Elias Jimenez

Long-Term Developmental Outcome of Infants with Iron Deficiency

BACKGROUND Iron-deficiency anemia has been associated with lowered scores on tests of mental and motor development in infancy. However, the long-term developmental outcome of infants with iron deficiency is unknown, because developmental tests in infancy do not predict later intellectual functioning. METHODS This study is a follow-up evaluation of a group of Costa Rican children whose iron status and treatment were documented in infancy. Eighty-five percent (163) of the 191 children in the original group underwent comprehensive clinical, nutritional, and psychoeducational assessments at five years of age. The developmental test battery consisted of the Wechsler Preschool and Primary Scale of Intelligence, the Spanish version of the Woodcock-Johnson Psycho-Educational Battery, the Beery Developmental Test of Visual-Motor Integration, the Goodenough-Harris Draw-a-Man Test, and the Bruininks-Oseretsky Test of Motor Proficiency. RESULTS All the children had excellent hematologic status and growth at five years of age. However, children who had moderately severe iron-deficiency anemia as infants, with hemoglobin levels less than or equal to 100 g per liter, had lower scores on tests of mental and motor functioning at school entry than the rest of the children. Although these children also came from less socioeconomically advantaged homes, their test scores remained significantly lower than those of the other children after we controlled for a comprehensive set of background factors. For example, the mean (+/- SD) adjusted Woodcock-Johnson preschool cluster score for the children who had moderate anemia in infancy (n = 30) was 448.6 +/- 9.7, as compared with 452.9 +/- 9.2 for the rest of the children (n = 133) (P less than 0.01); the adjusted visual-motor integration score was 5.9 +/- 2.1, as compared with 6.7 +/- 2.3 (P less than 0.05). CONCLUSIONS Children who have iron-deficiency anemia in infancy are at risk for long-lasting developmental disadvantage as compared with their peers with better iron status.

Poorer Behavioral and Developmental Outcome More Than 10 Years After Treatment for Iron Deficiency in Infancy

Objective. To determine the long-term effects of iron deficiency in infancy. Design. Longitudinal follow-up study of children who had been tested and treated for iron deficiency as infants. Setting. Periurban community near San Jose, Costa Rica. Participants. Of the original 191 participants, 87% were reevaluated at 11 to 14 years old (average age: 12.3 years). The children were free of iron deficiency and growing normally by US standards. Those who had chronic, severe iron deficiency in infancy (n = 48) were compared with those who had good iron status before and/or after iron therapy in infancy (n = 114). Outcome Measures. Comprehensive set of cognitive, socioemotional, and motor tests and measures of school functioning. Results. Children who had severe, chronic iron deficiency in infancy scored lower on measures of mental and motor functioning. After control for background factors, differences remained statistically significant in arithmetic achievement and written expression, motor functioning, and some specific cognitive processes (spatial memory, selective recall, and tachistoscopic threshold). More of the formerly iron-deficient children had repeated a grade and/or been referred for special services or tutoring. Their parents and teachers rated their behavior as more problematic in several areas, agreeing in increased concerns about anxiety/depression, social problems, and attention problems. Conclusions. Severe, chronic iron deficiency in infancy identifies children who continue at developmental and behavioral risk >10 years after iron treatment.

Iron-deficiency anemia and infant development: Effects of extended oral iron therapy

OBJECTIVE To determine whether extended oral iron therapy corrects lower developmental test scores in infants with iron-deficiency anemia. STUDY DESIGN Double-blind, controlled trial in Costa Rica involving 32 12- to 23-month-old infants with iron-deficiency anemia and 54 nonanemic control subjects. Anemic infants were treated with orally administered iron for 6 months; half the nonanemic children were treated with iron and half with placebo. Developmental test scores and hematologic status were evaluated before treatment, after 3 months, and after 6 months. RESULTS Iron-deficient anemic infants received lower mental test scores than nonanemic infants at all three time points (p < 0.05 pretreatment and at 3 months, p = 0.07 at 6 months). There were no significant differences in motor test scores. More of the anemic infants were rated as unusually tearful and unhappy. Anemic infants came from families with lower maternal education and less support for child development and were less likely to be breast fed, were weaned earlier, and consumed more cow milk. CONCLUSIONS Lower mental test scores persisted in infants with iron-deficiency anemia despite extended oral iron therapy and an excellent hematologic response. Iron-deficiency anemia may serve as a marker for a variety of nutritional and family disadvantages that may adversely affect infant development.

Iron deficiency in infancy and neurocognitive functioning at 19 years: evidence of long-term deficits in executive function and recognition memory

Abstract Iron deficiency in infancy negatively impacts a variety of neurodevelopmental processes at the time of nutrient insufficiency, with persistent central nervous system alterations and deficits in behavioral functioning, despite iron therapy. In rodent models, early iron deficiency impairs the hippocampus and the dopamine system. We examined the possibility that young adults who had experienced chronic, severe, iron deficiency as infants would exhibit deficits on neurocognitive tests with documented frontostriatal (Trail Making Test, Intra-/Extra-dimensional Shift, Stockings of Cambridge, Spatial Working Memory, Rapid Visual Information Processing) and hippocampal specificity (Pattern Recognition Memory, Spatial Recognition Memory). Participants with chronic, severe iron deficiency in infancy performed less well on frontostriatal-mediated executive functions, including inhibitory control, set-shifting, and planning. Participants also exhibited impairment on a hippocampus-based recognition memory task. We suggest that these deficits may result from the long-term effects of early iron deficiency on the dopamine system, the hippocampus, and their interaction.

Functional significance of early-life iron deficiency: outcomes at 25 years.

OBJECTIVE To evaluate adulthood function following chronic iron deficiency in infancy. STUDY DESIGN At 25 years, we compared 33 subjects with chronic iron deficiency in infancy to 89 who were iron-sufficient before and/or after iron therapy. Outcomes included education, employment, marital status, and physical and mental health. RESULTS Adjusting for sex and socioeconomic status, a higher proportion of the group with chronic iron deficiency did not complete secondary school (58.1% vs 19.8% in iron-sufficient group; Wald value = 8.74; P = .003), were not pursuing further education/training (76.1% vs 31.5%; Wald value = 3.01; P = .08; suggestive trend), and were single (83.9% vs 23.7%, Wald value = 4.49; P = .03). They reported poorer emotional health and more negative emotions and feelings of dissociation/detachment. Results were similar in secondary analyses comparing the chronic iron-deficient group with subjects in the iron-sufficient group who had been iron-deficient before treatment in infancy. Path analysis showed direct paths for chronic iron deficiency in infancy and being single and more detachment/dissociation at 25 years. There were indirect paths for chronic iron deficiency and not completing secondary school via poorer cognitive functioning in early adolescence and more negative emotions via behavior problems in adolescence, indicating a cascade of adverse outcomes. CONCLUSION The observational nature of this study limits our ability to draw causal inference, even when controlling for background factors. Nonetheless, our results indicate substantial loss of human potential. There may be broader societal implications, considering that many adults worldwide had chronic iron deficiency in infancy. Iron deficiency can be prevented or treated before it becomes chronic or severe.

No evidence of developmental III effects of low-level lead exposure in a developing country

Despite substantial controversy regarding the blood levels at which lead adversely affects neurobehavioral development, public health policy in some industrialized countries is prescribing ever more stringent screening criteria for all ages. This study addressed the question of ill effects of lead exposure at the new lower levels, specifically during the late infancy period, which has been targeted for maximum surveillance in pediatric practice. The sample of 184 participants consisted of 12− to 23-month-old healthy infants and toddlers who participated in a community-based study in a developing Central American country (Costa Rica) where extensive family and developmental information was collected. The mean infant blood lead level was 11.0 μg/dL, ranging from 5.4 to 37.0 μg/dL. Lead levels were not related to the Mental or Psychomotor Developmental Index of the Bayley Scales of Infant Development. When the children were 5 years old, they were reevaluated with complete physical and psychological testing. Blood lead levels in infancy did not predict any of the developmental outcome measures. Thus, among a group of healthy toddlers in a developing country, no ill effects on development of low blood lead levels were observed. J Dev Behav Pediatr 15:224–231, 1994. Index terms: low-level lead exposure, child development, developing countries.

Effects of iron therapy on infant blood lead levels.

OBJECTIVES To determine the effects of iron therapy on blood lead levels in infants with mildly elevated lead levels and varied iron status. METHODS Infants from a community-derived sample in Costa Rica were categorized into five groups. Group 1 had iron-deficiency anemia with hemoglobin levels <or=105 g/L. Infants in group 2 were iron-deficient with intermediate hemoglobin levels (between 106-119 g/L). These groups were treated with intramuscular iron or 3 months of oral iron. Group 3 (nonanemic iron-deficient) and group 4 (nonanemic iron-depleted) were treated with 3 months of oral iron. Group 5 (iron-sufficient) received oral placebo. RESULTS After 3 months of oral iron therapy, nonanemic iron-depleted infants had the greatest decrease in lead levels, followed by nonanemic iron-deficient infants and iron-deficient infants with hemoglobin levels <120 g/L. Lead levels increased among iron-deficient infants with hemoglobin levels <120 g/L who received intramuscular iron and iron-sufficient nonanemic infants who received placebo. CONCLUSIONS Changes in lead levels corresponded closely to changes in iron status and were plausible in terms of absorption mechanisms for lead and iron. Correcting and/or preventing iron deficiency appear to be rapid and effective means of improving infant lead levels, even in nonanemic infants.

Iron deficiency in infancy predicts altered serum prolactin response 10 years later

Serum prolactin may reflect CNS dopaminergic function. Because iron deficiency (ID) alters brain dopamine in rats, serum prolactin levels were previously investigated in infants with varied iron status. High serum prolactin levels correlated with behaviors typical of chronic ID. The objective of this study was to determine the effect of infant iron status on serum prolactin levels after a stressor in early adolescence. One hundred fifty-nine of 191 children enrolled in infancy (chronic ID, n = 46; good iron comparison group, n = 113) had serum prolactin measurements after catheter placement at 11–14 y of age. Serum prolactin levels were compared by sex, pubertal status and infant iron status and the pattern of change over time was compared by infant iron status controlling for pubertal stage and background factors. Males and less mature adolescents had lower serum prolactin concentrations than females and more mature adolescents. Controlling for these factors, the serum prolactin response pattern differed significantly by infant iron status. Serum prolactin declined earlier for the chronic ID group. In conclusion, an altered serum prolactin response pattern was observed 10 y after chronic ID in infancy and may suggest a long-lasting effect of ID on the regulation of prolactin.

Vitamin K-dependent clotting factors in normal breast-fed infants

BREAST-FEEDING has been implicated as a necessary factor in the pathogenesis of hemorrhagic disease of the newborn infant, ~ but little is known of its role in coagulation abnormalities beyond the neonatal period. Vitamin K is approximately four times more concentrated in cow milk than in breast milkfl and clotting factors depending on this vitamin are decreased in normal term infants, and even more reduced in premature infants. 3.4 Deficiency of vitamin K-dependent clotting factors with clinical bleeding has occasionally been reported in breast-fed infants older than one month, but these infants usually had also had diarrhea or had received antibiotic therapy? ,6 Since the levels ot ~ vitamin K-dependent clotting factors in healthy older breast-fed infants have not been systematically assessed, vitamin deficiency cannot be attributed to breast-feeding per se. To determine if breast-feeding during the first month of infancy is associated with an increased risk of bleeding caused by vitamin K deficiency, the present investigation compared coagulation studies and the levels of vitamin K-dependent clotting factors in normal breast-fed and bottle-fed infants.

Higher Infant Blood Lead Levels with Longer Duration of Breastfeeding

OBJECTIVE To determine whether longer breastfeeding is associated with higher infant lead concentrations. STUDY DESIGN Data were analyzed from 3 studies of developmental effects of iron deficiency in infancy: Costa Rica (1981-1984), Chile (1991-1996), and Detroit (2002-2003). The relation between duration of breastfeeding and lead levels was assessed with Pearson product-moment or partial correlation coefficients. RESULTS More than 93% of the Costa Rica and Chile samples was breastfed (179 and 323 breastfed infants, respectively; mean weaning age, 8-10 months), as was 35.6% of the Detroit sample (53 breastfed infants; mean weaning age, 4.5 months). Lead concentrations averaged 10.8 microg/dL (Costa Rica, 12-23 months), 7.8 microg/dL (Chile, 12 months), and 2.5 microg/dL (Detroit, 9-10 months). Duration of breastfeeding as sole milk source and total breastfeeding correlated with lead concentration in all samples (r values = 0.14-0.57; P values = .06-<.0001). CONCLUSIONS Longer breastfeeding was associated with higher infant lead concentration in 3 countries, in 3 different decades, in settings differing in breastfeeding patterns, environmental lead sources, and infant lead levels. The results suggest that monitoring lead concentrations in breastfed infants be considered.