Interactive classifications: the case of Attention-Deficit Hyperactivity Disorder in children 1 Classificações interativas: o caso do Transtorno de Déficit de Atenção com Hiperatividade infantil Clasificaciones interactivas: el caso del Trastorno de Déficit de Atención con Hiperactividad en niños

Fabíola Stolf
Brzozowski Jerzy <email@example.com>
André Brzozowski
Sandra Caponi III

I Doutoranda em Saúde Coletiva pela Universidade Federal de Santa Catarina
Florianópolis, Santa CatarinaBrasil

Rua Lauro Linhares
657 -ap. 401B88036-001FlorianópolisSCBrasil

II Doutorando em Filosofia pela Universidade Federal de Santa Catarina
Florianópolis, Santa CatarinaBrasil

Departamento de Saúde Pública
III Programa de Pós-Graduação em Saúde Pública
Universidade Federal de Santa Catarina
Florianópolis, Santa CatarinaBrasil

Ian Hacking
TDAH
clasificación de las personasla medicalización de la infancia

Interactive classifications: the case of Attention-Deficit Hyperactivity Disorder in children 1 Classificações interativas: o caso do Transtorno de Déficit de Atenção com Hiperatividade infantil Clasificaciones interactivas: el caso del Trastorno de Déficit de Atención con Hiperactividad en niños
EA3CAE5338FE0115A1317B0B63BFE191Ian HackingADHDlooping effectclassifying peoplemedicalization of childhood
Philosopher of science Ian Hacking writes that our world is one of classifications, and these classifications, or names, have a particular effect when they refer to the behavior of people.This article seeks to present what ADHD is and how it appears in children.It then discusses the conversion of undesirable behaviors into symptoms, which underlies the identification of ADHD as a disease.From these considerations, a more general model about the interaction between classifications and classified people is proposed, based on Hacking's distinction between indifferent and interactive kinds, and also on the concept of the looping effect proposed by that author.Finally, the model is applied to ADHD, and some remarks are made regarding the concepts of social control put forward by

INTRODUCTION

The world of Western man is highly systematized.Phenomena, objects, animals and people are analyzed, deconstructed and reduced to general concepts.The classification of entities with which human beings are incapable of communicating does not generate any interaction, but unexpected phenomena may arise when the targets of the classifications are also people.All classifications of people generate responses.Some ethnic or social groups (sometimes determined arbitrarily) end up becoming targets of prejudice, and even people who are considered ordinary or normal receive different labels.However, there are institutional or "official" classifications that are disseminated more readily and which have greater credibility in the eyes of society.The diagnosis of attention-deficit hyperactivity disorder (ADHD) can be considered to be an official classification, and if children with ADHD are classified as mentally ill, this has major implications.The aim in this study was firstly to present, along general lines, the way in which Ian Hacking described the interactions between classification and classified, and then from this point, to propose a more general model relating to this interaction, based on the distinction between indifferent kinds and interactive kinds, and also on Hacking's notion of the looping effect, in section 2 of the present paper.Section 3 presents ADHD, how it arises, its diagnostic criteria and the possible causes attributed to this classification.Following this, section 4 provides a discussion on conversion of undesirable behavior into symptoms, which lies behind identifying ADHD as a disease.Lastly, Hacking's proposed model is applied to ADHD in section 5, which also includes remarks on Peter Conrad's notions of social control.

Classifications

The philosopher of science Ian Hacking (2006) wrote that our world is a world of classifications and that these classifications or names have particular effects when they refer to people's behavior.As detailed in this section, individuals may be aware of their classification and, through this, they may modify their behavior.In order to understand the way in which a name or a diagnosis may influence individuals' behavior, and especially children's behavior, the distinction between Hacking's indifferent and interactive kinds needs to be delved into.

Classifications and science

According to a realistic conceptual view of science, the world is composed of kinds of entities, and the task of science is to create and refine classifications, so as to have increasingly faithful portrayals of the "true" types that constitute the world.One example of refinement of classifications occurred in the history of biology when, after many centuries of being considered to be fish, whales were then classified by Linnaeus as mammals.

In the words of Richard Boyd, one of the advocates of this position, the task of science is to accomplish an "accommodation of language to the causal structure of the world" (Boyd, 1986, p. 358; italics in the original).Over the course of scientific work, an image of the world as it is would gradually be built up, by cutting up nature "along its true joints".This definitive representation of the world, which science would approach asymptotically, would be formed by natural kinds corresponding to the entities that really exist.The philosophical discussion on natural kinds began in the middle of the nineteenth century and is still surrounded by controversy.For example, the extent to which the terms for natural kinds within ordinary language (such as "southern right whale") correspond to the scientific terms (such as "Eubalaena australis", the scientific name for the southern right whale) can be questioned.It may happen that the name of an animal in ordinary language corresponds to more than one biological species, or the same species may receive two names in ordinary language (if, for example, the male and female are very different from each other).Biological species are not the only natural kinds.The most classical examples are geometrical shapes (triangle, pentagon, etc.), chemical species (gold, water, etc.) and geological species (bauxite, pyrite, etc.).Recent philosophical analyses (Hacking, 1991) have tended to recognize that these objects are very different from each other, to the point that there is no such thing as a single concept of natural kind.What can be said, for example, about diseases?Can conditions like syphilis, dengue and depression be considered natural kinds?To discuss this point, Hacking (1999) introduced the distinction between indifferent kinds and interactive kinds.According to Hacking, the "classical" natural kinds (geometrical shapes and chemical, biological and geological species) are indifferent, in that they do not interact with the classification that they receive.For whales, nothing changes when they were classified as mammals instead of as fish.On the other hand, human kinds or kinds of people react to classifications that are imposed on them and, as argued by Hacking (2006), do this whether or not they are aware of such classifications2 .Individuals whose classification changes from "pretty" to "ugly" drastically change their behavior.However, Hacking seems to consider that the impetus of classifying individuals (which is deeply rooted in many different cultures) to be a continuation or variant of the attitude of classifying indifferent kinds.In a review of the philosophical literature on natural kinds (Hacking, 1991), while rejecting Richard Boyd's idea that there is only one true way to classify nature, Hacking drew attention to the pragmatic role that classifications have had in the history of civilizations.These dispositions of natural kinds (i.e.what they are capable of doing or what can be done with them) have aroused and maintain human interest in them.For example, it has been important to have good criteria for identifying copper among other metals because of its usefulness for civilization (to serve as an electricity conductor, etc.).Dispositions may also be important factors in refining classifications: it suffices to mention the implementation of procedures enabling differentiation between gold and pyrite (fool's gold).

Classifications in biomedicine

When the reasoning detailed in the preceding section is extended to kinds of people, institutions become necessary (Hacking, 2006;2007) in order to determine what dispositions are important for classification3 .It can be conjectured that at the outset of early civilizations, the human dispositions of greatest prominence were the capacities to work and procreate.A sick individual meant that there was one less in the contingent of the fit and fertile.From this arose the need to bring in procedures that would restitute the lost dispositions.Furthermore, diseases also have dispositions: to cite some examples, rabies is a fatal disease, stroke leaves psychomotor sequelae, leprosy causes losses of sensitivity at the extremities, and so on.In other words, the dispositions of diseases are their symptoms or the consequences from them.For this reason, as in the case of natural kinds, the dispositions of diseases make it possible to refine their own classification and consequently the diagnosis.

The diagnosis is the central point of the divergence between natural kinds and human kinds, and it is where the bifurcation between indifference and interaction occurs.From the practical point of view mentioned above, making a diagnosis signifies labeling or imposing a mark, in the same way that a suspicious nugget may be marked for inspection or cattle may be marked for slaughter.In this sense, the diagnosis represents an entry ticket into standardized and, especially, institutionalized procedures.However, whereas the behavior of the nugget does not change, regardless of whether it is classified as gold or pyrite (even though the subsequent procedure differs between the two cases), the behavior of individuals certainly changes in the light of a diagnosis of cancer.Hence, the disease itself may be an indifferent kind, insofar as it does not react according to whether it is classified as (for example) measles or chickenpox.This question is crucial, and it is connected with what will be referred to henceforth as the biological causes of the disease 4 .Here, diseases are taken to be complex phenomena with many causes, and each of these can be studied at a relatively autonomous level of analysis.Biological causes correspond to the set of causes commonly called etiology.They are the avatar of the disease at the level of biomedical analysis.For diseases to have biological causes, there has to be an unambiguous correspondence between the causes and the set of symptoms, and a set of symptoms cannot have more than one set of biological causes.Thus, from the biomedical perspective, diseases are sets of symptoms unambiguously caused by a set of biological causes.So far, with the possible exception of depression, the diseases that have been mentioned present relatively clear biological bases.In the cases of syphilis, dengue, measles and chickenpox, the biological causes are even embodied in the form of etiological agents, or more properly, in the relationship between these agents and their hosts.In the case of cancer, the biological causes are located in the patient's own organism (genetic defects relating to cell division, although "genetic" does not necessarily mean "hereditary" here).Depression is an example in which a set of symptoms may have more than one set of biological causes, or there may even not be a set of biological causes.In this case, depression would not be a disease in the strictly biomedical sense defined above.Hacking (1999) also suggested that some kinds (certain diseases like schizophrenia and autism) are at the same time both indifferent and interactive.The indifferent component of the disease is its biological causes, while the interactive component is the stereotype of the individual with the disease, which from the biomedical perspective refers to the set of symptoms.However, the stereotype of the individual with the disease also takes on a social characteristic, when embodied in the patient's own behavior.Thus, there are three elements from which the interaction between classification and classified are constructed: from the biomedical side, the biological causes and the set of symptoms, and from the social or extra-biomedical side, the patient's behavior.If this interaction is present, an effect that Hacking called the looping effect occurs."People and their classifications are in a situation of full interaction and bilateral evolution", wrote Hacking (2006, p. 308).The looping effect is a spiral that occurs when the classification changes an individual's behavior, which in turn alters the stereotype of the classification, and so on.Modification of an individual's behavior caused by a classification may present a positive feedback (the fact that the individual knows that he belongs to a certain class strengthens the attributes that characterize this class) or a negative feedback (individuals resist the knowledge that is linked to the classification) (Hacking, 2006).Hacking called these effects positive and negative feedback, not in the sense of qualifying the action as positive or negative, but to say that positive feedback amplifies the effects of the classification, while negative feedback suppresses the effects.Hacking explained this thus:

The name of a class carries general knowledge about the members of the class.The affirmation that I am in a class and that I am an N [...] establishes that I have the known attributes of the class [...].This may transform me.Perhaps the knowledge that I am an N will strengthen these attributes -a case of positive feedback.[...]There are also cases of negative feedback.In the simplest case, individuals resist the knowledge that is linked to the classification.They make efforts to get rid of the characteristics that are attributed to them.[...] This knowledge, say the people who are N, is untrue; what is said about people who are N is untrue.(Hacking, 2006, p. 307-8) The transformation of behavior that is taken to be undesirable, into symptoms of diseases, is one of the main ways in which looping effects are generated.In the following, a simple model aimed at describing how this transformation takes place is put forward, and the reason why this process is subject to the looping effect is shown.

A model for the genesis of a disease

An important clarification can be made regarding the looping effect, taking the three elements cited earlier into consideration (biological causes, set of symptoms and patient behavior), along with the role that each of these has in identifying a disease.Firstly, a scenario in which there is no looping effect is considered (Figure 1).In stage 1, a diffuse set of symptoms is perceived in a group of patients.Next, biological causes that explain a portion of the initial set of symptoms are postulated.The transition from stage 1 to stage 2 can be called biologization.Lastly, only the portion of the set of symptoms for which a biological basis can be ascribed is used to make the diagnosis.The transition from stage 2 to stage 3 can be called reduction.In this scenario, the looping effect is ignored.Identifying a disease, which may be the result from years of research, ultimately isolates a set of symptoms that are relevant in making the diagnosis (stage 3).Laboratory and other tests for this disease are used to link the symptoms.This scenario is not intended to be exhaustive: after stage 3, the healthcare team's work evidently continues.A patient who presents a set of symptoms that roughly corresponds to the set in stage 3 is marked (in the sense discussed earlier) for tests to be performed in order to identify the presence of biological causes that are commonly associated with that set of symptoms.If the clinician concludes that the results confirm the presence of these causes, the diagnosis is made and the patient is again marked, this time for the treatment process.In order to think about the significance of ADHD for children, it first of all needs to be understood what the disorder is, what criteria are used for diagnosing it and how its historical evolution has taken place.In some academic circles, ADHD is considered to be the commonest psychiatric diagnosis during childhood.It is characterized by three main symptoms: lack of attention, impulsiveness and hyperactivity (Vasconcelos, Junior, Malheiros et al., 2003).Chart 1 lists the DSM-IV criteria for diagnosing ADHD (DSM-IV-TR, 2002).(1) six (or more) of the following symptoms of inattention have persisted for at least 6 months to a degree that is maladaptive and inconsistent with developmental level: Inattention: (a) often fails to give close attention to details or makes careless mistakes in schoolwork, work, or other activities; (b) often has difficulty sustaining attention in tasks or play activities; (c) often does not seem to listen when spoken to directly; (d) often does not follow through on instructions and fails to finish school work, chores, or duties in the workplace (not due to oppositional behavior or failure to understand instructions); (e) often has difficulty organizing tasks and activities; (f) often avoids, dislikes, or is reluctant to engage in tasks that require sustained mental effort (such as schoolwork or homework); (g) often loses things necessary for tasks or activities (e.g., toys, school assignments, pencils, books, or tools); (h) is often easily distracted by extraneous stimuli; (i) is often forgetful in daily activities.

(2) six (or more) of the following symptoms of hyperactivity-impulsivity have persisted for at least 6 months to a degree that is maladaptive and inconsistent with developmental level: Hyperactivity: (a) often fidgets with hands or feet or squirms in seat; (b) often leaves seat in classroom or in other situations in which remaining seated is expected; (c) often runs about or climbs excessively in situations in which it is inappropriate (in adolescents or adults.may be limited to subjective feelings of restlessness); (d) often has difficulty playing or engaging in leisure activities quietly; (e) is often "on the go" or often acts as if "driven by a motor"; (f) often talks excessively.Impulsivity: (g) often blurts out answers before questions have been completed; (h) often has difficulty awaiting turn; (i) often interrupts or intrudes on others (e.g., butts into conversations or games).B. Some hyperactive-impulsive or inattentive symptoms that caused impairment were present before age 7 years.C. Some impairment from the symptoms is present in two or more settings (e.g., at school [or work] and at home).D. There must be clear evidence of clinically significant impairment in social, academic, or occupational functioning.E. The symptoms do not occur exclusively during the course of a Pervasive Developmental Disorder, Schizophrenia, or other Psychotic Disorder and are not better accounted for by another mental disorder (e.g., Mood Disorder, Anxiety Disorder, Dissociative Disorder, or a Personality Disorder).

ADHD was known by several names over the course of the twentieth century.Among these were "lethargic encephalitis", "minimal cerebral damage", "minimal cerebral dysfunction", "hyperkinesia", "attention deficit disease" (ADD) and "attention-deficit hyperactivity disorder".For each of these disease categories, sets of similar symptoms depicting deficits during childhood have been described.The following are some of the most cited symptoms, which are common to all these names: low performance at school, extreme extroversion, violent behavior, incapacity to complete tasks, thievery, disturbed sleep patterns, morality inconsistent with the age and forgetfulness (Rafalovich, 2001).The idea that agitation, low concentration and impulsiveness among children are medical phenomena is recent.Interest in children who presented low attention capacity and hyperactivity began at the start of the twentieth century when a pediatrician, Frederick Still, described a group of children who had an abnormal incapacity to maintain concentration, together with restlessness and irritability (Still, 2006(Still, [1902]]).The characteristics of hyperactivity and lack of attention among children were only correlated with each other with the emergence of the diagnosis of minimal cerebral damage, after the epidemics of encephalitis during the first decades of the twentieth century (Timimi, 2002).During the 1930s, the action of psychostimulants for reducing restlessness, hyperactivity and behavioral problems among children was discovered.In the 1940s, Strauss suggested that hyperactivity in the absence of histories of abnormalities in the family could be considered to be sufficient evidence for a diagnosis of cerebral damage (Timimi, 2002).However, as the years went by, no organic lesions were found in these agitated children.Thus, from 1960 onwards, the term "minimal cerebral damage" fell into disuse.On the other hand, even though this hypothesis was abandoned, there was increasing interest in syndromes that were defined behaviorally.Researchers started to believe that this syndrome was caused by some type of cerebral dysfunction.In the second edition of the DSM, the disease was called "hyperkinetic reaction of childhood" (Timimi, 2002).The third edition of the DSM was published in the 1980s, and the name became "attention deficit disorder" (ADD).The problem could be diagnosed with or without hyperactivity symptoms and was defined using three lists of symptoms: one for attention deficit, one for impulsiveness and one for hyperactivity.In the fourth edition of the DSM (DSM-IV), the criteria for the diagnosis changed again, this time towards a two-dimensional model: attention deficit in one subcategory and hyperactivity and impulsiveness in the other.It is important to highlight that, in each revision, the number of children with characteristics of the disease increased.The change from DSM-III to DSM-IV increased the prevalence of the disorder by around two thirds (Timimi, 2002).The prevalence of ADHD has been investigated in many countries, and studies using the criteria of the DSM-IV have tended to find prevalences of 3-6% among children of school age in the United States.In Brazil, the prevalence rate in studies of this type has been found to be 3.6 to 5% of the school-age population (Andrade and Scheuer, 2004).The proportions of the disorder between boys and girls, according to epidemiological studies, has ranged from 2:1 in population based studies to 9:1 in clinical studies, respectively (Rohde and Halpern, 2004).Despite the large number of studies that have already been conducted, the causes of ADHD remain unknown.The best-accepted idea among researchers working on this topic is that there are genetic and environmental factors that influence the development of the disease.In relation to genetics, there are hypotheses that correlate several genes of minor effect with vulnerability to the disorder, which may or may not develop, according to the environmental conditions.According to recent studies, the appearance of ADHD is also related to abnormalities in one or more neurotransmitters, such as catecholamines, particularly dopamine and noradrenaline.However, data on the relationship between ADHD and neurotransmitters are still very scarce (Rohde;Halpern, 2004).In relation to diet, some studies have suggested that certain preservatives like sodium benzoate and artificial food colorants may exacerbate hyperactive behavior among small children (Barrett, 2007).Another nutritional factor relating to this disorder is low serum ferritin levels, which indicate iron deficiency.According to studies on this subject, iron modulates dopamine and noradrenaline production: the quantities of these substances in individuals with ADHD are unbalanced (Konofal, Lecendreux, Deron et al., 2008).However, it is important to emphasize that in speaking of neuron and neurotransmitter development from the point of view of neuroevolution, a certain level of hyperactivity in children up to the age of around four to five years is acceptable, given that the prefrontal region (the location for the behavioral "motor brake" in humans) only becomes completely developed at this age (Rohde and Halpern, 2004).The treatment generally indicated by healthcare professionals encompasses psychosocial and/or psychopharmacological interventions.For psychosocial interventions, an educational approach is recommended, providing clear and precise information to the family regarding the disorder.Furthermore, school support is advisable, through implementing a consistent daily routine, physical activity and individualized attention, whenever possible (Zavaschi and Rohde;Lorenzon et al., 2004).In relation to pharmacological treatment, stimulants are considered by most professionals and researchers to be the first-choice medications.In Brazil, the only stimulant approved and available on the market is methylphenidate, under the commercial names Ritalina ® (Novartis) and Concerta ® (Janssen-Cilag).In cases of comorbidities, intolerance or lack of response to stimulants, tricyclic antidepressants are often used, for example imipramine (Zavaschi, Rohde, Lorenzon et al., 2004), under the commercial name Tofranil ® (Novartis).

Behavior and symptoms

It can be seen that ADHD is a recent phenomenon and that, prior to the twentieth century, characteristics that today are considered to be symptoms, such as restlessness, impulsiveness and hyperactivity, were regarded as normal behavior.Thus, it can also be seen that today, scientific knowledge and healthcare practices have made the threshold between health and disease, i.e. between normal and pathological, very tenuous.Individuals merely have to present behavior that society in general deems undesirable for them to be labeled as "depressive", "anxious", "crazy" or even "hyperactive".This comes about because the natural highs and lows of life and the correlated behavioral patterns that were previously considered to be normal have been converted into pathological states (Blech, 2005).According to Georges Canguilhem (1982), science describes normal human beings as those that fit within preestablished standards that are determined through averages.However, he posed a question: should deviations be considered to be abnormal?The models for normal individuals are produced from statistics, but in Canguilhem's view, real individuals diverge from this model and this is what makes them different from each other.With regard to children, the learning targets established for each age group at school show the great influence of the positions taken.Most children learn to read at a certain age; those that do not start to read together with the others can easily be regarded as deviant.The characteristics of ADHD are generally perceived at school, and children are referred to healthcare professionals from there.The words of a teacher about a "problem student" taken from the book by Cecília Collares and Maria Aparecida Moyses (1996) illustrate this point: "she's way behind.I think that she should be referred to the health services or a psychologist, because she has something; she's way behind.From her size and age, I think she should have learned by now.She's still at the pre-syllabic stage."(p.250).One necessary condition for individuals to have a social life is that everyone should share the same, previously established standards.When a rule is broken, such as not learning to read within the "normal period", restorative measures are taken: "success or failure in maintaining these standards has a very direct effect on individuals' psychological integrity" (Goffman, 1988, p. 138).According to Collares and Moyses (1996), school is a place that harbors prejudice relating to students, their families and school failure.Failure to keep up with the institutional standards always falls onto students and their parents:

Children do not learn because they are poor, because they are black, because they are from the Northeast of Brazil or from rural areas, because they are immature or slothful, because their parents are illiterate or alcoholics, because their mothers work outside of the home and do not teach anything to their children... (p.26)

The above citation is no more than a repertoire of reductionist explanations for learning problems.According to Richard Lewontin (Lewontin, Rose and Kamin, 2003), reductionists are people who try to explain the properties of complex systems (such as learning) by focusing on just a few aspects.From a reductionist perspective, the problem of non-learning lies in isolated characteristics such as skin color, socioeconomic level, place of origin and presence of diseases.Disease has been used as an explanatory factor for individuals' deviations within society, a phenomenon that can be called biologization.Thus, properties are reified, i.e. they gain localization and are treated medically.That is, they are seen as caused by events in individuals' brains that are associated with modifications in the quantities of certain chemical substances (Lewontin, Rose and Kamin, 2003).This process of biologization, especially of conflicting social issues, generally takes place at times of great social tension.For example, this occurred during the 1960s, when science "proved" that white men were genetically superior to black men, in intellectual terms; and that women and men presented intellectual differences because of neurological differences that were also genetically determined (Collares and Moysés, 1996).Biologization of non-learning is very common within the school environment, and it causes responsibility for academic failure and dropping out of school to fall on illnesses.In biologizing social issues, the entire social system becomes exempted from responsibility.At school, the lines of a political-pedagogical discussion are shifted to medical causes and solutions, which are inaccessible to education (Collares and Moysés, 1996).Thus, according to some teachers, doctors and parents, as well as the children themselves, very active individuals, who do not pay attention as they should, present some type of health problem (Conrad and Schneider, 1992).Dealing with this undesirable behavior as a medical problem was, and continues to be, well accepted within society, and there are various reasons for this.For doctors, the therapy is relatively simple (prescription of a medication) and the results may be excellent, from a clinical point of view.In turn, the diagnosis of ADHD indicates that this is a disease that can be treated, which diminishes the extent to which parents can be blamed, and means that parents may regard the diagnosis favorably.In addition, the medication frequently makes the child less agitated and hyperactive in the classroom and often facilitates learning, thereby also resolving the problem at school (Conrad and Schneider, 1992).Hacking (2007) writes that behind every classification, there is a structure that encompasses five primary factors: the classification, individuals, institutions, knowledge and specialists.The classification in itself generates the kinds of people.Children with ADHD are one kind of person, formed by individuals who share the same problem.This group of people has a name and their characteristics are determined as a function of this name.Individuals (or their families in the cases of ADHD) often only start to see certain characteristics of the classification as problems after receiving the diagnosis.Institutions confirm the existence of this classification and are a means of legitimizing that kind of person.One example of an institution in this case is the DSM-IV, which provides a means of legitimizing and justifying the diagnosis of mental disorders.The DSM-IV presents a series of behavioral characteristics, as can be seen in item 3, which indicate whether the child presents ADHD.These criteria are interpreted by specialists, through descriptions from the child's family and educators.Thus, knowledge and specialists have the power to decide who is ill and who is not; and who presents ADHD and who is normal.The diagnosis for the disorder is essentially clinical; there are no laboratory tests or imaging examinations that can aid in this decision.Specialists only have their technical knowledge, the criteria of the DSM-IV and information coming from people with links to the child available for outlining the diagnosis and indicating the appropriate therapy for the case.After the diagnosis has been made and, generally, after medication has been prescribed, these children go back home and back to school labeled with a psychiatric disorder.In section 2.2, it was mentioned that the classifications interact with the individuals classified, and that this interaction takes place through the looping effect.The tendency is to think that this looping effect only occurs in relation to people who are aware of the label that has been given to them, i.e. people who understand the significance of their disease.What about individuals who are unaware of the classification, such as people who cannot understand the language, babies or small children (Hacking, 2006)?Children are often diagnosed with ADHD before they are able to understand its significance.In such cases, it can be said that the feedback effect is impossible.However, Hacking (2006) stated that the looping effect involves much broader units, such as the family, and in the specific case of ADHD, it may also involve the school.It is impossible to believe that this label will not have an influence in many decisions that the family, and subsequently the adult diagnosed with ADHD during childhood, will make.From a well-established diagnosis, any unexpected behavior by the child comes justified by the disease that is presented.The attitudes of people around this child become modified because of the diagnosis and the characteristics that are taken to due to the disease.This change affects children with ADHD and makes them see themselves differently, thus giving rise to the looping effect.The words of a mother, retrieved from the study by Uribe and Roja (2007), illustrate how a diagnosis, i.e. a classification, may change the environment within which the child lives:

The looping effect in ADHD

[After he received the diagnosis] everyone understood.Everyone tried to change their attitudes towards him.[...] It's not that he pretends to be deaf.[...] the teacher told us that he changed one hundred percent in his attitude towards his colleagues and everything [...] [the teacher] had labeled him with.She had been judging him for things he hadn't done.Upon knowing that the boy had this [ADHD], the teacher also started to regard him differently.Such that she no longer regarded him as a child that was to blame for everything, but rather, as a hyperactive child.[..]Not because he meant it, let's put it like that.The diagnosis changed Rodrigo's life.A lot. (p.279) As mentioned in item 2.2, the looping effect may present two different effects, which Hacking called positive and negative feedback effects (Hacking, 2006).Thus, it might be suggested that most children with ADHD end up presenting a positive feedback, in response to their way of experiencing the condition and how their families and schools start to deal with them after the diagnosis has been made.These types of behavior reinforce the characteristics of the disease and may lead to a perception by the child that he is ill and may lead to acting as such.From the moment when someone enters the list of ill people, a treatment for this condition needs to be available.In general, it is believed that children with ADHD should receive medication in order to correct their deviant behavior, so that they can continue to live within society and enter within its standards and rules again.Peter Conrad (Conrad and Schneider, 1992) called this control over deviation and promotion of social conformity social control.Individuals who strayed from the standards would have to be controlled, so that society, or the family or the school could return to its "normal state".Conrad maintained that there were formal and informal levels of social control.Informal control would include both self-control (internalization of standards, beliefs, morals and so-called "conscience") and relational control (day-to-day relationships), and would inhibit individual behavior that was considered to be deviant.For example, somebody could go out from their home with a desire to pick a fight with the first person that he might meet on his way; however, he would not do so, both because of his moral beliefs and conscience and because of what other people would think and say about such an act.Formal social control encompasses institutional forms of control, such as the legal, police, educational and social care systems and even the healthcare system.These are the "official" forms of control: the ones that nobody is capable of questioning unless he is a specialist in this field.Because these are so well accepted and, in the case of healthcare, because it is backed by science, their consequences are generally much more profound and long-lasting, both for individuals and for society and the environment in which these individuals live (Conrad and Schneider, 1992).Thus, receiving a diagnosis of ADHD from an official institution leads to a change in behavior, not only among individuals with the diagnoses but also throughout their social network, which in turn also ends up influencing these individuals, and so on.This leads to the suggestion that a looping effect with positive feedback consists of acceptance and reinforcement of the characteristics through which the diagnosis was made, which should then be treated so that the environment returns to normality.

Final remarks

It is very common to think that various forms of distress, unwellness and psychological disorders can be caused, treated and cured solely through biological means (Legnani and Almeida, 2004).The practice of transforming social problems into pathological conditions takes away the responsibilities for deviations from the hands of the system, family, individual and society in general, thereby turning them into diseases that can be treated with a "magic bullet", to use Lewontin's term (Lewontin, Rose and Kamin, 2003).Agitated or inattentive behavior among children may become considered deviant.Schools that are overloaded with children are not in a position to deal with such situations and often transfer the responsibility for children who are considered to be problematic, to the healthcare system.In turn, the healthcare system is structured to diagnose and treat diseases and, for this reason, it generally provides a diagnosis and medication for individuals who seek care.The healthcare ideal of present-day so-called scientific medicine (which defines health as absence of disease) conceives of the body as a machine that can be repaired if it should happen to present a defect.This model does not take into consideration the fact that there is no perfect body machine in relation to another that could be considered defective, i.e. there is no perfect machine with which the others can be compared (Martins, 2004).The growth of cultural anxieties and demands regarding child development and wellbeing over recent years is the main factor, according to Timimi (200), responsible for the construction of ADHD as a biomedical disease.That is, in addition to the expectations regarding the functioning of the "machine", there are also expectations regarding its behavior.Perfect human beings would be those who obeyed the standards submissively.The highly subjective nature of the definition of ADHD enables a series of interpretations, thus turning this diagnosis into a repository for a variety of problems (Timimi, 2002), which are generally not resolved within the sphere of school.Because of this subjectivity, there is a risk of treating "normal" children as "ill", thus leading these children to incorporate this disease and consider themselves really to be ill.They may thus regard themselves, even after reaching adulthood, incapable of accomplishing day-to-day activities that are performed by other individuals who are considered to be "normal".Despite the looping effect with positive feedback that occurs in ADHD and the social control resulting from this condition, the diagnosis may present a beneficial side, consisting of "freeing" both the child and his own family from blame.The family thus ceases to be regarded as being to blame for the undesirable behavior.The child ceases to be labeled as badly brought up and becomes labeled as ill (Silva, 2009).His problem becomes located in the brain, in neurotransmitters, and is therefore relatively easier to "cure" or control.

It seems to us that the social tolerance for people who are different is very low, to the point that people prefer to be called mentally ill, rather than slothful or disorganized.A process may be taking place in which the illness is tolerated because it can be treated and controlled, whereas it is believed that personality (taken to be the factor that generates behavior) is less palpable and more difficult to control.To treat individuals with psychiatric disorders today, internment and confinement are no longer used but, rather, medicalization.Bodies are tamed not through physical confinement in a lunatic asylum, but through psychological confinement using psychoactive drugs that model conduct, habits and thoughts (Caponi, 2009).

Figure 1 .
1
Figure 1.Model for identifying a disease.See text for a detailed description of the stages.

Figure 2 .
2
Figure 2. Model for the looping effect in identifying a disease.See text for a detailed description of the stages.

Chart 1 .
1
Diagnostic criteria for ADHD in the DSM-IV-TR.Diagnostic criteria for Attention-Deficit/Hyperactivity Disorder A. Either (1) or (2)

This point is controversial, but pertinent to the case of ADHD. This topic is covered in greater detail in section 5.
It is true that classifications for natural kinds also require institutions, but in the case of people, classifications have a more prominent role.
The term is borrowed from Hacking [The Social Construction of What?] (p. 116), in an attempt to resolve the difficulty in finding an equivalent for the "hidden structure" put forward by Hilary Putnam. According to Putnam, the hidden structure is the "essence" that confers the properties of a kind and makes it possible to attach references to it. For example, the hidden structure of water is its chemical formula H 2 O. Thus, according to Putnam, whenever we speak of "water", we are referring to the kind that has the chemical formula H 2 O.
Cases in which there is a loping effect are now considered (Figure2). It should be noted that here, the "symptoms" are purely behavioral, and any biological bases found for sustaining them are always doubtful. The looping effect occurs in passing from stage 3 to stage 1, when a diagnosis causes a patient to change his behavior and thus, change the set of "symptoms" for that condition.Hacking (1999;2007) stated that in this case, the people thus classified are "moving targets", i.e. in changing their behavior, they even end up changing the stereotype of the classification. Hence, they are not stable subjects of knowledge. Jonathan Tsou (2007) criticized this point, through claiming that no matter how much an individual changes his behavior, he will be incapable of changing the biological causes of his condition. Tsou made particular reference to the biological causes of schizophrenia (excess of dopaminergic activity in the mesolimbic pathway): no matter how much a schizophrenic patient changes his behavior, he will be unable to diminish the dopamine concentration in his brain. It is possible that Tsou considered that this type of looping effect was as absurd as the idea that a cancer patient would be capable of removing the tumor just by "force of thought" or at least by behaving as if he had removed the tumor. However, the hypothesis that certain sets of symptoms described in the literature do not have unambiguous biological causes and thus do not constitute diseases in the biomedical sense needs to be taken into consideration. Tsou himself recognized that this was perhaps the case in a large proportion of the disorders listed in the DSM-IV(Tsou, 2007, p. 339n). It is very likely that ADHD fits into this group(Timimi, 2002, p. 88).
AUTHORS' CONTRIBUTIONSThis article derives from the master's degree project of Fabíola Stolf Brzozowski, under supervision from Prof. Dr. Sandra Caponi and with theoretical contributions from Jerzy André Brzozowski.
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Reticulocyte haemoglobin content as a diagnostic tool for iron deficiency and iron-deficiency anaemia in ill infants and children

P D R Swart
Department of Paediatrics and Child Health
University of the Free State
BloemfonteinSouth Africa

M B Chb
; K Rautenbach
Department of Paediatrics and Child Health
University of the Free State
BloemfonteinSouth Africa

MMed (Paed)M B Chb
Cert Med
Oncol
J E Raubenheimer
Department of Biostatistics
University of the Free State
BloemfonteinSouth Africa

Phd
Reticulocyte haemoglobin content as a diagnostic tool for iron deficiency and iron-deficiency anaemia in ill infants and children
10.7196/SAJCH.645
Background. The diagnosis of iron deficiency (ID) and iron-deficiency anaemia (IDA) in ill children is complicated by the unreliability of serum ferritin (S-ferritin). The presence of a microcytic, hypochromic anaemia suggests IDA but is not specific. There is a need for a diagnostic test that will be accessible, cost-effective and accurate for the diagnosis of ID in ill children. Studies done in healthy children have reported that reticulocyte haemoglobin content (CHr) is a reliable diagnostic test for ID, eliminating the need for S-ferritin determination. Objective. To evaluate the accuracy of CHr to diagnose ID and IDA in ill infants and children. Methods. A prospective, descriptive study was conducted. One hundred children, aged 6 months to 6 years, who were admitted to Pelonomi Regional Hospital, Bloemfontein, South Africa, during July 2012 and August 2012 were included. Results. The study group was divided into an iron-deficient group and an iron-sufficient group based on transferrin saturation (TfS). A statistically significant difference was found between mean corpuscular haemoglobin, serum transferrin and CHr in these two groups (p=0.0001). The sensitivity of a CHr level ≤29 pg to detect ID was 86%, and the specificity was 50%. Conclusion. CHr is an accurate diagnostic test for ID, and for IDA in combination with a low haemoglobin level, in ill infants and children.

RESEARCH

Iron deficiency (ID) is one of the main contributing factors of anaemia in infancy and childhood, with an average of 47% of pre-school children and 25% of school-age children affected globally, according to the World Health Organization (WHO). Sufficient iron stores are critical for the increased demands of growth during the first few years of life and during adolescence. [1] Recent research has indicated that ID has several unwanted neurological sequelae. Not only is it implicated to cause poor social interaction, [2] but it also seems to have a detrimental effect on development [3] and cognitive function. [4] ID has also been linked to sleep alterations, [5] breath-holding spells, [6] cerebral venous sinus thrombosis [7] and idiopathic intracranial hypertension. [8] With prolonged severe ID, the neurological sequelae may eventually become irreversible. [2] During the National Food Consumption Survey in 2005, it was noted that the proportion of children aged 1 -9 years who had ID and iron-deficiency anaemia (IDA) in the Free State Province of South Africa (SA) was 18.9% and 11.6%, respectively. [9] In 2010 the prevalence of suspected IDA at Pelonomi Regional Hospital in Bloemfontein was approximately 15%, assuming that a hypochromic, microcytic blood picture indicated IDA.

The causes of ID in childhood are multifactorial with inadequate dietary intake being the most common cause. The high prevalence of protein-energy malnutrition in SA also contributes as a result of impaired iron absorption. Blood loss in infants and childhood is not common, but cow's milk enteropathy and helminth infestations are well-known causes of occult bleeding in this population, and may contribute to IDA. [1] The gold standard for the diagnosis of ID and IDA is a bone marrow examination to assess iron stores, but this is a painful, invasive and costly procedure. Currently, the best alternative to diagnose ID is a low serum ferritin (S-ferritin) level, indicating low iron stores. Low S-ferritin in combination with a low haemoglobin (Hb) level is used to diagnose IDA. [10] Being an acute phase reactant, S-ferritin is an unreliable marker of ID in the presence of acute or chronic inflammation or illness. In ill or hospitalised children, the presence of hypochromic, microcytic red blood cells may indicate ID, but this is not specific. [12] Transferrin saturation (TfS) may also be used to assess for ID, but is seldom requested because of financial constraints. [10] There is a need for a diagnostic test that will be readily accessible, cost-effective and accurate for the diagnosis of ID in ill infants and children. Periods of hospitalisation may be the only opportunity to screen for ID and prevent its neurological sequelae before they become irreversible.

Studies among healthy children from Lithuania, Saudi Arabia and the USA, by Kiudeliene et al., [11] Bakr and Sarette, [13] and Ullrich et al., [14] respectively, have reported that the reticulocyte haemoglobin content (CHr) is a reliable diagnostic test for ID, and eliminates the need for iron studies. CHr measures the amount of Hb found in reticulocytes, providing an accurate measure of functional iron available for erythropoiesis over the preceding 3 -4 days. [10] CHr is not affected by inflammation, malignancy or anaemia of chronic illness. Although not currently used routinely because of poor availability and a lack of international, accredited reference ranges, studies have shown that CHr has potential as a diagnostic tool in ID and IDA in infants and children. [10] Studies that were performed internationally to assertain whether CHr is an accurate diagnostic test for ID and IDA used healthy infants and children as study subjects. According to our knowledge, no studies have been performed locally or among ill, hospitalised children. [11,13,14] Objective The primary objective was to evaluate the accuracy of using CHr to diagnose ID and IDA in ill, hospitalised infants and children.

The secondary objective was to assess the prevalence of ID and IDA in our study population.

Methods

We conducted a prospective, descriptive study. Children were included when they met the following inclusion criteria: (i) aged 6 months -6 years; (ii) admitted to the paediatric section of Pelonomi Regional Hospital; and (iii) the clinical information, as requested on the data form, was available. Children were excluded if they: (i) had a blood transfusion within the month prior to admission; (ii) were on iron supplementation during the past month; (iii) were known to have thalassaemia or other haematological diseases; (iv) were known to have a chronic illness (e.g. chronic renal failure or liver failure) or chronic infections (e.g. tuberculosis, although children who were HIVpositive without any other comorbidities were included); or (v) were known to have any malignancies. The study budget only allowed for the cost of the laboratory studies of 100 participants. Of the 436 children aged 6 months -6 years who were admitted to the paediatric section of Pelonomi Regional Hospital during July 2012 and August 2012, 100 (22.94%) were randomly selected to participate in the study.

HIV status was assessed on admission using either: (i) an HIV rapid test if HIV-unexposed or aged ≥18 months, taking into consideration whether the infant was still breastfeeding; (ii) an HIV polymerase chain reaction (PCR) test in exposed infants aged <18 months; or (iii) a history of HIV infection/receipt of antiretroviral therapy (ART).

Weight and height were assessed on admission and weight-for-age, height-forage and weight-for-height were plotted using the WHO Z-score growth charts.

Blood samples were collected for a full blood count, CHr and iron studies including S-ferritin, serum transferrin (S-transferrin) and serum iron (S-iron). The TfS value was calculated using the S-ferritin and Stransferrin levels. Special investigations were done by PathCare in Bloemfontein and the results were entered into a set data sheet per study participant.

The study group was divided into an iron-deficient and an iron-sufficient group based on the TfS level: ≤25% suggested ID and >25% suggested iron sufficiency. [12] These groups were further subdivided into anaemic and non-anaemic groups based on Hb values (Hb ≤11 g/dl). Since S-ferritin is an acute phase reactant and was expected to be raised in most ill children, this parameter was not used to determine iron status.

Statistical analysis

The analysis was done with assistance from the Department of Biostatistics, University of the Free State. Data from the groups which were identified were compared by the use of either the t-test or Fisher's exact test. Sensitivity and specificity were calculated using a 2×2 table with a DAG-stat Excel spreadsheet. [17] A p-value <0.05 was considered to be statistically significant, and where relevant, 95% confidence intervals (CIs) were calculated.

Ethics approval

Approval was granted by the University of the Free State's ethics committee. Informed consent was obtained from the parent/ caregiver before blood sample collection.

Results

Data were available for the 100 included patients. Baseline characteristics are shown in Table 1. The study group had significantly more males (95% CI 52.5 -70.9) than females. Iron sufficiency/deficiency and anaemia/ non-anaemia divisions were determined as seen in Fig. 1.

The CHr was assessed in relation to TfS. A CHr value ≤29 pg was used to indicate the presence of ID. [18] Table 2 indicates the classification of the study population based on CHr. A CHr level ≤29 pg was significantly useful for the diagnosis of ID and IDA (c 2 =21.70; df=3; Fisher's exact p<0.01).

Upon division of the sample into an irondeficient and iron-sufficient group only (i.e. only on the basis of TfS ≤25%), the mean CHr values were 24.74% and 28.67%, respectively, revealing a statistically significant difference (t=-4.34; p<0.01) ( Table 3).

Red blood cell parameters, S-ferritin and S-transferrin values are presented in Table 4. A statistically significant difference was found between the groups for mean corpuscular haemoglobin (MCH) (p=0.027), S-transferrin (p=0.0002) and CHr (p=0.0001).

The sensitivity of a CHr value ≤29 pg to detect ID was 86% (95% CI 77.3 -93.1) and the specificity was 50% (95% CI 26.0 -74.0).

An unexpected finding was that a group of children who presented with a TfS >25% (i.e. iron-sufficient) had an Hb level ≤11 g/ dl (i.e. anaemic), but a CHr level ≤29 pg ( Table   5). The TfS is calculated by using the S-iron and S-transferrin values; therefore, a low S-transferrin with a normal S-iron level will result in a normal TfS value. The known causes for low S-transferrin include chronic illness, malnutrition and S-transferrin being a negative acute phase protein. [15,16] In five of the eight cases with a normal TfS, anaemia and a low CHr, the S-ferritin level was well above normal, probably due to the current acute illness. Table 6 shows the haematological and biochemical parameters of the severely mal nourished children with oedema. All subjects had a low CHr suggestive of ID. The group also had low to borderline-normal S-transferrin levels, with two patients having very high S-ferritin levels suggestive of acute inflammation. Table 7 shows the haematological and biochemical parameters of the HIV-positive participants. All subjects had an Hb level ≤11 g/dl (i.e. anaemic); ten of the 12 (83%)

Discussion

ID in childhood not only causes anaemia, but also contributes to neuro developmental problems. [2][3][4][5][6] The current practice at Pelonomi Regional Hospital is to treat children with suspected IDA as indicated by haematological parameters, and prescribe iron supplementation upon discharge. On follow-up these haematological parameters are repeated to monitor the response to iron supplementation. The pitfall to this approach is that iron supplementation is only initiated in children in whom anaemia is already present -i.e. microcytic anaemia (mean corpuscular volume (MCV) <73 fl; Hb ≤11 g/dl). Children are not routinely screened for earlier phases of ID, when anaemia is not yet present. Another problem is that anaemia of chronic illness may also present with a low Hb level and microcytosis, in which case iron supplementation is not indicated. With anaemia of chronic disease, exogenous iron is diverted into the reticulo-endothelial system, which leads to the limited availability of iron for erythropoiesis. [16] We aimed to evaluate the accuracy of using CHr, a relatively new haematological test in our setting, to diagnose ID in acutely ill children. Reticulocyte production indices are known to be used to assess bone marrow activity, reflecting the balance between iron and erythropoiesis, with CHr serving as an accurate reflection of the available iron for erythropoiesis. [13] The aforementioned international studies used different reference ranges for CHr: Kiudeliene et al. used ≤28.55 pg, [11] Bakr and Sarette ≤26 pg [13] and Ullrich et al. ≤27.5 pg. [14] Since there is currently no international, accredited reference range for CHr and no reference range available for SA, we focussed on the upper limit of abnormal found in the literature, i.e. CHr ≤29 pg. [18] In our study, the group of children who had ID without anaemia (TfS ≤25% and Hb >11 g/dl) had a mean CHr level of 26.75 pg. This is comparable to the results found by Bakr and Sarette, [13] where the mean CHr for the iron-deficient group was 27.9 pg. The children with IDA in our study (Hb ≤11 g/dl and TfS ≤25%) had a mean CHr of 23.91 pg. In Bakr and Sarette's study, the IDA group's mean CHr was 23.1 pg. [13] Both Kiudeliene et al. and Ullrich et al. compared the iron-deficient group to a normal or control group. In Kiudeliene et al. 's study, the mean CHr for the iron-deficient and control groups was 25.58 pg and 29.25 pg, respectively. [11] In Ullrich et al. 's study, the mean CHr for the iron-deficient and iron-sufficient (control) groups was 26 pg and 28.1 pg, respectively. [14] The results of our study are comparable with these findings: the iron-deficient group (TfS ≤25%) had a mean CHr of 24.74 pg and the iron-sufficient group (TfS >25%) 28.67 pg (statistically significant difference; p=0.0001).

Table 4. Mean (±SD) v. median laboratory values between study population with and without ID based on TfS

Parameter

TfS ≤25%

t-value

The results of our study suggest that CHr, with a cut-off value of 29 pg, is an accurate marker for the diagnosis of ID, with a sensitivity of 86%. Kiudeliene et al. 's study, which used a lower cut-off value of 28 pg for CHr, had a sensitivity of 76%, [11] and Ullrich et al. 's study, which used a cut-off of 27.5 pg, had a sensitivity of 83%. [14] The specificity of using CHr as a diagnostic tool for ID in our study was 50%; that of Kiudeliene et al. 's study was 78.4%, [11] and Ullrich et al. 's study was 72%. [14] A possible explanation for the lower specificity in our study includes the presence of a sub-group of patients in our cohort who had anaemia with a normal TfS level,   but a low CHr level, suggestive of anaemia of chronic disease with underlying ID. As mentioned, our cohort included a group of infants and children who had a normal TfS but a low CHr level. This group may have represented a combination of anaemia of chronic disease and IDA. Another explanation might be that TfS levels were overestimated due to the use of a mathematical formula in their calculation. In clinical practice these patients would be followed up for their anaemia, and haematological and biochemical parameters would be repeated after resolution of acute illness, to assess the cause of anaemia.

The association between severe malnutrition and ID is of clinical significance. As noted, four study participants had severe malnutrition with oedema and 23 had severe malnutrition. The results showed that all of the study participants with severe malnutrition with oedema had IDA and a CHr ≤29 pg, and of the 23 participants with severe malnutrition, 14 (61%) had results suggestive of ID (i.e. TfS ≤25% with CHr ≤29 pg). Iron supplementation in the rehabilitation phase, as advocated by the WHO's 10 steps of managing severe malnutrition, is therefore justified.

Anaemia is a common occurrence in children with HIV infection, not only secondary to the disease, but also associated with ART. [19] The study had 12 participants who were HIV-reactive. This group's results suggested anaemia of chronic disease. In anaemia of chronic disease, as for instance with HIV infection, S-iron, S-transferrin and TfS levels are reduced, with a normal to high S-ferritin level. The seven cases observed with a low CHr level might have been attributed to the presence of both ID and anaemia of chronic illness. [16] It is our opinion that CHr will be an accurate and cost-effective marker for diagnosing ID in acutely ill infants and children. CHr interpreted together with the full blood count has a high sensitivity. Besides being falsely elevated in iron-deficient children with underlying disease, the assessment of S-ferritin costs approximately three times as much as that of CHr. When an infant/child is assessed to be irondeficient on the basis of CHr, the S-ferritin level can be determined after recovery from acute illness to confirm the presence of ID.

The prevalence of ID in our sample, based on TfS, was 82% (95% margin of error ±7.53%), with 70.7% of these children having IDA. This represents a significant amount of children who require iron supplementation and regular follow-up to evaluate their iron status in order to prevent neurodevelopmental sequelae such as learning delay, poor socio-emotional performance and sleep disturbances.

Study limitations

Study limitations included the broad age categories of the cohort, and the small size of the sample owing to financial constraints. Further studies are needed with larger samples and narrower age categories to assess the sensitivity and specificity of CHr as a diagnostic test for ID in acutely ill children.

Conclusion

The results of our study support the evidence that CHr is accurate in the diagnosis of ID, and of IDA in combination with a low Hb level, in ill, hospitalised infants and children. After an infant or child has recovered from their acute illness, S-ferritin can be determined to support the diagnosis.

Funding acknowledgement. This study was funded by PathCare laboratories, Bloemfontein, and Roche, SA.

Fig. 1 .
1Algorithm used for classification of the study population based on transferrin saturation (TfS). (Hb = haemoglobin; ID = iron deficiency; IDA = iron-deficiency anaemia.)

Table 1 .
1Baseline characteristics of the study populationCharacteristics
n

Gender
Male
Female

62
38

Age
6 -18 months
18 -36 months
36 months -6 years

51
29
20

HIV status
Negative
Positive

88
12

Diagnosis
Pneumonia
Gastroenteritis
Meningitis
Other

45
13
8
34

Nutritional status
Normal
Underweight
Severe malnutrition
Severe malnutrition with
oedema

60
13
23
4

Table 2 .
2Classification of the study population using CHrClassification
CHr ≤29 pg
n (%)
CHr >29 pg
n (%)

No anaemia (n=7)
1 (14.3)
6 (85.7)

Anaemia of other cause (n=11)
8 (72.7)
3 (27.3)

ID (n=24)
20 (83.3)
4 (16.7)

IDA (n=58)
51 (87.9)
7 (12.0)

Total (N=100)
80 (80.0)
20 (20.0)

CHr = reticulocyte haemoglobin content; ID = iron deficiency;
IDA = iron-deficiency anaemia.

Table 3 .
3CHr values for ID and IDA groupsGroup
TfS
Hb
n
Range
Median (95% CI) Mean (95% CI)
SD

No anaemia
>25%
>11 g/dl
7
27 -33
30 (27 -33)
30.29 (28.54 -32.04)
±1.89

Anaemia of other cause
>25%
≤11 g/dl
11
21 -33
27 (24 -33)
27.64 (25.23 -30.05)
±3.59

ID
≤25%
>11 g/dl
24
20 -34
27 (25 -29)
26.75 (25.26 -28.24)
±3.52

IDA
≤25%
≤11 g/dl
58
15 -32
24 (22 -25)
23.91 (22.79 -25.06)
±4.38

Table 7 .
7Haematological and biochemical parameters of HIV-positive childrenIndex case

Hb
>11 g/dl*

CHr
>29 pg*

S-iron
7.2 -21.5 mmol/l*

S-transferrin
2.0 -3.6 g/l*

TfS
25 -50%*

S-ferritin
13 -150 µg/l*

5
9.0
30.0
7
2.03
13.5
69

6
11.0
32.3
9
1.50
23.5
123

10
9.7
25.3
5
1.50
13.0
629

25
9.9
32.1
9
3.06
11.5
188

32
6.3
24.3
3
1.70
6.9
725

34
8.1
21.6
10
2.26
17.0
209

38
10.7
30.0
7
2.03
13.5
59

49
11.0
27.2
20
2.03
38.5
45

58
8.1
32.8
7
0.81
33.8
1100

68
8.7
23.9
6
2.23
10.5
161

86
7.0
18.3
4
1.32
12.0
981

90
10.1
20.8
3
2.71
4.0
291

Hb = haemoglobin; CHr = reticulocyte haemoglobin content; S-iron = serum iron; S-transferrin = serum transferrin; TfS = transferrin saturation; S-ferritin = serum ferritin.

*Normal reference ranges.

Table 6 .
6Haematological and biochemical parameters of children with severe malnutrition with oedemaIndex case

Hb
>11 g/dl*

MCV
73 -84 fl*

CHr
>29 pg*

S-transferrin
2.0 -3.6 g/l*

TfS
25 -50%*

S-ferritin
13 -150 µg/l*

36
6.3
97.0
24.3
1.70
6.9
725

71
8.7
71.4
25.7
0.64
104.0
169

74
9.7
68.7
19.3
2.42
6.5
50

90
7.0
71.2
18.3
1.32
12.0
981

Hb = haemoglobin; MCV = mean corpuscular volume; S-transferrin = serum transferrin; CHr = reticulocyte haemoglobin content; TfS = transferrin saturation;
S-ferritin = serum ferritin.

* Normal reference ranges.

Table 5 .
5TfS = transferrin saturation; Hb = haemoglobin; CHr = reticulocyte haemoglobin content.* Normal reference ranges.Subjects with normal TfS (>25%), anaemia (Hb ≤11 g/dl) and low CHr (≤29 pg)

Index case

CHr
>29 pg*

S-iron
7.2 -21.5 mmol/l*

S-transferrin
2.0 -3.6 g/l*

TfS
25 -50%*

S-ferritin
13 -150 µg/l*
Nutritional state

7
25.7
18
2.02
34.8
142
Normal

28
29.0
6
0.63
37.2
216
Severe malnutrition

30
27.3
14
2.14
25.6
243
Normal

71
25.7
17
0.64
104.0
169
Severe malnutrition
with oedema

87
26.7
16
1.96
30.0
23
Severe malnutrition

89
20.7
12
1.59
30.0
451
Normal

103
27.6
16
1.37
46.0
258
Normal

105
24.0
15
1.99
29.0
114
Normal

S Afr J CH 2014;8(1):23-27. DOI:10.7196/SAJCH.645
Acknowledgements.We extend our gratitude to all caregivers and children who participated in the study.
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