Marcelo Garrido

Iron Deficiency Anemia in Infancy: Long-Lasting Effects on Auditory and Visual System Functioning

Evoked potentials provide noninvasive measures of nerve transmission and CNS functioning. Auditory brainstem responses (ABR) and visual evoked potentials (VEP) show dramatic changes in infancy, largely as a result of progressive myelination. Because iron is required for normal myelination, pathway transmission in these sensory systems might be affected by early iron deficiency. We previously reported evidence to that effect: infants with iron-deficiency anemia (IDA) had slower transmission through the auditory brainstem pathway, uncorrected by iron therapy. To determine long-term effects, ABR and/or VEP of healthy Chilean children who were treated for IDA or were nonanemic in infancy were compared at approximately 4 y of age. Absolute latencies for all ABR waves and interpeak latencies (except I-III interval) were significantly longer in former IDA children. Longer latency was also observed for the P100 wave on VEP. The magnitude of differences was large—about 1 SD. These findings, with differences in latencies but not amplitudes, further support the hypothesis that IDA in infancy alters myelination and provide evidence that effects on transmission through the auditory and visual systems can be long lasting. Subtle changes in sensory pathway transmission might be an underlying mechanism for the derailment of other developmental aspects in early IDA.

Twenty-four-hour motor activity in human infants with and without iron deficiency anemia

Iron deficiency anemia (IDA) is a very common nutritional problem that alters motor activity. The aim of this study was to compare 24-h motor activity in the home in healthy 6-month-old infants with and without IDA. Activity was assessed via actigraphs on the leg during 24 continuous hours in 17 Chilean infants with IDA and 18 with normal hemoglobin levels. All infants were given oral iron, and activity was reassessed at 12 and 18 months. The frequency of movement units per minute was determined for each waking/sleep state during the day and night, and the duration of each state was computed. At 6 months of age, there were no differences between anemic and nonanemic infants in time per state. However, infants with IDA showed an overall increase in motor activity compared to controls. These differences were no longer observed at 12 and 18 months of age. Increased activity during the period of IDA raises the issue of a shared underlying mechanism with restless legs syndrome, a sensorimotor dysfunction where iron deficiency increases the severity of the symptoms and iron supplementation ameliorates them. Due to previous findings of decreased motor activity in the laboratory at 12 months during the waking time surrounding an afternoon nap, we also compared those data to a nap in the home. Infants with IDA were less active in the laboratory than in the home. The home versus laboratory results suggest that contextual factors affect the motor activity of IDA infants to a larger extent than controls.

Extracting Fuzzy Rules From Polysomnographic Recordings for Infant Sleep Classification

A neuro-fuzzy classifier (NFC) of sleep-wake states and stages has been developed for healthy infants of ages 6 mo and onward. The NFC takes five input patterns previously identified on 20-s epochs from polysomnographic recordings and assigns them to one out of five possible classes: Wakefulness, REM-Sleep, Non-REM Sleep Stage 1, Stage 2, and Stage 3-4. The definite criterion for a sleep state or stage to be established is duration of at least 1 min. The data set consisted of a total of 14 continuous recordings of naturally occurring naps (average duration: 143plusmn39 min), corresponding to a total of 6021 epochs. They were divided in a training, a validation and a test set with 7, 2, and 5 recordings, respectively. During supervised training, the system determined the fuzzy concepts associated to the inputs and the rules required for performing the classification, extracting knowledge from the training set, and pruning nonrelevant rules. Results on an independent test set achieved 83.9plusmn0.4% of expert agreement. The fuzzy rules obtained from the training examples without a priori information showed a high level of coincidence with the crisp rules stated by the experts, which are based on internationally accepted criteria. These results show that the NFC can be a valuable tool for implementing an automated sleep-wake classification system

Automated Sleep-Spindle Detection in Healthy Children Polysomnograms

We present a new methodology to detect and characterize sleep spindles (SSs), based on the nonlinear algorithms, empirical-mode decomposition, and Hilbert-Huang transform, which provide adequate temporal and frequency resolutions in the electroencephalographic analysis. In addition, the application of fuzzy logic allows to emulate experts procedures. Additionally, we built a database of 56 all-night polysomnographic recordings from children for training and testing, which is among the largest annotated databases published on the subject. The database was split into training (27 recordings), validation (10 recordings), and testing (19 recordings) datasets. The SS events were marked by sleep experts using visual inspection, and these marks were used as golden standard. The overall SS detection performance on the testing dataset of continuous all-night sleep recordings was 88.2% sensitivity, 89.7% specificity, and 11.9% false-positive (FP) rate. Considering only non-REM sleep stage 2, the results showed 92.2% sensitivity, 90.1% specificity, and 8.9% FP rate. In general, our system presents enhanced results when compared with most systems found in the literature, thus improving SS detection precision significantly without the need of hypnogram information.

Iron Deficiency Anemia in Infancy Is Associated with Altered Temporal Organization of Sleep States in Childhood

The highest prevalence of iron deficiency anemia (IDA) in infancy coincides with a time of rapid changes in sleep organization. Since IDA in infancy is associated with long-lasting neurofunctional effects despite iron treatment, the normal development of sleep patterns might be affected. Night polysomnographic recordings were performed in 55 healthy 4-y-old children (former IDA = 27, nonanemic controls = 28). Both groups were followed from infancy and were similar in background characteristics. The duration of each waking episode was measured, as was the duration of each episode of nonrapid eye movement (NREM) sleep stages 1 (NREM1), 2 (NREM2), and 3–4 (SWS), and rapid eye movement (REM) sleep. The data were analyzed according to the successive thirds of the total sleep time (TST). Relative to controls, former IDA children showed: a) longer duration of REM sleep episodes in the first third and shorter in the last third; b) more REM sleep episodes in the first third and fewer in the second third; and c) shorter latency to the first REM sleep episode and shorter NREM stage 2 and SWS episodes within the first sleep cycle. The results show that early IDA is associated with long-lasting alterations in the temporal organization of sleep patterns.

Sleep alterations and iron deficiency anemia in infancy

Iron deficiency anemia (IDA) continues to be the most common single nutrient deficiency in the world. An estimated 20-25% of the worlds infants have IDA, with at least as many having iron deficiency without anemia. Infants are at particular risk due to rapid growth and limited dietary sources of iron. We found that infants with IDA showed different motor activity patterning in all sleep-waking states and several differences in sleep states organization. Sleep alterations were still apparent years after correction of anemia with iron treatment in the absence of subsequent IDA. We suggest that altered sleep patterns may represent an underlying mechanism that interferes with optimal brain functioning during sleep and wakefulness in former IDA children.

Iron-Deficiency Anemia is Associated with Altered Characteristics of Sleep Spindles in NREM Sleep in Infancy

ObjectiveTo determine the effects of iron-deficiency anemia on the development of non-rapid-eye-movement (NREM) sleep stages, as indexed by sleep spindles.Study designPatterns of sleep spindles during NREM sleep stages 2 and 3–4 (slow-wave-sleep, SWS) were compared in 26 otherwise healthy 6-month-old Chilean infants with iron-deficiency anemia and 18 non-anemic control infants. From polygraphic recordings, EEG activity was analyzed for sleep spindles to assess their number (density), duration, frequency, and inter-spindle interval.ResultsIron-deficient anemic infants differed from the control group by having sleep spindles with reduced density, lower frequency, and longer inter-spindle intervals in NREM sleep stage 2 and SWS.ConclusionsThese results provide evidence of delayed sleep spindle patterns in iron-deficient anemic infants, suggesting that iron is an essential micronutrient for the normal progression of NREM sleep pattern development in the human.

Sleep and Neurofunctions Throughout Child Development : Lasting Effects of Early Iron Deficiency

Iron-deficiency anemia (IDA) continues to be the most common single nutrient deficiency in the world. Infants are at particular risk due to rapid growth and limited dietary sources of iron. An estimated 20% to 25% of the worlds infants have IDA, with at least as many having iron deficiency without anemia. High prevalence is found primarily in developing countries, but also among poor, minority, and immigrant groups in developed ones. Infants with IDA test lower in mental and motor development assessments and show affective differences. After iron therapy, follow-up studies point to long-lasting differences in several domains. Neurofunctional studies showed slower neural transmission in the auditory system despite 1 year of iron therapy in IDA infants; they still had slower transmission in both the auditory and visual systems at preschool age. Different motor activity patterning in all sleep-waking states and several differences in sleep states organization were reported. Persistent sleep and neurofunctional effects could contribute to reduced potential for optimal behavioral and cognitive outcomes in children with a history of IDA.

Expert-system classification of sleep/waking states in infants

This work is part of a project to develop an expert system for automated classification of the sleep/waking states in human infants; i.e. active or rapid-eye-movement sleep (REM), quiet or non-REM sleep (NREM), including its four stages, indeterminate sleep (IS) and wakefulness (WA). A model to identify these states, introducing an objective formalisation in terms of the state variables characterising the recorded patterns, is presented. The following digitally recorded physiological events are taken into account to classify the sleep/waking states: predominant background activity and the existence of sleep spindles in the electro-encephalogram; existence of rapid eye movements in the electro-oculogram; and chin muscle tone in the electromyogram. Methods to detect several of these parameters are described. An expert system based on artificial ganglionar lattices is used to classify the sleep/waking states, on an off-line minute-by-minute basis. Algorithms to detect patterns automatically and an expert system to recognise sleep/waking states are introduced, and several adjustments and tests using various real patients are carried out. Results show an overall performance of 96.4% agreement with the expert on validation data without artefacts, and 84.9% agreement on validation data with artefacts. Moreover, results show a significant improvement in the classification agreement due to the application of the expert system, and a discussion is carried out to justify the difficulties of matching the experts criteria for the interpretation of characterising patterns.

Interaction of iron deficiency anemia and neurofunctions in cognitive development.

During the last decades, the quantity of malnourished infants in the developing world has tended to decrease. Iron deficiency continues to be the single most common nutritional deficiency and the main cause of anemia (IDA) in infancy, childhood and pregnancy affecting more than 2,000 million persons worldwide [1]. It is prevalent in most of the developing world and it is probably the only micronutrient deficiency of public health relevance in industrialized countries [2]. In developing countries, the prevalence is usually greatest in infants, whereas in industrialized countries it is present mainly in women. The prevalence of iron deficiency in the developing world is high, due mainly to a low iron intake and/or poor bioavailability. IDA affects 20–40% of the infant population, mainly poor or minority infants worldwide [3–7]. Furthermore, infancy is considered the age range of highest vulnerability for the central nervous system (CNS) because it corresponds to the latter part of the brain growth spurt and the unfolding of fundamental mental and motor processes.