Povezanost histološki dokazanih upalnih promjena posteljice i kronične plućne bolesti u nedonoščadi : doktorski rad

Cilj istraţivanja: PosljednjihgodinamnogobrojnimsekliničkimieksperimentalnimispitivanjimapokušavarasvijetlitiodnosizmeĎuupaleposteljice i fetalnogupalnog sindroma s jedne, te kratkoročnogidugoročnogishodaprijevremenogporoda s druge strane.Nedonošče čestoideususretnizukroničnihzdravstvenihtegoba, meĎu kojima se po svojoj teţini i značajnosti utjecaja na kvalitetu ţivota, posebno ističukronične bolesti dišnog sustava. Pokronologijinjihovepojavnostimoţemoihpodijelitiuraneoblike, kao što je kronična plućna bolest nedonoščeta, te kasne oblike, kaoštosu bronhoopstruktivni sindrom ranog djetinjstva i simptomi astme. Nameće se potreba istraţivanja onih stanja koja najviše ugroţavaju čedo tijekom trudnoće, poroda i rane novoroĎenačke dobi te potreba intenzivnog praćenja i rane detekcije smetnji u razvoju, ali i pravovremenog predviĎanja kroničnih ne-neuroloških zdravstvenih problemanedonoščeta. Ispitanici i metode; Ovo istraţivanje je povijesna kohortna studija kojajeudesetogodišnjemrazdoblju, od1998. do 2008. godine uključila262 nedonoščadi gestacijskedobi≤ 32.tjedanatrudnoće, roĎeneuKlinici za ginekologiji i porodništvo, KBC Rijeka. Grupiranjeispitanikaunutarispitivaneskupineprovedeno je premanačelu„nestedcasecontrolstudy“. Unutarispitivaneskupineprovedenajeanalizaprenatalnihineonatalnihčimbenikarizikatemajčinih čimbenikarizikazanastanakkroničnihrespiratornihteškoća. Odčimbenikarizikaispitivanisu patohistološkinalazposteljice, gestacijskadob, spol, rodnamasa, načinporoda, prijevremeno prsnućeplodovih ovojnica, infekcijaplodovevode, Apgarocjena, terapijaegzogenimsurfaktantom, mehaničkaventilacija, teprisustvootvorenog arterijskogduktusainovoroĎenačkesepse. VIMeĎu majčinim čimbenicimarizikaispitivanajestručnasprema, dob, pušenjeutrudnoći, antimikrobnaterapijautrudnoćiteprisustvokroničnihrespiratornihsimptomaiatopije. Postupnik patomorfološke analize posteljice predviĎao je mikroskopskuanalizuminimalnodevetuzoraka, adefinicijapatohistološkognalazatemeljilasenabrojuleukocitaunutarpoljazasvakiuzoraktkiva. Rezultati: MeĎu našim ispitanicima u 40%(105/262) je patohistološki nalaz posteljice i plodovih ovoja dokazao korioamnionitis, a u 17%(45/262) dokazan je fetalni upalni odgovor. Kronična plućna bolest nedonoščeta dijagnosticirana je u 24% (62/262) ispitanika, 26% (68/262) nedonoščadi razvilo jebronhoopstruktivni sindrom rane dječje dobi, a 23% (59/262) razvilo je simptome astme dječje dobi. Prisustvo fetalnog upalnog odgovora značajan je čimbenik prijevremenog poroda. Njegova prisutnost značajno povećava omjer vjerojatnosti za gestaciju kraću od tjedana (OR 5.87), rodnu masu manju od 1000 grama (OR 3.84), APGAR indeks <6 u 5.minuti (OR 2.47), otvoreni arterijski duktus (OR 4.66), potrebu mehaničke ventilacije (OR 3.20), kronične plućne bolesti nedonoščeta (OR 17.8) i bronhoopstruktivnog sindroma rane dječje dobi (OR 4.49). Logističkom regresijom kao nezavisni čimbenici rizika za nastanak kronične plućne bolesti nedonoščeta pokazali su se rodna masa < 1000 grama (OR 4.10), mehanička ventilacija (OR 5.24) i prisustvo fetalnog upalnog odgovora (OR 18.83). Path-analiza ukazala je na izraziti direktni učinak majčine atopije na nastanak astme (0.60), fetalnog upalnog odgovora na kroničnu plućnu bolest nedonoščeta (0.59), mehaničke ventilacije na kroničnu plućnu bolest nedonoščeta (0.45) i kronične plućne bolesti na nastanak bronhoopstruktivnog sindroma (0.54). Neposredni utjecaj gestacijske dobi na nastanak kronične plućne bolesti je minimalan i zanemariv (0.04). VIIZaključak: KliničkadogaĎanjaunajranijojţivotnojdobi, aionaprijesamogroĎenja, odogromnesuvaţnostisobziromnapatogenezupromjenaudišnimputevima, uskopovezanusarazvojnimetapamasustavazadisanje. Sadašnja saznanja, u koja su se naši rezultati u potpunosti uklopili, naglašavaju ulogu prenatalne upale i fetalnog upalnog sindroma kao vodećih čimbenika rizika za prijevremeni poroĎaj te njihov temeljni značaj za postnatalni respiratorni morbiditet. Posljednjih godina učinjeno je mnogo pokušaja s ciljem definiranja o gestaciji neovisne uloge korioamnionitisa na novoroĎenački i postnatalni ishod. Rezultati naše path-analize dodatno rasvjetljavaju taj patogenetski prijepor i mogu biti jedan od putokaza u odreĎivanju smjera slijedećih istraţivanja.Objectives: In the last years, a huge number of clinical and experimental studies trying to elucidate the relationship between inflammation of the placenta and fetal inflammatory syndrome with short-term and long-term outcome of preterm delivery. Premature babies often have the burden of chronic health problems that could have a significant impact on quality of life, like long-lasting chronic respiratory disease. According to the chronology of their appearance it can be divided into early form, the chronic lung disease of prematurity, and late forms, such as wheezing in early childhood and early childhood asthma. The need for research of conditions that could threat the infants duringpregnancy, childbirth and early neonatal age is mandatory, as well as it is the need for intensive monitoring and early detection of chronic non-neurological medical problems of the prematurely born infant.PatientsandMethods: This study is a historical cohort study, with 262 preterm infants of gestational age ≤ 32 weeks, recruited in a ten-years period, born at the Department of Gynecology and Obstetrics, University Hospital Rijeka. Grouping of subjects within the study groups was carried out according to the "nested case control study." An analysis of maternal, prenatal and neonatal risk factors was carried out: pathohistological findings of the placenta, gestational age, sex, birth weight, mode of delivery, premature rupture of membranes, characteristics of the amniotic fluid, Apgar score, exogenous surfactant therapy, mechanical ventilation, presence of patent ductus arteriosus, and neonatal sepsis. Among the maternal risk factors we analyzed the education level, age, smoking during pregnancy, antimicrobial therapy during pregnancy and the presence of chronic IXrespiratory symptoms and atopy. The pathomorphological examination of the placenta includes microscopic analysis of at least nine samples, a definition of pathohistological findings based on the number of leukocytes in the fields for each tissue sample.Results:In our study 40%(105/262) of newborns had chorioamnionitis, whether 17% (45/262) had FIRS. 24% (62/262) of infants developed chronic lung disease of prematurity, 26% (68/262) had earlychildhood wheezing, and 23% (59/262) developed symptoms of early childhood asthma. The presence of FIRS had a significant impact on the gestational age less than 28 weeks(OR 5.87), birthweight less than 1000 grams (OR 3.84), APGAR score lower than 6 in the fifth minute of life (OR 2.47), presence of patent ductus arteriosus (OR 4.66), need for mechanical ventilation (OR 3.20), and presence of chronic lung disease of prematurity (OR 17.8) as well as early childhood wheezing (OR 4.49). With logistic regression analysis the birtweight < 1000 grams (OR 4.10), mechanical ventilation (OR 5.24) and FIRS-a (OR 18.83) showed up as indipendent risk factors for chronic lung disease. The path-analysis disclosed a strong direct impact of mother atopy on development ofearly childhood asthma (0.60), and strong impact of FIRS on chronic lung disease (0.59), as well as mechanical ventilation on chronic lung disease (0.45). Chronic lung disease had a strong direct influence on development of early childhood wheezing (0.54). The direct influence of gestational age on chronic lung disease is week and negligible (0.04).Conclusion: Clinical events in the early neonatal and, as we proved, in the prenatal period are of paramount importance with regard to the pathogenesis of changes in the airways, closely related to the developmental phases of the respiratory system. Our results are contributing to emphasize the importance ofprenatal infection and fetal inflammatory Xsyndrome as the leading risk factors for preterm delivery, and their fundamental importance for postnatal respiratory morbidity. In recent years a lot of attempts has be done to define the independent role of chorioamnionitis on neonatal and postnatal outcome. The results of our path-analysis sheds new light on the pathogenetic dispute and may be one of the clues in determining the direction of research in the future