427ISSN 1745-5111Pediatric Health (2010) 4(4), 427–43110.2217/PHE.10.35 © 2010 Future Medicine Ltd

With the onset of labor, the complexity of water movement increases with the goal of emptying the fetal lung in preparation for ventilation. Lung fluid production drops as epinephrine levels increase, which also accelerates fluid transport via sodium channels. Recent studies have demonstrated that certain genetic abnormalities in catecholamine receptors can predispose a newborn to TTN [5]. Although the squeeze of the neo natal thorax dur-ing vaginal delivery is classically taught to poten-tiate fluid transfer from the lungs, it is not com-pletely responsible for the process [6]. Decline in blood oxygen levels and increase in blood acidity are sensed by the newborn to stimulate the first breath. Clamping the umbilical cord also stimu-lates breath as it establishes the end of placenta circulation and the previous mechanisms for gas exchange and the beginning of pulmonary respira-tion. As these mechanisms are stimulated at the start of labor, one could see that these mechanisms can be impaired without labor initiation. When fluid persists without or despite these mechanisms, TTN can result.

Clinical aspects Transient tachypnea of the newborn represents the most frequent cause of neonatal respiratory distress amongst all newborns, constituting over 40% of cases. However, as it infrequently leads to mortal-ity and is considered benign by some practitioners, it may be underdiagnosed. Clinical and laboratory criteria for TTN have been established (Box 1) [7]. Tachypnea is only one sign of respiratory distress. Newborns with TTN may also have intercostal or subcostal retractions, grunting, nasal flaring and poor feeding. Cyanosis is not common but could

The newborn period incorporates significant transitions from the antenatal to the postnatal state, including considerable changes in the res-piratory system. Providers involved in obstetric and neonatal care must be aware of deviance from this normal transition as this departure can be life-threatening. The incidence of neonatal res-piratory distress in the newborn is approximately 7% [1]. Transient tachypnea of the newborn (TTN), first described by Avery in 1966, repre-sents the most common cause of this distress, and occurs in approximately six per 1000 births [1,2]. This article reviews the pathophysiology, clinical aspects and treatment options for TTN, as well as some new implications and future perspectives.

Fetal lung physiologyTo better understand the aberrancy associated with TTN, it is crucial to appreciate normal fetal lung physiology. There is a delicate transi-tion from the fluid contained in the lungs in utero to the reliance on gas exchange after delivery. In utero, fluid is produced by the neonatal lung. Some of this fluid is swallowed by the neonate and excreted by the kidneys resulting in amni-otic fluid. The fetal larynx periodically opens and closes so most of the fluid is swallowed but some fluid enters the lungs to keep them expanded [3]. However, much more amniotic fluid is made via micturition than from lung fluid contributions. Lung fluid is eventually transported to either the pulmonary circulation or lymphatic system via ionic transport channels and osmotic pressures. A delicate balance of sodium, potassium, chlo-ride and neurotransmitters chiefly coordinates the process of water movement [4].

REVIEW

Transient tachypnea of the newborn: common in the nursery, implications for beyondChristian L Hermansen†

Transient tachypnea of the newborn (TTN) is a frequently encountered form of neonatal respiratory distress. The underlying mechanism of pathology involves residual lung fluid that is delayed in clearance. TTN primarily occurs soon after birth and can last from 48 to 72 h. Risk factors for TTN include maternal asthma, male sex, macrosomia, polycythemia, maternal diabetes and cesarean section. Treatment is often supportive with observation and potential oxygenation. Infants with TTN carry an increased risk for developing chronic asthma. Clinicians providing obstetrical care should prepare parents for this potential. Clinicians providing neonatal care must be familiar with the background and course of this common disease.

†Downtown Family Medicine,Lancaster General Health Family Medicine Residency Program, 555 North Duke Street, Lancaster, PA 17603, USA Tel.: +1 717 544 1883 Fax: +1 717 544 4149 clherman@lghealth.org

Keywords

• cesarean section • delayed transition • meconium aspiration syndrome • pulse oximetry • respiratory distress syndrome • transient tachypnea of the newborn

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be present in severe cases. Symptoms can last from a few hours to over 2 or 3 days. Although hypoxemia is not typical, it can be present. Chest x-ray (CXR) can show parenchymal infiltrates, intralobar fluid accumulation or hyperaeration. CXR findings, however, are often conflicting with other causes of respiratory distress and rarely fit classical description. TTN diagnosis is usually based on the clinical course.

The use of ultrasound in TTN has recently showed promise. Copetti and Cattarossi dem-onstrated that differences in ultrasonographic findings between the upper and lower lung field could potentially be diagnostic of TTN and dif-ferentiate from other causes of respiratory distress. Although tested in a small study using a high-resolution linear probe, the authors achieved a sensitivity and specificity rate of 100%. These findings suggest the need for larger, blinded, prospective research [8].

Although the definition of TTN includes persistence greater than 12 h, many infants can have symptoms consistent with TTN but with a shorter duration. Some infants do undergo a ‘delayed transition’ in which some distress ensues, and this term is sometimes found in medical lit-erature. There is debate as to whether this brief period is a ‘short TTN’ or a prolonged adjust-ment to the process of gas exchange. Although semantically interesting, clinical end points do not change in delayed transition. However, if this transition affects the newborn’s ability to feed or maintain health, TTN should be considered and managed appropriately.

Risk factors for TTN include maternal asthma, male sex, macrosomia, polycythemia, maternal diabetes and cesarean section [9–11]. TTN infants also tend to have lower birthweights and this cor-relates with increasing TTN incidence at earlier gestational ages. Male sex has been shown to cause a longer duration of TTN for yet unproven rea-sons [7]. Although polycythemia has been alleged

as a TTN risk factor, anemia and leukopenia have been shown to increase the duration of TTN [12]. Infants who have a delay in the clamping of their umbilical cord may experience more tachypnea but without significant morbidity or need for major intervention [13]. Asthma and cesarean section will be addressed below.

The differential diagnosis of respiratory distress of the newborn must be considered when an ele-vated respiratory rate is encountered (Box 2). Early differentiation of TTN from the other causes of respiratory distress will allow for appropriate management and provide better outcomes. The onset of tachypnea can help narrow the possible diagnoses. Infection requires time to develop, often taking at least 24 and, more likely, 48 h. TTN, respiratory distress syndrome and meco-nium aspiration syndrome routinely have their onset at birth. The gestational age of the baby can also give clues. Meconium aspiration syndrome typically occurs in term or post-term babies; res-piratory distress syndrome occurs frequently in preterm births; TTN is more common in preterm or term children. Given the common use of anti-depressants in pregnancy, it is worth noting that selective serotonin reuptake inhibitor use in preg-nancy carries a higher rate of persistent pulmonary hypertension of the newborn [14].

TreatmentThe first aspect of treatment should entail anti-cipation of the potential for TTN at every birth. The provider should consider risk factors ante-natally that would predispose to such a condi-tion. Those clinicians providing prenatal care can provide anticipatory guidance to the parents.

The second aspect of treatment involves early recognition and generalized treatment to the neonate in distress. Airway, breathing, and cir-culation status should be considered. Typically, TTN only requires supportive care which can entail manual bulb suction of residual fluid, oxy-gen delivery, and frequent or constant observa-tion. However, newborns may display signs of respiratory compromise before cardiovascular collapse. Pulse oximetry can detect hypoxia and alter oxygen supplementation. Lumbar puncture can be considered if meningitis enters the differential diagnosis. CXR, blood tests, and possible specialist consultation may be needed if tachypnea persists. A ‘rule of 2 h’ for when to involve such consultation has been suggested (Box 3) [15]. Significant tachypnea, often greater than 80 breaths per minute, can prohibit oral feeding. In these situations, sustenance via intravenous or nasal tubular routes should be

Box 1. Clinical criteria for the diagnosis of transient tachypnea of the newborn.

• Onset of tachypnea (respiratory rate >60/min) within 6 h of birth

• Persistence of tachypnea of greater than 12 h

• Chest x-ray with one of the following:- Prominent central vascular markings

- Widened interlobar fissures of pleural fluid

- Symmetrical perihilar congestion

- Hyperaeration as evidenced by flatting and depression of the diaphragmatic domes or increased anteroposterior diameter or both

• Exclusion of all known other respiratory disorders

Adapted from [7].

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considered. Assessment of the peak respiratory rate at 36 h has been demonstrated to gauge the potential duration of tachypnea for the infant [7]. In rare cases, nasal continuous positive airway pressure could be utilized to maintain oxygena-tion. Generally, if necessary neonatal medical services exceed what the facility can provide, transfer of care to a higher acuity hospital is appropriate once stability can be achieved.

Various medications have been theorized to aid in the treatment of TTN. As excess fluid is causative in TTN, diuresis using oral furo-semide has been attempted but has not been shown to significantly improve respiratory status, however it can worsen electrolyte bal-ance [16]. Epinephrine has also been considered as it physiologically aides in fluid resorption. In a small study, inhaled racemic epinephrine showed no adverse effects but also no signifi-cant benefit in TTN [17]. At this time, the use of diuretics or epinephrine in TTN management is discouraged.

Thankfully, TTN is rarely a fatal disease. The above measures plus the tincture of time often results in a healthy baby. However, the morbidity is significant and TTN can lead to other immediate diagnoses requiring sepa-rate treatment, including pneumothorax and pulmonary hypertension.

A closer look at TTN, cesarean section & asthmaIncreasing evidence links TTN and cesarean section while the incidence of this surgery increases. Elective cesarean section performed before 38 weeks gestation imparts particular TTN risk [18]. The rate of cesarean section amongst all prenatal patients in the USA is over 31% [19]. In the UK, approximately one quarter of all deliveries are performed via cesar-ean section [20,101]. China has seen the rate of surgery increase from 8.9% in 1993 to triple that amount in 2002 and over five-times the rate in 2009 [21,102]. These statistics show the cesarean rate is much greater than the WHO recommended rate of 15% [22]. Considering the rising cesarean rate, studies showing an increase in respiratory distress in general and TTN in specific should be forthcoming.

Elective cesarean section prevents the neonate’s initiation of the fluid removal proc-ess of the lung and intercepts the thoracic squeeze on the baby via vaginal delivery. Infants delivered by cesarean also have lower hemocrits, which is associated with prolonged tachypnea [12]. TTN incidence can be lessened

in elective cases via antenatal cortico steroid administration given 48 h before the elective surgery if occurring at 37–39 weeks gesta-tion [23]. The use of corticosteroids may be more common in Europe than the USA. Delaying cesarean section until 39 weeks could also pro-vide benefit if not detrimentally impacting the mother. Regardless, any initiatives to reduce the cesarean section rate would affect the TTN incidence as well as assist with other health and financial endeavors.

Asthma also has associations with TTN. Approximately 38 million Americans and 8 million citizens of the UK are diagnosed with asthma in their lifetime [24,103]. Asthma prevalence increased by 75% from 1980 to 1994 and by 2025, the number of people affected worldwide will increase by 100 million [25,104]. Mothers with asthma are more likely to have children that experience TTN compared with mothers without an asthma diagnosis [26]. Conversely, having TTN as a neonate may predispose a child to an eventual diagnosis of asthma. This predisposition is even more likely in children who are male, children whose moth-ers held an urban address and children of non-white race [27]. TTN has also been linked to an increased risk of wheezing disorders of child-hood [28]. Clinicians providing primary pedi-atric care should ask about a history of TTN at birth in children being considered for the diagnosis of asthma. These studies also echo the need for excellent communication between the newborn facility and the primary care office

Box 2. Differential diagnosis of respiratory distress in the newborn.

• Transient tachypnea of the newborn

• Respiratory distress syndrome (hyaline membrane disease)

• Meconium aspiration syndrome

• Delayed transition

• Infection (pneumonia, sepsis and meningitis)

• Pneumothorax or other air-leak syndromes

• Persistent pulmonary hypertension of the newborn

• Nonpulmonary causes (congenital malformations, hematologic disorders, metabolic aberrancies, medications and hypoglycemia)

Box 3. Consider specialty consultation for tachypnea: ‘rule of 2 h’.

• Neonatal intensive care unit consult/transfer if one of the following are present:- Abnormal chest x-ray

- >40% of O2 needed to oxygenate

- Patient looks worse

- Patient does not improve in over 2 h

• May also consider laboratory tests/antibiotics if one is present

Adapted from [15].

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so that infants who recovered from TTN can be monitored as an outpatient for the potential future development of asthma.

Future perspectiveAlthough TTN is rarely fatal, it is a commonly encountered disorder and its morbidity and asso-ciated financial and emotional tolls warrant any preventative steps.

Future efforts in TTN will explore its patho-physiology and associated causes and conse-quences with asthma. Endeavors to reduce the cesarean section rate worldwide would also dimin-ish the incidence of TTN. Larger studies on TTN

can be explored as well as application of studies in clinical practice – especially the use of antenatal corticosteroids in elective cesarean section.

Financial & competing interests disclosureThe  author  has  no  relevant  affiliations  or  financial involvement  with  any  organization  or  entity  with  a financial interest in or financial conflict with the subject matter or materials discussed  in  the manuscript. This includes  employment,  consultancies,  honoraria,  stock ownership or options, expert testimony, grants or patents received or pending, or royalties. 

No writing assistance was utilized in the production of this manuscript.

Executive summary

Incidence

• Incidence for neonatal respiratory distress is 7%.

• Transient tachypnea of the newborn (TTN) represents 40% of those cases or approximately six out of 1000 births.

Pathophysiology

• Fetal lung fluid is needed to maintain its expansion but too much impairs gas exchange after birth.

• Fluid leaves the lung mainly through complex mechanisms involving ion channels but also minimally via external compression if the neonate is delivered vaginally.

• When fluid persists without or despite these mechanisms, TTN can result.

Clinical aspects

• Tachypnea, retractions, grunting, nasal flaring and poor feeding are all signs of neonatal respiratory distress.

• TTN typically lasts from 12 to 72 h.

• Risk factors for TTN include maternal asthma, male sex, macrosomia, polycythemia, maternal diabetes and cesarean section.

Treatment

• Treatment is mainly supportive with potential use of oral suctioning, oxygenation, support and observation.

• Medications, including diuretics and epinephrine have not been proven beneficial and can potentially be harmful.

Future perspective

• As cesarean section is increasingly on the rise, so likely will TTN.

• Antenatal steroids can reduce TTN incidence if given electively before cesarean section between 37 and 39 weeks; this practice could be adopted more universally.

• Children with TTN can go on to develop chronic asthma. Clinicians providing ongoing infant care should have an increased index of suspicion.

BibliographyPapers of special note have been highlighted as:• of interest

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