DEVELOPMENTAL PHYSIOLOGY OF THE INFANT

Organogenesis takes place within 8 weeks of conception, organ function develops during the second trimester, and the infant gains weight, primarily muscle and fat, during the third trimester.^[1] Any physiologic or pharmacologic injury or stress during the first trimester may cause abnormal organogenesis; in the second trimester, it may cause abnormal functional development of organs and, in the third trimester, smaller organs or reduced muscle and fat mass.^[2] Injuries and stress take the form of congenital viral infections, exposure to drugs, nutritional insufficiency (caloric or vascular), or other maternal illness. A genetic predisposition to developmental malformations can also produce adverse effects. Such interruptions in normal growth and development may cause a variety of physiologic abnormalities ranging from simple premature birth to a constellation of congenital malformations.^{[3] [4] [5] [6]}

A premature infant is one born before 37 weeks of gestation; a postmature infant is one born after 42 weeks of gestation. Any infant less than 2500 g is considered a low-birth-weight infant. Plotting weight against gestational age allows classification into three general categories: small for gestational age, appropriate for gestational age, or large for gestational age ( Fig. 60-1 ). Infants who are small or large for gestational age often have developmental problems or difficulties associated with maternal disease ( Table 60-1 ). A careful physical and neurologic examination at birth allows a fairly accurate estimate of gestational age. The anesthesiologist should be aware of this type of evaluation so that potential problems can be anticipated. A perinatal history regarding problems during pregnancy (e.g., maternal drug abuse, maternal infection, eclampsia, diabetes) or during and after delivery (e.g., fetal distress, meconium aspiration, postdelivery intubation) is also valuable for assessing possible anesthetic complications and specific considerations for anesthetic management. In the weeks after birth, measures of weight, height, and head circumference are plotted on standard developmental curves; deviations from the normal

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Figure 60-1 Plotting birth weight against gestational age for neonates determines whether infants are small, appropriate, or large for gestational age. Babies who are either small or large for gestational age are particularly likely to have a variety of problems such as metabolic, developmental, infectious, or structural abnormalities, as well as drug addiction and withdrawal. (Redrawn with modification from Battaglia FC: Intrauterine growth retardation. Am J Obstet Gynecol 106:1103–1114, 1970.)

The Cardiovascular System

The cardiovascular system undergoes dramatic physiologic and maturational changes during the first year of life. In utero, most of the cardiac output is directed from the placenta across the foramen ovale into the ascending aorta (oxygenated blood), whereas superior vena cava blood (deoxygenated) is directed to both the pulmonary artery and the ductus arteriosus. This pattern of circulation results in minimal intrauterine pulmonary blood flow. At birth, a number of events change hemodynamic interactions such that the fetal circulation becomes an adult-type circulation.^[7] Specifically, the placenta is removed from the circulation; portal blood pressure falls, which causes the ductus venosus to close and blood becomes oxygenated through the lungs; and exposure of the ductus arteriosus to oxygenated blood induces ductal closure. As a result of the combined effects of lung expansion, exposure of blood to oxygen, and loss of low resistance through placental blood flow, pulmonary vascular resistance decreases while peripheral vascular resistance rises rapidly. The fall in pulmonary vascular resistance occurs on the first day of life and continues to decrease gradually during the next several years as the architecture of the pulmonary vessels changes. An increase in pressure on the left side of the heart (caused by the rise in peripheral vascular resistance) induces mechanical closure of the foramen ovale. Thus all three connections between the right and left side

TABLE 60-1 -- Common neonatal problems associated with weight and gestational age

Gestational Age	Body Size	Increased Incidence of These Neonatal Problems
Premature	Small	Respiratory distress syndrome
		Apnea
		Hypoglycemia
		Hypomagnesemia
		Hypocalcemia
		Fetal alcohol syndrome
		Viral infection
		Thrombocytopenia
		Congenital anomalies
		Maternal drug addiction
		Neonatal asphyxia
		Aspiration pneumonia
Term	Small	Congenital anomalies
		Viral infection
		Thrombocytopenia
		Maternal drug addiction
		Neonatal asphyxia
		Hypoglycemia
		Fetal alcohol syndrome
Postmature	Small	Congenital anomalies
		Viral infection
		Thrombocytopenia
		Maternal drug addiction
		Neonatal asphyxia
		Aspiration pneumonia
		Hypoglycemia
		Fetal alcohol syndrome
Any gestational age	Large	Birth trauma
		Hyperbilirubinemia
		Hypoglycemia: infant of diabetic mother
		Transposition of great arteries
Modified from Todres ID: Growth and development. In Coté CJ, Ryan JF, Todres ID, et al (eds): A Practice of Anesthesia for Infants and Children, 2nd ed. Philadelphia, WB Saunders, 1993, p 76.

of the circulation close. Although closure of the ductus arteriosus probably occurs primarily in response to a rise in arterial oxygen concentration, its successful completion requires arterial muscular tissue.^[8] The fact that such tissue is less prevalent in premature infants may account, in part, for the high incidence of patent ductus arteriosus in premature infants. True mechanical closure by fibrosis does not occur until 2 to 3 weeks of age.^{[7] [8]}

During this critical period, the infant readily reverts from the adult circulation to a fetal type of circulation; this state is called transitional circulation. Many factors (hypoxia, hypercarbia, anesthesia-induced changes in peripheral vascular tone) can affect this precarious balance and result in a sudden return to fetal circulation. When such a "flip-flop" occurs, pulmonary artery pressure increases to systemic levels, blood is shunted past the lungs through the patent foramen ovale, and the ductus arteriosus may

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Risk factors increasing the likelihood of a prolonged transitional circulation include prematurity, infection, acidosis, pulmonary disease resulting in hypercarbia or hypoxemia (aspiration of meconium), acidosis, hypothermia, and congenital heart disease. Care must be directed to keeping the infant warm, maintaining normal arterial oxygen and carbon dioxide tension, and minimizing anesthetic-induced myocardial depression.

The myocardial structure of the heart, particularly the volume of cellular mass devoted to contractility, is significantly less developed in neonates than adults. These differences, as well as developmental changes in contractile proteins, produce a leftward displacement of the cardiac function curve and less compliant ventricles. This developmental myocardial immaturity accounts for the tendency toward biventricular failure, sensitivity to volume loading, poor tolerance of increased afterload, and heart rate-dependent cardiac output.^{[9] [10]} Another issue is that cardiac calcium stores are reduced because of immaturity of the sarcoplasmic reticulum; consequently, the neonate has a greater dependence on exogenous calcium and probably increased susceptibility to myocardial depression by potent inhaled drugs that have calcium channel blocking activity.^{[11] [12]}