Primitive Reflexes

The earliest motor neuromaturational markers are primitive reflexes that development during uterine life and generally disappear between the third and sixth months after birth. Newborn movements are largely uncontrolled, with the exception of eye gaze, head turning, and sucking. Development of the infant’s central nervous system involves strengthening of the higher cortical center that gradually takes over function of the primitive reflexes. Postural reflexes replace primitive reflexes between three and six months of age as a result of this development (Schott and Rossor, 2003). These reactions allow children to maintain a stable posture even if they are rapidly moved or jolted (Box 2-1).

The asymmetric tonic neck reflex (ATNR) or “fencing posture” is an example of a primitive reflex that is not immediately present at birth because of the high flexor tone of the newborn infant. When the neonate’s head is turned to one side, there is increased extensor tone of the upper extremity on the same side and increased flexor tone on the occipital side. The ATNR is a precursor to hand-eye coordination, preparing the infant for gazing along the upper arm and voluntary reaching. The disappearances of this reflex at 4 to 6 months allows the infant mobility to roll over and begin to examine and manipulate objects in the midline with both hands.

The palmar grasp reflex is present at birth and persists until 4 to 6 months of age. When an object is placed in the infant’s hand, the fingers close and tightly grasp the object. The grip is strong but unpredictable. The waning of the early grasp reflex allows infants to hold objects in both hands and ultimately to voluntarily let them go.

The Moro reflex is probably the most well-known primitive reflex and is present at birth. It is likely to occur as a startle to a loud noise or sudden changes in head position. The legs and head extend while the arms jerk up and out, followed by adduction of the arms and tightly clenched fists. Bilateral absence of the reflex may mean damage to the infant’s central nervous system. Unilateral absence could indicate birth trauma such as a fractured clavicle or brachial plexus injury.

Postural reflexes support control of balance, posture, and movement in a gravity-based environment. The protective equilibrium response can be elicited in a sitting infant by abruptly pushing the infant laterally. The infant will extend the arm on the contralateral side and flex the trunk toward the side of the force to regain the center of gravity (Fig. 2-1). The parachute response develops around 9 months and is a response to a free-fall motion, where the infant extends the extremities in an outward motion to distribute weight over a broader area. Postural reactions are markedly slow in appearance in the infant who has central nervous system damage. Children who fail to gain postural control continue to display traces of primitive reflexes. They also have difficulty with control of movement affecting coordination, fine and gross motor development, and other associated aspects of learning, including reading and writing. Table 2-2 is a list of the average times of appearance and disappearance of the more common primitive reflexes.

FIGURE 2-1 The protective equilibrium response is demonstrated in an infant being pushed laterally. Note the extended contralateral arm.

TABLE 2-2 Primitive Reflexes

Gross Motor Skills

One principle in neuromaturational development during infancy is that it proceeds from cephalad to caudad and proximal to distal. Thus, arm movement comes before leg movement (Feldman, 2007). The upper extremity attains increasing accuracy in reaching, grasping, transferring, and manipulating objects. Gross motor development in the prone position begins with the infant tightly flexing the upper and lower extremities and evolves to hip extension while lifting the head and shoulders from a table surface around 4 to 6 months of age. When pulled to a sitting position, the newborn has significant head lag, whereas the 6-month-old baby, because of development of muscle tone in the neck, raises the head in anticipation of being pulled up.

Rolling movements start from front to back at approximately 4 months of age as the muscles of the lower extremities strengthen. An infant begins to roll from back to front at about 5 months. The abilities to sit unsupported (about 6 months old) and to pivot while sitting (around 9 to 10 month of age) provide increasing opportunities to manipulate several objects at a time (Needleman, 1996). Once thoracolumbar control is achieved and the sitting position mastered, the child focuses motor development on ambulation and more complex skills. Locomotion begins with commando-style crawling, advances to creeping on hands and knees, and eventually reaches pulling to stand around 9 months of age, with further advancement to cruising around furniture or toys. Standing alone and walking independently occur around the first birthday. Advanced motor achievements correlate with increasing myelinization and cerebellum growth. Walking several steps alone has one of the widest ranges for mastery of all of the gross motor milestones and occurs between 9 and 17 months of age. Milestones of gross motor development are presented in Table 2-3 and Figure 2-2. The accomplishment of locomotion not only expands the infant’s exploratory range and offers new opportunities for cognitive and motor growth, but it also increases the potential for physical dangers (Vaughan, 1992).

TABLE 2-3 Cognitive and Language Communication Skills Development

FIGURE 2-2 Gross motor skills development chart.

Most children walk with a mature gait, run steadily, and balance on one foot for 1 second by 3½ years of age. The sequence for additional gross motor development is as follows: running, jumping on two feet, balancing on one foot, hopping, and skipping. Finally, more complex activities such as throwing, catching, and kicking balls, riding bicycles, and climbing on playground equipment are mastered. Development beyond walking incorporates improved balance and coordination and progressive narrowing of additional physical support. Complex motor skills also incorporate advanced cognitive and emotional development that is necessary for interactive play with other children. Figure 2-3 shows the red flags to watch for in the abnormal physical development of the infant.

FIGURE 2-3 Abnormal developmental findings. A, Difficulty lifting head and stiff legs with little or no movement. B, Pushing back with head, keeping hands fisted, and lacking arm movement. C, Rounded back, inability to lift head up, and poor head control. D, Difficulty bringing arms forward to reach out, arching back, and stiffening legs. E, Arms held back and stiff legs. F, Using one hand predominantly; rounded back and poor use of arms when sitting. G, Difficulty crawling and using only one side of the body to move. H, Inability to straighten back and cannot bear weight on legs. I, Difficulty getting to standing position because of stiff legs and pointed toes; only using arms to pull up to standing. J, Sitting with weight to one side and strongly flexed or stiffly extended arms; using hand to maintain seated position. K, Inability to take steps independently, poor standing balance, many falls, and walking on toes.

(Redrawn from What Every Parent Should Know [pamphlet], 2006, Pathways Awareness Foundation.)

Fine Motor Development

At birth, the neonate’s fingers and thumbs are typically tightly fisted. Normal development moves from the primitive grasp reflex, where the infant reflexively grabs an object but is unable to release it to a voluntary grasp and release of the object. By 2 to 3 months of age the hands are no longer tightly fisted, and the infant begins to bring them toward the mouth, sucking on the digits for self comfort. Objects can be held in either hand by age 3 months and transferred back and forth by 6 months. In early development, the upper extremities assist with balance and mobility. As the sitting position is mastered with improved balance, the hands become more available for manipulation and exploration. The evolution of the pincer grasp is the highlight of fine motor development during the first year. The infant advances from “raking” small objects into the palm to the finer pincer grasp, allowing opposition of the thumb and the index finger, whereby small items are picked up with precision. Children younger than 18 months of age generally use both hands equally well, and true “handedness” is not established until 36 months (Levine et al., 1999). Advancements in fine motor skills continue throughout the preschool years, when the child develops better eye-hand coordination with which to stack objects or reproduce drawings (e.g., crosses, circles, and triangles). Figure 2-4 lists and demonstrates the chronologic order of fine motor development.

FIGURE 2-4 Fine motor skills development chart.

Down’s Syndrome

Down’s syndrome is the most common genetic abnormality worldwide, with an estimated prevalence of 1 out of 800 children (Sherman et al., 2007). Although this syndrome was described centuries earlier, Dr. John Langon Down first reported its clinical description in 1866 (Megarbane et al., 2009). Down’s syndrome is the most recognizable and best known chromosomal disorder. The extra copy in chromosome 21 affects several organs and results in a wide spectrum of phenotypical changes (Hartway, 2009). Down’s syndrome is usually identified soon after birth by a characteristic pattern of dysmorphic features (Fig. 2-5) (Ranweiler, 2009). The diagnosis is confirmed by karyotype analysis with trisomy 21 present in 95% of persons with this syndrome (Gardiner and Davisson, 2000).

FIGURE 2-5 The congenital anomalies of Down’s syndrome.

(Modified from Ranweiler R: Assessment and care of the newborn with Down syndrome, Adv Neonatal Care 9:17, 2009; and Santamaria LB, Di Paola C, Mafrica F, et al: Preanesthetic evaluation and assessment of children with Down’s syndrome, The Scientific World Journal 7:242, 2007.)

Perioperative responsibility is shared between the anesthesiologist and the surgeon. The anesthesiologist is responsible for preoperative risk evaluation, perioperative management, and subsequent patient optimization (Hartley et al., 1998). The preoperative evaluation provides the best opportunity to stratify the potential risks, because children with Down’s syndrome often have multiple congenital anomalies, each of which has anesthetic implications (Fig. 2-5) (Santamaria et al., 2007). Important considerations in the operative management of these patients include assessment of their behavioral development, atlantoaxial instability, airway narrowing, and respiratory and cardiac malformations; these are critical issues that require special attention when considering anesthesia (Bhattarai et al., 2008). Wherever possible, preoperative therapeutic interventions must be initiated to reduce the risks associated with these concurrent diseases (Borland et al., 2004). For the anesthesiologist, a system-based approach to the patient with Down’s syndrome may be most useful. For a complete discussion of the anesthetic concerns related to Down’s Syndrome, see Chapter 36, Systemic Disorders.

Attention Deficit Hyperactivity Disorder

Attention deficit hyperactivity disorder (ADHD) is a disorder of inattention, hyperactivity, and impulsivity that affects 8% to 12% of children worldwide, with boys overrepresented by a ratio of about 3:1 (Biederman and Faraone, 2005). During child and adolescent development, ADHD is associated with greater risks for low academic achievement, poor school performance, retention in grade level, school suspensions and expulsions, poor peer and family relations, anxiety and depression, aggression, conduct problems, and delinquency (Barkley, 1997). The means of inheritance acquisition is probably multifactorial, but family, twin, and adoption studies have documented a strong genetic basis for ADHD (Thapar et al., 1999). The cellular theory suggests the frontosubcortical cerebellar regions of the brain have inadequate dopamine and noradrenaline to effectively provide inhibitory regulation (Biederman and Faraone, 2005).

Both the American Academy of Pediatrics (AAP) and the American Academy of Child and Adolescent Psychiatry (AACA) recommend psychoactive medications for children, adolescents, and adults with ADHD. These medications are classified as stimulants or nonstimulants. Perioperative consequences of these medications include resistance to premedication, cardiovascular instability, altered anesthesia requirements (monitored anesthesia care), lower seizure thresholds, and increased postoperative nausea and vomiting (Forsyth et al., 2006).

As an example of medication interaction, one patient required large doses of midazolam while receiving methylphenidate (Ririe et al., 1997). ADHD drugs are associated with increased blood pressure as a result of increased catecholamine levels, but the chronic use of stimulants can deplete these stores or down-regulate catecholamine receptors. Prolonged hypotension has been reported in older patients with ADHD, and cardiac arrest (requiring cardiopulmonary resuscitation) during anesthetic induction was reported in a teenager (Bohringer et al., 2000; Perruchoud and Chollett-Rivier, 2008).

Medications such as buproprion are associated with seizures in a dose-related manner. The seizure threshold can be lowered by concomitant administration of drugs such as antipsychotics, antidepressants, systemic steroids, tramadol, and sedating antihistamines. In addition, bupropion inhibits the enzyme responsible for converting tramadol to morphine, thereby reducing the analgesic effect of tramadol (Corner et al., 2002).

These cases highlight the potential difficulties of the drug–drug interactions while a patient is undergoing general anesthesia. Based on these observations, the anesthesiologist should request more details about the medications a patient is taking for ADHD, particularly if they are stimulants or nonstimulants, and the length of time the patient has been taking the medications. As in cardiac arrest, the implications and ramifications of anesthesia can be quite significant (Tables 2-5 and 2-6) (Perruchoud and Chollett-Rivier, 2008).

TABLE 2-5 The Mechanisms of Action of Commonly Used ADHD Medications

From Forsyth I et al.: Attention deficit hyperactivity disorder and anesthesia, Paediatric anaesthesia, 16:371, 2006.

TABLE 2-6 Possible Drug–Drug Interactions with ADHD

SSRI, Selective serotonin reuptake inhibitor; MAOI, monoamine oxidase inhibitor.

From Forsyth I et al.: Attention deficit hyperactivity disorder and anesthesia, Paediatric anaesthesia, 16:371, 2006.

Autism

Autism affects 5 to 7 in 10,000 births, is found in all racial, ethnic, and social backgrounds, and is four times more common in males than females (Rudolph and Rudolph, 2003). Current data suggest that the actual rate is 40 out of 10, 000 births and that one out of every 150 children in the United States is affected (Rutter, 2005). Autism is now recognized a psychiatric childhood disorder, and is listed in the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) under the section of Pervasive Developmental Disorders (PDD). The diagnostic criteria for autistic disorders include qualitative impairments in social interactions, impairment in verbal and nonverbal communications, restricted range of interests, and resistance to change (APA, 2000). These children exhibit hyperactivity and patterns of behavior, activity, and interests that are restrictive, repetitive, and stereotyped.

The etiology is unknown in the vast majority of the cases. However, there is a small minority of patients with notable coexisting medical diseases, including macrocephaly (15% to 35%), seizure disorders (30%), fragile X syndrome (2% to 8%), and tuberous sclerosis (1% to 3%) (Box 2-2) (Bailey and Rutter, 1991; Williams et al., 2008).

Children with autism can present perioperative challenges to a pediatric anesthesia team (van der Walt and Moran, 2001). They are less able to understand the need for the procedures involved in surgery and have difficulty adjusting to the new routine of the hospital visit. Their perioperative anxiety level can be very high, and it may be difficult for them to interact with strangers, even caring and attentive perioperative staff. They are more sensitive to the visual and auditory stimuli of the hospital, particularly in the operating room, and even simple tactile stimuli such as the face mask may overwhelm their senses. Overall, these children are at high risk for severe distress and anxiety; consequently, morbidity and cost may be increased, and patient and parental satisfaction may be decreased.

Premedication varies depending on the requirements of each child, as well as the preferences of the individual anesthesiologist, who might generally use oral, intramuscular, or intravenous medications. Most institutions employ oral midazolam 0.5 mg/kg; however, the side effects are unpredictable and may not allow optimal anesthetic induction (Rainey and van der Walt, 1998). Ketamine is also an effective preoperative sedative, available in intravenous, intramuscular, and oral dosing. Oral ketamine has a 17% bioavailability, compared with 93% when given intramuscularly or intravenously (Clements et al., 1982). An effective transmucosal dosing combines ketamine 3 mg/kg mixed with midazolam 0.5 mg/kg (Funk et al., 2000).

If possible, the patient should undergo conditioning to become familiar with the hospital and the upcoming procedure (Nelson and Amplo, 2009). Diminished waiting time in the preoperative area can lessen fear and stress. Short, clear commands, with empathic positive and negative reinforcements, can help guide the patient through this difficult ordeal. Anesthesia management can be optimized by judicial use of premedication and parental presence during induction. The actual administration of an adequate dose of premedication can be the biggest challenge for the anesthesiologist working with an uncooperative or frightened child with delayed cognitive abilities. A balanced approach can help minimize the use of force, which is sometimes necessary, but nonetheless upsetting to the patient, the family, and the perioperative team. A discussion regarding the potential use of restraints during the perioperative period is imperative to clearly define the caregiver’s expectations regarding this treatment modality. In summary, children with autism can present perioperative challenges, but thoughtful psychosocial and medical interventions can improve patient and parent satisfaction.

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