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.

TABLE 19-1

Factorial Estimate of Protein Components of Weight Gain in a Normal Full-Term Pregnancy.

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.

Amino Acid Utilization

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.

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 species have formed the basis estimation of protein accretion in the fetus. Hytten and Leitch (1971) reviewed classic studies of human body composition (Kelly et al., 1951; Widdowson and Dickerson, 1964) and estimated fetal protein requirements to be approximately 440 g over the course of pregnancy and the placental protein requirement to be an additional 100 g (Table 19-1). Other reviewers, using much of the same published data on humans, estimated a nitrogen accumulation of 50 to 60 g for 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 differences 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 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 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.

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 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 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.

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 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.

Supplementation Studies

A large body of literature documents the results of protein supplementation 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 studies, 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 Columbia, investigators examined the effect of a supplement containing 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 (Mora 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 Women 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 significant decreases in both gestational length and birth weight and marginally significant increases in mortality and preterm birth rate with high-density 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, compared 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 effects 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 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.

To 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 durations; 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-protein 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 powders) is not recommended during pregnancy.

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Footnotes

*

An average WIC package for pregnant women provides 90 to 1,000 kcal of energy and 40 to 50 g of protein daily.