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Razvoj metaregresijskega modela za vrednotenje vpliva onesnaževal v zunanjem zraku na izbrane izide v nosečnosti
Kešpert, Blaž (Author), Locatelli, Igor (Mentor) More about this mentor... This link opens in a new window, Kukec, Andreja (Co-mentor)

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Abstract
Naraščajoče število raziskav ugotavlja značilno povezanost med visokimi koncentracijami onesnaževal v zunanjem zraku ter neželenimi izidi v nosečnosti (prezgodnji porod, nizka porodna teža, zastoj v fetalni rasti), pri čemer se ocene učinkov med študijami precej razlikujejo. V pregledanih objavljenih metaanalizah, ki proučujejo ta vpliv, je opaziti veliko heterogenost rezultatov, ki pa zaenkrat ostaja nezadostno pojasnjena. Namen raziskovalnega dela je zbrati novejše raziskave v okviru sistematičnega pregleda literature in nadgraditi delo v okviru raziskave Klepac in sod. 2018. Cilj je razviti metaregresijski model, s katerim bi raziskali vpliv razlik med lastnostmi raziskav in pojasnili heterogenost med izsledki izvornih raziskav. Sistematični pregled je izveden v iskalniku PubMed za raziskave, objavljene v bibliografski bazi Medline med 7. 11. 2017 in 21. 2. 2020. Iskane izvorne epidemiološke raziskave morajo proučevati izpostavljenost nosečnic ob povišanih koncentracijah onesnaževal delcev manjših od 10 µm (PM10), delcev manjših od 2,5 µm (PM2.5) ter plinov dušikovega diokida (NO2), ozona (O3) in ogljikovega oksida (CO) za neželena izida prezgodnji porod (PTB) ali nizko porodno težo (LBW). Slednja je lahko izražena tudi kot absolutna razlika v porodni teži (BW). Podatki so zbrani ločeno za obe skupini metodologije ocene izpostavljenosti: MS, ki se opira na podatke merilnih postaj in MA, temelji na računalniškem modeliranju različnih vhodnih podatkov za oceno širjenja onesnaževal v ozračju. Kakovost izvedbe izbranih raziskav je ocenjena s pomočjo priročnika za Newcastle-Ottawa lestvico (NOS). Metaanaliza je bila izvedena v programih Review Manager 5.4.1 in STATA 16.0. Slednji program je uporabljen tudi za analizo podskupin ter za razvoj metaregresijskega modela. Analiza podskupin vključuje podatke o vrsti študije, metodologiji ocene izpostavljenosti nosečnic, geografskega območja, vključitvenih kriterijih za populacijo, prilagoditvenih dejavnikov upoštevanih v regresijskih modelih, ter oceni NOS. Metaregresijski modeli so zasnovani tako, da pojasnijo čim več heterogenosti med rezultati raziskav, pri čemer ostajajo kot celota statistično značilni. Metaanaliza obsega 121 raziskav. Pri izidih PTB in LBW so rezultati predstavljeni kot skupna razmerja obetov (OR). Povedo, za kolikokrat se obeti za določen izid pri nosečnicah, ki so bile izpostavljene 10µg/m3 višjim koncentracijam posameznega onesnaževala, povečajo. Razlika v porodni teži pri BW je predstavljena kot skupni koeficient β, ki pove kolikšna je razlika v masi novorojenčkov pri izpostavljenih nosečnicah. Med onesnaževali v zunanjem zraku ugotavljamo statistično značilno povezanost pri povečanju koncentracij PM10, PM2.5, NO2, O3 za 10µg/m3 ter CO za 100µg/m3 za obdobje celotne nosečnosti ob metodi z merilnimi postajami (MS). Ob metodi ocene širjenja onesnaževal v zraku (MA) so rezultati, tudi zaradi manjšega števila raziskav, manj konsistentni. Med naštetimi onesnaževali imajo pri vseh izbranih izidih največji vpliv delci s PM2.5, in sicer ob metodi MS: skupno razmerje obetov (OR): 1,094 s 95% IZ [1,032; 1,159]; za PTB, 1,040 s 95% IZ [1,016; 1,064] za LBW, -17,11 g s 95% IZ [-23,04 g; -11,18 g] za BW. Rezultati ob metodi MA se bistveno ne razlikujejo. Ugotavljamo, da ima med časovnimi okni največji vpliv povečanje koncentracij opazovanih onesnaževal v celotni nosečnosti. Pri izidu PTB za vpliv povečanja koncentracij delcev PM10 ter PM2.5 ugotavljamo, da je med trimestri najbolj kritično povišanje v drugem, medtem ko pri izidih LBW in BW težje izberemo večji vpliv povišanja koncentracij onesnaževal v posamičnem trimestru. Na podlagi rezultatov lahko sklepamo, da so onesnaževala v zunanjem zraku, še posebej delci PM2.5, pomemben dejavnik pri pojavu prezgodnjega poroda in (nizke) porodne teže. Kljub temu da so vplivi PM10 in NO2 precej manjši, še vedno lahko pomembno prispevajo k celostnemu bremenu učinka onesnaženega zraka na opazovane izide. Rezultati za izpostavljenost povišanim koncentracij O3 in CO sicer nakazujejo značilen vpliv pri določenih kombinacijah onesnaževalo - izid, vendar menimo, da je variabilnost med raziskavami še vedno prevelika za podajanje zanesljivih zaključkov. Naši metaregresijski modeli so se izkazali za uporabne predvsem za izid razlika v porodni teži (BW), kjer sta kot ključni komponenti prevladovali primerjava za geografsko svetovno regijo ter prilagoditev ocene učinka za socio- ekonomski status matere oziroma gospodinjstva (SES).

Language:Slovenian
Keywords:Onesnaženje zunanjega zraka, izidi v nosečnosti, sistematični pregled, metaanaliza, metaregresijski model
Work type:Master's thesis/paper (mb22)
Organization:FFA - Faculty of Pharmacy
Year:2021
Views:163
Downloads:30
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Secondary language

Language:English
Title:Influence of ambient air pollution on the selected pregnancy outcomes: development of a metaregression model
Abstract:
The growing number of studies have concluded there is an evident correlation between rises in ambient air pollutants' concentration and adverse birth outcomes, nevertheless there are still inconsistent reports on the degree of an influence. The studied published meta-analyses mostly agree on the high heterogeneity between original studies but fail to substantially profile its sources. The aim of our study is to gather newer studies as a part of a systematic review and include them in our existing database of the research of Klepac et al 2018. We are conducting a meta-analysis in order to compare merged effects of exposure assessment method, type of pollutant and window of exposure. Furthermore, we are assessing each study based on its properties and covariates that might variate between studies. Based on these results, we are intending to develop meta-regression models for each pair of pollutant – adverse and birth outcome that would help to explain the heterogeneity of discovered effect estimations between studies. Systematic review is conducted for the period of 7.11.2017 – 21.2.2020 on Pubmed, a search engine for the Medline, the bibliographical database. Included studies must be original research work, that study the relation of mothers’ exposure of pollutants of particulate matter with the diameter less than 10 µm (PM10), less than 2,5 µm (PM2.5) and gasses: nitrogen dioxide (NO2), ozone (O3) or carbon oxide (CO) for the adverse birth outcomes of preterm birth (PTB) or low birth weight (LBW). The former could also be studied as an absolute difference of the birth weight (BW). The quality of the studies' methodology is assessed with the Newcastle-Ottawa Scale manual. Meta-analysis is conducted first in Review Manager 5.4.1 and then again in STATA 16.0. Subgroup analysis and meta-regression model development are also performed in the latter. Subgroup analysis includes data on methodology, geographical area, population, inclusion criteria, covariates for regression models’ effect adjustment, average concentrations and NOS-based quality score. Models are developed in a way that they explain as much heterogeneity as possible while staying statistical significant as entities. Meta-analysis included 121 studies. For the outcomes of PTB and LBW the results are presented as unified odds ratios (OR) and difference in birth weight in grams is presented as factor β. We find statistically significant correlations between rises in concentration of PM10, PM2.5, NO2, O3 for 10µg/m3 and CO for 100µg/m3 in the entire pregnancy in studies which applied MS exposure assessment method. Results for those that applied MA method were not as consistent, possibly because of the lower number of studies. Amongst pollutants, the PM2.5 has the greatest effect on the chosen outcomes (results from STATA 16.0; entire pregnancy): 1,094 with 95% CI [1,032; 1,159] for PTB, 1,040 with 95% CI [1,016; 1,064] for LBW, -17,11g with 95% CI [-23,04; -11,18] for BW. Results for studies that apply the method MA provide similar results. Among the trimesters we find the rises in concentration of PM10 and PM2.5 in the second trimester to be the most critical in the PTB. We can conclude that ambient air pollution, especially PM2.5 is a considerable factor in the preterm birth and (low) birth weight. Even though rises PM10 and NO2 are shown to have marginal effects in comparison to PM2.5, they may also be a factor in the cumulative burden of the influence of air pollution on the studied outcomes. The results for the rises in concentration of O3 and CO are shown to have a significant influence on certain outcomes, however they are still too variable to enable us to declare a definitive conclusion. Our meta-regression models have proven to be possibly applicable only for the outcome of birth weight, with comparison for a global region and adjustment for a socioeconomic status of the mother or the household (SES) as the key covariates.

Keywords:Ambient air pollution, pregnancy outcomes, systematic review, meta-analysis, meta-regression models

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