In which of the following infants would the nurse be most alert for the development of transient tachypnea?

Transient Tachypnea of the Newborn

Transient tachypnea of the newborn (TTN) is characterized by mild to moderate respiratory distress that gradually improves during the first 48 to 72 hours of life. TTN results from the delayed clearance of fetal lung fluid and is more commonly observed in infants with a history of maternal diabetes and those born via cesarean section.45-47 The CXR shows normal to mildly overexpanded lungs with a diffuse hazy appearance and increased interstitial streaky shadowing extending to the periphery. Small pleural effusions, typically seen as prominence of the interlobar fissures, are common (Fig. 9-11). Early CXRs in TTN can appear similar to those of more serious conditions such as infection, surfactant deficiency, or cardiac failure.

Transient Tachypnea of the Newborn.

Transient tachypnea of the newborn (TTN), sometimes called wet lungs, is a common self-limited disease of term newborns that results from delayed lung fluid clearance.42 This deficit is probably secondary to immature sodium epithelium channel (ENaC). Furosemide has been proposed to hasten fluid lung clearance and thus improve the pulmonary condition. In a randomized study, the oral administration of 2 mg/kg followed by 1 mg/kg 12 hors later increased weight loss but did not improve the severity or duration of symptoms.43 A Cochrane analysis of the study concluded that oral furosemide could not be recommended as treatment of TTN.44 Whether infants with TTN could benefit from IV furosemide remains to be demonstrated.

Transient Tachypnea of the Newborn

Transient tachypnea of the newborn (TTNB) is among the most common causes of respiratory distress in the newborn period, affecting 0.5% to 4% of all late preterm and term neonates. Symptoms of respiratory distress typically start within the first several hours after birth and result from failure of adequate absorption of fetal lung fluid. Studies have consistently shown that risk factors for TTNB include prematurity, delivery by cesarean section (particularly without preceding labor), and male sex (Jain et al, 2009; Riskin et al, 2005).

Early theories of lung fluid clearance focused on the role of thoracic compression during vaginal delivery and were supported by the observation that TTNB is more common among babies born by cesarean section (Milner et al, 1978). However, more recent studies have demonstrated that the complex process of lung liquid clearance likely begins well before term birth (Brown et al, 1983). During fetal life, the lung epithelium is responsible for the production of a substantial volume of alveolar fluid, a process that is essential for normal fetal lung growth (Olver and Strang, 1974). With parturition, increased levels of epinephrine, glucocorticoids, and other hormones effectively cause the lung epithelia to transition from a secretory to a resorptive phenotype (Baines et al, 2000; Barker et al, 1990). Activated endothelial sodium channels (ENaC) at the apical surface of lung type II epithelial cells transport sodium and water from the alveolar space into the type II cells (Olver et al, 1986). Sodium is then actively moved from the type II cell into the interstitium by Na/K ATPase, causing passive movement of water, which is then resorbed into the pulmonary circulation and lymphatics. Supporting a possible role for abnormal activity of ENaC and Na/K ATPase in TTNB, a recent study found that genetic polymorphisms in β-adrenergic receptor encoding genes (which regulate expression of these channels) are more common in babies with TTNB (Aslan et al, 2008).

The diagnosis of TTNB remains problematic for clinicians. The most typical presenting symptoms, tachypnea/respiratory distress and the need for supplemental oxygen, are common among most neonatal respiratory disorders, and unfortunately, there exist no reliable diagnostic tests for TTNB (Guglani et al, 2008). For those reasons, the diagnosis remains one of exclusion, and vigilance for other, more severe disorders is imperative. Typically, symptoms of TTNB develop within the first several hours after birth. The degree of respiratory impairment, including the respiratory rate, use of accessory respiratory muscles, and impairment in gas exchange, varies widely. Chest radiographs should be considered in any baby presumed to have TTNB. Although radiographs commonly show prominent perihilar markings and fluid in the fissures, clinicians and radiologists often disagree in their interpretation of these findings in TTNB (Kurl et al, 1997).

Once a presumptive diagnosis of TTNB is made, treatment is largely supportive. Oxygen should be provided to maintain normal arterial oxygen saturations. The degree of tachypnea and respiratory distress should determine whether a baby is allowed to feed by mouth. If there is a suspicion of pneumonia or sepsis, empiric antibiotic therapy should be considered. A controlled trial of furosemide administration to accelerate clearance of lung fluid showed no benefit in attenuating the course of TTNB (Wiswell et al, 1985). Alternative or additional diagnoses should be considered in any infant who is deteriorating or requires mechanical ventilation. With supportive care, full recovery is to be expected after TTNB. However, compared with well infants of a similar gestational age, the diagnosis of TTNB is associated with a significantly prolonged hospital course (Riskin et al, 2005). Moreover, recent epidemiologic studies have suggested that newborns with TTNB are at a mildly increased risk for the later development of asthma (Birnkrant et al, 1996; Liem et al, 2007; Schaubel et al, 2006).

Transient Tachypnea of the Newborn

Transient tachypnea of the newborn (TTNB) is among the most common causes of respiratory distress in the newborn period, affecting 0.5%–4% of all late preterm and term neonates. The symptoms of respiratory distress typically start within the first several hours after birth and result from failure of adequate absorption of fetal lung fluid. Studies have consistently shown that risk factors for TTNB include prematurity, birth by cesarean delivery, and male sex (Riskin et al., 2005; Jain et al., 2009; Silasi et al., 2010). Among babies born by elective cesarean delivery, a recent study suggests that delivery before 39 weeks increases the risk of TTNB by more than twofold (Doan et al., 2014).

Early theories of lung fluid clearance focused on the role of thoracic compression during vaginal delivery and were supported by the observation that TTNB is more common among babies born by cesarean delivery (Milner et al., 1978). However, more recent studies have demonstrated that the complex process of lung liquid clearance likely begins well before term birth (Brown et al., 1983). During fetal life the lung epithelium is responsible for the production of a substantial volume of alveolar fluid, a process that is essential for normal fetal lung growth (Olver and Strang, 1974). With parturition, increased levels of epinephrine, glucocorticoids, and other hormones effectively cause the lung epithelia to transition from a secretory to a resorptive phenotype (Barker et al., 1990; Baines et al., 2000). Activated endothelial sodium channels (ENaC) at the apical surface of lung type II epithelial cells transport sodium and water from the alveolar space into the type II cells (Olver et al., 1986). Sodium is then actively moved from the type II cell into the interstitium by sodium-potassium pump (Na/K-ATPase), causing passive movement of water, which is then resorbed into the pulmonary circulation and lymphatics. Supporting a possible role for abnormal activity of ENaC and Na/K-ATPase in TTNB, it has been found that genetic polymorphisms in β-adrenergic receptor–encoding genes (which regulate expression of these channels) are more common in babies with TTNB (Aslan et al., 2008).

The diagnosis of TTNB remains problematic for clinicians. The most typical presenting symptoms, tachypnea/respiratory distress and the need for supplemental oxygen, are common among most neonatal respiratory disorders, and unfortunately, there exist no reliable diagnostic tests for TTNB (Guglani et al., 2008). For those reasons the diagnosis remains one of exclusion, and vigilance for other, more severe disorders is imperative. Typically, symptoms of TTNB develop within the first several hours after birth. The degree of respiratory impairment, including the respiratory rate, use of accessory respiratory muscles, and impairment in gas exchange, differs widely. CXRs should be considered in any baby presumed to have TTNB. Although radiographs commonly show prominent perihilar markings and fluid in the fissures, clinicians and radiologists often disagree in their interpretation of these findings in TTNB (Kurl et al., 1997).

Once a presumptive diagnosis of TTNB has been made, treatment is largely supportive. Oxygen should be provided to maintain normal arterial oxygen saturations. The degree of tachypnea and respiratory distress should determine whether a baby is allowed to feed by mouth. If there is a suspicion of pneumonia or sepsis, empiric antibiotic therapy should be considered. A controlled trial of furosemide administration to accelerate clearance of lung fluid showed no benefit in attenuating the course of TTNB (Wiswell et al., 1985). A prospective study suggests that moderate fluid restriction for the first 72 hours reduced the duration of respiratory support and cost of hospitalization (Stroustrup et al., 2012). Alternative or additional diagnoses should be considered in any infant who is deteriorating or requires mechanical ventilation. With supportive care, full recovery is to be expected after TTNB. However, compared with well infants of a similar gestational age, newborns with TTNB have a significantly prolonged hospital course (Riskin et al., 2005). Moreover, recent epidemiologic studies have suggested that newborns with TTNB are at a mildly increased risk of the later development of asthma (Birnkrant et al., 1996; Schaubel et al., 2006; Liem et al., 2007).

Epidemiology, Risk Factors, and Pathogenesis

Transient tachypnea of the newborn affects 1% to 2% of all newborns,90 primarily full-term infants. Several perinatal risk factors, including elective cesarean section,91 excessive administration of fluids to the mother during labor,92 male gender, and macrosomia, have been linked to the development of TTN.90 Meta-analysis of clinical trials does not currently support a role for delayed clamping of the umbilical cord in TTN.93

The removal of fetal lung liquid from the lung at birth is an essential step for newborn adaptation to extrauterine life. The clearance of such liquid has been attributed at least in part to the mechanical compression of the chest at birth.94 More importantly, there is an antenatal reduction in fetal lung liquid95 that results from a shift of fluid from the lung lumen into the interstitium.96 The initiation and process of labor is an important factor in this antenatal redistribution and absorption of lung liquid,97 explaining, in part, the higher incidence of TTN observed after elective cesarean section.98,99

The secretion of fetal lung liquid is decreased or stops during labor. Fetal epinephrine levels increase and activate b-adrenoreceptors, which increase Na+ transport and fluid resorption. The absorption of fetal lung fluid can be blocked by the administration of amiloride—an Na+ channel antagonist.100 Other hormones, including thyroxine and glucocorticoids, also upregulate Na+ channel-mediated fluid absorption. Additionally, arginine vasopressin, somatostatin, dopamine, and serotonin rise during labor in a similar fashion to epinephrine and are candidates as regulatory hormones for lung fluid resorption. Male sex101 and maternal history of asthma are associ-ated with the development of TTN.102 Genetic predisposition to b-adrenergic hyporesponsiveness is proposed as a mechanism to the association between TTN and maternal asthma.103

With aeration of the lungs at birth, the fetal lung fluid absorbed across the pulmonary epithelium initially accumulates in the interstitial fluid of ventilated regions of the lung, particularly around the perivascular spaces. Lung fluid is slowly resorbed from the interstitium over a 2 to 6 hour period via vascular and lymphatic systems. The lymphatic system accounts for around 11% of fluid resorption of animals in labor,96 and up to 50% of fluid resorption for animals not in labor. Any condition that increases hydrostatic pressure in the pulmonary vasculature can interfere with the appropriate resorption of fluid into the pulmonary circulation. Increased hydrostatic pressure can explain the higher incidence of TTN observed after excessive administration of fluids to the mother. Mild left ventricular dysfunction has also been described in infants with TTN.104 An excessive amount of liquid in the lung may explain lower neonatal thoracic gas volumes after cesarean section compared to vaginal delivery. Infants born via cesarean section take up to 48 hours to establish their full lung volume.105

PATHOPHYSIOLOGY

TTN is a benign, self-limited disorder that occurs during the transition from uterine to extrauterine life and results from the delayed clearance of excess lung fluid. TTN was first described in 1966 when it was observed that a subset of newborns exhibited respiratory distress, consisting primarily of tachypnea, at or shortly after birth. Although the tachypnea persisted for several days, it subsequently resolved completely without sequelae.1

Inadequate or delayed clearance of fetal lung fluid results in TTN, whereas surfactant deficiency results in respiratory distress syndrome. These categorizations are not absolute, however; some have suggested that TTN is associated with a relative surfactant dysfunction,2 but other studies found no association between TTN and surfactant mutation.3

Delivery via elective cesarean section increases the risk for TTN. Although the physiologic mechanisms are not understood, this risk is significantly decreased if the mother undergoes a trial of labor.4-6 Additional risk factors for TTN include male sex and macrosomia.7 Although the mechanism is obscure, being born to an asthmatic mother appears to be a risk factor for TTN.8 Infants born to women with gestational diabetes also appear to be at increased risk. This observation may be related to a corresponding increase in the rate of cesarean sections among these mothers.9

PPHN commonly occurs in full-term and near-term infants (>34 weeks) and has an estimated incidence of 0.2% of live births.10 After birth, PPHN occurs when there is an insufficient or delayed decrease in pulmonary vascular resistance, which results in right-to-left shunting of blood through the ductus arteriosus or foramen ovale and severe hypoxemia. PPHN typically arises in the setting of a structurally normal heart, either with or without associated pulmonary disease. Perinatal risk factors that increase pulmonary vasoconstriction include hypoxia, acidosis, alveolar atelectasis, sepsis, direct lung injury, hypoglycemia, and cold stress.11,12 The most common causes are meconium aspiration syndrome (50%), idiopathic PPHN (20%), sepsis (20%), and respiratory distress syndrome (5%).11

Despite the array of conditions associated with PPHN, one common feature is an underlying abnormality of the pulmonary vasculature. This abnormality can be broadly categorized into three groups.10,11 In the first group, the vasculature is abnormally constricted due to parenchymal lung disease. This group is the most common and includes meconium aspiration syndrome, sepsis, and respiratory distress. The second group is associated with structurally abnormal pulmonary vasculature and includes idiopathic PPHN. The pulmonary vasculature of these infants shows significant thickening and does not appropriately vasodilate in response to birth stimuli (particularly nitric oxide and endothelin signaling pathways). The vasculature of the third group is hypoplastic, usually due to congenital diaphragmatic hernia or, much less commonly, a rare malformation of lung development known as alveolar-capillary dysplasia.10

Transient tachypnoea of the newborn

Transient tachypnea of the newborn (TTN) occurs in 4 to 6 per 1000 at-term infants. An incidence of 10 per 1000 has been reported in premature infants,88 but coexisting problems (e.g., RDS) may mask the presentation. TTN is due to delayed fetal lung fluid clearance89; neonates with TTN have an immaturity of the lung epithelial transport90 (see later in the chapter). In fetal life, the lung is filled with liquid; fetal lung fluid is produced initially at a rate of 2 mL/kg/hour, increasing to 5 mL/kg/hour at term. It contributes one third to one half to the daily turnover of amniotic fluid. Compared to either amniotic fluid or plasma, lung liquid has a high chloride concentration, but a low bicarbonate and protein concentration. The secondary active transport of chloride ions from the interstitial space into the lung is the main force for lung liquid secretion, sodium ions, and water following passively down electrical and osmotic gradients. The presence of lung liquid is essential for normal lung development; chronic drainage results in pulmonary hypoplasia. The volume of fetal lung liquid is regulated by the resistance to lung liquid efflux through the upper airway; a pressure in the lumen of the lung is generated that is approximately 1 cm of water greater than that in the amniotic cavity. During labor and delivery, the concentration of epinephrine increases, the chloride pump responsible for lung liquid secretion is inhibited, and lung liquid secretion ceases. In addition, lung liquid resorption commences as the raised epinephrine levels stimulate sodium channels on the apical surface of the pulmonary epithelium, via which fetal lung liquid absorption occurs. Thyroid hormone and cortisol are necessary for maturation of the response of the fetal lung to epinephrine; steroids are highly effective in enhancing the expression of highly selective sodium channels in the lung epithelial cells.91 Exposure to postnatal oxygen tension increases sodium transport across the pulmonary epithelium. Although some liquid is squeezed out under high vaginal pressure during the second stage of labor, the majority is absorbed into the pulmonary lymphatics and capillaries. Air entry into the lung displaces liquid from the terminal respiratory units into the perivascular space, the hydraulic pressure in the pulmonary circulation is reduced, and blood flow is increased. As a consequence, the effective vascular surface area for fluid exchange is increased, facilitating water absorption into the pulmonary vascular bed. The replacement of lung liquid by air is largely accomplished within a few minutes of birth.

TTN is more common in infants who are born by caesarean section without labor92 because lung fluid clearance will not have occurred. Respiratory distress is more likely to occur if a caesarean section without labor is performed at 37 rather than 38 weeks of gestation.92 Surfactant deficiency may be important in the pathogenesis of TTN. Other risk factors for TTN include male sex and a family history of asthma. Infants of asthmatic mothers may have a genetic predisposition to β-adrenergic hyporesponsiveness. Resorption of fetal lung fluid is a catecholamine-dependent process and β1 and β2 adrenoreceptor polymorphisms (known to alter catecholamines) are operative in TTN.93

Infants with TTN are tachypneic with respiratory rates up to 100 to 120 breaths/minute. However, they rarely grunt because their lungs are not atelectatic. The chest may be barrel-shaped as a result of hyperinflation. The chest radiograph shows hyperinflation, prominent perihilar vascular markings due to engorgement of the periarterial lymphatics (Fig. 22-2), edema of the interlobar septae, and fluid in the fissures. Cerebral irritation from subarachnoid blood or perinatal hypoxic ischemia should be considered in the differential diagnosis of a tachypneic infant, but such infants have a respiratory alkalemia. The chest radiograph appearance of TTN may be mimicked by heart failure.

Management includes supplementary oxygen; very unusually infants with TTN have been reported to require very high concentrations of oxygen or even mechanical ventilation. Intravenous antimicrobials should be administered until infection has been excluded and nasogastric tube feeds should be withheld until the respiratory rate settles. Diuretics appear to be of no benefit, but they have only been adequately investigated in one randomized trial.94 By definition TTN is self-limiting, and affected infants have usually made a complete recovery within a few days of birth. Complications are rare, though air leaks may occur, particularly if the infant has required CPAP or IPPV. There is debate as to whether infants who had TTN are more likely to wheeze at follow-up.

TRANSIENT TACHYPNEA OF THE NEWBORN

Transient tachypnea of the newborn (TTN) occurs when the removal of intrapulmonary fluid from the neonatal lung is delayed. Under normal conditions, the alveolar fluid would be removed by the pulmonary lymphatics in the hours after birth. When removal is delayed, the child presents with tachypnea, mild retractions and cyanosis (Avery et al 1966, Adams et al 1971). TTN is a benign, self-limiting condition. In the healthy term newborn, fetal lung fluid triggers the J receptors, which increase respiratory rate. As the fluid is absorbed, the rate decreases. The condition usually resolves within 48 h after birth, but in severe cases may continue for 3 or more days. There is a higher incidence of TTN in children delivered by cesarean section, presumably because the thoracic compression occurring during vaginal delivery facilitates movement of pulmonary fluids (Milner et al 1978, Lee et al 1999). Alterations in intrathoracic pressures facilitates lymphatic drainage from the thorax. The majority of children with TTN who have been examined osteopathically (chart review of newborns examined in the newborn nursery at the Waterville Osteopathic Hospital, 1988–1993) present with restriction of normal newborn respiratory mechanics, usually involving the thoracolumbar and pelvic areas, particularly the quadratus lumborum muscles. Dysfunction in the mechanics of the scalene muscles is also frequently found. While there are no published data on the efficacy of osteopathic treatment in this condition, anecdotal data suggest that osteopathic evaluation and treatment focused on improving fluid mechanics in these children will almost always result in a fairly rapid resolution of the tachypnea.

Transient Tachypnea of the Newborn.

Transient tachypnea of the newborn (TTN), sometimes called wet lungs, is a common self-limited disease of term newborns that results from delayed lung fluid clearance.42 This deficit is probably secondary to immature sodium epithelium channel (ENaC). Furosemide has been proposed to hasten fluid lung clearance and thus improve the pulmonary condition. In a randomized study, the oral administration of 2 mg/kg followed by 1 mg/kg 12 hours later increased weight loss but did not improve the severity or duration of symptoms.43 A recent survey by the Cochrane Neonatal Group indicated that furosemide was not effective in promoting reabsorption of lung fluid and concluded that diuretics could not be recommended for the treatment of TTN.44 The possibility that furosemide given to the mother before cesarean section might shorten the duration of the illness remains to be investigated.

Transient tachypnea of the newborn

Transient tachypnea of the newborn (TTN) is the most common cause of respiratory distress in term and late preterm newborns. It usually presents within a few hours of birth and manifests as tachypnea with or without other signs of respiratory distress including grunting, nasal flaring and retractions. It is caused by delayed resorption of fetal lung fluid leading to fluid retention and generally resolves spontaneously within 72 h of delivery. Risk factors for TTN include cesarean delivery (especially without trial of labor), lower gestational age, maternal diabetes mellitus, and macrosomia (Guglani et al., 2008). It is usually a clinical diagnosis, although chest x-ray may show retained fluid in the fissures and increased interstitial markings. Infants should be monitored closely for oxygen desaturations, but treatment is otherwise supportive. If respiratory symptoms develop after the first few hours of life, persist for more than a few hours after birth, or progressively worse, it is important to evaluate for more serious causes of respiratory distress, such as infection, meconium aspiration syndrome, pneumothorax, or respiratory distress syndrome in preterm infants.