The Neonate

Pulmonary Development

Lung development and maturation require a carefully regulated interaction of anatomic, physiologic, and biochemical processes. The outcome of these events provides an organ with adequate surface area, sufficient vascularization, and the metabolic capability to sustain oxygenation and ventilation during the neonatal period. Five stages of morphologic lung development have been identified in the human fetus : (1) the embryonic period, from 0 to 6 weeks postconception; (2) the pseudoglandular period, from 6 to 16 weeks; (3) the canalicular period, from 16 to 24 weeks; (4) the saccular period, from 24 to 38 weeks; and (5) the alveolar period, from 36 weeks’ gestation to 2 years of age.

The lung arises as a ventral diverticulum from the foregut during the fourth week of gestation, in the embryonic period . During the ensuing weeks, in the pseudoglandular period, branching of the diverticulum occurs and forms a tree of narrow tubes with thick epithelial walls composed of columnar cells. Molecular mechanisms involved in lung development include expression of transcription factors important for specification of the foregut endoderm, endogenous secretion of polypeptides important for pattern formation, and the production of growth and differentiation factors critical to cell development. By 16 weeks, the conducting portion of the tracheobronchial tree up to and including the terminal bronchioles has been established. The vasculature derived from the pulmonary circulation develops concurrently with the conducting airways, and by 16 weeks, preacinar blood vessels are formed. The canalicular period is characterized by differentiation of the airways, with widening of the airways and thinning of epithelium. In addition, primitive respiratory bronchioles begin to form, marking the start of the gas-exchanging portion of the lung. Vascular proliferation continues, along with a relative decrease in mesenchyme, which brings the vessels closer to the airway epithelium. The saccular period is marked by the development of the gas-exchanging portion of the tracheobronchial tree (acinus) composed of respiratory bronchioles, alveolar ducts, terminal saccules, and finally, alveoli. During this stage, the pulmonary vessels continue to proliferate with the airways and surround the developing air sacs. The final phase of prenatal lung development, the alveolar period, is marked by the formation of thin secondary alveolar septa and the remodeling of the capillary bed.

Throughout these periods, mesenchymal and epithelial cell cross-talk directs the normal processes of lung alveolarization and vascularization. Several million alveoli will form before birth, which emphasizes the importance of the last few weeks of pregnancy to pulmonary adaptation. Postnatal lung growth is characterized by generation of alveoli, and over 85% of alveolarization takes place after birth.

The critical determinants of extrauterine survival are the formation of the thin air-blood barrier and production of surfactant. By birth, the epithelial lining of the gas-exchanging surface is thin and continuous with two alveolar cell types: type I cells are thin and contain few subcellular organelles, whereas type II cells contain subcellular organelles that aid in the production of surfactant ( Fig. 23.1 ). Surfactant lipids and surfactant proteins (SPs) B and C are secreted by exocytosis as lamellar bodies and unravel into tubular myelin. The other SPs, SP-A and SP-D, are secreted independently of the lamellar bodies. Tubular myelin is a loose lattice of phospholipids and surfactant-specific proteins. The surface active component of surfactant then adsorbs at the alveolar interface between air and water in a monolayer. With repetitive expansion and compression of the surface monolayer, material is extruded that is either cleared by alveolar macrophages through endocytic pathways or taken up by the type II cell for recycling back into lamellar bodies.

Because of the development of high surface forces along the respiratory epithelium when breathing begins, the availability of surfactants in terminal airspaces is critical to postnatal lung function. Just as surface tension acts to reduce the size of a bubble in water, it also acts to reduce lung inflation, which promotes atelectasis. This is described by the Laplace law, which states that within a sphere the pressure (P) is directly proportional to surface tension (T) and is inversely proportional to the radius (r) of curvature ( Fig. 23.2 ). Surfactant has the physical property of variable surface tension dependent on the degree of surface area compression. In other words, as the radius of the alveolus decreases, surfactant serves to reduce surface tension, which prevents collapse of the alveolus. If this property is extrapolated to the lung, smaller alveoli will remain more stable than larger alveoli because of their lower surface tension. This feature is emphasized in Fig. 23.3 , which compares pressure-volume curves from surfactant-deficient and surfactant-treated preterm rabbits. Surfactant deficiency is characterized by high opening pressure, low maximal lung volume, and lack of deflation stability at low pressures.

Natural surfactant contains mostly lipids, phospholipids specifically, and some protein ( Fig. 23.4 ). Approximately half of the protein is specific for surfactant. The principal classes of phospholipids are:

• Saturated phosphatidylcholine compounds, the surface tension-reducing component of surfactant, 45%—more than 80% of which is dipalmitoylphosphatidylcholine (DPPC)

• Unsaturated phosphatidylcholine compounds, 25%

• Phosphatidylglycerol, phosphatidylinositol, and phosphatidylethanolamine, 10%

Saturated phosphatidylcholine is found in lung tissue of the human fetus earlier in gestation than in other species. Surfactant is released from storage pools into fetal lung fluid at a basal rate during late gestation and is stimulated by labor and the initiation of air breathing. Four unique surfactant-associated proteins have been identified, and all are synthesized and secreted by type II alveolar cells. Surfactant protein A (SP-A) functions cooperatively with the other SPs and lipids to enhance the biophysical activity of the surfactant, but its most important role is in the innate host defense of the lung. SP-B and SP-C are lipophilic proteins that facilitate the adsorption and spreading of lipid to form the surfactant monolayer. SP-B deficiencies are associated with neonatal pulmonary complications and death, whereas SP-C deficiencies are associated with interstitial lung disease that presents at a more variable age. SP-D plays a role in the regulation of surfactant lipid homeostasis, inflammatory responses, and host defense mechanisms.

Several hormones and growth factors contribute to the regulation of pulmonary phospholipid metabolism and lung maturation: glucocorticoids, thyroid hormone, thyrotropin-releasing hormone, retinoic acid, epidermal growth factor, and others. Glucocorticoids are the most important and are used clinically to augment the synthesis of surfactant and accelerate morphologic development. Pregnant women with anticipated preterm delivery have received corticosteroid treatment since 1972. Numerous controlled trials have since been performed. Based on a meta-analysis, a significant reduction of about 50% in the incidence of respiratory distress syndrome (RDS) is seen in infants born to mothers who received antenatal corticosteroids, irrespective of sex, race, or ethnicity. The time between steroid administration and delivery impacts the response to treatment. A 70% reduction in RDS was seen among babies born between 24 hours and 7 days after corticosteroid administration. In addition, evidence suggests reductions in mortality and RDS even with treatment started less than 24 hours before delivery. Of note, this meta-analysis included studies performed between 1972 and 1994, and included very few neonates born at less than 30 weeks GA. However, a clear reduction in RDS was evident when the population of babies less than 31 weeks was examined. Furthermore, performing randomized trials to demonstrate the precise benefit of antenatal corticosteroids at these very early gestational ages (22 to 28 weeks GA) would prove difficult given the impact demonstrated on neonatal morbidity and mortality in more mature neonates. Given the paucity of data on the benefit of steroids at the threshold of viability, a joint statement from the National Institute of Child Health and Human Development (NICHD), Society for Maternal-Fetal Medicine, American Association of Pediatrics (AAP), and American College of Obstetrics and Gynecology (ACOG) provides for discretionary use during the periviable period (20 ^0/7 to 25 ^6/7 ). The most recent ACOG Committee Opinion recommends ACS for “pregnant women between 24 ^0/7 weeks and 33 ^6/7 weeks of gestation who are at risk of preterm delivery within 7 days” and “may be considered for pregnant women starting at 23 ^0/7 weeks of gestation who are at risk of preterm delivery within 7 days, based on a family's decision regarding resuscitation.”

Corticosteroids also accelerate maturation of other organs in the developing fetus, including the cardiovascular, gastrointestinal (GI), and central nervous systems (CNSs) . Corticosteroid therapy reduces the chances of periventricular hemorrhage (PVH) and intraventricular hemorrhage (IVH) in addition to necrotizing enterocolitis (NEC). The significant reductions in serious neonatal morbidity are also reflected in a reduction in the risk of early neonatal mortality. The short-term beneficial effects of antenatal corticosteroids are enhanced by reassuring reports about long-term outcome. The children of mothers treated with antenatal corticosteroids before 34 weeks’ gestation have better neurologically intact survival and a lower chance of having severe or minor disability, a mental or performance developmental index less than 70, and cerebral palsy. There also is no effect of antenatal corticosteroids on long-term growth compared with untreated infants.

Since the advent of antenatal steroids for the prevention of RDS, other therapies have been introduced that decrease mortality and morbidity. Surfactant replacement therapy to treat specifically the surfactant deficiency that is the cause of RDS has been shown to decrease mortality and the severity of RDS. The effects of antenatal corticosteroids and postnatal surfactant appear to be additive in terms of decreasing the severity of RDS and the mortality caused by it.

First Breaths

A critical step in the transition from intrauterine to extrauterine life is the conversion of the lung from a fluid-filled organ to one capable of gas exchange. This requires aeration of the lungs, establishment of an adequate pulmonary circulation, ventilation of the aerated parenchyma, and diffusion of oxygen and carbon dioxide through the alveolar-capillary membranes. This process has its origins in utero as fetal breathing.

Fetal Breathing

Fetal respiratory activity is initially detectable at 11 weeks. The most prevalent pattern is rapid, small-amplitude movements (60 to 90 per minute), which are present 60% to 80% of the time. Less commonly, irregular low-amplitude movements interspersed with slower, larger amplitude movements are seen. Fetal breathing is responsive to chemical stimuli and other agents. Acute hypercapnia stimulates breathing. Hypoxia abolishes fetal breathing, whereas an increase in oxygen tension to levels above 200 mm Hg induces continuous fetal breathing. Although peripheral and central chemoreflexes—as well as vagal afferent reflexes—can be demonstrated in the fetus, their role in spontaneous fetal breathing appears to be minimal. The role of fetal breathing in the continuum from fetal to neonatal life is still not completely understood. Fetal respiratory activity is probably essential to the development of chest wall muscles, including the diaphragm, and serves as a regulator of lung fluid volume and thus lung growth.

The mechanism responsible for the transition from intermittent fetal to continuous neonatal breathing is unknown. Prostaglandins may be involved in addition to other factors that surround birth, including blood gas changes and various sensory stimuli. Another possibility is the “release” from a placental inhibitory factor that is removed after cord occlusion.

Mechanics of the First Breath

With its first breaths, the neonate must overcome several forces that resist lung expansion: (1) viscosity of fetal lung fluid, (2) resistance provided by lung tissue itself, and (3) the forces of surface tension at the air-liquid interface. Viscosity of fetal lung fluid is a major factor as the neonate attempts to displace fluid present in the large airways. As the passage of air moves toward small airways and alveoli, surface tension becomes more important. Resistance to expansion by the lung tissue itself is less significant. The process begins as the infant passes through the birth canal; the intrathoracic pressure caused by vaginal squeeze is up to 200 cm H ₂ O. With delivery of the head, approximately 5 to 28 mL of tracheal fluid is expressed. Subsequent delivery of the thorax causes an elastic recoil of the chest. With this recoil, a small passive inspiration (no more than 2 mL) occurs. This is accompanied by glossopharyngeal forcing of some air into the proximal airways (frog breathing) and the introduction of some blood into pulmonary capillaries. This pulmonary vascular pressure may have a role in producing continuous surfaces throughout the small airways of the lung, into which surfactant can deploy.

The initial breath is characteristically a short inspiration, followed by a more prolonged expiration. The initial breath begins with no air volume and no transpulmonary pressure gradient. Considerable negative intrathoracic pressure during inspiration is provided by diaphragmatic contraction and chest wall expansion. An opening pressure of about 25 cm H ₂ O usually is necessary to overcome surface tension in the smaller airways and alveoli before air begins to enter. The volume of this first breath varies between 30 and 67 mL and correlates with intrathoracic pressure. The expiratory phase is prolonged, because the infant's expiration is opposed by intermittent closure at the pharyngolaryngeal level with the generation of significant positive intrathoracic pressure. This pressure serves to aid both in maintenance of a functional residual capacity (FRC) and with fluid removal from the air sacs. The residual volume after this first breath ranges between 4 and 30 mL, averaging 16 to 20 mL. No major systematic differences are apparent among the first three breaths, which demonstrate similar pressure patterns of decreasing magnitude. The FRC rapidly increases with the first several breaths and then increases more gradually. By 30 minutes of age, most infants attain a normal FRC with uniform lung expansion. The presence of functional surfactant is instrumental in the accumulation of an FRC.

In utero, alveoli are open and stable at a nearly neonatal lung volume because they are filled with fetal lung liquid, probably produced by ultrafiltration of pulmonary capillary blood as well as by secretion by alveolar cells. Transepithelial chloride secretion appears to be a major factor responsible for the production of luminal liquid in the fetal lung. Normal expansion and aeration of the neonatal lung is dependent on removal of fetal lung liquid. Liquid is removed by a combination of mechanical drainage and absorption across the lung epithelium. This process begins before a normal term birth because of decreased fluid secretion and increased absorption. Once labor is initiated, a reversal of liquid flow occurs across the lung epithelium. Active transcellular sodium absorption drives liquid from the lumen to the interstitial space, where it is drained through the pulmonary circulation and lymphatics. In normal circumstances, the process is complete within 2 hours of birth. Cesarean-delivered infants without benefit of labor and premature infants have delayed lung fluid clearance. In both groups, the prenatal decrease in lung water does not occur. In addition, in the premature neonate, fluid clearance is diminished by increased alveolar surface tension, increased left atrial pressure, and hypoproteinemia.

Circulatory Transition

The circulation in the fetus ( Fig. 23.5 ) has been studied in a variety of species using several techniques (see Chapter 2 ). Umbilical venous blood returning from the placenta has a PO ₂ of about 30 to 35 mm Hg. Because of the left-shifted fetal hemoglobin-oxyhemoglobin disassociation curve, this corresponds to a saturation of 80% to 90%. About 60% of this blood perfuses the liver, mainly to the middle and left lobes, and it ultimately enters the inferior vena cava (IVC) through the hepatic veins. The remainder (40% in mid-gestation, 20% at term) bypasses the hepatic circulation through the ductus venosus and empties directly into the IVC. Because of streaming in the IVC, the more oxygenated blood from the ductus venosus and left hepatic vein, as it enters the heart, is deflected by the crista dividens through the foramen ovale to the left atrium. The remainder of left atrial blood is the small amount of venous return from the pulmonary circulation. The less oxygenated IVC blood from the lower body and the renal, mesenteric, and right hepatic veins streams across the tricuspid valve to the right ventricle. Almost all the return from the superior vena cava (SVC) and the coronary sinus passes through the tricuspid valve to the right ventricle, with only 2% to 3% crossing the foramen ovale. In the near-term fetus, the combined ventricular output is about 450 mL/kg/min; two-thirds from the right ventricle and one-third from the left ventricle. The blood in the left ventricle has a PO ₂ of 25 to 28 mm Hg (saturation of 60%) and is distributed to the coronary circulation, brain, head, and upper extremities with the remainder (10% of combined output) passing into the descending aorta. The major portion of the right ventricular output (60% of combined output) is carried by the ductus arteriosus to the descending aorta, with only 7% of combined output going to the lungs. Thus 70% of combined output passes through the descending aorta, with a PO ₂ of 20 to 23 mm Hg (saturation of 55%) to supply the abdominal viscera and lower extremities. Forty-five percent of combined output goes through the umbilical arteries to the placenta. Thus blood of a higher PO ₂ supplies the critical coronary and cerebral circulations, and umbilical venous blood is diverted to where oxygenation is critical.

The diversion of right ventricular output away from the lungs through the ductus arteriosus is caused by the very high pulmonary vascular resistance (PVR) in the fetus. This high PVR is maintained by multiple mechanisms. With advancing gestational age, an increase in the number of small pulmonary vessels occurs that increases the cross-sectional area of the pulmonary vasculature. This contributes to the gradual decline in PVR that begins during later gestation ( Fig. 23.6 ). With delivery, a variety of factors interact to decrease PVR acutely; these include mechanical ventilation, increased oxygen tension, and the production of endothelium-derived relaxing factor or nitric oxide.

With the increase in pulmonary flow, left atrial return increases with a rise in left atrial pressure ( Table 23.1 ). In addition, with the removal of the placenta, IVC return to the right atrium is diminished. The foramen ovale is a flap valve, and when left atrial pressure increases over that on the right side, the opening is functionally closed. It is still possible to demonstrate patency with insignificant right-to-left shunts in the first 12 hours of life in a human neonate, but in a 7- to 12-day newborn, such a shunt is rarely seen. Anatomic closure is not complete for a longer time.

With occlusion of the umbilical cord, the low-resistance placental circulation is interrupted, which causes an increase in systemic pressure. This coupled with the decrease in PVR serves to reverse the shunt through the ductus arteriosus to a predominantly left-to-right shunt. By 15 hours of age, shunting in either direction is physiologically insignificant. Although functionally closed by 4 days, the ductus arteriosus is not anatomically occluded for 1 month. The role of an increased oxygen environment and prostaglandin metabolism in ductal closure is well established. Ductal closure occurs in two phases: constriction and anatomic occlusion. Initially, the muscular wall constricts, followed by permanent closure achieved by endothelial destruction, subintimal proliferation, and connective tissue formation. The ductus venosus is functionally occluded shortly after the umbilical circulation is interrupted.

Birth Asphyxia

Even normal infants may experience some limitation of oxygenation (asphyxia) during the birth process. A variety of circumstances can exaggerate this problem and can result in respiratory depression in the infant, including (1) acute interruption of umbilical blood flow, as occurs during cord compression; (2) premature placental separation; (3) maternal hypotension or hypoxia; (4) any of the above-mentioned problems superimposed on chronic uteroplacental insufficiency; and (5) failure to execute a proper resuscitation. Other contributing factors include anesthetics and analgesics used in the mother, mode and difficulty of delivery, maternal health, and prematurity.

The neonatal response to asphyxia follows a predictable pattern. Dawes investigated the responses of the newborn rhesus monkey ( Fig. 23.7 ). After delivery, the umbilical cord was tied, and the monkey's head was placed in a saline-filled plastic bag. Within about 30 seconds, a short series of respiratory efforts began. These were interrupted by a convulsion or a series of clonic movements accompanied by an abrupt fall in heart rate. The animal then lay inert with no muscle tone. Skin color became progressively cyanotic and then blotchy because of vasoconstriction in an effort to maintain systemic blood pressure. This initial period of apnea lasted about 30 to 60 seconds. The monkey then began to gasp at a rate of 3 to 6 breaths/min. The gasping lasted for about 8 minutes, becoming weaker terminally. The time from onset of asphyxia to last gasp could be related to postnatal age and maturity at birth; the more immature the animal, the longer the time. Secondary or terminal apnea followed, and if resuscitation was not quickly initiated, death ensued. As the animal progressed through the phase of gasping and then on to terminal apnea, heart rate and blood pressure continued to fall, which indicated hypoxic depression of myocardial function. As the heart failed, blood flow to critical organs decreased and resulted in organ injury.

The response to resuscitation is qualitatively similar in many species, including humans. During the first period of apnea, almost any physical or chemical stimulus causes the animal to breathe. If gasping has already ceased, the first sign of recovery with initiation of positive-pressure ventilation is an increase in heart rate. The blood pressure then rises, rapidly if the last gasp has only just passed, but more slowly if the duration of asphyxia has been longer. The skin then becomes pink, and gasping ensues. Rhythmic spontaneous respiratory efforts become established after a further interval. For each minute past the last gasp, 2 minutes of positive-pressure breathing is required before gasping begins, and it takes 4 minutes to reach rhythmic breathing. Later, the spinal and corneal reflexes return. Muscle tone gradually improves over the course of several hours.

Delivery Room Management of the Newborn

A number of situations during pregnancy, labor, and delivery place the infant at increased risk for asphyxia: (1) maternal diseases, such as diabetes mellitus and hypertension, in addition to third-trimester bleeding and prolonged rupture of membranes; (2) fetal conditions, such as prematurity, multiple gestation, growth restriction, fetal anomalies, and rhesus isoimmunization; and (3) conditions related to labor and delivery, including fetal distress, meconium staining, breech presentation, and administration of anesthetics and analgesics.

When an asphyxiated infant is expected, a resuscitation team should be in the delivery room. The team should comprise at least two people, one to manage the airway and one to monitor heart rate and provide whatever assistance is needed. The necessary equipment for an adequate resuscitation can be found in the Textbook of Neonatal Resuscitation. The equipment should be checked regularly and should be in a continuous state of readiness. The steps in the resuscitation process are outlined in the algorithm in Fig. 23.8 . Some key points of the algorithm follow.

• 1

  For anticipated complex resuscitations, antenatal counseling and a resuscitation team briefing should occur before delivery if time allows.

• 2

  Do not allow the infant to become hyperthermic under the warmer.

• 3

  The best criteria to use for assessing the infant's condition are respiratory effort—whether it is apneic, gasping, or regular—and heart rate (>100 or <100 beats/min).

• 4

  If the infant is apneic, has gasping respirations, or a heart rate below 100 beats/min, a pulse oximeter should be placed on the infant's right hand and one should consider placing a three lead electrocardiograph monitor .

• 5

  Most neonates can be effectively resuscitated with a bag or T-piece resuscitator connected to a face mask. For the initial inflations peak inspiratory pressures of 20 to 25 cm H ₂ O should be used, though pressures of 30 to 40 cm H ₂ O may be necessary to overcome surface active forces in the lungs. Adequacy of ventilation is assessed by observing expansion of the infant's chest with bagging and watching for a gradual improvement in color, perfusion, and heart rate. Rate of bagging should be 40 to 60 beats/min.

• 6

  Initial resuscitation of infants greater than or equal to 35 weeks’ gestational age should begin with 21% fractional inspired oxygen. For infants less than 35 weeks’ gestational age resuscitation should begin with 21% to 30% fractional inspired oxygen. Oxygen concentrations should be titrated based on age-specific saturation targets (see Fig. 23.8 ) and the patient's clinical status.

• 7

  If the infant does not initially respond to bag and mask ventilation, try to reposition the head in slight extension, reapply the mask to achieve a good seal, consider suctioning the mouth and oropharynx, and try ventilating with the mouth open. It may be necessary to increase the pressure used. However, if no favorable response is seen in 30 to 40 seconds, proceed to placement of a laryngeal mask or endotracheal tube airway.

• 8

  Failure to respond to ventilation with an instrumented airway can result from mechanical causes or severe asphyxia. The mechanical causes listed in Table 23.2 should quickly be ruled out.

  TABLE 23.2

  Mechanical Causes of Failed Resuscitation

  Category	Examples
  Equipment failure	Malfunctioning bag, oxygen not connected or running
  Endotracheal tube malposition	Esophagus, right mainstem bronchus
  Occluded endotracheal tube
  Insufficient inflation pressure to expand lungs
  Space-occupying lesions in the thorax	Pneumothorax, pleural effusions, diaphragmatic hernia
  Pulmonary hypoplasia	Extreme prematurity, oligohydramnios

• 9

  It is very unusual for a neonatal resuscitation to require either cardiac massage or drugs, and almost all newborns respond to ventilation with supplemental oxygen. If compressions are required, they need to be coordinated with bagging at a 3 : 1 ratio (90 compressions to 30 breaths/min). It is even less common to need medications. The optimal delivery route for medications is through an umbilical venous catheter.

• 10

  The appropriateness of continued resuscitative efforts should always be reevaluated in an infant who fails to respond to all of the previously mentioned efforts. Today, resuscitative efforts are made even in “apparent stillbirths,” that is, infants whose 1-minute Apgar scores are 0 to 1 ( Table 23.3 ).

  TABLE 23.3

  The Apgar Scoring System

  Modified from Apgar V. A proposal for a new method of evaluation of the newborn infant. Anesth Analg. 1953;32:260.

  Sign	0	1	2
  Heart rate	Absent	<100 beats/min	>100 beats/min
  Respiratory effort	Apneic	Weak, irregular gasping	Regular
  Reflex irritability a	No response	Some response	Facial grimace, sneeze, cough
  Muscle tone	Flaccid	Some flexion of arms and legs	Good flexion
  Color	Blue, pale hands and blue feet	Body pink	Pink

  a Elicited by suctioning the oropharynx and nose.

In addition to the initial fraction of inspired oxygen used, other considerations for the resuscitation of preterm infants should be made. Minimizing heat loss is critical. For babies born less than 32 weeks’ gestation place a thermal mattress under a blanket on a radiant warmer. Instead of drying the baby with towels, very preterm babies should be covered or wrapped up to their neck in polyethylene plastic immediately after birth. Monitor the baby's temperature frequently and consider placing a temperature sensor on the newborn. Maintain the baby's axillary temperature between 36.5°C and 37.5°C. Other measures to consider when resuscitating a preterm newborn include the following: handle the baby gently, do not position the baby's legs higher than the head, avoid delivering excessive pressure during positive pressure ventilation or continuous positive airway pressure administration, use a pulse oximeter and blood gases to monitor and adjust ventilation and oxygen concentration, and do not rapidly infuse intravenous (IV) fluids.

Recent changes to the approach to the newborn with meconium-stained amniotic fluid have been made. It should be remembered that the presence of meconium stained amniotic fluid may indicate fetal distress. However, the presence of meconium stained amniotic fluid no longer changes the initial steps of newborn care and resuscitation. Routine intubation for tracheal suctioning is no longer indicated due to the presence of meconium stained amniotic fluid. This approach is based on data from large multicenter, prospective, randomized controlled trials that assessed selective intubation of apparently vigorous and nonvigorous meconium-stained infants. Compared with expectant management, intubation and tracheal suction did not result in a decreased incidence of meconium aspiration syndrome or other respiratory disorders. Finally, oropharyngeal suction on the perineum before delivery of the shoulders does not prevent meconium aspiration syndrome, and so the obstetrician should carefully performs bulb suctioning of the oropharynx and nasopharynx after delivery of the baby.

Cord Clamping

According to the Neonatal Resuscitation Program, the optimal timing for cord clamping for most vigorous term and preterm newborns should be between 30 and 60 seconds. During the period between birth and clamping of the cord, the initial steps of resuscitation should be commenced. This includes thermoregulation, which for a term newborn may include placing the baby skin-to-skin on the mother's chest or abdomen. Historically, clamping and cutting of the umbilical cord took place within seconds; however, it has been found that delaying this separation of the newborn from the placental circulation for 30 to 60 seconds results in (1) a more gradual perinatal transition after birth, (2) transfusion of placental blood to the newborn, and (3) a variety of improved outcomes. This practice is now endorsed for preterm births by the American College of Obstetricians and Gynecologists (ACOG), although specific patient populations and situations require further study. In cases where there has been a disruption of the placental circulation, like abruption, previa with bleeding, and cord avulsion, the cord should be clamped immediately after birth. For the infant who is not vigorous, it is unclear whether cord clamping should be delayed.

Sequelae of Birth Asphyxia

The incidence of birth asphyxia is about 0.1% in term infants, with an increased incidence in infants at lower gestational ages. The acute sequelae that need to be managed in the neonatal period are listed in Table 23.4 . With asphyxia, widespread organ injury is evident. Management focuses on supportive care and treatment of specific abnormalities; this includes careful fluid management, blood pressure support, IV glucose, and treatment of seizures. Hypothermia (whole body or selective head cooling) improves outcomes at 6 to 7 years of age, especially if started within the first 6 hours of life. The roles of oxygen free-radical scavengers, erythropoiesis stimulating agents, excitatory amino acid antagonists, and calcium channel blockers in minimizing cerebral injury after asphyxia are still being investigated.

If the infant survives, the major long-term concern is permanent CNS damage. The challenge lies in the identification of criteria that can provide information about the risk of future problems for a given infant. The best predictor of outcome is the severity of the neonatal neurologic syndrome. Infants with mild encephalopathy survive and do not have an increased risk of severe handicap on follow-up examination. Moderate encephalopathy carries a 25% to 50% risk of severe handicap or death, whereas the severe syndrome carries a greater than 75% risk of death or disability. Although outcomes are improved with hypothermia initiated in the first 6 hours of life, these patients remain at high risk for poor neurodevelopment. Electroencephalograms and magnetic resonance imaging (MRI) scans can aid in predicting outcome. The circulatory response to hypoxia is to redistribute blood flow to provide adequate oxygen delivery to critical organs (e.g., brain, heart) at the expense of other organs. Thus an insult severe enough to damage the brain should be accompanied by evidence of other organ dysfunction.

The long-term neurologic sequelae of intrapartum asphyxia are cerebral palsy with or without associated cognitive deficits and epilepsy. Although cerebral palsy can be related to intrapartum events, the large majority of cases are of unknown causes. Furthermore, cognitive deficits and epilepsy, unless associated with cerebral palsy, cannot be related to asphyxia or to other intrapartum events. To attribute cerebral palsy to peripartum asphyxia, there must be an absence of other demonstrable causes, substantial or prolonged intrapartum asphyxia (fetal heart rate abnormalities, fetal acidosis), and clinical evidence during the first days of life of neurologic dysfunction in the infant ( Box 23.1 ).

Physiology

The range of environmental temperatures over which the neonate can survive is narrower than that of an adult as a result of the infant's inability to dissipate heat effectively in warm environments and, more critically, to maintain temperature in response to cold. This range narrows with decreasing gestational age.

Although some increases in activity and shivering have been observed, nonshivering thermogenesis is the most important means of increased heat production in the cold-stressed newborn. It can be defined as an increase in total heat production without detectable (visible or electrical) muscle activity. The site of this increased heat production is brown fat located between the scapulae; around the muscles and blood vessels of the neck, axillae, and mediastinum; between the esophagus and trachea; and around the kidneys and adrenal glands. Brown fat cells contain more mitochondria and fat vacuoles and have a richer blood and sympathetic nerve supply compared with white fat cells.

Heat loss to the environment is dependent on both an internal temperature gradient, from within the body to the surface, and an external temperature gradient, from the surface to the environment. The infant can change the internal gradient by altering vasomotor tone and, to a lesser extent, by postural changes that decrease the amount of exposed surface area. The external gradient is dependent on purely physical variables. Heat transfer from the surface to the environment involves four routes: radiation, convection, conduction, and evaporation. Radiant heat loss, heat transfer from a warmer to a cooler object that is not in contact, depends on the temperature gradient between the objects. Heat loss by convection to the surrounding gaseous environment depends on air speed and temperature. Conduction, heat loss to a contacting cooler object, is minimal in most circumstances. Heat loss by evaporation is cooling secondary to water loss at the rate of 0.6 cal/g water evaporated and is affected by relative humidity, air speed, exposed surface area, and skin permeability. In infants in excessively warm environments, such as those under overhead radiant heat sources, or in very immature infants with thin, permeable skin, evaporative losses increase considerably. Table 23.6 summarizes the neonate's efforts to maintain a stable core temperature in the face of cold or heat stress. It is advantageous to maintain an infant in a neutral thermal environment ( Fig. 23.9 ). The neutral thermal environment for a given infant depends on size, gestational age, and postnatal age. In general, maintaining the abdominal skin temperature at 36.5°C minimizes energy expenditure.

Delivery Room

In utero, fetal thermoregulation is the responsibility of the placenta and is dependent on maternal core temperature; fetal temperature is 0.5°C higher than maternal temperature. At birth, the infant's core temperature drops rapidly from 37.8°C because of evaporation from its wet body and radiant and convective losses to the cold air and walls of the room. Even with an increase in oxygen consumption to the maximum capability of the newborn (15 mL/kg per minute), the infant can produce only 0.075 cal/kg per minute and will rapidly lose heat. Measures taken to reduce heat loss after birth depend on the clinical situation. For the well term infant, drying the skin and wrapping the baby with warm blankets is sufficient. When it is necessary to leave an infant exposed for close observation or resuscitation, the infant should be dried and placed under a radiant heat source. The room temperature can be elevated as an added precaution for the low-birthweight (LBW) infant, with other steps taken for preterm newborns as noted in the above section describing the resuscitation of newborns.