Did you know...

Figure 1. Click on the image to view ultrasound footage which shows a fetus breathing and hiccupping

...that a fetus practices breathing for months before birth?

Fetal breathing movements are episodic and irregular, interspersed with periods of apnea [1], and in humans they become detectable by ultrasound at 10-11 weeks gestation [2, 3]. Fetal breathing movements become more regular and uniform as gestational age increases [4]. Breathing movement frequency increases until the 10 weeks before birth, when periods of apnea increase [5, 6].

General fetal movement has been used for centuries to monitor fetal well being. Hippocrates believed that movement began 70-90 days after conception, and that males moved more vigorously than females [7]. Paré, a 16th century French surgeon and obstetrician, recognized that absence of fetal movement could be a sign of intrauterine death [7]. The first recorded observations of intrauterine breathing movements in a human fetus were made in 1888 by the German doctor von Ahlfeld. He and his student, Weber, used a kymograph to record 'periodic, rhythmic intrauterine fetal movements' that they attributed to breathing motions [8]. Many of their contemporaries dismissed the theory that these were fetal breathing movements because no one had ever visually observed such movements in a fetus.  In 1911 another German scientist, Reifferschied, published simultaneous kymograph recordings of fetal breathing movements, maternal respiration, and maternal pulse [8]. He noted that these actions all occurred at different rates. Although the scientific community remained skeptical, his measurements would later prove to be remarkably accurate.

It was not until the 1970s that two landmark studies answered the question of whether fetal breathing movements normally occurred in vivo. The work was performed by two groups - Merlet and her colleagues from France, and British scientists led by Dawes. In 1970 and 1972, these groups published papers with data obtained from fetal lambs in utero. The authors showed that breathing movements normally occur during gestation and do so at irregular intervals [1, 9]. Later work with animals proved that eliminating fetal breathing movements results in immature, underdeveloped lungs [10, 11].

More recent in vitro studies have investigated the signaling pathways between fetal breathing movements and lung development. Fetal breathing movements stretch the lungs and move fluid in and out of the lungs. Mechanical stretch upregulates the release of serotonin via mechano-sensitive channels [12], which promotes differentiation of epithelial cells. Stretch also increases epithelial cell proliferation [13, 14] and stimulates secretion of lung surfactant lipids from type II epithelial cells [15]. Parathyroid hormone-related protein (PTHrP) is the product of a stretch sensitive gene expressed by the lung which is essential for normal lung development [16]. In the absence of PTHrP, lipofibroblasts spontaneously transdifferentiate into myofibroblasts [17]. Lipofibroblasts are the source of the lipids necessary for surfactant synthesis. Over-distension of alveolar epithelial cells caused loss of PTHrP mRNA [17], resulting in a less mature lung phenotype and mirroring the effects of ventilation in premature infants.

While the importance of fetal breathing movements is now widely accepted, the underlying mechanisms of lung development dependent on these movements are still being revealed with both in vivo and in vitro studies. These scientific results will hopefully lead to improvements in patient care, as they show that fetal breathing movements in utero are vital for postnatal lung function.

References 

  1. Dawes GS, Fox HE, Leduc BM, Liggins GC, Richards RT. Respiratory movements and rapid eye movement sleep in the foetal lamb. The Journal of physiology 1972;220:119-43.
  2. Boddy K, Dawes GS. Fetal breathing. British medical bulletin 1975;31:3-7.
  3. Kisilevsky BS, Hains SM, Low JA. Maturation of body and breathing movements in 24-33week-old fetuses threatening to deliver prematurely. Early human development 1999;55:25-38.
  4. Trudinger BJ, Knight PC. Fetal age and patterns of human fetal breathing movements. American journal of obstetrics and gynecology 1980;137:724-8.
  5. Florido J, Cortes E, Gutierrez M, Soto VM, Miranda MT, Navarrete L. Analysis of fetal breathing movements at 30-38 weeks of gestation. Journal of perinatal medicine 2005;33:38-41.
  6. Patrick J. Fetal breathing movements. Clinical obstetrics and gynecology 1982;25:787-807.
  7. Do fetal movements reflect fetal wellbeing? British medical journal (Clinical research ed 1981;282:588-9.
  8. Wilds PL. Observations of intrauterine fetal breathing movements--a review. American journal of obstetrics and gynecology 1978;131:315-38.
  9. Merlet C, Hoerter J, Devilleneuve C, Tchobroutsky C. [Demonstration of respiratory movements in lamb fetus in utero during the last month of gestation]. C R Acad Sci Hebd Seances Acad Sci D 1970;270:2462-4.
  10. Wigglesworth JS, Desai R. Effect on lung growth of cervical cord section in the rabbit fetus. Early Hum Dev 1979;3:51-65.
  11. Nagai A, Thurlbeck WM, Jansen AH, Ioffe S, Chernick V. The effect of chronic biphrenectomy on lung growth and maturation in fetal lambs. Morphologic and morphometric studies. Am Rev Respir Dis 1988;137:167-72.
  12. Pan J, Copland I, Post M, Yeger H, Cutz E. Mechanical stretch-induced serotonin release from pulmonary neuroendocrine cells: implications for lung development. American journal of physiology 2006;290:L185-93.
  13. Liu M, Xu J, Tanswell AK, Post M. Stretch-induced growth-promoting activities stimulate fetal rat lung epithelial cell proliferation. Experimental lung research 1993;19:505-17.
  14. Liu M, Tanswell AK, Post M. Mechanical force-induced signal transduction in lung cells. Am J Physiol 1999;277:L667-83.
  15. Scott JE, Yang SY, Stanik E, Anderson JE. Influence of strain on [3H]thymidine incorporation, surfactant-related phospholipid synthesis, and cAMP levels in fetal type II alveolar cells. American journal of respiratory cell and molecular biology 1993;8:258-65.
  16. Torday JS, Sanchez-Esteban J, Rubin LP. Paracrine mediators of mechanotransduction in lung development. The American journal of the medical sciences 1998;316:205-8.
  17. Torday JS, Torres E, Rehan VK. The role of fibroblast transdifferentiation in lung epithelial cell proliferation, differentiation, and repair in vitro. Pediatric pathology & molecular medicine 2003;22:189-207.

Author: Rebekah Morrow
Chief editor: Donna Cioffi, Ph.D., November, 2012

 

Email Newsletters

Connect With Us