, J.G, E. Pollitt, W.H. Mueller, and R. Bigelow. 1983. Ibe Bacon Chow study: maternal supplementation and infant growth. Early Hum. Dev. 9:79-91. Yudilevich, D.L., and J.H. Sweiry. 1985. Transport of amino acids in the placenta. Biochim. Biophys. Acta 822:169-201. Ziegler, E.E., ~M. O'Donnell, S.E. Nelson, and S.J. Fomon. 1976. Body composition of the reference fetus. Growth 40:329-341.