<div><b>Fetal lung fluid: Not the same as amniotic fluid</b></div><div>Author: Hemananda Muniraman MBBS, FAAP, FRCPCH</div><div>Affiliations:</div><div>Creighton University School of Medicine, Phoenix Campus, Arizona, US</div><div>Corresponding Author: Hemananda Muniraman, MBBS, FAAP, FRCPCH</div><div>Assistant Professor of Pediatrics Affiliate, Creighton University School
of Medicine</div><div>Phoenix Campus, 350 W Thomas Rd, Phoenix, AZ, US 85013</div><div>Email; Hemu_Muniraman@mednax.com, Phone: +16022564628 Fax: +16026276325</div><div>Conflict of Interest Disclosure: I have no conflicts of interest
relevant to this article to disclose. Funding/Support.</div><div>No funding to be reported</div><div>Key words: Extreme preterm, neonates, pneumatocele, fetal lung fluid</div><div>Dear Dr Murphy</div><div>Editor in chief, Pediatric Pulmonology</div><div>I read with interest the recently published article “Pulmonary
pneumatoceles in neonates” by Dr Rocha. [1] It is a well written
comprehensive review of pulmonary pneumatoceles in neonates and an
important resource for the clinicians in decision making, that I found
to be very insightful whilst recently managing an extreme preterm with a
large pneumatocele.</div><div>However, I wanted to bring attention to a statement in the introduction
where the author states that the “preterm infants’ lungs are filled
with amniotic fluid”. This is not accurate and appears to be a common
misconception, particularly among medical students and junior residents
despite recognition of fetal lung fluid as being a separate entity from
the amniotic fluid as originally described in 1948 by Jost and Policard.
[2] I believe this is an important knowledge gap that needs to be
addressed. Understanding of metabolism and role of fetal lung fluid in
lung development and postnatal transition is essential to clinicians
involved in the care of newborns and infants.Though a comprehensive
review of fetal lung fluid is beyond the scope of this letter, I provide
a brief basic overview of fetal lung fluid with references for more
comprehensive reading.</div><div>Fetal lung fluid is a chloride rich acidic fluid produced with in the
fetal lungs by secretion of chloride across the distal lung epithelial
cells and is a major determinant for fetal lung growth and development.
The fluid lung volume is maintained by transglottic pressure gradient
with periodic egress of excess fluid during fetal breathing. Decreased
lung fluid volume is associated with pulmonary hypoplasia and
conversely, upper airway lesions obstructing the egress of lung fluid
leads to increase in fetal lung fluid and volume, a principle used in
fetal interventions such as endoluminal tracheal occlusion to enhance
pulmonary growth in conditions namely congenital diaphragmatic hernia.
[2,3,4]</div><div>As important the fetal lung fluid is for lung development, clearance of
lung fluid is crucial for normal postnatal transition and establishment
of air filled lungs for effective gas exchange. Clearance of lung fluid
is a complex and coordinated process that starts before the process of
birth itself. The rate of lung fluid secretion diminishes before labor
at term gestation. Catecholamines namely epinephrine released during
labor upregulates the epithelial sodium channels (ENaC) promoting influx
of sodium and fluid from lumen into pulmonary interstitial space thereby
reversing the direction of fluid movement in the perinatal period. Lung
fluid is decreased to about 35% following active labor and birth which
are further cleared with neonatal cry and breathing and inflow of air
after birth. The fluid from the interstitial space is cleared over the
next few hours via pulmonary circulation and lymphatic drainage. However
this process is impaired in infants delivered by elective cesarean
sections leading to increased retained lung fluid after birth and
resulting in transient respiratory distress and tachypnea of newborn
(TTN). In preterm infants, catecholamine induced fluid reabsorption via
ENaC is limited and may contribute to respiratory distress after birth.
Prenatal maternal steroids and triiodothyronine administration is known
to induce expression of messenger RNA for ENaC subunits in the fetal
lungs and may facilitate lung fluid clearance. [2,4]</div><div>Lastly, amniotic fluid aspiration into fetal lungs, with and without
meconium contamination, has been reported to be the cause of respiratory
distress with case reports of massive amniotic fluid aspiration noted on
postmortem histological examination of newborn lungs. [5]</div><div>References:</div><div>Rocha G. Pulmonary pneumatoceles in neonates. Pediatr Pulmonol. 2020 Jul
21. doi: 10.1002/ppul.24969. Epub ahead of print. PMID: 32691976.</div><div>Katz C, Bentur L, Elias N. Clinical implication of lung fluid balance in
the perinatal period. J Perinatol. 2011 Apr;31(4):230-5. doi:
10.1038/jp.2010.134. PMID: 21448181.</div><div>Hooper SB, Harding R. Fetal lung liquid: a major determinant of the
growth and functional development of the fetal lung. Clin Exp Pharmacol
Physiol. 1995 Apr;22(4):235-47. doi: 10.1111/j.1440-1681.1995.tb01988.x.
PMID: 7671435</div><div>Kallapur S, Jobe A; Fetal Lung fluid. Richard J. Martin, Avroy A.
Fanaroff, Michele C. Walsh. Fanaroff And Martin’s Neonatal-Perinatal
Medicine : Diseases of the Fetus and Infant, 10th edition. Philadelphia,
PA :Elsevier/Saunders, 2015</div><div>Lavezzi AM, Poloniato A, Rovelli R, Lorioli L, Iasi GA, Pusiol T et al.
Massive Amniotic Fluid Aspiration in a Case of Sudden Neonatal Death
With Severe Hypoplasia of the Retrotrapezoid/Parafacial Respiratory
Group. Front Pediatr. 2019 Apr 4;7:116. doi: 10.3389/fped.2019.00116.
PMID: 31019904</div>