The Journal of Nutrition Vol. 128 No. 10 October 1998, pp. 1688-1691

Increased Height Gain of Children Fed a High-Protein Diet during Convalescence from Shigellosis: A Six-Month Follow-Up Study^1,2

Iqbal Kabir³, Mohammad M. Rahman, Rukhsana Haider, Ramendra N. Mazumder, Mohammed A. Khaled, and Dilip Mahalanabis

International Centre for Diarrhoeal Disease Research, Bangladesh (ICDDR,B) Dhaka 1000, Bangladesh

	ABSTRACT

Abstract Introduction Methods Results Discussion References

The impact of dietary supplementation on catch-up growth was evaluated in 69 malnourished children ages 24-60 mo after recovery from shigellosis. They were fed either a high-protein (HP) diet with 15% of energy as protein, or a standard-protein (SP) diet with 7.5% energy as protein, for 3 wk in a metabolic study ward. Children were followed up bi-weekly for 6 mo by trained health assistants when anthropometric measurements and information of any illness were collected. Thirty-one children in the HP group and 28 children in the SP group completed 6-mo follow-up. The increase in height (mean ± SD) was 5.3 ± 1.0 cm vs. 4.1 ± 1.1 cm for HP and SP groups, respectively (P < 0.001), whereas increase in body weight was 1.39 ± 0.58 and 1.29 ± 0.72 kg for children fed HP and SP, respectively (P = 0.59). The proportion of children who were severely stunted (< 2 SD height-for-age) decreased from 45 to 29% in the HP group compared to 50 to 46% in the SP group (P < 0.05) at 6-mo follow-up. The number of diarrheal episodes per child tended to be lower in the HP vs. SP than in the SP group (1.9 vs. 2.3, P = 0.41). These results demonstrate that feeding an HP diet to the malnourished children during recovery from shigellosis enhanced linear growth with a modest reduction in diarrheal morbidity during the 6-mo follow-up period.

	INTRODUCTION

Abstract Introduction Methods Results Discussion References

In many third world countries 30% or more children under 5 y of age may be diagnosed as malnourished on the basis of low height, or length, for their age, based on international standards (Waterlow 1994). Stunting is not only very common, it has important social implications since it is widely regarded as an index of poverty. Stunting occurs primarily in the first 2 to 3 y of life and is a reflection of the interactive effects of poor energy and nutrient intake, and infections.

Growth faltering of children as a consequence of diarrheal diseases was studied in Bangladesh. Dysentery due to Shigella sp. had a significant negative effect on linear growth, whereas, diarrhea due to Escherichia coli had a negative effect on weight faltering in children (Black et al. 1984, Henry et al. 1987). The reason for this stunting may be partly explained by the severe nature of infection in shigellosis. In addition to loss of appetite, malabsorption of nutrients, and vomiting are common in most diarrheal diseases; children with shigellosis also have high fever leading to increased catabolism, loss of blood and serum protein through the inflamed intestine (Scrimshaw 1977). Because many children in the developing countries suffer from malnutrition, severe infection such as shigellosis is likely to worsen their nutritional status. It is, therefore, important and necessary to enhance catch-up growth of children by supplementing additional energy and protein during recovery from diarrhea.

We showed earlier that feeding a high-protein (HP)⁴ energy diet for 21 d to children recovering from dysentery resulted in significant weight and height gain (Kabir et al. 1993), but we did not know if this increment would be sustained when children were given their regular home diet. This paper reports the effect of the supplementation on growth and morbidity in the same children during the 6-mo follow-up period.

	SUBJECTS AND METHODS

Abstract Introduction Methods Results Discussion References

Subjects.  This study was conducted at the International Centre for Diarrhoeal Disease Research, Bangladesh (ICDDR,B) Hospital in Dhaka, which provides treatment to approximately 100,000 patients annually. Nonbreastfed children ages 24-60 mo with a history of passing bloody mucoid stools for less than 5 d were selected for the study. If the stool microscopic examination showed red blood cells and pus cells >20 per high-power field and stool culture grew Shigella sp., parents' consent was taken and the children were enrolled in the study.

Treatment.  All the children were treated with nalidixic acid (55 mg·kg¹ d¹) in four divided doses for 5 d except those infected with a Shigella sp. resistant to this drug were treated with pivmecillinam (60 mg·kg¹ d¹) in four divided doses for 5 d. A standard hospital diet, based on milk and rice powder, and containing 40 g whole milk powder, 40 g rice powder, 25 g sugar, 25 g soybean oil, 0.5 g magnesium chloride, 1.5 g potassium chloride, 2 g calcium lactate, per liter was fed to both groups of children during the first 5 d.

Randomization.  After 5 d of treatment with an effective antibiotic, the patients were randomly allocated to receive an HP diet or a standard-protein (SP) diet by using a random number table. The randomization was done by a person who was not otherwise directly involved with treatment or anthropometric evaluation of the subjects. A sealed envelope containing treatment allocation was opened just before the entry of each subject to the study.

Diet.  The details of dietary composition have been described elsewhere (Kabir et al. 1993). Briefly, children in the HP diet group received bread and egg for breakfast, rice and chicken curry for lunch and supper, and a special milk formulation with soy oil every 2 h between the major meals. This diet provided 15% of total energy as protein. The SP group received bread and sugar for breakfast, rice and lentil for lunch and supper, and a milk-rice powder-based formula every 2 h to provide 7.5% of energy as protein. These diets were fed to the subjects for 21 d in a metabolic study ward. Following this feeding, the subjects were discharged from the hospital, and the parents were asked to feed them their usual diets at home.

Anthropometry and follow-up morbidity.  Children were weighed daily at a scheduled time, each morning for 21 d in the metabolic study ward on a weighing scale (Detecto Scale Co., Brooklyn, NY) with a precision of 20 g. Length was measured to the nearest 1 mm on a locally made length board. Children's parents were then asked to bring their children for a follow-up every 15 d for 6 mo and to report the occurrence of diarrhea, fever, cough and other illnesses during the previous 15 d. Each child was assigned to one trained health assistant who was responsible for obtaining anthropometric measurements and recording them on a precoded data form for that child until the study was over.

Statistical analysis.  Data were entered into a microcomputer with a StatPac Gold package (Walonick Associates, Minneapolis, MN) and were analyzed with the SPSS/PC⁺ statistical package (SPSS Inc., Chicago, IL). For normally distributed data, Student's t test was applied and for nonnormal distribution, a nonparametric test (Mann-Whitney U test) was used. An NCHS package (NCHS, Center for Disease Control, Atlanta, GA) was used for anthropometric calculations.

	RESULTS

Abstract Introduction Methods Results Discussion References

Thirty-one children in the HP group and 28 children in the SP group completed 6-mo follow-up. Five children in each group were lost on follow-up due to migration. However, their physical and clinical characteristics were similar to those who completed the follow-up.

The baseline characteristics of the study children are shown in Table 1. The mean age, body weight, length and nutritional status of the children did not differ between groups.

The mean energy intake was 588 kJ·kg¹·d¹ (95% CI, 578-603 kJ) for HP children and 603 kJ·kg¹·d¹ (95% CI, 586-620 kJ) for SP children. The mean protein intake was 5.2 g·kg¹·d¹ (95% CI, 5.26-5.5 g) and 2.3 g·kg¹·d¹ (95% CI, 2.55-2.77 kg) for HP and SP children, respectively. The dietary zinc (mean ± SD) intake was 5.72 ± 1.22 mg·kg¹·d¹ and 2.92 mg·kg¹·d¹, and the dietary iron intake was 6.34 ± 2.3 mg·kg¹·d¹ and 3.96 ± 1.04 mg·kg¹·d¹, for HP and SP children, respectively. Serum zinc concentration <14.0 µmol/L was found in 62% of the HP group compared to 54% of the SP group.

Table 2 shows the changes in body weight, height, weight-for-age, height-for-age and other nutritional variables in the two groups. Even though the mean increase in body weight was not significantly different between the groups, the height increment was significantly higher in the HP group (P < 0.001). The changes in nutritional status were calculated as SD score (Z-score) of study children at 6-mo follow-up. There were no significant differences in Z-score values of weight-for-age and weight-for-height between the HP and the SP groups. However, the changes in Z-score values in height-for-age were significantly greater in the HP group compared with the SP group (P < 0.001). These results suggest that the children in the SP group remained significantly stunted at 6 mo when compared with the children in the HP group.

Figure 1 shows the monthly increment in the heights of children in the HP and SP groups compared with the monthly increment in the 50th percentile of the NCHS curve. The monthly height increment (growth velocity) of children in the HP group was significantly greater than of those in the SP group (P < 0.05). The monthly height increment in the HP group exceeded the rate of height increment according to the NCHS median values of children of that age group.

View larger version (12K): [in this window] [in a new window]   Fig 1. Cumulative height increment of children fed a high-protein and standard protein diet and comparison with NCHS median. The rate of height gain was significantly higher in the high-protein (HP) group at all points (monthly) compared to standard-protein (SP) group (P < 0.01).

The number of children who were severely stunted (< 2 SD height-for-age) was calculated before intervention and at the 6-mo follow-up. The proportion of children who were severely stunted decreased from 45 to 29% in the HP group, whereas it decreased from 50 to 46% in the SP group at 6 mo.

Table 3 shows the disease morbidity of the HP and the SP groups over the 6-mo period. The number of diarrheal episodes was 1.9 per child in the HP group compared to 2.3 per child in the SP group during the 6 mo (P = 0.41). The average number of febrile episodes was 2.5 and 2.8 per child (P = 0.42), and respiratory tract infection episodes were 3.9 and 4.3 per child, (P = 0.37) for the HP and SP groups, respectively. Overall, 19% fewer diarrheal episodes occurred in the HP group, suggesting improved nutritional status protects against diarrhea.

	DISCUSSION

Abstract Introduction Methods Results Discussion References

The results of this study show that children who were fed an HP diet in the hospital during recovery from shigellosis maintained a significantly larger growth in height during the following 6 mo. No significant difference in the rate of weight gain between the HP and the SP groups existed. The rate of height increment, on the other hand, exceeded the 50th percentile of NCHS median for children in this age group. This has been observed in other studies where accelerated weight and height gain rates have been documented in severely malnourished children during catch-up period (Ashworth 1979, Varma et al. 1984).

The overall rate of catch-up growth and weight gain during recovery from malnutrition is determined by the metabolizable energy intake, but for any given energy intake the relative proportions of deposited fat or lean tissue will be determined in part by the ability to synthesize lean tissue. Suggestions have been made that limited gain in lean tissue reflects an inappropriate intake of protein either in quality or quantity (MacLean and Graham 1980).

The results of our study indicate that protein is a key factor in determining growth in height. Similar results have been reported from studies of New Guinea school children who were fed an HP diet (Lampl et al. 1978) where height gain was directly related to the quantity of supplementary protein, while addition of fat in the diet did not result in any protein-sparing effect. Similarly, several other studies from Colombia, Mexico and Peru have shown that diarrhea-associated linear growth retardation could be prevented by supplementing the children with a protein-energy rich diet (Lutter et al. 1989).

Growth in children seems to occur in spurts often after infection or disease (Ashworth 1979). During those periods of rapid catch-up, children may grow at twice or more the normal rate when protein requirement is consequently increased (Torres et al. 1994). The reasons for sustained height increment in our study children during the follow-up period are perhaps due to the growth spurt that occurs during the convalescence period by supplementation and is later maintained. Possibly protein supplementation results in earlier recovery of gut mucosa and better absorption of energy and protein (Kabir et al. 1994). Similar phenomena have been observed in patients with inflammatory bowel diseases, where positive nitrogen balance, weight gain and increased linear growth occurred after providing the energy and protein requirements for growth (Grand et al. 1977).

Both the quality and quantity of protein are important for growth, although it is not clear which component of the diet is critical for linear growth (Allen et al. 1992). In our study, the major source of dietary protein in the HP diet was animal products (milk, egg, chicken), providing essential amino acids.

The role of sulfur as an essential nutrient for skeletal growth is emphasized. Most diets in third world countries are very low in sulfur (Simmons 1971), and further loss caused by excess mucus production may explain why diseases of the large intestine and trichuriasis seem to be associated with severe stunting (Cooper et al. 1990, Golden 1994). Therefore, the children in our study who lost mucus and blood were also possibly sulfur-deficient. Supplementing children with animal protein containing sulfur might enhance their skeletal growth.

Reports are inconsistent in the literature of the growth-promoting benefits of single nutrients probably because several nutrient deficiencies occur simultaneously in growth-stunted children. In our study, children in the HP group received almost twice the amount of dietary zinc, calcium, iron and vitamin A of those receiving the SP diet. A beneficial effect of zinc supplementation on weight gain of malnourished children has been demonstrated, but not an effect on height gain (Castillo-Duran et al. 1987, Golden et al. 1989, Schlesinger et al. 1992). Few studies showed height gain after zinc supplementation in severely marasmic children (Schlesinger et al. 1992, Behrens et al. 1990). In our study, however, the serum zinc concentration was similar in the groups (Kabir et al. 1993).

While the effect of HP dietary supplementation on linear growth of children recovering from shigellosis is obvious, its impact on diarrhea and respiratory tract infection was not marked perhaps due to the small sample size. Nevertheless, there was a 19% lower incidence of diarrhea in the children fed an HP diet during convalescence. Fewer diarrheal episodes in these children may have resulted in a constant growth rate compared to the children in the SP group.

The implications of the above study's results are important. Supplementation with an HP energy diet during convalescence from shigellosis sustains linear growth. In acute shigellosis, children often have severe anorexia which limits food intake (Rahman et al. 1992). Therefore, it is reasonable to provide extra energy and protein during convalescence when appetite returns. Diarrheal morbidity can also be reduced, likely due to improvement of nutritional status of the supplemented children.

One of the major limitations of this study is that the diet containing animal protein such as milk, chicken and egg fed to the children in the HP group may not be affordable by the underprivileged community in most developing countries. Further research is therefore required to evaluate locally available inexpensive plant-protein-based diets for catch-up growth in children with shigellosis.

	FOOTNOTES

Manuscript received 27 May 1997. Initial reviews completed 9 August 1997. Revision accepted 15 June 1998.

	ACKNOWLEDGMENTS

This study/publication was funded by the United States Agency for International Development (USAID) under grant no. DPE-5928-A-00-6002-00 with the International Centre for Diarrhoeal Disease Research, Bangladesh (ICDDR,B). The ICDDR,B is supported by the aid agencies of the Governments of Australia, Bangladesh, Belgium, Canada, Japan, The Netherlands, Norway, Saudi Arabia, Sri Lanka, Sweden, Switzerland, the United Kingdom and the United States; international organizations including Arab Gulf Fund, Asian Development Bank, European Union, the United Nations Children's Fund (UNICEF), the United Nations Development Programme (UNDP), the United Nations Population Fund (UNFPA), the World Health Organization (WHO), and the International Atomic Energy Agency (IAEA); private foundations including Aga Khan Foundation, Child Health Foundation (CHF), Ford Foundation, Population Council, Rockefeller Foundation, Thrasher Foundation and the George Mason Foundation; and private organizations including East West Inc., Helen Keller International, Lederle & Praxix, New England Medical Centre, Procter Gamble, RAND Corporation, Social Development Center of Philippines, Swiss Red Cross, the Johns Hopkins University, the University of Alabama at Birmingham, UCB Sidac, Wander A.G. and others.

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