Abstrakt
Termin „spektrum autystyczne” odnosi się do grupy niepełnosprawności neurorozwojowych, powodujących znaczne trudności socjalizacyjne, komunikacyjne i behawioralne. Chociaż spektrum autystyczne wykazuje bardzo dużą zmienność fenotypową oraz genetyczną różnorodność, nie ma jak dotąd jego jasnych markerów biologicznych. Jednakże niemowlęta ze spektrum autyzmu moż-na odróżnić od typowo rozwijających się już przed 12. miesiącem życia, moż-na podstawie skojarzone-go występowania braku typowych zachowań i obecności zachowań atypowych. W rezultacie badań nad behawioralnymi markerami spektrum autyzmu powstały liczne instrumenty do badań przesie-wowych, które proponuje się już w wieku 5 miesięcy. Artykuł opisuje podstawowe badanie bardzo wczesnych symptomów autyzmu, przeprowadzone przez the Mifne Center w latach 1997–2007, które doprowadziło do rozwoju badań przesiewowych małych dzieci na obecność symptomów pre-auty-zmu (Early Signs of Pre-Autism Screening in Infants-ESPASI), odpowiedniego dla dzieci w wieku 5–15 miesięcy. Przebadano 110 dzieci, u których zdiagnozowano autyzm w wieku 2–3 lat, poprzez analizę retrospektywną taśm wideo z pierwszych miesięcy ich życia, nagranych przez rodziców, za-nim powstało jakiekolwiek podejrzenie wadliwego rozwoju. Analiza nagrań wideo, zawierająca kate-gorie: tworzenia więzi, rozwoju motorycznego, jedzenia, zainteresowania otoczeniem, doprowadziła do wyodrębnienia 8 zmiennych związanych z wczesnymi oznakami autyzmu w pierwszym roku życia dziecka. Są to: nadmierna pasywność, nadmierna aktywność, brak kontaktu wzrokowego, brak reakcji, odmowa jedzenia, awersja do dotyku, opóźniony rozwój motoryczny, obwód głowy. Wyniki tych badań wskazują na możliwość wyodrębnienia oznak związanych z wczesnym screeningiem w pierwszym roku życia. Skorzystanie z tej możliwości poprzez odpowiednią stymulację może wpływać na rozwój połączeń neuronowych i w ten sposób przyczynić się do zminimalizowania intensywności fenotypo-wej prezentacji autyzmu.
Słowa kluczowe: spektrum autyzmu, wczesne symptomy, niemowlęta, screening, ESPASI.
Introduction
Autism Spectrum Disorder (ASD) refers to a group of neurodevelopmental dis-abilities causing significant social, communicative and behavioral difficulties. Even though ASD demonstrates great phenotypic variability and genetic heterogeneity, there are as yet no clear biological markers for ASD. Despite the lack of biological markers evidence exists for the presence of behavioral markers for autism already in the first 2 years of life (Bauman 2003; Alonim, 2004; 2007; Massie, 2007; St. Clair et al., 2007; Courchesne et al., 2011; Pierce et al., 2011; APA, 2013). Infants with ASD can be distinguished from typically developing infants already from 12 months based on a combination of lack of typical behaviors and the presence of atypical behaviors (Wetherby and Woods, 2008). The American Academy of Pediatrics rec-ommends screening for ASD from 18 months (Johnson & Myers, 2007). Research
into behavioral markers of ASD has led to a number of screening instruments be-ing proposed from as early as 5 months of age. These include, among others, the Mifne Center’s Early Signs of Pre-Autism Screening in Infants (ESPASI) suitable for infants between 5–15 months (Alonim, 2007); the Autism Observation Scale for Infants (AOSI) applied from 6–18 months (Bryson & Zwaigenbaum, 2014); the Communication and Symbolic Behavior Scales Developmental Profile (CSBS DP) applied from 12–24 months (Weatherby & Prizant 1998, 2002); and the Modified Checklist for Autism in Toddlers (M-CHAT) applied from 18–30 months (Robins et al., 2001). This paper describes the foundational study of very early signs of au-tism conducted by the Mifne Center that subsequently led to the development of the ESPASI screening instrument.
Methodology
A study conducted from 1997 until 2007 examined 110 infants who were even-tually diagnosed with autism at the age of 2–3 years, using a retrospective analysis of video-recordings of the first months of their lives made by their parents before any suspicion concerning defective development arose. 84 (76.4%) boys and 26 (23.6) girls between the ages of 3–15 months participated in this study. Since all the tod-dlers in this group were diagnosed with autism between the ages of 2–3; their first year of life was analyzed as a self-control group.
The parents arriving for an interview with their child who had been diagnosed on the autism spectrum were asked whether they had any videos of their child from the first year of life, before there was any suspicion of any sort of defect in his/her development. There were 2 criteria for inclusion of children in this retrospective evaluation of home videos: a. The film records sent by the parents covered a peri-od from at least 3 months old until 15 months at the latest, including at least three different phases of 4 months’ duration. b. All the children who were filmed on the videotapes had received a diagnosis of autism at the ages of 2 to 3 years. Parents who agreed to participate in the study signed a consent form when delivering the video-tapes. The cassettes were encoded according to different stretches of time from 3 months, 5 months etc. Eventually, 110 video cassettes were collected relating to 110 different infants.
4 trained researchers, who were experts in child development and who did not know the children, watched the films in pairs of 2. Each pair of researchers watched the films separately and was instructed to observe for any variables that appeared to depart from the norm of age appropriate infant behavior. Additionally, the DSM-IV (1994) provided the baseline categories of behavioral variables associated with the autism spectrum. However, this was not sufficient, since the criteria mentioned in the DSM-IV relate to older children, above the age of 3 years, and did not include criteria relating to eating, motor development and bonding.
Investigated variables were listed under 4 general categories: bonding, motor development, eating, and interest in environment. Bonding included eye contact and physical touch. Motor development included physical development, develop-mental milestones, passivity, activity, and head circumference. Eating included en-joyment, resistance, types and amount of food. Interest in environment included attention, following persons, following objects, and reaction to people. The variables in these categories were further evaluated in terms of age appropriate behavior and context. It is important to stress that the variables associated with early signs of au-tism detailed in this study were developed through the process of this study, and did not exist in their full clinical descriptions prior to the study’s completion.
Let us consider one example: eye contact. An infant’s eye contact was exam-ined according to the following parameters: turning the gaze towards the person opposite the baby, duration of the gaze, the focus of the gaze, deviation of the gaze, and distraction of the gaze. This was measured according to a scale from 1 (there is no eye contact) to 10 (full eye contact). Measurement was conducted after deter-mining a uniform standard for the meaning of each grade on the scale. All the data from these evaluations were then collected and processed on the computer into categories relating to eye contact for each infant at different stages: 3–6 months, 6–9 months, 9–12 months, and 13–15 months.
Additionally, questionnaires were distributed to the parents including, inter alia, the following questions: When did you first notice your infant’s development problem? Who noticed the problem? How did you react? An anamnesis of the in-fant’s eating and sleeping habits was also obtained.
Results
The retrospective analysis of the 110 videos in terms of the 4 general research categories – bonding, motor development, eating, and interest in environment – re-sulted in the identification of 8 variables associated with early signs of autism in the first year of an infant’s life. These include excessive passivity, excessive activity, lack of eye contact, lack of reaction, refusal to eat, aversion to touch, motor development delay, and head circumference. These 8 variables are described below.
Excessive passivity – was defined in cases of: lack of crying, lack of movement, lack of interest in what was happening in the surroundings, not tracking people with their gaze, lack of effort to attain an object, infants being “easy to take care of”, all measured according to parameters of time and frequency of the phenomenon (Alonim, 2004).
Excessive activity – was defined in the case of consistent restless movement, con-sistent crying, and obsessive preoccupation with an object, measured according to parameters of time and frequency of the phenomenon (St. Clair, et al., 2007).
An analytic observation of all the components of the infants’ development pointed to a lack of regulation, which was expressed in many cases by over-activity.
Certain brainstem functions, essentially the ABR function, first emerge around 30–33 weeks’ gestation, a period at which many premature births occur. This peri-od is critical for major developmental changes in the equilibrium and the auditory pathways in the brainstem, including myelination (Jiang et al., 2009). Disruptions in myelination may disrupt white matter maturation and the integrity of neural con-nectivity, and synchronization of neural oscillations. These in turn may bear impli-cations for the establishment of emotional and attentional functions (Doesburg et al., 2011). Brainstem injury has been found to disrupt physiological regulation and homeostasis. These disruptions impact the autonomic nervous system (Karlsson et al., 2005); they also affect circadian arousal regulation, as well as visceral homeosta-sis modulation of internal states, such as hunger and thirst (Batterham et al., 2007).
All of these systems are interrelated and moderate emotional and attention regula-tion in infants during the neonatal phase (Geva et al., 1999).
Lack of eye contact – the infant’s eye contact with the parents or other caregivers was examined. This variable evaluates the infant’s focus of attention, in terms of his/her tendency to follow objects rather than people, or vice-versa. Measures of eye contact included the following: in which direction the infant looked; for how long; when the infant lowered their gaze; whether the infant ignored the object; eye contact during closeness, during feeding, during play, or averting gaze (Ayer, 2003;
Alonim, 2004).
From the very beginning, human infants are acutely sensitive to social stimuli, especially faces (Maurer & Salapatek, 1976; Morton & Johnson, 1991; Striano &
Rochat, 1999), and from 3 to 5 months their gaze and affective behavior reflect in-creased sensitivity to their partner’s slight deviations in gaze and facial expressions (Symons et al., 1998; Striano & Stahl, 2005). Indicators of brain functioning may be sensitive predictors, and atypical eye contact is characteristic of the syndrome (Baron-Cohen, et al., 1997).
Lack of reaction – is defined as: no turning of the head, no deflection of the baby’s gaze, no smile or babbling, and no attempt to divert attention. There is no reaction to the parents’ departure (Alonim, 2004).
Video analyses showed that the infants who did not react to voices also did not react to presence, and vice-versa. There were no infants amongst those examined who reacted to presence but did not react to voices, a phenomenon that characteriz-es infants with hearing loss. Neverthelcharacteriz-ess, most infants reacted to hearing the voice of his/her parent singing.
Refusal to eat – although eating problems are not mentioned as part of the di-agnosis of autism in the DSM-IV (1994), abnormalities in eating habits are listed as associated features of the autism disorder (Wing, 1987). Most of the children who have been diagnosed on the autism spectrum display characteristics of eating disorders.
Nutrition difficulties are common in children with autism from the early stages of life. “How we eat and how we learn to eat are important, so is what we eat” (Ait-ken, 2009). This category was divided into a main element of refusal to eat and three sub-categories: refusal to move on to fruits/vegetables, refusal to move on to solid foods, and fixation on certain foods. This observation by video tapes also relied on parents’ reports.
The development of eating skills is influenced by several integrative factors: the baby’s anatomical development and growth, the infant’s medical state, the infant’s emotional and social development, and type of environment (Eicher, 1997). Disor-ders of eating behavior in infants are represented by a range of patterns that include:
an abnormal sucking reflex, rejection of breast feeding, refusal to eat, difficulty in swallowing (sometimes as a result of feeding via a tube), persistent and excessive spitting up (reflux has been cancelled out), lack of adjustment to solid food, abnor-mal chewing motion, fixation on miniabnor-mal variety of foods, lack of curiosity regard-ing food, and aversion to various smells and textures.
Food refusal is defined as the consumption of fewer than the number of calories necessary or the rejection of food (Riordan, et al., 1980; Luiselli, 1989).
Food over-selectivity is defined as choosing only a limited number of food stuffs to be consumed or consuming an inadequate variety of food stuffs (Luiselli, 1989;
Munk & Repp, 1994). Most of the eating problems in children with autism can be included in the category of behavioral and sensory disturbances (Alonim, 1999;
Schwartz, 2003). Many children are afraid of the change in texture in their mouths, of chewing, which changes the consistency of the food, of swallowing, which has the aspect of disappearance, of the lack of ability to contain the change, and of a sense of guilt because of this (Alonim, 2004). The fear of loss of the food is also connected with problems in sensory functions involved in the planning of the movement (Ad-rien et al., 1992; Baranek, 1999). The DSM-5 states that, “sensory sensitivities may interfere with eating”.
Aversion to touch – physical touch relates to the amount of mass and physical proximity that the infant allows (Carvill, 2001). Aversion to touch relates to the infant’s contraction or arching back and an expression of dissatisfaction when the baby is held, cuddled or kissed. The difficulty in allowing contact usually stems from a tactile overload that makes the infant feel discomfort or even pain. Difficulties in sensory processing are characteristic of autism. Although for decades the research literature reported a lack of responsiveness as a sensory deficiency, in the last two decades it has become clear that it is, in fact, over-sensitivity in the tactile, visual, audio and oral systems that involves a deficiency of integration between the sys-tems, thus causing a lack of sensory modulation (Dunn & Westman, 1995). A lack of sensory modulation may create confusion and anxiety, and in order to overcome
this state the infant holds on to fixated habits that may help them to decrease his/
her anxiety.
Motor development – did the baby roll over, crawl, sit, stand, walk at the appro-priate development times, was the baby hypotonic? The importance of sensory-mo-tor developmental issues is increasingly recognized as an early indicasensory-mo-tor for the diagnosis of autism (Baranek, 1999). Teitelbaum et al. (1998) argued that almost all of the movement disturbances in autism can be interpreted as infantile reflexes that are not inhibited or fail to appear at the appropriate age of development. A study by Phagava et al. (2008) detected abnormalities in spontaneous motor activity – abnor-mal fidgety movements – of infants later diagnosed with autism.
Head circumference – was also examined according to the local Mother and Baby Wellness Clinic records. According to the study of Courchesne et al. (2011), brain overgrowth in males with autism involved an abnormal excess number of neurons in the PFC, which is also responsible for emotional and behavioral pro-cessing. “Normal brain development is not a monologue but a dialogue, in which the brain generates neural circuits and the child’s experiences determine which ones survive” (Bauman, 2003). Although prefrontal abnormality has been theorized to underlie some autistic symptoms, the cellular defects that cause abnormal over-growth remain unknown.
In accordance with the aim of this study, the statistical analysis focused on iden-tifying the striking and common signs and the paired correlates between them. The
Graph 1: Eight Variables Associated with Autism in Early Infancy (All the graphs/table/diagrams/ relate to n = 110)
procedure occurred accordingly in two phases. In the first phase, a baseline evalu-ation was conducted of the frequency of the identified indicative signs that were reported to occur amongst the infants. This statistical procedure demonstrated tho-se indicative signs occurring frequently among the infants, as well as thotho-se signs that occurred infrequently amongst a small portion of the investigated infants. In the second phase, a cross-sectional study was conducted comparing each identified sign against all the others, in order to identify “pairs” of signs, i.e., pairs of variables whose common occurrence was clearly apparent. In this manner, it was possible to identify a number of shared indicative signs occurring with high frequency, a find-ing that may prove important in identifyfind-ing the early signs of autism.
The table shows the results for the co-existence of two variables, each of which represents a percentage of the variable both in the first and also in the second co-lumn. Key variables that can be identified to constitute important factors in the diagnosis of the infants include excessive passivity, lack of eye contact, and delayed motor development. In older ages, the weights of these variables may of course alter.
Table 1: Results for the co-existence of two symptoms