Gestation	Relative Weight	Neonatal Problems at Increased Incidence
Preterm (<37 weeks)	SGA	Respiratory distress syndrome
		Apnea
		Perinatal depression
		Hypoglycemia
		Polycythemia
		Hypocalcemia
		Hypomagnesemia
		Hyperbilirubinemia
		Viral infection
		Thrombocytopenia
		Congenital anomalies
		Maternal drug addiction
		Fetal alcohol syndrome
	AGA	Respiratory distress syndrome
		Apnea
		Hypoglycemia
		Hypocalcemia
		Hypomagnesemia
		Hyperbilirubinemia
	LGA	Respiratory distress syndrome
		Hypoglycemia: infant of a diabetic mother
		Apnea
		Hypocalcemia
		Hypomagnesemia
		Hyperbilirubinemia
Normal (37-42 weeks)	SGA	Congenital anomalies
		Viral infection
		Thrombocytopenia
		Maternal drug addiction
		Perinatal depression
		Hypoglycemia
	AGA	—
	LGA	Birth trauma
		Hyperbilirubinemia
		Hypoglycemia: infant of a diabetic mother
Postmature (>42 weeks)	SGA	Meconium aspiration syndrome
		Congenital anomalies
		Viral infection
		Thrombocytopenia
		Maternal drug addiction
		Perinatal depression
		Aspiration pneumonia
		Hypoglycemia
	AGA	—
	LGA	Birth trauma
		Hyperbilirubinemia
		Hypoglycemia: infant of a diabetic mother

AGA, Appropriate for gestational age; LGA, large for gestational age; SGA, small for gestational age.

After birth, physical growth continues at a rapid pace during the first 6 months of extrauterine life but slows by about 2 years of age. Physical growth accelerates a second time during the pubertal period. A simple way to remember how rapidly the infant grows is that birth weight doubles by 6 months of age and triples by 1 year. Length doubles by 4 years of age. This scale, however, does not affect all organs or functions in the same way. It is important to be able to assess correctly and precisely the stage of development of the child, because any abnormal slowdown requires investigation to find the cause.

Gestational Age Assessment

The gestational age of an infant may be assessed in one of three ways. The most accurate means of assessing gestational age is by measuring the crown-rump length of the fetus during a first-trimester ultrasonographic examination. Another method involves calculating gestational age from the first day of the mother’s last menstrual period, but this is commonly inaccurate, leading to errors in estimation. Finally, the Dubowitz scoring system is a well-accepted method combining neurologic and physical criteria of the infant to provide an accurate assessment of gestational age.^1,² A summary of the more significant neurologic and physical signs of maturity is presented in Table 2-3.

TABLE 2-3 Neurologic and External Physical Criteria to Assess Gestational Age

Physical Examination	Preterm (<37 weeks)	Term (≥37 weeks)
Ear	Shapeless, pliable	Firm, well formed
Skin	Edematous, thin skin	Thick skin
Sole of foot	Creases on anterior third	Whole foot creased
Breast tissue	Less than 1 mm diameter	More than 5 mm diameter
Genitalia
Male	Scrotum poorly developed Testes undescended	Scrotum rugated Testes descended
Female	Large clitoris, gaping labia majora	Labia majora developed
Limbs	Hypotonic	Tonic (flexed)
Grasp reflex	Weak grasp	Can be lifted by reflex grasp
Moro reflex	Complete but exhaustible (>32 weeks)	Complete
Sucking reflex	Weak	Strong, synchronous with swallowing

Weight and Length

Assessment of growth is measured by changes in weight, length, and head circumference. Percentile charts are valuable for monitoring the child’s growth and development. Deviation from growth within the same percentile for a child of any age is of greater significance than any single measurement (Figs. 2-1 and 2-2). Weight is a more sensitive index of well-being, illness, or poor nutrition than length or head circumference and is the most commonly used measurement of growth. Change in weight reflects changes in muscle mass, adipose tissue, skeleton, and body water and thus is a nonspecific measure of growth. Measurement of length provides the best indicator of skeletal growth because it is not affected by changes in adipose tissue or water content.

FIGURE 2-1 Postnatal growth curve (weight) for term male infants. This figure represents normal growth curves. Triangles indicate a normal child. Circles demonstrate failure to thrive in a child with severe renal failure.

FIGURE 2-2 Postnatal growth curve (weight) for preterm infants. This figure represents normal growth curves for preterm infants. Triangles indicate a normal preterm infant. Circles demonstrate failure to thrive in an infant with bronchopulmonary dysplasia.

Term infants may lose 5% to 10% of their body weight during the first 24 to 72 hours of life from loss of body water. Birth weight is usually regained in 7 to 10 days. A daily increase of 30 g (210 g/week) is satisfactory for the first 3 months. Thereafter, weight gain slows so that at 10 to 12 months of age it is 70 g each week (Table 2-4).

TABLE 2-4 Approximate Relationship of Age to Weight

Age (years)	Weight (kg)
1	10
3	15
5	19
7	23

When plotting the weight of a preterm infant on a growth chart, it is common to use the infant’s corrected gestational age (postmenstrual age; postconceptual age is taken from conception and is approximately 2 weeks shorter) instead of his or her chronologic age (postnatal age, i.e., from birth) during the first 2 years of the infant’s life in order to correct for prematurity.

Weight and length are important but changes affect the composition of the body itself, especially total body water, which decreases at the expense of the extracellular compartment, with adult levels attained at 1 year of age.^3,⁴ This finding has implications for drug dosing and distribution in the infant. Males have a greater percentage of water, whereas females have a slightly greater percentage of fat. The percentage decrease in extracellular water is greater than the decrease in total body water because of the simultaneous increase in intracellular water (Table 2-5).⁵

TABLE 2-5 Relationship of Age to Body Water

Another, more precise way to assess development is to calculate the body surface area (BSA).⁶

BSA can also be described using an allometric equation with an exponent of (see Chapter 6):

Head Circumference

Head size reflects growth of the brain and correlates with intracranial volume and brain weight. Changing head circumference reflects head growth and is a part of the total body growth process; it may or may not indicate underlying involvement of the brain. An abnormally large or small head may indicate abnormal brain development, which must alert the anesthesiologist to possible underlying neurologic problems. A large head may indicate a normal variation, familial feature, or pathologic condition (e.g., hydrocephalus or increased intracranial pressure), whereas a small head may indicate a normal variant, familial feature, or pathologic condition such as craniosynostosis or abnormal brain development.

During the first year of life, head circumference normally increases 10 cm, and it increases 2.5 cm in the second year. By 9 months of age, head circumference reaches 50% of adult size, and by 2 years it is 75%. Head circumference is closely followed on standard percentile growth curves. As with weight, deviations of growth of the head within the same percentile are more significant than a single measurement.

The anterior fontanel should be palpated to assess whether it is sunken (dehydration) or bulging abnormally (suggesting increased intracranial pressure as in hydrocephalus, infection, hemorrhage, or increased partial pressure of carbon dioxide in the arterial blood [PaCO₂]). If it is bulging, the sutures should be palpated for abnormal separation as a result of increased intracranial pressure. The anterior fontanel closes between 9 and 18 months of age; the posterior fontanel closes by 2 to 4 months of age (Fig. 2-3). Cranial molding occurs particularly in LBW infants and is usually of no clinical importance.

FIGURE 2-3 Cranial development. A and B depict the skull of a neonate with wide-open suture. C and D depict the skull of a 7-year-old boy with fused sutures.

Face

Although the cranial vault increases rapidly in size, the face and base of the skull develop at a slower rate. At birth, the mandible is small; but as a child develops, forward growth occurs, reducing the obliquity of the mandibular angle. Failure of prenatal development of the mandible may be associated with severe congenital defects (e.g., Pierre Robin, Treacher Collins, or Goldenhar syndromes). These syndromes often have other associated anomalies. After 2 years of age, the cranial vault increases only marginally in size, whereas the facial configuration undergoes substantive changes. The upper jaw grows rapidly to accommodate the developing teeth. In addition, the frontal sinuses develop by 2 to 6 years of age, and the maxillary, ethmoidal, and sphenoidal sinuses appear after 6 years of age.

Teeth

The first tooth, usually a lower incisor, erupts at approximately 6 months after birth (deciduous dentition). Eruption of all deciduous teeth is usually complete by 28 months of age. Permanent teeth appear at 6 years, with the shedding of the deciduous teeth; this process takes place during the next 6 to 8 years. Abnormally developed teeth occur with hereditary disorders, Down syndrome, cerebral palsy, medications (eg., tetracycline) and nutritional defects. Preterm infants may show severe enamel hypoplasia in their primary dentition.^7,⁸

Comportment and Behavior

The neurologic status and social acquisition of the child are part of the development assessment and will be described later in this chapter.

Airway and Respiratory System

Airway development includes a large number of structures including cranial vault and base, craniovertebral development, face, branchial apparatus, larynx and oral cavity.

These structures are involved in the respiratory function (to provide enough oxygen and to remove carbon dioxide) but also to separate the circulation of air from the circulation of liquid and food. A variety of processes, including ventilation, perfusion, and diffusion, are involved in fulfilling these functions. Specifically, the anesthesiologist has to consider these developmental changes because of their implication in airway management and ventilation.

Upper Airway Development

During the course of development, the infant upper airways undergo deep anatomic modifications that include changes in size, shape, and interrelationship; this is particularly prominent during the first few years of life.

The face and the nasal chamber, the oropharynx with the tongue, and the laryngotracheal lumen are the three main parts of the upper airway involved. The development of the neurocranium will lead to the maturation of the cranial vault and skull base, and the development of the viscerocranium to the skeletal part of the face. The primordial areas involved in forming the covering of the tongue appear early in the second month of development.

The larynx is developed embryologically from ectodermal, endodermal, and mesodermal tissues that are derived from the third, fourth, and sixth branchial arch and pouch apparatus. The development of the larynx and airway in the neonate is outlined in detail in Chapter 12. The laryngeal opening (epiglottis and vocal cords) in a neonate and 2-year-old boy are shown in Figure 2-4. Note the omega-shaped long epiglottis and the pearly white vocal cords in the neonate.

FIGURE 2-4 Larynx development from neonate to 2 years old. The larynx in the neonate (A and B), with the long epiglottis (A) and the vocal cords (B, close-up). The larynx in a 2-year-old (C and D), with a shorter epiglottis (C) and the vocal cords (D, close up).

The skull base grows rapidly until age 6 years, with relatively slower growth thereafter. The cranial base flexes postnatally in a rapid growth trajectory that is complete by 2 years of age.

The depth of the nasopharynx increases due to remodeling of the palate as well as changes in the angulation of the skull base. During childhood, the soft tissues of the pharyngeal structures surrounding the upper airway grow proportionally to the skeletal structures. After birth, the dimensions of the nasal cavity increase very rapidly. During the first year of life, the total minimal cross-sectional area is increased by 67%, and the volume of the anterior 4 cm of the nasal airways by 36%.⁹

The volume of the oral cavity in the neonate is proportionally less than that in the adult, owing to a significantly shorter mandibular ramus. The volume of the oral cavity significantly increases during the first 12 months because of rapid growth in the height of the mandibular ramus.

Compared with the adult, the tongue in the neonate contains considerably less fat and soft tissue, but overall is large in size relative to the dimensions of the mouth, with relatively larger extrinsic musculature and a less developed superior longitudinal muscle resulting in a flat dorsal surface with poor lateral mobility (see also Chapter 12).

Respiratory System Development

The development of the respiratory system begins during week 4 of gestation. Three “laws” that describe the temporal development of the conducting airways, alveoli, and pulmonary vessels govern normal lung growth.

Airways: The bronchial tree down to and including the terminal bronchioles forms by week 16 of gestation. The acinus, consisting of all the airway structures distal to the terminal bronchiole and the entire gas-exchanging apparatus, develops throughout the remainder of gestation.

Alveoli: Alveoli develop mainly after birth, increasing in number until approximately 8 years of life and in size until growth of the chest wall ceases.

Pulmonary vessels: Arteries and veins accompanying the bronchial tree form by week 16 of gestation. Those vessels lying within the acinus follow the development of the alveoli. The appearance and growth of arterial smooth muscle lags behind the sprouting of new vessels and is not completed until late adolescence.

Transition to Air Breathing

Fetal breathing movements have been detected as early as 11 weeks of gestational age; they are interspersed with long periods of apnea and produce little tidal movement of lung fluid.^10,¹¹ The critical event in the change from placental to pulmonary gas exchange is the first inspiration, which initiates pulmonary ventilation, promotes the clearance of lung fluid, and triggers the change from the fetal to the neonatal pattern of circulation.

The first breath is a gasp that generates a transpulmonary distending pressure of 40 to 80 cm H₂O.¹² This moves the tracheal fluid (100 times more viscous than air), overcomes surface forces that develop as the air−fluid interface reaches the small airways, and overcomes tissue resistance. In some children, the removal of lung fluid may be delayed, producing the syndrome called transient tachypnea of the newborn.¹³ Tachypnea lasts for 24 to 72 hours and is associated with a characteristic chest radiographic appearance consisting of increased perihilar markings, fluid in the interlobar fissures, and streaky linear opacities in the parenchyma.

With the onset of pulmonary ventilation, pulmonary blood flow sharply increases. Decreased pulmonary vascular resistance (PVR) and increased peripheral systemic vascular resistance (loss of the umbilical circulation) are the two crucial events involved in the immediate transition from the fetal circulation to the normal postnatal pattern. The increase in systemic afterload causes an immediate closure of the flap valve mechanism of the foramen ovale and reverses the direction of shunt through the ductus arteriosus. Until these fetal shunt pathways close anatomically, the pattern of circulation is unstable. Increased pulmonary vascular reactivity in response to hypoxia and acidosis may precipitate a reversal to right-to-left shunting (“flip-flop” circulation).

In the first few minutes of life, a state of “normal” asphyxia exists as a result of impairment of placental blood flow during labor. The partial pressure of oxygen in arterial blood (PaO₂) and pH are low, whereas the PaCO₂ is increased immediately after birth, but these parameters change rapidly in the first hour of life. Extrapulmonary shunting through fetal channels and intrapulmonary shunting, probably through unexpanded regions of the lung, persist for some time after birth, so that in neonates the physiologic right-to-left shunt is about three times that in adults.¹⁴

Mechanics of Breathing

Chest Wall and Respiratory Muscles

The accessory muscles of inspiration are relatively ineffective in infants because of an unfavorable anatomic rib configuration. In infancy, the ribs extend horizontally from the vertebral column, moving little with inspiration.¹⁵ These factors increase the workload on the diaphragm. Consequently, and in contrast to an adult, thoracic cross-sectional area is fairly constant throughout the breathing cycle, and inspiration occurs almost entirely as a result of diaphragmatic descent.

The chest wall of a neonate is floppy because it comprises noncalcified cartilage, its musculature is poorly developed, and the ribs are incompletely calcified.^16,¹⁷ As the work of breathing increases, diaphragmatic displacement must also increase to maintain the tidal volume. The increased workload may lead to diaphragmatic fatigue and respiratory failure or apnea, especially in preterm infants.^18,¹⁹

The tendency to respiratory muscle fatigue is the result of the metabolic characteristics of the diaphragm, which has very little type I (slow twitch, high oxidative capacity) muscle fibers (see Fig. 12-11).

Elastic Properties of the Lung

Changes in the static pressure−volume relationship of the lungs during growth are caused by increases in volume and changes in the elastic properties of lung tissue. Volume is the principal factor that determines lung compliance, which increases throughout childhood. Specific lung compliance remains relatively constant throughout childhood.²⁰ In contrast, specific compliance of the chest wall declines throughout childhood and adolescence, reflecting the progressive calcification of the ribs and the increasing bulk of the thoracic muscles.

Static Lung Volumes

Detailed information expressing static lung volumes on the basis of body weight are detailed in Table 2-6.

TABLE 2-6 Age-Dependent Respiratory Variables

Total Lung Capacity

Adults have a markedly greater total lung capacity (TLC) than infants (Fig. 2-5). This difference reflects the fact that TLC is an effort-dependent parameter, depending on the strength and efficiency of the inspiratory muscles, which can be estimated by the maximum inspiratory pressure at functional residual capacity (FRC). An adult can generate negative pressures in excess of 100 cm H₂O; negative inspiratory pressures as high as 70 cm H₂O have been recorded for neonates, a surprisingly high value in view of their underdeveloped musculature and highly compliant chest wall. This may be a consequence of the small radius of curvature of an infant’s rib cage, which by the Laplace relationship converts a small tension into a large pressure difference.²¹

FIGURE 2-5 Lung volumes in infants and adults. Note that, in infants, tidal volume breathing occurs at the same volume as closing volume. CC, Closing capacity; FRC, functional residual capacity; VC, vital capacity.

(Modified from Nelson NM. Respiration and circulation after birth. In: Smith CA, Nelson NM editors. The physiology of the newborn infant. Springfield, Ill.: Charles C Thomas; 1976. p. 207.)

Functional Residual Capacity

FRC is similar on a per-kilogram basis at all ages, but the mechanical factors on which it is based are different in infants and adults.²² In adults, FRC is the same as the volume at which the elastic forces generated by the passive recoil of the chest wall are balanced by the recoil of the lung (Fig. 2-6); this is the volume attained at end-expiration with an open glottis.