Effect of iron supplementation on cognition in Greek preschoolers.

OBJECTIVE: To examine effects of iron supplementation on vigilance, attention and conceptual learning in preschool children in Greece. DESIGN: Randomized Double-Blind Placebo Controlled trial of iron. Randomization stratified by iron status and day care center (DCC). SETTING: Nine public DCCs in Athens, Greece. SUBJECTS: In all, 49 3-4-y olds (21 anemic, 28 good iron status) with birth weight not less than 2500 g, currently healthy; benign past medical history, IQ > or =1 s.d. below the age-adjusted mean, serum Pb < or =200 ppb (none exceeded 50 ppb), and height, weight and head circumference for age > or =10th percentile. Anemia defined as: (1) pretreatment Hgb <112 g/l and TS <16% and ferritin <12 microg/L OR (2) Hgb rise of >10 g/l (T2-T0) with iron supplementation. Good iron status was defined as baseline levels of Hgb >120 g/l and either TS >20% or serum ferritin >12 microg/l. INTERVENTION: The intervention consisted of a 2-month supplementation of 15 mg iron (and MV) vs placebo (MV alone). RESULTS: After iron treatment, the anemic subjects made significantly fewer errors of commission (14% higher specificity, P<0.05), exhibited 8% higher accuracy (P<0.05) and were significantly more efficient (mean difference=1.09, P<0.05) than those given placebo. These effects of iron were not found among preschoolers with good iron status. No effects of iron treatment were found on the Oddity Learning task. CONCLUSIONS: This study demonstrated that iron supplementation of iron-deficient anemic preschoolers results in an improvement in discrimination, specifically selective attention.

Effects of iron supplementation and anthelmintic treatment on motor and language development of preschool children in Zanzibar: double blind, placebo controlled study.

OBJECTIVE: To measure the effects of iron supplementation and anthelmintic treatment on iron status, anaemia, growth, morbidity, and development of children aged 6-59 months. DESIGN: Double blind, placebo controlled randomised factorial trial of iron supplementation and anthelmintic treatment. SETTING: Community in Pemba Island, Zanzibar. PARTICIPANTS: 614 preschool children aged 6-59 months. MAIN OUTCOME MEASURES: Development of language and motor skills assessed by parental interview before and after treatment in age appropriate subgroups. RESULTS: Before intervention, anaemia was prevalent and severe, and geohelminth infections were prevalent and light-Plasmodium falciparum infection was nearly universal. Iron supplementation significantly improved iron status, but not haemoglobin status. Iron supplementation improved language development by 0.8 (95% confidence interval 0.2 to 1.4) points on the 20 point scale. Iron supplementation also improved motor development, but this effect was modified by baseline haemoglobin concentrations (P=0.015 for interaction term) and was apparent only in children with baseline haemoglobin concentrations <90 g/l. In children with a baseline haemoglobin concentration of 68 g/l (one standard deviation below the mean value), iron treatment increased scores by 1.1 (0.1 to 2.1) points on the 18 point motor scale. Mebendazole significantly reduced the number and severity of infections caused by Ascaris lumbricoides and Trichuris trichiura, but not by hookworms. Mebendazole increased development scores by 0.4 (-0.3 to 1.1) points on the motor scale and 0.3 (-0.3 to 0.9) points on the language scale. CONCLUSIONS: Iron supplementation improved motor and language development of preschool children in rural Africa. The effects of iron on motor development were limited to children with more severe anaemia (baseline haemoglobin concentration <90 g/l). Mebendazole had a positive effect on motor and language development, but this was not statistically significant.

The developmental and probabilistic nature of the functional consequences of iron-deficiency anemia in children.

It is often assumed that the psychometric tools currently available measure accurately the effects of iron-deficiency anemia (IDA) on cognition in young children and that such effects are rooted in cerebral changes. It is also assumed that snapshots of development within a clinical trial can document such effects. I challenge these assumptions on the basis of four considerations. The first is that there are multiple biological, physical and social-psychological factors that reorient the trajectory of different psychobiological domains in early life after intense and prolonged stress. Further, psychobiological development changes are not necessarily caused by brain changes; there are other mechanisms that also affect development (e.g., biomechanics). A second consideration focuses on intraindividual, interindividual and intergroup differences concerning the nature of the effect of IDA and the response to iron treatment. Individual and group factors can moderate the effects of IDA; for example, different stages of iron deficiency involve different systemic changes, which in turn affect different psychobiological domains. The third consideration is that differences in the time of measurement of an intervention within a randomized trial could lead to detecting effects in different domains or effects of different intensity within the same domain. Finally, developmental assessments with the traditional developmental scales during the first 18 mo of life yield equivocal findings. Snapshots of development will overlook the course of effects of a nutrition intervention over time. Repeated measures over time within the same domain are considered particularly useful to draw the course of development.

The eco-cultural context of the undernourished children in a study on the effects of early supplementary feeding in Indonesia.

OBJECTIVES: This paper describes the ecological and cultural backdrop of the subjects enrolled in an experimental study to test the validity of a conceptual model about the intellectual delay of undernourished children. DESIGN: The experiment was a 12-month clinical, randomized trial on the effects of early supplementary feeding on two cohorts of children classified as nutritionally-at-risk. Three different supplements (condensed milk + micronutrients; skimmed milk + micronutrients; skimmed milk) were given to the children during 6 or 12 months of the study. SETTING: The plantations are 1500-1800 m above sea level in Pangalengan, 50 km south of Bandung, West Java. Temperature fluctuates from 10 to 17 degrees C. A high yearly precipitation is approximately 3000 mm. Communities are laid out at 5-15 km from one another. Living conditions are modest. SUBJECTS: The 156 subjects were recruited from 24 day-care-centers (DCC) that serviced families of 24 communities in six tea plantations. The 12- and 18-month-old cohorts included 73 and 83 children, respectively; each cohort included three subgroups that received distinct supplements. OBSERVATIONS: The interactions of the caretakers with the children in the DCCs were consistent with the socialization for survival mode. A primary concern was the physical growth, health, cleanliness, sanitation and safety of the children. Stimulating children, providing toys and initiating play or other activities that would emphasize educational development had a low priority.

A developmental view of the undernourished child: background and purpose of the study in Pangalengan, Indonesia.

OBJECTIVES: This is the first of a series of reports published in this supplement of an experimental study to test the validity of a conceptual model about the intellectual delay of undernourished children. This paper describes the model and outlines its empirical and theoretical basis. The model provides a conceptual framework for the multiple relationships among growth and developmental domains presumably affected by malnutrition. It allows for a statistical statement regarding the goodness of fit between data and theory. The model also identifies particular hypotheses regarding multiple distinct pathways of human development. The following questions were addressed: (1) what are the effects of early supplementary feeding on the physical growth, motor development and activity, mental development and behavior of infants and toddlers who are nutritionally at risk? (2) What are the effects of a micronutrient supplement in the presence and absence of a high-energy supplement? (3) What are the moderating effects of developmental level and timing of the intervention. DESIGN: The study was a randomized clinical trial involving two cohorts (12 and 18 months old) of nutritionally-at-risk children living in Pangalengan, West Java, Indonesia and three types of supplements: condensed milk + micronutrients; skimmed milk + micronutrients; and skimmed milk. The children were tested every 2 months for a period of 12 months.

Effects of an energy and micronutrient supplement on growth and development in undernourished children in Indonesia: methods.

OBJECTIVES: To describe the methodologies of a clinical trial on the effects of an energy and micronutrient supplement on the growth and development of undernourished children. DESIGN: This trial included two cohorts of children classified as nutritionally-at-risk who were randomly assigned to three treatments (condensed milk + micronutrients (E); skimmed milk + micronutrients (M); skimmed milk (S)). Supplements were given for a period up to 12 months. SETTING: Six tea plantations in Pangalengan, West Java were the site for this study. SUBJECTS: A 12-month-old (N=53) and an 18-month-old (N=83) cohort were recruited from 24 day-care-centers (DCC). Twenty children that received the S supplement were part of the 12- and 18 month-old cohort. Criteria for case inclusion were absence of chronic disease; length-for-age < or = -1 standard deviation (s.d.) and weight-for-length between -1 and -2 s.d. of the median of the reference of the World Health Organization. VARIABLES: Social variables included assessment of health facilities, childcare, housing, income and parental education. Nutrition and growth variables included dietary intake measured over a 24 hr period every 2 months; hemoglobin and three iron indicators measured at baseline, 6 and 12 months; anthropometry measured every 2 months and skeletal maturation measured every 6 months. Cognition and behavior included the assessment of mental and motor development and the behavior of the child under natural conditions. DATA ANALYSIS: An ANOVA was the statistic most frequently used to test inter-group differences and structural equation modeling was used to test the internal validity of the conceptual model of the study.

A preliminary test of a developmental model for the study of undernourished children in Indonesia.

OBJECTIVES: Structural equation modeling of an abbreviated version of the conceptual model of the effects of micronutrient and energy supplementation on growth and development of undernourished children in West Java. The study focused on the baseline data from the Pangalengan longitudinal project. DESIGN: This trial included two cohorts of children classified as nutritionally-at-risk who were randomly assigned to three treatments (condensed milk + micronutrients (E); skimmed milk + micronutrients (M); skimmed milk (S)). Supplements were given for a period of up to 12 months. SETTING: The sites were six tea plantations in Pangalengan. SUBJECTS: A 12-month-old (n=53) and an 18-month-old (n=83) cohort were recruited from 24 day care centers. Twenty children that received the S supplement were part of the 12- and 18-month-old cohorts. Criteria for inclusion were: no chronic disease; length-for-age < -1 standard deviation (s.d.) and weight-for-length between -1 and -2 s.d. of the median of the reference of the World Health Organization. VARIABLES: Indicators of socioeconomic status were economic and educational resources; length-for-age and weight-for-length were used as indicators of nutritional status; motor development and motor activity were measured with custom-made procedures; and carrying by caretaker and manipulation of objects were used as indicators of caretaking and exploratory behavior. RESULTS: The model fitted the data of the older but not of the younger cohort (chi2 statistic and three other indices of goodness to fit). However, there were no differences between cohorts in the estimation of the models.

Community-level determinants of child growth in an Indonesian tea plantation.

OBJECTIVES: The paper presents the results of an ecological-economic approach to identifying community-level factors that influence the physical growth of young children. DESIGN: A cross-sectional design was used to obtain both the anthropometry and the ecological-economic data. SETTING: The sites were 24 communities located in a tea plantation near Bandung, West Java, Indonesia. SUBJECTS: 415 children between the ages of 6 and 18 months. METHODS: Epidemiological and ethnographic methods were used to measure community infrastructure and services related to child growth. Anthropometry was used to measure child growth. Econometric methods, including probit and ordinary least squares regression, were used to analyze the effect of community-level factors on child growth. RESULTS: Community vaccination programs, child care services, environmental sanitation and latrines were associated with better child growth. We concluded that community-level goods and services substantially contributed to health in early childhood.

Nutritional intake of an undernourished infant population receiving an energy and micronutrient supplement in Indonesia.

OBJECTIVES: This paper reports the dietary intake (home, day care centers, supplement and breast milk) of the children in the clinical trial in Pangalengan. DESIGN: Two cohorts of children were randomly assigned to three treatments: E = 1171 kJ + 12 mg iron; M = 209 kJ + 12 mg iron; S = 104 kJ. Supplementation was given for 12 months. SETTING: The sites were six tea plantations in Pangalengan, West Java. SUBJECTS: A 12-month-old (n = 53) and an 18-month-old (n = 83) cohort were recruited from day-care-centers. Twenty children who received S belong to the 12- and 18-month-old cohorts. Inclusion criteria were: no chronic disease; length-for-age < or = -1 standard deviation (s.d.) and weight-for-length between -1 and -2 s.d. of the median of the reference of the World Health Organization. METHODS: E = 1171 kJ + 12 mg iron; M = 209 kJ + 12 mg iron; S = 104 kJ. Supplementation was given for 12 months. Evaluations of intake were made at baseline and every 2 months thereafter. RESULTS: For the 12-month-old cohort the mean increase in daily energy intake approximately 2931 kJ for E, approximately 1675 kJ for M, and approximately 837 kJ increase over the 6 months for the S group. For the 18-month-old cohort the changes were approximately 2512 kJ for E approximately 1675 for the M group and approximately 1047 for the S group.

Effects of an energy and micronutrient supplement on motor development and motor activity in undernourished children in Indonesia.

OBJECTIVES: This paper reports the effects of an energy and micronutrient supplement on the motor development, motor milestones and motor activity of nutritionally at risk infants and toddlers in Pangalengan, Indonesia. DESIGN: Two cohorts of children were randomly assigned to three treatments E = 1171 kJ + 12 mg iron; M = 209 kJ + 12 mg iron; S = 104 kJ. Supplementation was given for 12 months. SETTING: The sites were six tea plantations in Pangalengan, West Java. SUBJECTS: A 12-month-old (n = 53) and an 18-month-old (n = 83) cohort were recruited from day-care-centers. Twenty children that received S belonged to the 12- and 18-month-old cohorts. Inclusion criteria were: no chronic disease; length-for-age < or = -1 standard deviation (s.d.) and weight-for-length between -1 and -2 s.d. of the median of the reference of the World Health Organization. METHODS: Evaluations of intake were made at baseline and every 2 months thereafter. Motor development was assessed with the Bayley Scale and with a custom-made scale to assess gross motor development leading to bipedal locomotion. Motor activity was assessed through 4 h continuous observations of the child's interaction with the social and physical environment. RESULTS: In the 12-month-old cohort, as compared to the M and S groups the children that received the E supplement walked at an earlier age, had higher scores in the Bayley Scale and were motorically more active. Similar intergroup differences were observed in the 18-month-old cohort in the total motor activity score.

Effects of an energy and micronutrient supplement on skeletal maturation in undernourished children in Indonesia.

OBJECTIVES: This paper reports the effects of an energy and micronutrient supplement on skeletal maturation of nutritionally at risk infants and toddlers in Pangalengan, Indonesia. DESIGN: Two cohorts of children were randomly assigned to three treatments: E = 1171 kJoule + 12 mg iron; M = 12 mg iron + 209 kJ; S = 104 kJ. Supplementation was given for 12 months. SETTING: The sites were six tea plantations in Pangalengan, West Java. SUBJECTS: A 12-month-old (n = 53) and an 18-month-old (n = 83) cohort were recruited from day-care-centers. Twenty children that received S belonged to the 12- and 18-month-old cohorts. Inclusion criteria were: no chronic disease; length-for-age < or = -1 standard deviation (s.d.) and weight-for-length between -1 and -2 s.d. of the median of the reference of the World Health Organization. METHODS: Skeletal maturation was measured by X-ray of the left hand and wrist. The number of ossified centers and two different measures of skeletal age (Skel-1 and Skel-2) were the outcome variables measured. RESULTS: In the 12-month-old cohort, there were intergroup differences 6 and 12 months after baseline. First, the children in the E group were about 2 months more advanced in ossified centers than the children in the S group (P < 0.10). At 12 months, the children in the E group were about 3 months more advanced in skeletal age than the children in the M group. M group children were about 2.5 months behind the children in the S group.

Effects of an energy and micronutrient supplement on growth and activity, correcting for non-supplemental sources of energy input in undernourished children in Indonesia.

OBJECTIVES: This paper investigates simultaneously the growth and activity of children that received an early energy and micronutrient supplement, adjusting for all non-supplemental energy intakes. Any additional change in growth and activity after this adjustment was then compared across supplements at three points felt to be representative of the study. DESIGN: Two cohorts of children were randomly assigned to three treatments: E = 1171 kJ + 12 mg iron; M = 209 kJ + 12 mg iron; S = 104 kJ. Supplementation was given for 12 months. SETTING: The sites were six tea plantations in Pangalengan, West Java. SUBJECTS: A 12-month-old (n = 53) and an 18-month-old (n = 83) cohort were recruited from day-care-centers. Twenty children that received S belonged to the 12- and 18-month-old cohorts. Inclusion criteria were: no chronic disease; length-for-age < or = -1 standard deviation (s.d.) and weight-for-length between -1 and -2 s.d. of the median of the reference of the World Health Organization. METHODS: Length was measured with a portable measuring board; a Detecto scale with an accuracy of 0.1 kg was used for the measurement of body weight. Arm and head circumferences were measured using similar fiberglass tapes. Motor activity was assessed through continuous 4 h observations at home and at day care centers. Anthropometry and activity were measured every two months over 12 months. RESULTS: After correcting for non-supplemental sources of energy intake, the effects of the supplement on weight and activity were observed at 2 months; effects on length and activity were observed at 6 months; and effects on weight alone were observed at 12 months.

Effects of an energy and micronutrient supplement on anthropometry in undernourished children in Indonesia.

OBJECTIVES: This paper reports the effects of early supplementary feeding on body weight, length, head circumference and arm circumference among the children in the Pangalengan study. DESIGN: Two cohorts of children were randomly assigned to three treatments: E = 1171 kJ + 12 mg iron; M = 209 kJ + 12 mg iron; S = 104 kJ. Supplementation was given for 12 months. SETTING: The sites were six tea plantations in Pangalengan, West Java. SUBJECTS: A 12-month-old (n = 53) and an 18-month-old (n = 83) cohort were recruited from day-care centers. Twenty children that received S belonged to the 12- and 18-month cohorts. Inclusion criteria were: no chronic disease; length-for-age < or = -1 standard deviation (s.d.) and weight-for-length between -1 and -2 s.d. of the median of the reference of the World Health Organization. METHODS: Length was measured with a portable measuring board; a Detecto scale with an accuracy of 0.1 kg was used for the measurement of body weight. Arm and head circumferences were measured using similar fiberglass tapes. RESULTS: Body weight showed effects on both cohorts at 2, 8 and 12 months; head circumference showed effects at 4 months in the 12-month-old cohort and at 10 months among the females of the 18-month-old cohort; and arm circumference showed effects across cohorts at 2, 8 and 12 months. In general the benefits are clearer for females and for the 12-month-old cohort.

Effects of an energy and micronutrient supplement on mental development and behavior under natural conditions in undernourished children in Indonesia.

OBJECTIVES: This paper reports the effects of an energy and micronutrient supplement on mental development and on the social cognitive and emotionally regulatory behaviors of nutritionally at risk infants and toddlers in Pangalengan, Indonesia. DESIGN: Two cohorts of children were randomly assigned to three treatments: E = 1171 kJ + 12 mg iron; M = 12 mg iron + 209 kJ; S = 104 kJoule. Supplementation was given for 12 months. SETTING: The sites were six tea plantations in Pangalengan, West Java. SUBJECTS: A 12-month-old (N = 53) and an 18-month-old (N = 83) cohort were recruited from day-care-centers. Twenty children who received S belonged to the 12- and 18-month-old cohort. Inclusion criteria were: no chronic disease; length-for-age < or = -1 standard deviation (s.d.) and weight-for-length between -1 and -2 s.d. of the median of the reference of the World Health Organization. METHODS: Evaluations of intake were made at baseline and every 2 months thereafter. Motor development was assessed with the Bayley Scale and with a custom-made scale to assess gross motor development leading to bipedal locomotion. Four hours of continuous observations were made of the child's interaction with the social and physical environment. RESULTS: In the 12-month-old cohort, as compared with the M and S groups, the children who received the E supplement walked at an earlier age, had higher scores in the Bayley Scale and showed more mature social-cognitive and emotional regulatory behaviors. Similar intergroup differences were observed in the 18-month-old cohort in social cognition and regulation of emotions.

Effects of an energy and micronutrient supplement on play behavior in undernourished children in Indonesia.

OBJECTIVES: This paper reports the effects of an energy and micronutrient supplementation on quantitative and qualitative aspects of play among poorly nourished children. At issue is whether the supplement led to a progression in complexity of play. DESIGN: Two cohorts of children were randomly assigned to three treatments: E = 1171 kJ + 12 mg iron; M = 12 mg iron + 209 kJ; S = 104 kJ. Supplementation was given for 6 months. Evaluations of play behavior were repeated four times. SETTING: The sites were six tea plantations in Pangalengan, West Java. SUBJECTS: The present study utilized a subsample of 55 children recruited for the larger Pangalengan project 6 months into the study. Thirty-eight children were recruited late enough to allow for longitudinal observations. The remaining cases were used for cross sectional observations only. Inclusion criteria were: no chronic disease; length-for-age < or = -1 standard deviation (s.d.) and weight-for-length between -1 and -2 s.d. of the median of the reference of the World Health Organization. METHODS: The children were videotaped during play. These tapes were coded for eight mutually exclusive categories of activities. Four activities coded represented manipulative, relational, functional and symbolic play. RESULTS: Treatment did not affect qualitative play. Girls that received E increased functional play but boys showed the opposite effect. Children in the S group were breastfed more during play as compared to the E group. Children in the E group waited less to begin play.

A developmental view of the effects of an energy and micronutrient supplement in undernourished children in Indonesia.

OBJECTIVES: This paper presents the results of a structural equation model testing whether the longitudinal data of the Pangalengan subjects fit the theoretical model regarding the intellectual delay of undernourished children. DESIGN: Two cohorts of children were randomly assigned to three treatments: E = 1171 kJ + 12 mg iron; M = 12 mg iron + 209 kJ; S = 104 kJ. Supplementation was given for 6 months. SETTING: The sites were six tea plantations in Indonesia. SUBJECTS: A 12-month-old (n = 53) and an 18-month-old (n = 83) cohort were recruited from day-care-centers. Inclusion criteria were: no chronic disease; length-for-age = < 1 standard deviation (s.d.) and weight-for-length between -1 and -2 s.d. of the median of the reference of the World Health Organization. METHODS: Twenty-four-hour dietary intakes were assessed using the weighted individual inventory technique. Body weight and length were obtained using standard procedures; motor development was assessed with the Bayley Scale and with a custom made scale for motor development leading to bipedal locomotion. Four-hour observations were made of the child's interactions with the environment. Carrying a child in the arms and exploratory behavior were used as indicators of caregiving and exploration. All measurements were obtained every 2 months. RESULTS: The original model did not fit the data. The model was then modified with the inclusion of two new pathways: from activity and from motor development to mental development. Following these adjustments the model fit the data for each cohort and for both cohorts combined.

Effects of an energy and micronutrient supplement on iron deficiency anemia, physical activity and motor and mental development in undernourished children in Indonesia.

OBJECTIVES: This paper reports the effects of an energy and micronutrient supplementation on mental and motor development, activity and behavior under natural conditions of children classified as iron deficient anemic and iron replete. DESIGN: Children were randomly assigned to two different nutritional supplements: (1) 12 mg iron + either 1171 or 209 kJ; (2) 104 kJ + 0 iron. Treatment lasted for 6 months. SETTING: The sites were six tea plantations in Pangalengan, West Java. SUBJECTS: Eighteen anemic subjects (hemoglobin < 110 g/L; transferrin saturation (TS) < 16%) and 18 matched (sex and age) controls (hemoglobin > 110 g/L; TS > 16%) were selected from a pool of children with the following characteristics: no chronic disease; length-for-age < or = -1 standard deviation (s.d.) and weight-for-length between -1 and -2 s.d. of the median of the reference of the World Health Organization. METHODS: Hemoglobin, ferritin, transferrin saturation and erythrocyte protoporphyrin were evaluated before and 6 months after treatment. The following psychological measurements were obtained at baseline and 2, 4 and 6 months later. Mental and motor development was evaluated with the Bayley Scale. Motor activity was measured by 4 h continuous observations at home and at day care centers. The interactions between the child and its social and physical environment were also evaluated during 4 h of observations. RESULTS: Anemic children showed faster motor development and greater physical activity than the control children did. None of the other tests showed inter-group differences.

Developmental sequel from early nutritional deficiencies: conclusive and probability judgements.

Results from quasi-experimental longitudinal studies of children and from experimental research with animal models have led several investigators to state that early iron deficiency anemia leaves a permanent cognitive deficit. However, neither source of information provides a basis for such a claim. Some key confounders were not controlled by the quasi-experimental studies, and the external validity of the animal data is questionable. Further, three decades of research on the functional consequences of protein-energy malnutrition have shown that the social environment moderates the effects of an early nutritional insult; it can keep such effect unchanged, or increase or decrease its severity. The prediction of later life on the basis of a particular nutritional event carries a large error factor, which suggests that the search would be more fruitful if we tracked probability statements.