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The INCAP follow-up study (1988-89)

Objectives and design. The INCAP follow-up study of 1988-89 was a cross-sectional evaluation of former participants of the INCAP longitudinal study of 1969-77. At the time of the measurement, former participants of the longitudinal study ranged in age from 11 to 27 y. Also included in the follow-up study were subjects of the same age living in three nearby communities that INCAP had identified as potential study sites in the 1960s but which were not chosen in the end (referred to as "comparison" villages).

The main hypothesis of the follow-up study was as follows: Nutritional improvements in the critical period of gestation and the first; three years of life ultimately produce adolescents with a greater potential for leading healthy, productive lives. An equivalent, but briefer statement of the central hypothesis is that "improved nutrition in early childhood leads to enhanced human capital formation".

The richness of the longitudinal study data set allows for several ways of operationalizing improved nutrition in early childhood. Foremost, this can be done relative to the nutrition intervention by classifying subjects as belonging to Atole, Fresco or comparison villages. Also, information about daily attendance and intake of supplement permit estimates to be made of energy and nutrient intakes from supplement over any time period for all individuals. Finally, the study permits many other alternative definitions of childhood nutritional status which are not based on the nutrition intervention but that rely instead on the longitudinal information. available for children. Although not anchored in an experimental design, measures such as growth rate s or degree of stunting, by virtue of being responsive to the full range of factors which influence child health (i.e. diet, infection and their determinants), provide a wider range in nutritional status than measures of supplement. An advantage of anthropometric measures is that they are widely used as indicators of nutritional status and hence are familiar to the international nutrition community.

The central hypothesis of the follow-up study refers to "greater potential for leading healthy, productive lives" in recognition of the fact that productivity, particularly in an economic sense, was not measured as well as potential. Greater potential was operationalized as improved status in terms of measures of physical growth and body composition, maturation, work capacity, information processing, intelligence, functional competence (reading, numeracy, general knowledge) and educational achievement (Rivera et al.1992). Some productivity data were collected; labor participation and earnings were obtained for all subjects for the previous year. Nonetheless, many of the follow-up study subjects, particularly those exposed to supplement during pregnancy and the first three years of life, were too young in 1988-89 to allow for a meaningful exploration of the links between early nutrition and productivity. These aspects can be more adequately studied as the subjects become older and settled into an occupation.

A range of impact was predicted depending upon age at exposure to the nutrition intervention. Maximum effects at follow-up were predicted for subjects born from 1969-1974 (Table 3). These subjects were exposed to supplement during "critical phases" of growth and development, namely pregnancy and the first 3 y of life. The basis for this claim was the greater degree of growth retardation observed at these ages and the lack of demonstrated effect of the supplement on physical growth rates after 3 y of age (Martorell and Klein 1980; Schroeder et al. 1995).

The investigators argued to NIH, the agency that funded the research, that the follow-up study was unique because it was the first long-term, comprehensive follow-up of a nutrition intervention. Specifically, the follow-up study was expected to address whether the benefits of nutrition interventions on growth and development in early childhood persist into adolescence and beyond, to inform about effects and functions that can only be measured later in life and to contribute to understanding the importance of early growth and development for future status. Also, the investigators argued that the policy implications were clear and compelling. The following statement was included in the abstract to the first proposal submitted to NIH:

If valid, it will demonstrate that there are strong linkages among malnutrition, human capital formation and poverty which justify investments in health and nutrition as components of economic development strategies.

In designing the study, the investigators were troubled by two questions: should the study be longitudinal or cross-sectional and should the study be carried out sometime in the future when subjects reach maturity or should the study take place as soon as possible? The limitations of a cross-sectional evaluation were recognized readily. It is well known that the dynamic process of growth and maturation during adolescence can not be adequately studied through a cross-sectional design. Also, important areas such as fertility, employment history and wage earnings are difficult to collect accurately from single interviews. Although a longitudinal design would have provided better data for many outcomes, it would have increased dramatically the complexity and the cost of the study. Cost estimates, even for a cross-sectional survey, were already very high. For these reasons, a cross-sectional approach was selected.

The next question had to do with the timing of the study, when to do it? The study could proceed immediately while the subjects were adolescents or young adults or it could be postponed till most subjects were adults. The advantages of studying adults were recognized. One would be the elimination of the need to control for maturity in the analyses. By virtue of studying adults, information about truly long-term outcomes would be collected and the assessment of effects on fertility, occupation and earnings would be more definitive. Nonetheless, it was decided to proceed as soon as possible even though many subjects were still adolescents, partly to learn about effects on maturity and adolescence but more importantly, because the opportunity to carry out the study existed and it was feared that suitable conditions may not present themselves later. At this time, there was a team of interested researchers in place, enthusiasm was high and funding prospects looked reasonable.

The follow-up study, as noted, included data collection in three comparison villages chosen from six villages considered but not selected for in the longitudinal study in 1969. These villages were of interest because they were presumably similar to the Atole and Fresco and offered the theoretical possibility of shedding light on what might have occurred in the study villages in the absence of INCAP. However, it was not clear why they were not ultimately selected for the longitudinal study. Clearly, they were not felt to be the ideal choices. Still, the decision was made to include three of the previously unselected communities in the follow-up study. To reduce costs and travel time, three of the villages that were closest in distance to the four longitudinal study villages were included for study (i.e., Subinal, Las Ovejas and El Caulote).

Another issue that was carefully considered was that of migration. It was feared that to leave migrants out of the study would leave open the possibility of selection bias. On the other hand, the inclusion of migrants would complicate the logistics of data collection and increase costs. A compromise was reached. Migrants were included but only those who migrated to Guatemala City, Sanarate and El Jicaro (the last two being the provincial towns nearest to the study villages). Tracking down migrants to more dispersed areas, it was felt, would have been too costly.

Subjects studied Census data were collected between October 1 and December 1, 1987 and included general information about the family (e.g., religion, number of family members, characteristics of the dwelling) and about each family member (e.g., birth date, place of birth, migration history, education and occupation). Follow-up data collection took place between May 1988 and June 1989; the census was continuously updated throughout this period. The principal targets of the follow-up study were adolescents and young adults but other groups were studied as well as noted below.

Adolescents and young adults (follow-up cohorts). These subjects were born between January 1962 and February 1977. Records for 2393 children meeting these criteria were generated from a computer master file prepared jointly by Cornell University and INCAP in 1983. Of the 2393 children included in the master file 224 (9.4%) had died when the follow-up study began, for the most part in early childhood. The 2169 subjects alive in 1988 were the target sample in the supplemented villages, a number greater than that given in Table 3 (i.e., 1992) because it includes subjects with no anthropometric measures available from the longitudinal study. The target sample in the three comparison villages (929 individuals) were subjects who had lived in these villages between January 1969 and February 1977, according to information obtained in the 1987 census. The total target sample therefore, including subjects from supplemented and comparison villages, consisted of 3098 subjects. For simplicity, these subjects are referred to hereafter as the "follow-up cohorts". The functional domains measured in the entire follow-up cohorts included physical growth and body composition, maturation, strength, physical health and retrospective life history.

Special sample for the behavioral component. Measures of information processing, intelligence, functional competence and educational achievement were collected on all subjects born in 1966 and later. A large number of outcome variables in the behavioral area were of interest; therefore, the time demands for testing each subject were high. To reduce costs and the duration of the study, the cohorts born between 1962 and 1965 were excluded. These cohorts had received supplementation at noncritical developmental periods (ages 4-7) and thus, minimal effects were expected. Their exclusion was unfortunate because they would have been a useful contrast group to that selected.

Special work capacity sample. This is a sample of ~25% of the follow-up cohorts, excluding migrants, (539 subjects) for whom measurements of work capacity, bioelectrical impedance, bone density and physical activity were obtained. Based on the 1987 census, a stratified random sample of 25% of the follow-up cohorts was selected. Details about the selection of these subjects are provided by Haas et al. (1995).

Parents of follow-up cohorts. Anthropometric measurements of resident parents of the follow-up cohorts were obtained to better interpret growth patterns in the follow-up study cohorts.

A retrospective life history was conducted through interviews of mothers, including those who had migrated to Guatemala City and to the two provincial cities closest to the study villages (Sanarate and El Jicarol.) This information was required to complete the reproductive histories of women for the entire reproductive period and to obtain information about events that took place in the families of the follow-up cohorts between 1977 and 1988, and. that could have influenced the outcomes of interest: at adolescence. All parents were included in the study, irrespective of whether their follow-up cohort child (or children) still lived with them or had formed. an independent family.

Wives of the follow-up cohorts. All wives of the follow-up cohort males, whether or not they were former participants of the INCAP longitudinal study, were interviewed for the collection of retrospective life history information.

Heads of households. All heads of households in which at least one of the spouses or dependents was a follow-up cohort subject were interviewed to obtain information on income and wealth of the family. The sample of households included the newly formed households as well as the parents' households.

Children <5 y of age. Anthropometric measurements were obtained on all children <5 y of age in the seven villages to assess their nutritional status. These data were seen as useful for estimating the degree of secular change in the study villages through comparisons of the results with those collected earlier in children in the longitudinal study.

Tests, exams, measurements and interviews. The tests, exams, measurements and interviews made on the different groups are described briefly below. For a more detailed description of the methods and a presentation of the data forms used see Rivera (1989) and Castro and Rivera (1992).

Follow-up cohorts. The following measurements and examinations were made in the follow-up cohorts:

1) Anthropometric measurements, including height, sitting height, and weight; five body breadths: biacromial, bicristal, knee, elbow and wrist; six circumferences: head, arm, waist, hip, thigh and calf; and seven skinfolds: biceps, triceps, sub scapular, midoxillary, suprailiac, anterior thigh and medial calf. Indirect estimates of body composition (fat-free mass, percent body fat) were obtained using predictive equations from a validation study conducted at INCAP as part of the follow-up study (Conlisk et al.1992).

2) A clinical examination by a physician, including a medical history, a detailed physical examination, the measurement of blood pressure, heart and respiratory rates, body temperature and the assessment of age at menarche (status quo and history). In addition, a vision test was performed and examination for signs of vitamin A deficiency and goiter were made. Abnormalities and diagnoses of diseases were recorded and treatment was provided when needed.

3) A blood sample was collected, that was further used to determine anemia lie and iron status.

4) A hand-wrist X-ray was obtained in males and in nonpregnant females 18 y and younger. The X-rays were later used to assess skeletal age by the Tanner and Whitehouse-2 method of rating. A gravindex test on urine was performed in females 18 y and younger who had reached menarche to identify early pregnancies. Pregnant women were not exposed to X-rays.

5) Hand strength was measured for right and left hands using a dynamometer.

6) Follow-up cohorts were interviewed for the collection of retrospective life history information. Spouses of follow-up subjects also were interviewed. The female retrospective life history included information about current reproductive status, parity and gravidity; a detailed reproductive history (for every pregnancy: pregnancy outcome, newborn birth date, mortality, feeding mode at time of death, prenatal care and delivery care); breast feeding and weaning practices for any child in the last 5 y, contraceptive use, marital/union status and history; education, occupation and migration history; and the characteristics of the dwelling where the women had lived. The male life history included income, occupation, education and migration history as well as some information about accumulated wealth. In addition it contained information about marital/union status, dependents and their ages and sexes.

7) School performance. Information from school records was recorded including: age at first enrollment, grades attended, attendance rate and test scores.

Sample for the behavioral component. Full details about the behavioral data collected are given by Pollitt et al (1993). The following tests were included:

1) Information processing. This test was applied using a microcomputer. Computer programs were designed specifically for the purposes of this study. Test of simple and choice reaction time, a short memory task, and a paired associates test comprised the computerized battery.

2) Tests of functional performance. The battery included tests of literacy, numeracy and general knowledge, which were developed locally, and two standardized educational achievement tests of reading and vocabulary. The achievement tests were part of the Interamerican Series used extensively in Guatemala by faculty from the Universidad del Valle.

3) Intelligence. Intelligence was assessed with the Raven's Standard Progressive Matrices.

Work capacity sample. Physical work capacity was determined as the oxygen consumption at maximum physical e xertion (VO₂max) on a motorized treadmill.

Besides the work capacity test, measurements of bioelectrical impedance and bone density, using photon absorptiometry, were made in the work capacity sample. In addition, physical activity was investigated through a questionnaire.

Parents of follow-up cohorts.

1) Anthropometric data were collected in men and women. Men: height, sitting height, weight, six circumferences (head, arm, waist, hip, thigh and calf) and five skinfolds (biceps, triceps, subscapular, anterior thigh and medial calf). Women: as detailed above for follow-up cohorts.

2) A retrospective life history was completed, identical to the one obtained by interview in follow-up subjects.

3) Heads of households. A detailed questionnaire regarding the family's income during the previous year, as well as accumulated wealth over the years was applied to heads of households. Information obtained included land tenure, crops produced, agricultural inputs (including labor, production and operation costs), time spent in agricultural jobs by crop produced and family member, production, revenue and income from agriculture and other sources and inventory of livestock ownership.

Preschool children. The following anthropometric measurements were obtained: length, crown-rump length, weight, knee breadth, three circumferences (head, arm and calf) and five skinfolds (biceps, triceps, subscapular, midaxillary and medial calf).

Organization and logistics of data collection. Six working teams conducted the tests, exams, measurements and interviews: two focused on the follow-up cohorts, one on parents of the follow-up cohorts, one on children's anthropometry, one on work capacity and one on migrants. Details about the composition of these teams and about coordination and supervision of their work are given in Rivera, Martorell and Castro (1992).

Logistics of data collection. Rotation of teams. The data collection teams were rotated among villages. Also, data collection in each village was staggered over the study to include both rainy and dry seasons.

Program of appointments for follow-up cohorts. The order in which subjects were measured was random. Subjects were scheduled to complete all tests, measurements and interviews in three visits but most subjects chose to complete them in 2 d and in some cases, in 1 d.

Informed consent was followed. When possible, the behavioral tests were done before the medical examination, which involved blood collection, because this procedure caused anxiety in some subjects. When possible, the behavioral tests were spread across visits to avoid fatigue.

Average durations of testing were as follows: Anthropometric measurements, hand-wrist X-rays and hand strength tests (25 min), medical examination and collection of urine and blood samples (25 min), functional competence and intelligence tests (160 min) and life history interview (20 min). In general, subjects tolerated the time involvement in the study better than expected.

Some subjects (3.6% of participants) refused to visit the testing center but were willing to be measured at home where all but X-rays and information processing tests could be completed. In contrast, most of the income and wealth interviews of heads of households and a large number of life history interviews of mothers and anthropometric measurements of parents of follow-up cohorts were made at home, because these subjects had less time to attend the centers.

The teams worked ~8 h/d but schedules were flexible to accommodate the preferred hours of participation of the subjects in each village and season. In all the villages, the teams had to work some weekends to allow for participation of subjects who worked in the fields during weekdays until late in the afternoon, subjects who worked out of the villages and returned during the weekends and migrants who visited their families during the weekends.

Training, supervision and data flow. Training. Training took ~2 mo and rigorous standardization exercises were held in all areas. Technical errors of measurement in anthropometry were equal or better than those reported in the literature (Pareja et al. 1989). For life history and income and wealth questionnaires as well as for functional performance tests, the percent agreement among interviewers usually exceeded 95%. Detailed results of the standardization procedures are given elsewhere (Rivera 1989; Castro and Rivera 1992).

Supervision and quality control. Supervision was continuous. All supervisors spent ³ 2 or 3 d/wk in the field, providing direct supervision to field workers and examining and correcting data collection forms.

Ranges of permissible values in anthropometry were used to detect outliers; then, either obvious errors were corrected or subjects were reexamined. Errors in the behavioral area, the life history and the income and wealth interviews were detected through the review of data forms. In the work capacity area, the supervisors participated directly in data collection. After each test, the team reviewed the results and in this manner detected and corrected obvious errors.

Repeated measurements were made in ~10% of cases in anthropometry and in ~4% of cases in other areas. Analyses of these data are reported in the methods sections of papers in this volume.

Data flow, entry, verification and cleaning. Data were key punched twice at the INCAP computer center. The data then were cleaned using valid ranges of values and consistency checks across variables to detect errors and outliers. Values suspected to be incorrect were sent back to the field where the supervisor of each area corrected coding errors. For anthropometry and the life history questionnaires, subjects were reexamined whenever errors other than coding were found.

Primary health care activities. Efforts to strengthen the primary health care in each of the villages were implemented in coordination with the Ministry of Health.

A physician, hired by INCAP, instructed the nurses in several areas, especially the government's child survival program. He visited each village once a week to examine cases referred to him by the nurses as well as to attend to anyone in the village wishing to see him. Drugs and medicines were donated to the clinics to make up for the unpredictability of government supplies. In the two villages lacking clinics, INCAP established clinics in buildings donated by the community and hired nurses to staff them. At the end of the study, all medical equipment in the new clinics was donated to the communities.

Minimal dental services were provided through an arrangement with the University of San Carlos' dental school.

Coverage rate. Coverage is defined as the rate "participants/target sample." Participants being subjects for whom data were available for at least one study area (Tables 5-7).

Table 5 shows rates of coverage by village and type of village. Overall coverage was 7l. 7% with rates being slightly greater for supplemented villages (72.6%) than for comparison villages (69.5%). Coverage rates did not differ significantly between Atole and Fresco villages.

Overall coverage rates were greater for females (74.5%) than for males (68.9%); this pattern was similar in supplemented (females: 799/1060 = 75.4% and males: 775/1109 = 69.9%) and comparison villages (females: 343/473 = 72.5% and males: 303/456 = 66.4%).

TABLE 5 Overall coverage in the follow-up cohorts

¹ Large Fresco village, Santo Domingo; small Fresco village, Espiritu Santo.
² Large Atole village, Conacaste; small atole village, San Juan; T. target sample; P. participants; % = coverage.

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