Transient Tachypnea of the Newborn (TTN): A Role for Polymorphisms of Surfactant Protein B (SP-B) Encoding Gene?

Abstract

Background: Transient tachypnea of the newborn (TTN) is usually a benign self-limiting respiratory disorder in the immediate neonatal period. The lipophilic surfactant-associated protein B (SP-B) was demonstrated to be the most relevant structural component of the surfactant system for immediate postnatal pulmonary adaptation. We hypothesized genetic variations of surfactant protein B (heterozygous 121 ins 2 mutation er intron 4 polymorphisms) to be related to TTN. Patients and Method: We screened genomic DNA of 83 healthy term neonates (gestational age: 39 (37 - 41) completed weeks [median and range]; birth weight: 3325 ± 541 grams [mean ± SD]) and 75 infants presenting with TTN (gestational age: 38 (37 - 41) completed wecks [median and range]; birth weight: 3091 ± 435 grams [mean ± SD]) by means of PCR-amplification, fragment length and sequence analysis. TTN was diagnosed an the basis of the clinical signs with respiratory rate > 60 breaths/minute, fraction of inspired oxygen > 0.21, and characteristic radiographic findings within less than 24 hours after birth. Newborns with any infection, pulmonary or cardiac congenital malformations, postnatal asphyxia and infants born to diabetic mothers were excluded. Results: In TTN-group the frequency of male infants (68.4 % versus 44.6 %, p < 0.05) and caeserian section were significantly higher (68.4 % versus 30.1 %, p < 0.05). We did not find any statistical difference in frequency of intron 4 variations between controls and TTN-group (8.4 % versus 10.7 %). None of the infants were heterozygous for the 121ins2 SP-B mutation. Conclusions: WC conclude polymorphisms of intron 4 and heterozygous 121 ins 2 mutation not to associated with TTN.

Zusammenfassung

Hintergrund: Die transiente Tachypnoe des Neugeborenen (TTN) ist in der Regel ein selbstlimitierendes Krankheitsbild in der unmittelbaren neonatalen Periode. Das lipophile surfactantassoziierte Protein B (SP-B) ist das wichtigste Element des Surfactantsystems für die postnatale pulmonale Adaptation. Ziel unserer Arbeit war es, einen möglichen Zusammenhang zwischen genetischen Variationen des SP-B (heterozygote 121ins2 Mutation oder Polymorphismen im Intron 4) und der TTN zu untersuchen. Patienten und Methode: Wir analysierten die DNA von 83 gesunden Neugeb. (Gestationsalter: 39 (37 - 41) SSW ([Median (Minimum-Maximum)], Geburtsgewicht: 3325 ± 541 g [Mittelwert ± SD]) und 75 Reifgeborenen mit TTN (Gestationsalter: 38 (37 - 41) SSW [Median (Minimum-Maximum)], Geburtsgewicht: 3091 ± 435 g [Mittelwert ± SD]) mittels PCR, Fragmentlängenanalyse und Gensequenzierung. Die Diagnose der TTN basierte auf klinischen Zeichen mit Atemfrequenz > 60/min, FiO₂ > 0,21 und charakteristischen radiologischen Befunden innerhalb der ersten 24 h nach Geburt. Neugeborene mit Infektionen, angeborenen kardialen oder pulmonalen Fehlbildungen, Asphyxie und Kinder diabetischer Mütter wurden ausgeschlossen. Ergebnisse: In der TTN-Gruppe war der Anteil an männlichen Neugeborenen (68,4 % versus 44,6 %, p < 0.05) und Sectio-Entbindungen im Vergleich zur Kontrollgruppe signifikant höher (68,4% versus 30,1 %, p < 0,05). Die Häufigkeit der Intron 4-Polymorphismen unterschied sich nicht zwischen Kontroll- und TTN-Gruppe (8,4 % versus 10,7 %). Bei keinem der untersuchten Patienten fand sich eine heterozygote 121ins2-Mutation. Schlussfolgerung: Polymorphismen in den untersuchten Genabschnitten sind nicht für das Krankheitsbild der TTN verantwortlich.

Transient tachypnea of the newborn - SP-B polymorphisms - respiratory failure

Transiente Tachypnoe - SP-B Polymorphismen - Lungenversagen

References

• 1 Avery M E, Gatewood O B, Brumley G. Transient tachypnea of newborn. Possible delayed resorption of fluid at birth.  Am J Dis Child. 1966;  111 380-385
• 2 Bonafe L, Rubaltelli F F. The incidence of acute neonatal respiratory disorders in Padova county: an epidemiological survey.  Acta Paediatr. 1996;  85 1236-1240
• 3 Clark J C, Weaver T E, Iwamoto H S. et al . Decreased lung compliance and air trapping in heterozygous SP-B-deficient mice.  Am J Respir Cell Mol Biol. 1997;  16 46-52
• 4 Dani C, Reali M F, Bertini G. et al . Risk factors for the development of respiratory distress syndrome and transient tachypnoea in newborn infants. Italian Group of Neonatal Pneumology.  Eur Respir J. 1999;  14 155-159
• 5 Demissie K, Marcella S W, Breckenridge M B, Rhoads G G. Maternal asthma and transient tachypnea of the newborn.  Pediatrics. 1998;  102 84-90
• 6 Floros J, Kala P. Surfactant proteins: molecular genetics of neonatal pulmonary diseases.  Annu Rev Physiol. 1998;  60 365-384
• 7 Floros J, Veletza S V, Kotikalapudi P. et al . Dinucleotide repeats in the human surfactant protein-B gene and respiratory-distress syndrome.  Biochem J. 1995;  305 (Pt2) 583-590
• 8 Haataja R, Ramet M, Marttila R, Hallman M. Surfactant proteins A and B as interactive genetic determinants of neonatal respiratory distress syndrome.  Hum Mol Genet. 2000;  9 2751-2760
• 9 Hamvas A, Trusgnich M, Brice H. et al . Population-based screening for rare mutations: high-throughput DNA extraction and molecular amplification from Guthrie cards.  Pediatr Res. 2001;  50 666-668
• 10 Hummler E, Horisberger J D. Genetic disorders of membrane transport. V. The epithelial sodium channel and its implication in human diseases.  Am J Physiol. 1999;  276 G567-571
• 11 Landmann E, Gortner L, Reiss I, Weller E, Tegtmeyer F K. Protein content and biophysical properties of tracheal aspirates form neonates with respiratory failure.  Klin Padiatr. 2002;  214 1-7
• 12 Makri V, Hospes B, Stoll-Becker S, Borkhardt A, Gortner L. Polymorphisms of surfactant protein B encoding gene: modifiers of the course of neonatal respiratory distress syndrome?.  Eur J Pediatr. 2002;  161 604-608
• 13 Manroe B L, Weinberg A G, Rosenfeld C R, Browne R. The neonatal blood count in health and disease. I. Reference values for neutrophilic cells.  J Pediatr. 1979;  95 89-98
• 14 Miller L K, Calenoff L, Boehm J J, Riedy M J. Respiratory distress in the newborn.  JAMA. 1980;  243 1176-1179
• 15 Nogee L M, de Mello D E, Dehner L P, Colten H R. Brief report: deficiency of pulmonary surfactant protein B in congenital alveolar proteinosis.  N Engl J Med. 1993;  328 406-410
• 16 Nogee L M, Garnier G, Dietz H C. et al . A mutation in the surfactant protein B gene responsible for fatal neonatal respiratory disease in multiple kindreds.  J Clin Invest. 1994;  93 1860-1863
• 17 Pitkanen O. Lung epithelial ion transport in neonatal lung disease.  Biol Neonate. 2001;  80 (Suppl 1) 14-17
• 18 Pryhuber G S. Regulation and function of pulmonary surfactant protein B.  Mol Genet Metab. 1998;  64 217-228
• 19 Robertson B, Kobayashi T, Ganzuka M, Grossmann G, Li W Z, Suzuki Y. Experimental neonatal respiratory fafure induced by a monoclonal antibody to the hydrophobic surfactant-associated protein SP-B.  Pediatr Res. 1991;  30 239-243
• 20 Song G W, Sun B, Curstedt T, Grossmann G, Robertson B. Effect of amiloride and surfactant an lung liquid clearance in newborn rabbits.  Respir Physiol. 1992;  88 233-246
• 21 Spillman T, Cotton D B, Golunski E. Detection frequency by thin-layer chromatography of phosphatidylglycerol in amniotic fluid with clinically functional pulmonary surfactant.  Clin Chem. 1988;  34 1976-1982
• 22 Stastny B, Kind C. Acute pulmonary oedema due to transient myocardial dysfunction: an uncommon cause of respiratory distress in the term neonate.  Eur J Pediatr. 1998;  157 59-62
• 23 Taylor P M, Allen A C, Stinson D A. Benign unexplained respiratory distress of the newborn infant.  Pediatr Clin North Am. 1971;  18 975-1004
• 24 Weaver T E. Synthesis, processing and secretion of surfactant proteins B and C.  Biochim Biophys Acta. 1998;  1408 173-179
• 25 Weaver T E, Beck D C. Use of knockout mice to study surfactant protein structure and function.  Biol Neonate. 1999;  76 (Suppl 1) 15-18
• 26 Wesenberg R L, Graven S N, McCabe E B. Radiological findings in wet-lung disease.  Radiology. 1971;  98 69-74
• 27 Wiswell T E, Bent R C. Meconium staining and the meconium aspiration syndrome. Unresolved issues.  Pediatr Clin North Am. 1993;  40 955-981