1. Transient Tachypnea of the Newborn
Kelley Zagol
University of Virginia
My name is Kelley Zagol and I was in the Newborn Nursery this month. In this presentation, I will present a case and then review the definition and physiology of Transient Tachypnea of the Newborn. I will then review a 2010 article in Pediatrics and a 2009 Journal of Maternal-Fetal and Neonatal Medicine

2. BH 37.1/ 38 (Dubowitz) 30 year old G6P5 PNL Issues: none
PNL Labs: GBS unknown
Delivery: repeat CS
Maternal Blood Type: AB+
Apgars: 7, 9
Initial PE: tachypnea, retractions, nasal flaring, grunting, acrocyanosis, glandular hypospadias
Saturations to the low 80s with transient desaturations to the mid 70s
BH is a 37.1 weeker by dates, 38 weeker by Dubowitz who was born to a 30 year old G6P5 Orthodox mother delivered via repeat CS. Mom’s pregnancy was uncomplicated and the CS was scheduled. APGARs were 7 and 9 at 1 and 5 minutes. In the nursery, BH was noted to by tachypnic with nasal flaring, grunting, and substernal retractions. Saturations were initially in the low 80s with transient desats to the mid 70s.
Figure 1. Acrocyanosis

3. DDX for Respiratory Distress
Congenital Pneumonia
Pneumomediastinum
Pneumothorax
Respiratory Distress Syndrome
Congenital Heart Disease
Transient Tachypnea of the Newborn
Persistent Pulmonary Hypertension
Cerebral Hyperventilation
Metabolic Acidosis
Meconium Aspiration Syndrome
Neonatal Sepsis
The differential diagnosis for respiratory distress includes

4. DDX for Respiratory Distress
Congenital Pneumonia
Pneumomediastinum
Pneumothorax
Respiratory Distress Syndrome
Congenital Heart Disease
Transient Tachypnea of the Newborn
Persistent Pulmonary Hypertension
Cerebral Hyperventilation
Metabolic Acidosis
Meconium Aspiration Syndrome
Neonatal Sepsis
The most common causes of respiratory distress in the newborn are RDS, TTN, and Meconium aspiration syndrome

5. TTN Figure 3. CXR depicting RDS, MAS, and TTN
The diagnosis of TTN is often confirmed by radiograph.
The first picture depicts RDS. This X-ray shows a bell shaped thorax and under aeration consistent with RDS. The lung parenchyma has a diffused reticulogranular pattern with peripherally extending air bronchograms.
The second picture depicts Meconium Aspiration Syndrome. This Xray shows air trapping with diffuse coarse nodular opacities with areas of focal emphysema
The third picture depicts TTN. Transient hyperaeration and bilateral reticulogranular densities that disapper with ventilation are consistent with TTN. In contrast, these opacities are present for at least 3-4 days in RDS
Figure 3. CXR depicting RDS, MAS, and TTN

6. TTN Most commonly reported cause of neonatal respiratory distress
Incidence: 1-2% of all newborns
Usually presents within a few hours of birth with tachypnea, retractions, grunting, and occasional supplemental 02 requirements
Symptoms usually resolve by 72 hours
Diagnosis based on clinical and radiologic findings
TTN is the most commonly reported cause of neonatal respiratory distress
The incidence is 1-2% of all newborns
TTN usually presents within a few hours of birth with tachypnea, retractions, grunting, and occasional 02 requirements.
These symptoms usually resolve by 72 hours

7. TTN
5 major events that establish the lungs as the organ of gas exchange
Clearance of fetal lung fluid
Establishment of spontaneous breathing
Decrease in pulmonary vascular resistance
Release of surfactant
Cessastion of right to left shunting of venous blood returning to the heart
Why does TTN occur? This may be explained by the pathophysiology of the transition between fetal lung to the neonatal lung.
Five major events must occur to establish the lung as the organ of gas exchange.
Clearance of Fetal lung fluid
Establishment of spontaneous breathing
Decrease in pulmonary vascular resistance
Release ofsurfactant
Cessation o f right to left shunting of venous blood returning to the heart

8. Physiology of TTN
Fluid produced by fetal lung tissue contributes 1/3 to ½ of the daily turnover of amniotic fluid
Fetal lung volume regulated by the larynx, which acts as a one way valve and creates a pressure gradient
Distension of lung volume essential for lung growth
Pulmonary epithelium secretes chloride into the alveolus
Chloride enters the lung epithelial cell across the basolateral membrane via Na/K/2Cl cotransporter
Chloride ions are secreted into the alveolus
Potassium extrudes through the basolateral potassium w channels
Sodium follows chloride
Water follows sodium through aquaporins
Figure 4. Fetal Lung

9. Physiology of TTN
Total lung volume decreases a few days prior to spontaneous vaginal delivery
Vaginal squeeze of the thorax and Starling forces contribute to a small proportion of lung fluid resorption
Most interstitial lung liquid moves into the pulmonary circulation, some drains via the lung lymphatics
Adrenergic stimulation near birth activates epithelial sodium channels which are believed to be closed during fetal life but become activated. ENAC channel mediate alveolar fluid clearance is mediated by cyclic adenosine monophosphate and Ca2+ likely acts as a intracellular second messenger; sodium then moves in the interstitium via ouabain sensitive basolateral NA/K ATpase and inhibition of this channel reduces lung liquid clearance; movement of sodium into the interstitium helps to move chloride and water passively along with it throuh the paracellular and intracellular pathways
Figure 5. Neontal Lung

10. Risk Factors Cesarean section Delivery at a lower gestational age
Male sex
Maternal asthma
Macrosomia
Maternal diabetes

11. Tutdibi et al. Figure 6. Study population.
In recent decades, the rates of cesarean section, especially those performed electively at term and partly at maternal request, have shown an increasing. In 2005, the rate for all CS was 30.2% nationally, a relative increase of 45% since 1997 (from 20.8%. The aim of this study was to assess the effect of labor on the risk and course of transient tachypnea of the newborn in term neonates.
Figure 6. Study population.

12. Tutdibi et al. Study infants with TTN were more likely:
To have an inappropriate birth weight for GA
To be male
To be born before 40 weeks
To be born without labor
To have inappropriate birth weight for GA (small for GA: 15.8% vs 9.6%, large for GA 13.5% vs : P<0.001)
To be male (60.35 vs P<0.001)
The TTN rate was linked inversely to GA and decreased with advancing GA from 37 completed weeks onward
TTN was greatly increased at each GA from 37 to 40 weeks for the no labor group, comared with the labor group. In the labor group, the prevalence of TTN remained nearly unchanged between 10.6% and 13.0% from week 42 to week 37. In the non-labor group, there was was a significant incidence of TTN with decreasing GA from weeks (P< 0.01)

13. Tutdibi et al. Figure 7. Risk of TTN
These last two points are summarized in this figure. It demonstrates that the relative risk of TTN from weeks of gestation for newborns delivered vaginally or through secondary CS (labor group) or ECS ( no labor group) is significantly increased in the non laboring group. This is supported by the proposed physiology of fetal lung fluid clearance discussed earlier. Labor enhances the releaswe of catecholamines in materanl and fetalcirculation which in turn up regulates surfactant synthesis and transepithelial sodium iontransport with subsequent fluid reabsorption
Figure 7. Risk of TTN

14. Jain et al. Figure 8. Trends in neonatal complications
The aim of this study was to examine whether the rates of selected neonatal complications vary by mode of delivery and whether these rates are changing as a result of the increasing cesarean delivery rate
EBC records were matched to hospital discharge records for all mothers and newborns delivered in NJ from
N= 1,004,116
Outcome: RDS, TTN, IVH, Injuries
In 2005, TTN occurred almost twice as commonly (3-4 per 100 births) as injuries to the newborn (2.6 per 100 births) and RDS (2.4 per 100 births). IVH occurred much less frequently at 0.4 per 100 births. Therefore, the trends in the neonatal complications,regarless of mode of deliveryover the time period showed that TTN increawsed from3.3% to 3.9%
Figure 8. Trends in neonatal complications

15. Jain et al. Figure 9. TTN by mode of delivery
The rates of TTN was higher for CNL (6-7 per 100 births in 2005) and for CTL (5 per 100 births); about 2-3X higher than the rate for both VUD and IVD. The trends show an increase in the rate of tTN after CNL< but are relatively stable after any trial for vaginal delivery.
Similar trends were observed in the other study outcomes
Figure 9. TTN by mode of delivery

16. Jain et al.
Figure 10. TTN by mode of delivery and gestational age

17. Conclusion
TTN usually presents within a few hours of birth with tachypnea, retractions, grunting, and occasional 02 requirements. These symptoms usually resolve by 72 hours.
In recent decades, the rates of cesarean section, especially those performed electively at term, have increase.
The risk of TTN decreases with increasing gestational age
The risk of TTN increases when newborn is delivered without labor.

18. Bibliography
Elias N, O’Brodovich H. Clearance of fluid from airspaces of newborns and infants. NeoReviews :88-93
Guglani L, Lakshminrusimha S, Ryan R. Transient Tachypnea of the Newborn. Pediatrics in Review : 59-64
Nelsons
Jain N, Kruse L, Demissie K. Khandelwal M. Impact of mode of delivery on neonatal complications: Trends between 1997 and The Journal of Maternal-Fetal and Neonatal Medicine :
Tutdibi E, Gries K. Bucheler M. Misselwitz b, Schlosser R, Gortner L. Impact labor on outcomes in transient tachypnea of the newborn: population based study. Pediatrics :