Abraham W. Wolf

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.

Alcohol teratogenicity in the human: A detailed assessment of specificity, critical period, and threshold

Though the occurrence of alcohol-related birth defects is well documented in the human and in animal models, definition of specificity, critical period, and dose-response threshold with a precision adequate for clinical risk assessment and management has been lacking. Data from a cohort of 359 neonates, from a large prospective observational study in which chronic alcohol problems and maternal drinking were assessed during pregnancy and standardized neonatal examinations were blinded for prenatal information, were analyzed with the use of multivariate techniques, with uniform control for confounding by eight factors. Craniofacial abnormalities were found to be definitively related to prenatal alcohol exposure in a dose-response manner (p less than 0.001); a significant, but less striking, relationship was observed for other anomalies (p less than 0.01). The critical period for alcohol teratogenicity was confirmed to be around the time of conception. Risk for anatomic abnormalities in the offspring was clearly defined among the 5.6% of infants whose mothers drank more than three ounces of absolute alcohol, that is, more than six drinks, per day. Because of a trend toward an increase in craniofacial abnormalities with increasing embryonic alcohol exposure at lower levels, a clear threshold could not be defined. These are not experimental data and the results should not be overinterpreted. Nevertheless, pending further studies with larger samples, the findings suggest that to completely avoid alcohol-related anatomic abnormalities, advice to discontinue drinking or at least to reduce it to a minimal level before conception is clinically appropriate.

The effects of short-term oral iron therapy on developmental deficits in iron-deficient anemic infants

To assess the effects of iron therapy on developmental test scores in infants with iron deficiency anemia, 68 Guatemalan babies 6 to 24 months of age, with and without mild iron deficiency anemia, were tested with the Bayley Scales of Infant Development before and after one week of oral iron treatment. The two major findings of the study were developmental deficits in the anemic group prior to treatment, and lack of rapid improvement with short-term oral iron therapy. The mean pretreatment Mental Development Index of the anemic group was significantly lower than that of nonanemic infants. The anemic groups pretreatment Psychomotor Development Index was also lower than that of the nonanemic control group. In a double-blind randomized study, six to eight days of oral iron therapy did not reverse these deficits. Consequently, the deficits of the anemic group cannot be unequivocably attributed to iron lack. However, no significant differences were found between anemic and nonanemic groups in birth histories, socioeconomic level, or general nutritional status which might otherwise explain the lower developmental test scores of the anemic babies.

Low level lead exposure in the prenatal and early preschool periods: Intelligence prior to school entry☆

The hypothesis that low level lead exposure in the fetal and early preschool years is related to neuropsychological deficit is being examined in a prospective study of development through the preschool years. Clear and consistent support for the hypothesis was not obtained in previously reported findings relating maternal and cord blood lead level (PbB) and PbB from venous samples through age three years to a series of developmental tests. It was concluded the relationship of lead level and cognitive development was primarily a function of the dependence of each on the quality of the caretaking environment. The cohort has now been examined at age four years, ten months, an age selected to assess development just prior to school age. The test used was the Wechsler Preschool and Primary Scale of Intelligence. We found statistically significant correlations between most of the PbB measures and the intelligence test scores, but these were attenuated, not statistically significant and not consistent in direction when relevant confounding variables were considered. Possible biases or threats to validity were reviewed. Effect sizes relating both prenatal and preschool lead exposure to intellectual development were small, not statistically significant, and not consistent in direction.

Intrauterine Exposure to Low Levels of Lead: The Status of the Neonate

It has been suggested that lead (Pb) at low exposure levels is a behavioral teratogen. Blood lead (Pb-B) was measured in 185 samples of maternal blood and in 162 samples of cord blood drawn from members of a cohort of mother-infant pairs. Routine newborn assessments, an examination for minor anomalies, the Brazelton Neonatal Behavioral Assessment (NBAS), and part of the Graham/Rosenblith Behavioral Examination (G/R) were administered. Maternal and cord Pb-B correlated 0.80. In regression analyses, Apgar scores, birthweight, length, head circumference, neonatal anomalies, and seven behavioral scales were unrelated to either maternal or cord Pb-B. Three scales--the NBAS Abnormal Reflexes, the G/R Neurological Soft Sign, and the G/R Muscle Tonus Scales--were related minimally to either cord or maternal Pb-B. Because of the contrast in maternal and cord results, despite the high correlation of maternal and cord Pb-B, the data were reanalyzed for 132 cases with paired data. Only the Soft Sign Scale remained significant and that only for cord, but not maternal Pb-B. Regression analysis revealed a suppression with the Soft Sign Scale related to the variance of the cord Pb-B that was not common with maternal Pb-B. The possibility that the fetus under stress tends to accumulate Pb was considered.

Low level lead exposure in the prenatal and early preschool periods: Early preschool development☆

The hypothesis that low level lead exposure in the fetal and early preschool years is related to neuropsychological deficit was examined in a prospective study of child development. We also tested the hypothesis of reverse causality, i.e., that lead level is a function of prior developmental status. Fetal lead exposure was measured in maternal and cord blood while preschool lead level was measured in venous blood samples at ages six months, two years and three years. These blood lead measures (PbB) were related to concurrent and ensuing scores on developmental measures at six months, one year, two years, and three years. With statistical control of covariate measures (age, sex, race, birth weight, birth order, gestational exposure to other toxic substances, maternal intelligence, and several indicators of the quality of the caretaking environment) as well as potentially confounding risk factors (gestational exposure to alcohol and other toxic substances), most statistically significant associations of PbB with concurrent and later development were completely attenuated. Effects of lead exposure, significant or not, were not consistent in direction. In reverse-causality analyses, PbB was not related significantly to prior measures of developmental retardation or acceleration. It was concluded that the relationship of lead level and measures of development in these early years was primarily a function of the dependence of each on the quality of the caretaking environment.

Associations among alcoholism, drug abuse, and antisocial personality: a review of literature.

Current practice through both diagnostic systems and clinical approaches tends to view alcoholism, drug abuse, and antisocial personality as completely distinct systems. In the course of research with other goals, the authors noted the apparent associations of each pair within this triad. As prior reviews of the literature on associations among these did not deal with implications of frequent association, this literature was re-evaluated with a more comprehensive assessment of the studies and reports bearing on these associations. After a broad search, studies were examined that reponed statistics indicating an association or none between one or more of the pairs of the triad. About 75% to 80% of the studies meeting the criteria showed positive associations between pairs. Also, a common etiological matrix may predispose one to behaviors diagnostic of each aspect of the triad: alcoholism, drug abuse, and antisocial personality. Although many studies contained methodological difficulties, the review suggests where diagnosis of one aspect is made, the other two should be suspected and the patient so evaluated.

Object Attachment, Thumbsucking, and the Passage to Sleep

Cross-cultural studies suggest that children who sleep in the same room as their parents and who are breast-fed are less likely to use an attachment object. The present study examined childrearing practices that emphasize physical proximity of parent and child and use of an attachment object and thumbsucking at bedtime with 126 healthy U.S. infants. Four child-rearing practices were focused on: presence or absence of a caregiver when the child actually fell asleep; mode of feeding; location of the childs bed or sleeping place; whether or not the child slept with the parents during the night. Children who had an adult present as they fell asleep were less likely to use an attachment object or suck their thumbs. In contrast to cross-cultural research, the results of the present study suggest that where a child sleeps during the night or how the child is fed is not as important an influence on the bedtime use of an attachment object or thumbsucking as whether an adult is present as the child actually falls asleep.