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Results and Implications of the INCAP follow-up study(╣,▓)


Literature cited


REYNALDO MARMOREAL│

Department of International Health, The Rollins School of Public Health of Emory University, Atlanta, CA 30322

╣ Presented in the symposium on Nutrition in Early Childhood and its Long-term Functional Significance, FASEB, April 6, 1992, Anaheim, CA. Published as a supplement to The Journal of Nutrition. Guest editors for this supplement publication are Reynaldo Martorell, The Rollins School of Public Health of Emory University, Atlanta, GA and Nevin Scrimshaw, The United Nations University, Boston, MA.

▓ Supported by NIH grant number HD22440.

│ To whom correspondence should be addressed: Department of International Health, The Rollins School of Public Health of Emory University, 1518 Clifton Road, N.E., Atlanta, GA 30322

ABSTRACT This article is a critical synthesis of 12 papers included in this supplement. The set deals with the short- and long-term effects of improving nutrition in Cuatemalan villages characterized by deficient diets, high rates of infection and pronounced growth retardation in the first 3 y of life. The data reviewed come from two studies carried out over two decades: the Institute of Nutrition of Central America and Panama (INCAP) longitudinal study (1966 - 1977) and its followup (1988-1989). The longitudinal study included a nutrition intervention that improved the energy and nutrient intakes of women and preschool children. Its effects included improved birthweights, reduced infant mortality rates and improved growth rates in children<3 y of age. Growth rates from 3 to 7 y of age, similar to those of wellnourished children, were not affected by the intervention. The follow-up study was conducted when the subjects were 11-27 y old. Among the long term effects found were greater stature and fat-free mass, particularly in females, improved work capacity in males and enhanced intellectual performance in both genders. The nutrition intervention did not, on the other hand, accelerate maturation during adolescence, as measured by skeletal age or age at menarche. It is concluded that improved nutrition in early childhood has important long-term effects in the adolescent and adult. J. Nutr. 125: 1127S-1138S, 1995.

INDEXING KEY WORDS:

• nutritional
• supplementation• adolescence
• malnutrition
• growth and development

This article is an overview of papers included in this volume, with emphasis on the main findings and policy implications of the Institute of Nutrition of Central America and Panama (INCAP) follow-up study (1988-89). A previous set in the Food and Nutrition Bulletin (Vol. 14, number 3, 1992) concentrated on the study which preceded the follow-up, namely the INCAP longitudinal study (1969-77).

To provide readers with the context necessary to interpret the findings of the follow-up study, the first three papers of this volume (Habicht et al.1995, Martorell et al. 1995a, Schroeder et al. 1995) present essential information from the earlier INCAP longitudinal study, the next seven papers deal with the follow-up study and the last one is a comparison of our findings to those of the Nutrition Collaborative Research Support Program (ASP) studies (Allen 1995).

This effort is an attempt to provide a critical summary of the findings and is guided by the following questions: What has been learned from the INCAP studies that is important? Are these results believable and internally consistent? What lessons for policies and programs can be drawn from these results? The first section is a discussion of the original INCAP longitudinal study and its results and is followed by sections dealing with design and analytic issues and with the key findings of the follow-up study. The article ends by addressing the program and policy implications of the results of the INCAP and follow-up studies.

The INCAP Longitudinal Study (1969-77)

The villages. The studies took place in four small villages of eastern Guatemala. When chosen in 1968, two had ~900 inhabitants each and two had ~500 each but had grown to 1,200 and 800 by 1975, respectively. Mean household incomes per year in these villages, where the primary occupation was subsistence agriculture, ranged from US $291 to $463 in 1975. Maternal literacy ranged from 25 to 40% in 1967, and 10 years later, this had risen from 35 to 50%. Although all villages had schools when the study began, it was not until around 1980 that instruction up to 6 y of elementary schooling was offered. Electricity became available in the midst of the study in the two small villages and, in the 1980s, in the larger ones. Most families obtained water from wells or rivers and few had latrines. Typical houses were small, one to two rooms, and made of adobe. Driving into these villages was difficult, particularly during the rainy season, but one village close to the highway was more accessible. The dietary staples, as in most of rural Guatemala, were corn and beans, complemented occasionally by small amounts of meat and by fruits and vegetables when in season. Additional details are provided by Bergeron (1992), Engle et al. (1992) and Martorell et al. (1995a) but enough information has been given to illustrate the setting of poverty and rural isolation in which the study took place.

The supplementation program. The longitudinal study was designed to test the hypothesis, in vogue in the 1960s, that malnutrition retards mental development. Researchers operationalized the study as an assessment of the impact of significantly improving protein intakes in mothers during pregnancy and lactation and in children during the first 7 y of life. The treatment was a drink called Atole, rich in high quality protein, the nutrient then thought to be the main constraint to nutrition in developing countries. However, the Atole contributed much more than protein because it is impossible to provide a food-based supplement that is rich in it without simultaneously providing energy, as well as important amounts of some vitamins and minerals. There were additional considerations about the treatment. The researchers feared that the setting in which the Atole was made available, an attractively painted large room with blue tables and chairs set about and with uniformed attendants serving the Atole in brightly colored cups, would be conducive to considerable social interactions among consumers that, in turn, might affect psychological development in the target sample, independent of the nutritional effects of the Atole. Consequently, a protein-free beverage called Fresco was provided under the same set of conditions as the Atole in two villages to serve as control to the two receiving Atole. The careful almost fastidious recording of attendance and amount of supplement provided (subjects were free to drink as many cups as desired, each containing 180 mL) and of the measurement of leftovers was a feature in both Atole and Fresco villages. Attendance and consumption records were kept for pregnant and lactating women and for children (7 y; although all villagers were free to attend, the participation of men, older women and children >7 y old was unrecorded.

Four villages were selected in 1969 for the study. The pair of large villages was randomized to receive Atole or Fresco, as was the pair of small villages. Although great care was taken to choose pairs of villages that were similar to each other, important differences existed then or surfaced later in nutrition and health as well as in social, educational and demographic conditions, but these differences do not favor any village systematically; rather, there is considerable variability in the comparative rankings by village depending upon the aspect considered (Bergeron 1992, Engle et al. 1992, Martorell et al. 1995a).

The Fresco was devoid of protein and because empty calories were thought to be potentially harmful, it contained only enough sugar and flavoring to make a palatable refreshing drink. A number of vitamins (thiamin, riboflavin, niacin, vitamin A, ascorbic acid) and minerals (iron, fluoride) were added to the Fresco early in the study to make its composition similar to that of the Atole except with regard to protein; the obvious differences in terms of energy, which favored the Atole, were not thought to be nutritionally significant at the time. The Atole, but not the Fresco, also contained calcium and phosphorus, as well as other nutrients whose presence hers gone unrecognized in publications about the study, such as zinc, vitamin B - 6, folacin and B - 12 (Allen 1995). The content per cup of the Atole was 11.5 g of protein and 163 kcal/682 kJ per cup l 180 mL) and of the Fresco was 0 g protein and 59 kcal/247 kJ per cup. Both the Atole and Fresco drinks were similar to local preparations and both were liked, but patterns of intake differed. In mothers, attendance was similar but the Fresco was consumed, on a volume basis, at about twice the rate of the Atole (Delgado et al. 1982). This is understandable in that the Fresco was light and thirst quenching and the Atole was thick and served hot. Patterns in children were much different (Schroeder et al. l 992). Attendance below 3 y of age was greater in Atole villages as was the volume consumed; after 3 y, attendance was similar but the volume consumed was greater in Fresco villages (Fig.1, Fig. 2).

FIGURE 1 Attendance of participants at the feeding center (percentage of days in interval) by age and village. From Schroeder et al. 1992.

FIGURE 2 Mean volume of supplement consumed per day by age and village (nonparticipants included). From Schroeder et al. 1992.

The nature of the intenrention. What was the nature of the intervention? l his can be answered in

the narrow sense in terms of improvements in nutrient intakes in mothers and children. In mothers, average intakes of energy from the supplements during the entire pregnancy were 107 kcal/448 kJ per day in Atole villages and 81 kcal/339 kJ per day in Fresco villages (Delgado et al. 1982). Thus, the greater consumption of the Fresco nearly made up for its lower energy concentration. Average daily protein intakes from the Atole were ~7.5 g; the Fresco had no protein. Intake of a number of vitamins and minerals common to both drinks was about twice greater in Fresco villages, because Fresco was consumed that much more and the concentration was similar in Atole and Fresco villages. The rate of replacement of home diet is not known with precision but is estimated to have been 22% for energy (Habicht et al 1995).

In children 15-36 mo, average total energy intakes per day (i.e., home diet and supplement combined were greater in Atole compared with Fresco villages by ~ 101 kcal/423 kJ in boys and 89 kcal/372 kJ in girls; this is equivalent to ~ 1.1% of the total intake in Fresco villages. Comparisons of total intake of protein favored Atole boys by 8.6 g and Atole girls by 8.8 g, equivalent to ~ 40% of the intake in Fresco villages (Table 1). Children in Atole villages, because they ingested significantly greater volumes of supplement from 15 to 36 mo of age than children in Fresco villages did (Fig. 2), also had significantly greater intakes of many vitamins and minerals.

TABLE 1 Contribution of the supple(nments to total energy and protein intakes in children 15-36 mo of are'

 

Males

Females


Atole (n = 128)

Fresco (n = 135)

Atole (n = 118)

Fresco (n = 104)

Pooled SD

Energy, kcal/d






Home diet

785

814

718

756

213

Supplement

156

26a

150

23a

79

Total Intake

941

840a

868

779b

226

Energy, kj/d






Home diet

3,284

3,406

3,004

3,163

891

Supplement

653

109a

628

96a

331

Total Intake

3,937

3,515a

3,632

3,259b

946

Protein, g/d






Home diet

20.1

22.5

19.3

21.0

5.9

Supplement

11.0

0.0a

10.5

0.0a

5.4

Total Intake

31.1

22.5a

29.8

21.0a

7.5

╣ Home diet values are averages of as many as eight recall surveys conducted at 15 mo and every 3 mo thereafter until 36 mo (adapted from Martorell, 1982).

aP<0.001.
bP<0.01.

The preceding makes it clear that the intent in 1969 of creating a contrast between village types in terms of protein was realized but along with other effects. Supplement intakes during pregnancy in Atole women were improved substantially in terms of protein, but both Atole and Fresco women received nearly similar amounts of energy from the supplements and the Fresco group ingested greater amounts of a number of vitamins and minerals. In children <3 y of age, intakes of protein were increased in Atole villages but so were those of energy, vitamins and minerals. In children 37 y of age, protein intakes were increased in Atole villages, but despite the greater volume of Fresco consumed as children got older, the energy consumed from the Fresco was still less than that from the Atole, but the gap narrowed considerably as children neared 7 y of age (Fig. 3). Finally, the contribution from the supplements of those vitamins and minerals found in equal concentrations in both drinks was greater from Fresco than from Atole after ~4 y of age when more of the Fresco began to be consumed.

FIGURE 3 Mean energy intake per day from supplement by age and supplement type (with and without nonparticipants). From Schroeder et al. 1992.

Was the Fresco, as originally intended, an adequate control for the socialization effects that might result from the social interaction at the feeding centers? The answer appears to be a qualified yes in that patterns of attendance were similar in Atole and Fresco villages in the case of pregnant women and older children but not in young children. Fortunately, attendance and consumption of supplement were measured, permitting researchers to control for participation in contrasting Atole and Fresco communities, particularly important in the analyses of behavioral outcomes (Pollitt et al. 1995). Living closer to the feeding center and being from a larger family predicted participation in children in both village types; however, children of poorer families had greater participation in the supplementation program only in Atole villages (Schroeder et al. 1992). Failure to control for socioeconomic status in analyses of the relationship between Atole intake and outcomes might therefore bias the results against the hypothesis that consumption leads to improved status.

In addition to the supplementation program, INCAP established a medical care program in all four communities (Martorell et al. 1995a). These services were provided by auxiliary nurses under the careful supervision of a physician. A range of curative services, with appropriate referral in case of complications, was given. Also, periodic examinations during the prenatal period and during early childhood were carried out. Vaccines were administered in these visits. These efforts, although important, fell short of the ideal in that community nutrition and health education were not provided outside the context of medical care visits. Also, there were no programs implemented in environmental sanitation, formal education or economic development.

Finally, another component of the intervention, the very presence of INCAP investigators asking questions and examining women and children, must have had some unspecified effects, but these, because of careful rotation among personnel and similar research activities in all four villages, cannot bias the comparison of Atole and Fresco villages (Habicht et al. 1995).

In summary, the nature of the intervention is a contrast between villages receiving different types of supplements but identical medical services and similar but unintended effects of having a research team present for about 8 years. In children 15-36 mo of age, exposure to different supplements increased total energy intakes by 1.1% and total protein intakes by 40% in Atole villages relative to Fresco villages. Also, total intakes of many vitamin and minerals also were substantially greater in Atole compared with Fresco villages. Because of the uncertainty about the energy requirements of children, it is impossible to say how far the extra 100 kcal/4 18 kJ per day went toward meeting needs, but it is unlikely that adequate levels were reached. Average energy intakes of Atole and Fresco children, combining home diet and supplement, were ~93 and 83 kcal/kg (389 and 347 kJ/kg) at 24 mo of age, respectively, compared with estimated requirements of ~110 kcal/kg (460 kJ/kg) given by FAO/WHO/UNU (1985). This would mean that children in Atole and Fresco villages had intakes equivalent to 85% and 75%, respectively, of the requirement. Allowancesances for catch-up growth, usually taken into account by using ideal rather than actual body weights, would of course increase the apparent energy gap substantially. For protein, on the other hand, average intakes exceeded allowances even before considering the contribution of the Atole; average total protein intakes were 3.1 and 2.2 g/kg in Atole and Fresco villages compared with the safe level of 1.8 g/kg at 24 mo of age (adjusted conservatively for an amino acid score of 60 and a digestibility score of 85).

Approachs to analyses., A meta-analysis of nutrition interventions during pregnancy and birthweight excluded the findings of the INCAP longitudinal study from all consideration (Kramer, 1993). The reason given was that the analyses were not carried out according to the randomized design.

The randomized design calls for village to be the unit of analysis. Because the comparison of village means involves only two Fresco and two Atole villages, statistical power is extremely low (Habicht et al. 1995). It is doubtful that those who designed the study intended for it to be analyzed in this manner. If the randomized design is used to test for birthweight differences, no effect is found; mean birthweights in Atole are slightly greater than those in Fresco villages, but this small difference is not. statistically significant (3077 + 334 and 3027 + 461 g, respectively; Delgado et al. 1982). As reviewed earlier, the mean intake of energy from the supplements during pregnancy also was slightly greater in Atole than in Fresco villages. It turns out that energy intakes from the supplements, irrespective of whether accompanied by protein, were related to birthweight (Habicht et al. 1995). The similarity in the dose-response relationship in Atole and Fresco samples, when expressed in terms of energy, implies that vitamins and minerals present in both drinks in equal concentrations could not account for the findings. If this were the case, regression coefficients would be more than twice larger for Fresco, when expressed per units of energy, and similar to those for Atole, when given per units of volume. Thus, because energy turned out to be limiting for birthweight and because both the Atole and Fresco contributed nearly equal amounts of energy during pregnancy, the randomized design became inappropriate.

The reasons for abandoning the randomized design in the analyses of birthweight are justified but the credibility of the results, as exemplified by Kramer's decision to exclude the study, suffers. However, others have given considerable importance to the individual level analyses of supplement intake and birthweight, giving due weight to their internal consistency and the careful efforts to control for confounding. Thus, the finding that 20,000 kcal/83,684 kJ provided during pregnancy will reduce the prevalence of low birthweight by half (Lechtig et al. 1975) has helped to justify maternal nutrition programs worldwide.

The randomized design is used by Habicht et al. (1995) to analyze the effects of exposure to Atole on attained lengths at 3 y of age. Baseline values of length at 3 y of age in 1968 (before the study) are used to estimate, for each of the four villages, the differences in length with respect to values for children born after the study began in 1969. Using village means, Habicht et al. l 19951 estimated that the Atole sample grew ~ 2.5 cm more than children in Fresco villages (P<0.005, df = 2). This may be a conservative estimate of the impact of Atole because children in Fresco villages grew ~0.5 cm more compared with baseline values, perhaps because of the small amounts of energy and other nutrients received from the Fresco and/or because of the medical care program, among other possible reasons. It should be noted that the small degree of change in Fresco villages implies that the medical care program and energy supplementation during pregnancy appear to have had little impact on post natal growth.

An extension of the randomized design also has been used by Martorell (1992) in examining time trends in severe stunting (i.e., lengths that are >3 SD below the reference mean) in Fresco and Atole villages. The prevalence of severe stunting was ~45% in both Atole and Fresco villages at the beginning of the study in 1969 and declined at the end of the study, in 1976-77, to <20% in Atole villages but remained at about the same level in Fresco villages. A logistic regression of trends by village with treatment, sex and year as independent variables and village as the unit of analysis showed a statistically significant decline only in Atole villages (P<0.01).

Also, a village level analysis has been used in assessing changes in infant mortality, using data collected through retrospective women's life histories (Rose et al. 1992). Relative to baseline levels in 194968, infant mortality rates declined by 66% in Atole villages and by 24% in Fresco villages, but the rates of decline were not significantly different from each other (P>0.05). Data collected in three of the villages considered for selection but not included in the longitudinal study showed a rate of decline of 19% over the same period, presumably reflecting general trends in rural Guatemala. The rates of decline in Atole villages, but not those in Fresco villages, were significantly different (P<0.05) from those observed in these three undistbed villages.

Thus, despite low statistical power, analyses using the randomized design have demonstrated a significant impact of Atole ingestion on physical growth at 3 y of age and on infant mortality. In both these situations we had baseline data available that permitted a before/after design, thereby increasing precision of the estimate of change in each village. We lack baseline data for birthweight (never collected) and for all the psychological variables in the infant and preschool batteries (some data apparently were collected but these cannot be found despite careful searches).

Instead of the randomized design, analyses of the psychological data, as indeed many of those dealing with physical growth, have used the individual as the unit of analysis, which vastly increases statistical power. These analyses are of two types. One compares means in Atole villages to those in Fresco villages, in analyses of covariance that adjust for potentially confounding factors such as socioeconomic status, with the degrees of freedom determined by the number of individuals and the model used. A second type of analysis examines the dose-response relationship between supplement intake and outcomes, controlling for potentially confounding factors.

These analyses do not have the rigor of the randomized design, which incorporates the potential effects of confounding factors in the design (Habicht et al. 1995). Instead, the individual level analyses deal with confounding through the analyses. Although previous analyses of our data almost always have included adjustment for potentially confounding factors, this was necessarily limited to those aspects measured in the study and incorporated in the analysis.

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