Differential Diagnosis of Congenital Pneumonia in Newborns with Low and Extremely Low Body Weight (Morphological Study)

The purpose of the study is a comprehensive assessment of morphological changes in the placenta and lungs to detect early signs of congenital pneumonia in extremely premature infants.

Materials and methods. Protocols of post-mortem examinations of 23 preterm newborns died from severe respiratory failure were analyzed. The average gestational age of the newborns was 26.4±2.7 weeks and the body weight at birth was 972.4±355.8 grams. In the sample, 78.3% of infants had an extremely low birth weight (ELBW). At birth, all newborns presented severe asphyxia. Newborn underwent several types of respiratory therapy since birth: Mechanical ventilation was performed in 65.2% of newborns since their birth, non-invasive ventilation was performed in 26.1% of cases, and 8.7% of patients underwent oxygenotherapy through a facial mask. In all cases, there was an unfavorable course of the neonatal period, a progressive deterioration of newborns' condition, and a lethal outcome. A comprehensive histological examination of the placenta and the lungs of deceased premature newborn infants was performed.

Results. Congenital infections of different localizations remain the leading cause of death.Congenital pneumonia and generalized infections are clinically manifested at birth by severe perinatal hypoxia and respiratory failure. In the case of congenital pneumonia, the morphological patterns are polymorphic and characterize the severity of lung damage. For some newborns, these patterns include accumulation of exudates and fibrin, segmented leukocytes, fragments of basophilic coccal microflora, and a large number of colony forming bacilli, and desquamated alveolocytes with a deformed nucleus are visualized in the deformed lumen of the alveoli and bronchi. Diffuse lymphoid-leukocyte infiltration in the septa and respiratory parts of the lungs are typical for other infants. Histological examination find lumpy or lamellar eosinophilic hyaline membranes in alveoli in specimens from these newborns. Diffuse, focal or confluent segmentonuclear infiltration in various lung structures is commonly combined with hyaline membranes of various localizations and sizes. Hyaline membranes were detected in 93.5% of cases.

Conclusion. Very early preterm delivery is associated with intrauterine pneumonia and systemic infection in extremely premature infants. Early clinical and laboratory signs of intrauterine infectious lung include severe perinatal hypoxia, very low Apgar score and laboratory test findings (hypoxaemia and decompensated metabolic lactate acidosis) that are resistant to standard resuscitation measures. Hypoxemia and decompensated metabolic acidosis persisting during the first hours of postnatal life indicate the severity of intrauterine lung damage and require a rapid change of treatment aimed at normalization of lung function, prevention of complications in the respiratory system, hemostasis and central nervous system. Clinicians should be better informed about the features of early postnatal adaptation of extremely premature infants with congenital pneumonia to provide appropriate treatment.

1. Vogel E.R., Britt R.D., Trinidad M.C., Faksh A., Martin R.J., MacFarlane P. M., Pabelick C.M., Prakash Y.S. Perinatal oxygen in the developing lung. Can. J. Physiol. Pharmacol. 2015; 93 (2): 119–127. DOI: 10.1139/cjpp-2014-0387. PMID: 25594569

2. Liu L., Johnson H.L., Cousens S., Perin J., Scott S., Lawn J.E., Rudan I., Campbell H., Cibulskis R., Li M., Mathers C., Black R.E.; Child Health Epidemiology Reference Group of WHO and UNICEF. Global, regional, and national causes of child mortality: an updated systematic analysis for 2010 with time trends since 2000. Lancet. 2012; 379 (9832): 2151–2161. DOI: 10.1016/S0140-6736(12)60560-1. PMID: 22579125

3. World Health Statistics: 2010. Geneva: World Health Organization; 2010: 177.

4. Liu L., Oza S., Hogan D., Chu Y., Perin J., Zhu J., Lawn J.E., Cousens S., Mathers C., Black R.E. Global, regional, and national causes of under-5 mortality in 2000-15: an updated systematic analysis with implications for the Sustainable Development Goals. Lancet. 2016; 388 (10063): 3027-3035. DOI: 10.1016/S0140-6736(16)31593-8. PMID: 27839855

5. Lawn J.E., Blencowe H., Oza S., You D., Lee A.C., Waiswa P., Lalli M., Bhutta Z., Barros A.J., Christian P., Mathers C., Cousens S.N.; Lancet Every Newborn Study Group. Every Newborn: progress, priorities, and potential beyond survival. Lancet. 2014; 384 (9938): 189-205. DOI: 10.1016/S0140-6736(14)60496-7. PMID: 24853593

6. Zaidi A.K., Ganatra H.A., Syed S., Cousens S., Lee A.C., Black R., Bhutta Z.A., Lawn J.E. Effect of case management on neonatal mortality due to sepsis and pneumonia. BMC Public Health. 2011; 11 (Suppl 3): S13. DOI: 10.1186/1471-2458-11-S3-S13. PMID: 21501430

7. Kyozuka H., Yasuda S., Hiraiwa T., Ishibashi M., Kato K., Fujimori K. Histological chorioamnionitis as a risk factor for preterm birth without disturbing fetal heart rate: a case-control study. Tohoku J. Exp. Med. 2017; 243 (4): 289-295. DOI: 10.1620/tjem.243.289. PMID: 29249732

8. Britt R.D.Jr., Faksh A., Vogel E., Martin R.J., Pabelick C.M., Prakash Y.S. Perinatal factors in neonatal and pediatric lung diseases. Expert. Rev. Respir. Med. 2013; 7 (5): 515-531. DOI: 10.1586/17476348.2013.838020. PMID: 24090092

9. Ericson J.E., Laughon M.M. Chorioamnionitis: implications for the neonate. Clin. Perinatol. 2015; 42 (1): 155-165. DOI: 10.1016/j.clp.2014.10.011. PMID: 25678002

10. Jobe A.H., Kallapur S.G. Long term consequences of oxygen therapy in the neonatal period. Semin. Fetal. Neonatal. Med. 2010; 15 (4): 230-235. DOI: 10.1016/j.siny.2010.03.007. PMID: 20452844

11. Gebb S.A., Jones P.L. Hypoxia and lung branching morphogenesis. Adv. Exp. Med. Biol. 2003; 543: 117-125. DOI: 10.1007/978-1-4419-8997-0_8. PMID: 14713117

12. Glukhovets B.I., Glukhovets N.G. Ascending infection of the feto-placental system. Moscow: MEDpress-inform; 2006: 240. ISBN 5-98322-141-8. [In Russ.]

13. van Tuyl M., Liu J., Wang J., Kuliszewski M., Tibboel D., Post M. Role of oxygen and vascular development in epithelial branching morphogenesis of the developing mouse lung. Am. J. Physiol. Lung Cell Mol. Physiol. 2005; 288 (1): L167-L178. DOI: 10.1152/ajplung.00185.2004. PMID: 15377493

14. Hartman W.R., Smelter D.F., Sathish V., Karass M., Kim S., Aravamudan B., Thompson M.A., Amrani Y., Pandya H.C., Martin R.J., Prakash Y.S., Pabelick C.M. Oxygen dose responsiveness of human fetal airway smooth muscle cells. Am. J. Physiol. Lung Cell Mol. Physiol. 2012; 303 (8): L711L719. DOI: 10.1152/ajplung.00037.2012. PMID: 22923637

15. Keglowich L., Baraket M., Tamm M., Borger P. Hypoxia exerts dualistic effects on inflammatory and proliferative responses of healthy and asthmatic primary human bronchial smooth muscle cells. PLoS One. 2014; 9 (2): e89875. DOI: 10.1371/journal.pone.0089875. PMID: 24587090

16. Baek K.J., Cho J.Y., Rosenthal P., Alexander L.E., Nizet V., Broide D.H. Hypoxia potentiates allergen induction of HIF-1 , chemokines, airway inflammation, TGF1, and airway remodeling in a mouse model. Clin. Immunol. 2013; 147 (1): 27-37. DOI: 10.1016/j.clim.2013.02.004. PMID: 23499929

17. Tan C.D., Smolenski R.T., Harhun M.I., Patel H.K., Ahmed S.G., Wanisch K., Yáñez-Muñoz R.J., Baines D.L. AMP-activated protein kinase (AMPK)-dependent and -independent pathways regulate hypoxic inhibition of transepithelial Na+ transport across human airway epithelial cells. Br. J. Pharmacol. 2012; 167 (2): 368-382. DOI: 10.1111/j.14765381.2012.01993.x. PMID: 22509822

18. Wójkowska-Mach J., Borszewska-Kornacka M., Doman´ska J., Gadzinowski J., Gulczyn´ska E., Helwich E., Kordek A., Pawlik D., Szczapa J., Klamka J., Heczko P.B. Early-onset infections of very-low-birthweight infants in Polish neonatal intensive care units. Pediatr. Infect. Dis. J. 2012; 31 (7): 691-695. DOI: 10.1097/INF.0b013e3182567b74. PMID: 22466319

19. Machado J.R., Soave D.F., da Silva M., de Menezes L.B., Etchebehere R., Monteiro M., dos Reis M., Corrêa R., Celes M.. Neonatal sepsis and inflammatory mediators. Mediators Inflamm. 2014; 2014: 269681. DOI: 10.1155/2014/269681. PMID: 25614712

20. Perepelitsa S.A., Golubev A.M., Moroz V.V., Alekseyeva S.V., Melnichenko V.A. Placental inflammatory changes and bacterial infection in premature neonates with respiratory failure. Obshchaya Reanimatologiya = General Reanimatology. 2012; 8 (3): 18-24. DOI: 10.15360/1813-9779-2012-3-18. [In Russ., In Engl.]

21. Milaya O.V., Ionov O.V., Degtyareva A.V., Levadnaya A.V., Degtyarev D.N. Clinical and laboratory manifestations of congenital infectious and inflammatory diseases in extremely low and very low birth weight infants. Akusherstvo i Ginekologiya. 2014; 10: 66-71. [In Russ.]

22. Shah B.A., Padbury J.F. Neonatal sepsis: an old problem with new insights. Virulence. 2014; 5 (1): 170-178. DOI: 10.4161/viru.26906. PMID: 24185532

23. Morton S.U., Brodsky D. Fetal physiology and the transition to extrauterine life. Clin. Perinatol. 2016; 43 (3): 395-407. DOI: 10.1016/j.clp.2016.04.001. PMID: 27524443

24. Sharma D., Sharma P., Shastri S. Golden 60 minutes of newborn’s life. Part 2: term neonate. J. Matern. Fetal. Neonatal. Med. 2017; 30 (22): 2728-2733. DOI: 10.1080/14767058.2016.1261399. PMID: 27844484