What is one significant reason for the advances in fine motor skills in children 6 to 8 years old?

Fine Motor Milestones

Fine motor development progresses in the upper extremity most notably in the proximodistal direction, beginning at the shoulder girdle and progressing to the crucial milestone of the mature pincer grasp. When first observed in the newborn, the primitive reflexes limit the purposeful arm movements to general writhing movements, as previously described, with all other movements being obligatory and reflexive. The palmar grasp reflex allows a newborn to clench an object when pressure and touch are applied to the palm; however, this is not volitional in nature.

The first readily recognizable fine motor skill that is crucial to normal development is unfisting. With the loss of palmar grasp reflex, the infant can extend the fingers and maintain the hand in an open position at 4 months of age, paving the way for further progressive fine motor development (Accardo and Capute, 2005). The child's generalized writhing and fidgety movements, emanating primarily from the shoulder and upper arm, advance with the diminishing of the ATNR, tonic labyrinthine, and Moro reflexes into more refined and purposeful movements in the distal direction. These advances are first shown at 3 to 4 months when the infant can bring his or her hands to midline and manipulate and play with his or her fingers (Accardo and Capute, 2005) (Table 66-3). Infants typically put their hands in their mouth at this time. While placing the hands in midline position, the infant's fine motor skills remain unilateral at this time with an inability to cross this midline. Improved control of movements from the shoulder girdle and upper arm allows the infant to swipe crudely and imprecisely at dangled objects.

At 5 months, the infant can take an object offered close to the chest and held at midline and grasp it in a single hand through simple unfisting on the other side. The skills advance across the midline at 6 months with the development of the corpus callosum. At this time, the infant is no longer bound to ipsilateral grasping. Dangled objects such as rings and held objects such as 1-inch blocks are easily grabbed. The infant can be observed grabbing an object with one hand, passing it to the midline, and transferring it to the contralateral side. As grasping skills and arm control advance, transfer of smaller objects is seen.

The infant's grasp progresses from the proximal palm toward the distal fingertips over the next several months and from the ulnar (medial) to the radial (lateral) side. The first grasping at 5 months involves an overhand raking movement. A large object is approached with the palm from above, the fingers flexing together and grasping the object. With the skills advancing more distally and in a radial or lateral direction, the infant relies less on palm support and gains control of movement of individual fingers originating on the ulnar side with the fifth digit. Beginning first with five-finger grasping, the child develops increasing finger strength, allowing him or her to grasp progressively smaller objects with fewer fingers, shifting from five to three or four and then two fingers.

The infant's grasp reaches the crucial milestone of the mature pincer grasp at 10 months, when the child can grasp a small object, such as a bead or small food snack, through apposition of the thumb and first finger only. This mature finger control also is observable at this age with isolated first finger pointing (“the pointer”) and placing of the finger in small holes (testable in a pegboard). Infant fine motor development culminates with the crucial and often unnoted voluntary release response at 12 months, shown with purposeful dropping of an object, handing it to another person, or placing it.

Cerebellar amyloid in AD and DS

Although neuropathological reports suggest that the reduced size of the DS cerebellum leads to a delay in fine motor development[25, 50], studies of AD neuropathology in this structure during gestation are minimal. We found scattered diffuse amyloid-like plaques, some containing a dense central core immunoreactive for APP/Aβ1–16 (6E10) in the white matter and granular cell layer of the cerebellum at postnatal day 10 and between 4 and 20 weeks of age in DS. Another study reported virtually no amyloid plaque pathology between 0 and 53 years of age using the 4G8 antibody (APP/Aβ17–24), but beyond this age all cases displayed various levels of Aβ pathology in DS [38]. The difference between earlier and a more current study [38] may be related to the sequence specificity of the 4G8 antibody [51]. However, in both the adult AD and DS cerebellum, amyloid deposition visualized using an antibody against the Aβ peptide (Aβ4) appears as amorphous patches, which often occur perpendicular or parallel to the pial surface within the molecular layer (ML) [52]. We recently investigated the deposition of amyloid using antibodies that detect different epitopes of the Aβ sequence in cerebellar cortex obtained from demented (average age 51.2; range 45–59) and nondemented (average age 50.3; range 44–60) individuals with DS (average age 81.7; range 71–98) and healthy aged controls (average age 70.9; 51–85). Cerebellar tissue reacted with an antibody that recognizes both APP and Aβ (6E10), revealed patches of APP/Aβ in the ML that was greater in both DS groups compared to AD and nondemented healthy subjects (Fig. 3A–D). Since the elevation of levels of the long form of Aβ, Aβ42, compared to the short form, Aβ40, plays a role in the early events underlying the pathogenesis of AD, we evaluated Aβ42 and Aβ40 immunoreactivity within cerebellar tissue from these same adult cases. Aβ42, but not Aβ40 immunoreactivity, was found in the cerebellum of both DS groups but to a lesser extent in AD (Fig. 3E–H). In DS, Aβ42 appeared as bands perpendicular to the pial surface within the ML (Fig. 3F and G). Interestingly, only scattered patches of APP/Aβ and Aβ42 were seen in the cerebellar ML in AD (Fig. 3D and H). Both demented and nondemented individuals with DS had significantly higher Aβ42 plaque loads in the ML compared to nondemented controls. Cerebellar Aβ42 loads in demented individuals with DS were significantly increased compared to AD [53].

CASE STUDY

John is a 9-year-old male who was referred for assessment due to a history of academic difficulties. A review of John's developmental and medical history indicated that John was born full-term after a normal pregnancy. Developmental gross motor milestones were attained within normal limits; fine motor development was slightly delayed. Developmental language milestones were also obtained within normal limits.

John's educational history indicated that he began experiencing reading difficulties in kindergarten. During the primary grades, John continued to have difficulty with reading; he demonstrated poor phonetic and word attack skills and displayed number and letter reversals. During grade 4, John's grades tended to be inconsistent across subjects. The teacher noted that John also had difficulty following spoken directions and appeared inattentive.

John was a willing participant during the testing sessions; his use of language was fluent and prosodic but was marked by mild word-finding difficulties. He also experienced difficulty expressing himself orally when the material was complex. Although his comprehension at the sentence level was good, he appeared to have difficulty retaining directions and had to repeat them to himself frequently. In general, John's attention span, activity level, and impulsivity appeared to be age-appropriate within the context of the testing session. He displayed good motivation and task persistence throughout testing.

Among others, the following tests were administered during the session: WISC-III, CMS, WIAT, and Woodcock-Johnson Tests of Achievement—Revised. (See Table 1.3 for tests administered and accompanying scores.) Intellectual functioning, as measured by the WISC-III, was found to be in the high average range. John obtained an FSIQ of 116 (CI = 110–121); VIQ of 112 and PIQ of 119. In general, John's verbal and visual-spatial reasoning abilities were uniformly developed. Analysis of factor/index scores revealed a relative strength in speed of processing and a relative weakness in focused auditory attention/working memory (VC = 113; PO = 113; FD = 96; PS = 126).

TABLE 1.3. Student Scores on Assessment Protocols

Source: From case study data provided courtesy of Dr. M. J. Cohen.

In order to assess learning and memory, John was administered the CMS. Analysis of his performance on the subtests constituting the Attention/Concentration Index indicated that John exhibited focused auditory attention/working memory skills that were discrepant from his measured intellect. He also demonstrated reduced working memory for material presented orally. Further, he had difficulty reciting the alphabet during the Sequences subtest. Comparison of John's superior General Memory Index (GMI = 133) with his best estimate of intellectual potential (FSIQ =116) indicated that his ability to learn and remember was above expectancy. However, a more detailed analysis of John's performance indicated that he was demonstrating significant variability in his ability to learn and remember. Comparison of John's auditory/verbal and visual/nonverbal index scores indicated that his visual learning and memory were superior overall. In contrast, his verbal learning and memory ranged from average to superior. John demonstrated above average ability to learn concise rote verbal material (Word Pairs) presented three times and superior ability to recall the material after a 30-minute delay. However, his ability to learn lengthy verbal material presented once (Stories) was average. John had difficulty encoding material presented at the beginning of the paragraphs.

On the Woodcock-Johnson Tests of Achievement—Revised, John demonstrated low average phonetic word attack skills and average reading comprehension. As a measure of written expression, John was administered the Written Expression subtest from the WIAT. John performed in the low average range on this subtest.

In summary, the results of the assessment indicated that John was currently functioning within the high average range of intellectual ability. He demonstrated relative strengths in areas of visual-spatial perception/construction, sustained attention, and visual learning and memory. These were contrasted by relative weaknesses in phonological processing, focused auditory attention/working memory, and verbal learning and memory for lengthy material presented once. During testing, John was also noted to exhibit reduced auditory working memory, having to repeat directions to himself before completing tasks. Academically, John demonstrated relative strengths in arithmetic contrasted by relative weaknesses in basic reading and written expression that were of learning disability proportion. It is likely that the inattention noted at home and school was due to his reduced auditory processing as opposed to an attention deficit disorder per se, given his average performance in sustained attention for visual material. Taken together, this pattern of test performance was consistent with a diagnosis of Specific Learning Disability in Reading and Written Expression. As a result, it was recommended that John receive special education services designed for children with learning disabilities. John's teachers were made aware that his word attack skills and knowledge of sight words were weak, given his measured intellect. Because his visual learning and memory were superior and his phonological processing skills were poor, it was recommended that reading/writing instruction should emphasize visual and multisensory approaches. Further, it was recommended that John would benefit from approaches that relied heavily on tactile input and experiential learning. Given his learning disabilities and reduced auditory attention, a reduction in the amount, but not the difficulty level, of assignments was recommended in order to assist John in completing classroom tasks and homework in a timely manner.

4.4 Intervention studies

Only five studies identified in the review targeted improving fine motor skills in children with DS. This research includes intervention (Aparicio & Balaña, 2009; Patton & Hutton, 2016; Zareian & Delavarian, 2014) and case study approaches (Berg, Becker, Martian, Danielle, & Wingen, 2012; Lersilp, Putthinoi, & Panyo, 2016). Only one of these studies examined infants with DS. Aparicio and Balaña (2009) found that infants who started an individualized clinician-directed fine motor stimulation program at 4–6 months of age had higher fine motor development quotients as measured by the Brunet-Lèzine Scale at 18 months than infants who did not start the intervention until they were 8–9 months of age. These results suggest that intervening early in fine motor skills for children with DS may be beneficial, although more research is needed to support this claim.

One intervention study conducted in infants with DS that was not specifically focused on fine motor skills and yet is likely to be relevant for developing these skills was a “tummy time” intervention (Wentz, 2017). In this study, the researchers instructed parents of infants with DS to provide 90 min of activity in the prone position (accumulated over the course of a day) while at home until the infant's achieved independent transitioning in and out of sitting. Parents were given several different versions of tummy time using materials that are often found in the home such as towels, couch cushions, and the parent's own body. The main outcome measure was the Bayley Motor Composite score, which provides an assessment of gross motor and fine motor skills. The results indicated that this intervention was effective in promoting motor skill development. Additional analyses revealed that infants who began the tummy time intervention before 11 weeks of age showed significantly more improvement than those who began after 11 weeks of age. The results support the idea of beginning regular tummy time in infants with DS as early as medically feasible to do so.

The remainder of the fine motor skill intervention work has been in older children with DS. Zareian and Delavarian (2014) devised an intervention for 7- to 11-year-old children with DS based on the game of sport stacking, which involves coordinating both hands to stack cups into specified patterns as quickly as possible. After 8 weeks of practice with the task, children exhibited improvements in circle cutting, drawing lines, card sorting, and bead stringing as measured by the BOT-2. Berg et al. (2012) also implemented an 8-week intervention and measured motor outcomes with the BOT-2. In this case study involving a 12-year-old with DS, playing weekly games on Nintendo Wii in a family context improved upper-limb coordination and manual dexterity. Lersilp et al. (2016) implemented a shorter 5-week intervention in a case study of an 8-year-old child with DS and measured pre/post fine motor abilities with the BOT-2. There were improvements in bilateral hand coordination, hand prehension, manual dexterity, and in-hand manipulation following a fine motor program of 45 activities that included functional skills like folding paper, pouring water from a bottle, fastening buttons, and writing. Finally, Patton and Hutton (2016) conducted an 8-month intervention focused on improving handwriting production in a sample of 5- to 11-year-old children with DS using the curriculum Handwriting Without Tears. Teachers, parents, and occupational therapists worked together to create individualized goals for each child and then worked with the children to achieve these goals. Several obstacles to success were identified, such as (a) conflicts between the child's needs and the standard curriculum and (b) teachers' lack of training in handwriting instruction, especially how to teach handwriting to children with disabilities. When these conflicts were addressed and the three-person team worked with each child to bring them closer to their goals, they had considerable success. Most of the children made progress toward their goals, with only 18% finishing the intervention with no ability to write any letters. This study highlighted the limited research on handwriting in children with DS, and the need for collaboration between teachers, parents, and occupational therapists to develop successful interventions.

NORMAL DEVELOPMENT OF SELF-CONTROL AND SELF-REGULATION

Many of the antecedents of normal self-regulation are present during brain development in the human fetus. The bulk of neurons are produced prenatally, and pruning occurs postnatally. Normal neuron cell migration occurs between 5 to 6 and 25 to 26 weeks of gestation, and errors in this migration will result in brain abnormalities, which can adversely affect many functions.

After birth, the most obvious self-control process begins in motor areas. Myelination of long tracts occurs rapidly in the first year of life as control of motor development proceeds from head to feet. A normal infant develops control of arms before legs and gradually demonstrates accuracy in reaching, grasping, transferring, and manipulating. By a year of age, the infant has control of the fine pincer grasp, and this is about the time that infants have sufficient control of legs to begin to walk. The sequence of gross motor and fine motor development has been well documented, and delays in expected motor control can be easily recognized through careful observation and neurologic examinations (Brazelton, 1973).

Essential to self-control of thinking, including information processing and memory, is normal brain development. By 1 year, myelination of all regions of the corpus callosum is under way, and this is essential for increased speed of information processing as the child matures. Studies of the electrophysiologic organization of the central nervous system indicate that there is relative immaturity during the first 2 to 4 months after birth. Maturation is evident with increased regularity in sleep-wake cycles, and the infant manifests increasing self-regulation of behavior. Both axons and dendrites develop well into the second year and lead to formation of synapses and synthesis of neurotransmitters. As this occurs, the toddler manifests increasing self-modulation.

A normal toddler manifests increasing self-control of motor, language, and cognitive skills. Normal control tasks of toddlers include bowel and bladder control, use of utensils to eat, undressing and dressing, and ability to interact positively with peers and to begin sharing and taking turns. Gradually, the toddler abandons tantrums as a means of coping with frustration and becomes more adept at explaining his or her frustrations. Yet noncompliance with adult requests remains frequent in preschoolers as they struggle for autonomy. Normal children are most likely to develop self-control and self-reliance if parents are authoritative and firm but also warm, encouraging, and rational (Sturner and Howard, 1997).

As a normal child moves into preschool and early school years, he or she acquires increasing control of motor skills, often learning and enjoying many physical activities, including riding a tricycle, riding a bicycle, and playing jump rope, T ball, soccer, and games such as hide-and-seek. He or she increases drawing skills and coloring skills and learns to read. As the child experiences successes, he or she is motivated to develop further skills.

A normal child will be motivated to improve self-control throughout grade school, especially in areas of special interest. At this time, many children develop skills in computer games or sports or chess. However, the child does not yet have abstract reasoning ability and, in spite of skills in many areas, should not be given responsibilities that require abstract reasoning.

Young adolescents often have problems of self-control over the new domains in their lives and make poor judgments with respect to use of drugs and sexual behavior. Their brains are not yet mature. Adult levels of synapses in the middle frontal gyrus (i.e., prefrontal cortex) are not reached until middle to late adolescence. This development is associated with development of abstract reasoning ability and increased executive function as well as abilities in multitasking. Most normal adolescents, after the age of 16 years, will improve their self-control, including their judgment and decision making. Some adolescents, depending on the extent of early brain injury from many possible causes, may never develop normal self-control or executive functions.

The neural basis of self-control and self-regulation relies heavily on the prefrontal cortex. The prefrontal cortex is located anterior to the motor cortices in the frontal lobe of the brain. It begins to develop in late infancy and continues to develop throughout adolescence. This region of the brain plays a fundamental role in internally guided behavior through working memory and executive control operations. The different subregions may have separate functions related to executive control (Wagner et al, 2001). The dorsolateral prefrontal cortex is implicated in attention and working memory. The ventromedial prefrontal cortex, with connections to and from the amygdala, is implicated in controlling emotions, such as fear. The orbitofrontal cortex is implicated in sensory integration and decision making.

There are several studies indicating that stressors can cause working memory deficits through increased catecholamine levels (Arnsten and Li, 2005). Chapter 50 provides definitions of stress, the physiologic correlates, and the nature of coping. In situations of high stress, interventions to reduce stress and to encourage coping (see Chapter 50) or adjustment (see Chapter 42) can be anticipated to improve prefrontal cortical function and subsequent self-control and self-regulation.

2.1.5 Physical development

Comparatively, physical development of homeless children and youth -- specifically gross and fine motor development -- has been explored the least, with even fewer studies specifically targeting infants and toddlers. Based on existing literature, some delays in visual, fine, and gross motor development have been documented (e.g., Rescorla et al., 1991); though these studies suggest that physical development delays primarily emerge in later preschool and school-age years (Haskett et al., 2016). In infancy and toddlerhood, physical development consists of increasingly refined gross and fine motor skills (Adolph & Franchak, 2017). However, even within the general population, variation exists in emergence and mastery of early motor milestones, creating wide ranges for normative physical development (e.g., normative range for walking to emerge is between 8–18 months; (Centers for Disease Control and Prevention, 2020). Due to these ranges, delays in physical development in infancy and toddlerhood may be overlooked or obscured until they reach the far end of the normative range in later preschool and early school age. Additionally, gross and fine motor skills tend to build on each other creating developmental cascades, with a previous milestone (e.g., rolling from back to belly, fist or palm grasps) contributing to the development of later milestones (e.g., sitting unassisted, pincer grasp). Thus, as children grow older and their motor skills become increasingly more complex, delays in later physical development may be more apparent than subtle differences in infancy and toddlerhood.

Importantly, anecdotal accounts from mothers and service providers indicate that infants and toddlers experiencing homelessness spend a significant amount of time in car seats, strollers, and other confined spaces such as pack-and-plays, swings, or cribs (Brinamen, Taranta, & Johnston, 2012; Volk, 2014). To date, to my knowledge, no studies have explored how young homeless children experience this physical confinement nor the implications it may have for their physical development. In addition, environments of homeless families may restrict infant and toddler exploration and opportunities for motor development (Bradley, McGowan, & Michelson, 2018; Wingate-Lewinson, Hopps, & Reeves, 2010). Shelter space or equipment may be ill equipped or developmentally inappropriate for infant and toddler play - perhaps being too cold, having hard surfaces/floors, or parents may feel they are in the way of others due to limited space. Shelter policies may restrict child gross motor play (e.g., running, crawling) for general safety reasons (Bradley, McGowan, & Michelson, 2018). Families living doubled-up and living at a hotel/motels may feel confined to their room, limiting physical exploration and movement. In in-depth interviews conducted by Wingate-Lewinson and colleagues (2010) with families living at an extended-stay hotel, families described “feeling boxed in”, “wanting to leave but cannot”, and overall feeling trapped.

7 Concluding remarks

Spontaneous activity is a quintessential feature of the nervous system. Already at early fetal age motor behavior is organized by means of activity of basic networks in the brainstem and spinal cord that is modulated by supraspinal activity: the phase of primary variability starts (Fig. 7). The supraspinal activity, first brought about by the cortical subplate and later by the cortical plate, induces movement variation (Hadders-Algra, 2018). In this initial phase of development, the phase of primary variability, movement variation especially serves exploration; its associated afferent information is primarily used to sculpt the developing nervous system, and less to adapt motor behavior to the specifics of the environment. The phase of secondary variability, in which movement variation starts to serve adaptation, begins at function-specific ages (Fig. 7). In sucking and swallowing - functions with a high survival value - secondary variability emerges shortly before term age. In gross and fine motor development, and in oral motor behavior involved in chewing and speech, it emerges from 3 to 4 months post-term onwards, i.e., from the time that the cortical subplate has disappeared in the primary sensory and motor cortices and development focuces on the permanent cortical circuitries (Kostović et al., 2014, 2015). With increasing age, and increasing emergence of the permanent circuitries in the frontal, parietal and temporal association cortices, the infants abilities to vary improve. The infant continues to explore by means of trial and error. The experience and its accompanying developmental processes allow the infant increasingly better to use in an adaptive and efficient way upright motor behaviors, manual activites and vocalizations belonging to the native language. As a result, most typically developing infants have achieved by the age of 12 to 18 months the milestones of independent walking, the use of the pincer grasp, and the first words. It takes, however, many years of additional exploration, experience and developmental changes in the brain, before the adult configuration of secondary variability with its efficient adaptability and its freedom to vary is achieved.

Currently we know little about the exact nature of the supraspinal network correlates underlying the transitions from primary to secondary variability. Future studies may address this issue with approaches in which various assessment techniques are combined, e.g., detailed observation of infant motor behaviour, EMG- and kinematic recordings, and multichannel EEG-recordings or resting state functional magnetic resonance imaging – preferrably in a longitudinal design.

4.4 Future directions

Future research should continue efforts to subtype children with ASD based on sensory reactivity profiles in addition to other, sensorimotor, behavioral, neurological, and functional measures. Sensory processing differences are not limited strictly to sensory modulation (responsivity and sensory seeking). Therefore it is important that future studies address other dimensions of sensory processing including sensory discrimination and motor planning (praxis). Aspects of sensory modulation, such as hypo- or hyperresponsivity may have direct correlations with discrimination and affect the overall processing within different sensory domains. For example, either hypo- or hyperresponsivity could affect the ability to develop intact tactile discrimination, and poor tactile discrimination could adversely influence fine motor development and motor planning skills. Incorporating a more complete picture of sensory processing will help clarify how the different components of the theoretical diagnostic categories of sensory processing materialize and overlap in real populations. In addition, it would be useful to examine more comprehensive sensory-based subtypes within the general population and compare to children with ASD in order to substantiate whether or not ASD sensory profiles are truly unique.

Findings from the current review indicate that some overlap exists between sensory-based subtypes in children with ASD, children with SPD, developmental delays and typically developing children. Within the population of children with ASD it does appear that there is a higher prevalence of more extreme sensory processing scores or dysfunction, yet whether or not sensory-based subtypes differ only by severity between clinical and typical groups, or if there are in fact unique sensory profiles between groups, is unclear. This is an area that warrants further investigation.

Subsequent studies should also examine functional impairments and behavioral profiles associated with subtype membership. The initial study conducted by Lane and colleagues (2010) found that subtype groupings were predictive of communication and maladaptive behaviors, yet these results have not been replicated. Additional studies are needed to examine how or if sensory-based subtypes are related to observable, functional outcomes that could better inform intervention pathways. Assessing clinical symptomatology (e.g., internalizing or externalizing behaviors), challenging behaviors (e.g., aggression, self-injurious behaviors) and types of repetitive behaviors in relationship to sensory subtypes would also help to qualify and characterize group membership. Although it would be hypothesized that children falling into a subtype with global sensory processing differences would have greater overall functional impairments, this has not yet demonstrated empirically. In addition, the presence of other comorbid diagnoses such as the possible association between hyperresponsivity and anxiety or withdrawal would also provide meaningful prognostic information. Children with ASD also demonstrate a wide variety of challenging and repetitive behaviors that may or may not be related to sensory processing differences. When determining a course of intervention, such as sensory-based approaches versus behavioral modification, it will be important to understand if the function of these behaviors can be associated with atypical sensory processing.

Examination of neurological profiles may contribute to a better means of classifying subtypes, or could also be a method for examining underlying neurological processes in more established subtyping schemes. Nervous system activity in response to sensory stimuli or sensory challenges may present differentially and redefine subtype divisions. On the other hand, patterns of autonomic nervous system response could help to explain differences in responsivity that could better characterize existing subtypes. For example, if parasympathetic and sympathetic nervous system activity differed for children within a combined “mixed” responsivity subtype, this could provide evidence that these groups should instead be separate. Exploration of how these patterns are expressed across different sensory domains would also be useful and could include both responsivity and discrimination.

Although it may be challenging, it may also be useful to consider consolidating the different sensory-based subtyping schemes that have been proposed for children with ASD. Deriving additional empirical evidence in support of one subclassification scheme would help to strengthen distinct sensory processing profiles that could be used conjunction with an ASD diagnosis. In order to attain this goal, additional studies would be necessary to help objectively demonstrate differences in subtypes such as using neurophysiological measurement (Ausderau et al., 2014). In addition, cross-referencing scores on different measurement tools such as the SEQ, SPA or Sensory Processing Measure (SPM) would give therapists a wider variety of tools for subclassification. Further characterization of the subtypes using other measurements would provide a more detailed clinical picture. For example, replicating previous subtype correlations with adaptive behavior and anxiety scales, in addition to examining language, social, and emotional rating scales could deepen the understanding of how sensory dysfunction affects different functional profiles for each subtype. The inclusion of additional measures of sensory discrimination and sensory-motor performance would also help to broaden the understanding of the relationships between sensory profiles and overall functioning in children with ASD.

Well-established subtypes should eventually become the platform for examining differential response to intervention. Once a subtyping scheme (or schemes) has been comprehensively developed and replicated, future endeavors should determine if these subtypes respond differently to clinical interventions. Types of interventions may include sensory-based approaches, behavioral modification programs, or cognitive behavioral therapies, including duration and frequency.

4.4 Infant/child health problems, mental development and internalizing/externalizing behaviors

In one study, postpartum anxiety was related to infant health problems at four–six months postpartum while infant sleep problems were related to postpartum depression (Clout & Brown, 2015). The postpartum anxiety tended to persist when mothers had experienced a cesarean delivery and had sleep problems and when their infants had health problems.

In a study from India, 420 women were enrolled during the perinatal period and the mothers’ anxiety and depression were assessed across the first 30 months following childbirth using anxiety and depression scales based on DSM-IV criteria (Ali, Mahmud, Khan, & Ali, 2013). The infants’ development was assessed on the Early Childhood Development Scale including social emotional, language, cognitive, gross motor and fine motor development. Significant associations were noted between postpartum anxiety and depression with delayed development on all five of the early childhood development scales.

In a path analysis model, the relative contributions of prenatal and postnatal anxiety and depression to internalizing/externalizing behaviors were examined in a sample of 3298 mother –infant pairs both at 32 weeks prenatally and 1.5 years postpartum (Barker, Jaffee, Uher, & Maughan, 2011). Maternal anxiety appeared to be more specific to internalizing behaviors of the infant.

In a sample of 577 women, logistic regression models suggested that exposure to prenatal depression was associated with lower anxiety symptoms in male offspring (Glasheen et al., 2013). In contrast, male offspring who were exposed to medium and high prenatal and postnatal anxiety had greater odds of conduct disorder than males with low exposure levels. Curiously, females exposed to medium or high prenatal and postnatal anxiety were less likely to have conduct disorder than females with low exposure. These findings were difficult to interpret.

These developmental effects of postnatal anxiety only appear in a relatively recent literature, likely because mothers were only recently being screened for postpartum anxiety. Screening is still predominantly focused on postnatal depression. This may relate to postpartum depression being more apparent or because anxiety might be expected in primiparous women because of the novelty, uncertainty and difficulties of being a first-time mother. In multiparous women anxiety might be expected because those mothers have overwhelming caregiving responsibilities for earlier-born children. Based on this literature review, it would appear that periodic screening would be indicated starting immediately after delivery for both postpartum anxiety and depression. The State-Trait anxiety scale was the most frequently used in the research reviewed here, and the CES-D (Center for Epidemiological Studies-Depression Scale) was the most frequently used in a recent review on postpartum depression (Field, 2017). The postnatal anxiety effects on the offspring’s development are sufficiently severe and long-term that both screening and preventive interventions are needed.

3.1 Motor development with a focus on fine motor functions

According to family questionnaires, 80–90% of infants later diagnosed with RTT were able to sit without support (Fehr et al., 2011; Huppke et al., 2003; Neul et al., 2014), although some did not achieve this milestone before the age of 30 months (Fehr et al., 2011). Independent walking was achieved by 46% (Fehr et al., 2011) to 53% (Neul et al., 2014) of infants, though also with a delay in half of the patients (Fehr et al., 2011). It remains a remarkable finding that none of the 25 infants (later diagnosed with RTT or PSV-RTT) who were assessed for endogenously generated general movements during the first 4 months of life (General Movement Assessment, GMA; Einspieler and Prechtl, 2005; Prechtl et al., 1997) achieved a normal score (Einspieler et al., 2005a, 2005b, 2014a, 2014b; Marschik et al., 2009a), which is an integrity marker of the developing nervous system. However, no specific abnormal general movement pattern for RTT could be identified (Einspieler et al., 2014b).

Here, we focus on the fine motor development of infants later diagnosed with RTT or PSV-RTT. Analysing videos of 22 infants recorded during the first 6 months of life, Einspieler et al. (2005a) observed abnormal finger movements in half of the cases assessed. Some infants showed continuous fisting until 4 months, others excessive finger spreading or abnormal bilateral, synchronised opening and closing of all fingers. By the age of 5 or 6 months, a third of the infants touched toys with extended fingers without manipulating them (Einspieler et al., 2005a). One girl with a later diagnosis of PSV-RTT touched objects with her fingers mainly extended, performing undifferentiated movements (Marschik et al., 2009a). Monozygotic twins with RTT even fisted until 10 months or longer; finger movements were sporadical and with limited variability (Einspieler et al., 2014a). Health visitors and midwifes who watched family videos taken during the infants’ first 12 months of life commented extensively on clenched, crossed, or spread fingers (Burford et al., 2003).

More than 30 years ago, Witt-Engerström (1987) found RTT to be affecting arm and hand movements before certain hand skills were lost. She documented that only 11/20 infants had acquired to pincer grasp, and only 7/20 had displayed finger feeding (Witt-Engerstöm, 1992a,b). The British Isles Survey for Rett Syndrome also documented the absence of hand use such as finger feeding or drinking from a mug before the period of regression (Kerr and Prescott, 2005). And a natural history study (Neul et al., 2014) revealed that 9 to 26% of 542 children were never able to transfer objects, hold a bottle, pincer grasp or finger feed. It is important to note that the majority of children who acquired these milestones did so with a delay.

In a prospective cohort study including 62,624 toddlers a checklist assessment at the age of 18 months revealed that none of the six females later diagnosed with RTT were able by that age to fetch objects and take them to others. This fine motor behaviour was observed in 97% of the total cohort (Marschik et al., 2018).