{"id":10927,"date":"2026-04-10T09:20:35","date_gmt":"2026-04-10T09:20:35","guid":{"rendered":"https:\/\/www.proefschriftmaken.nl\/portfolio\/suzan-cochius\/"},"modified":"2026-04-23T07:10:15","modified_gmt":"2026-04-23T07:10:15","slug":"suzan-cochius","status":"publish","type":"us_portfolio","link":"https:\/\/www.proefschriftmaken.nl\/en\/portfolio\/suzan-cochius\/","title":{"rendered":"Suzan Cochius"},"content":{"rendered":"","protected":false},"excerpt":{"rendered":"","protected":false},"author":8,"featured_media":12360,"comment_status":"closed","ping_status":"closed","template":"","meta":{"_acf_changed":false,"footnotes":""},"us_portfolio_category":[45],"class_list":["post-10927","us_portfolio","type-us_portfolio","status-publish","has-post-thumbnail","hentry","us_portfolio_category-new-template"],"acf":{"naam_van_het_proefschift":"One Size Does Not Fit All","samenvatting":"Er is geen Nederlandse samenvatting beschikbaar. De Engelse samenvatting vind je <a href=\"https:\/\/www.proefschriftmaken.nl\/en\/portfolio\/suzan-cochius\/\">hier<\/a>.","summary":"The research described in this thesis addresses several aspects of the perinatal and neonatal management of patients with CDH. Most research is conducted in cooperation with members of the CDH Euro Consortium, a clinical and scientific collaboration between tertiary medical centers in Europe with expertise in the treatment of CDH patients.\n\nPART I Introduction\nIn Chapter 1 the historical background of CDH is described. Also the importance of predicting outcome is discussed. Thereafter, prenatal parameters, such as observed to expected lung-to-head ratio (O\/E LHR), and their clinical relevance are explained. Additionally, postnatal parameters and models are discussed, next to the role of biochemical biomarkers in the prediction of chronic lung disease (CLD) and pulmonary hypertension (PH) in CDH patients. The focus of the international guidelines is described, preventing ventilator induced lung injury and establishing cardiovascular stability. Subsequently, the three major pathways involved in regulation of the pulmonary vascular resistance are explained and the drugs that act on different steps of the pathway. Lastly, the survival, but also the morbidity and long-term follow-up are discussed briefly.\n\nPART II Prediction\nChapter 2 presents an editorial on a new prediction tool, the preoperative chest radiographic thoracic area (CRTA), tracing the lung on an anterior-posterior chest x-ray. The role of CRTA is discussed and placed in a broader perspective of prediction tools used in CDH patients. This new tool seems to be a relatively reliable new tool, but will need additional validation. Many tools used in this group of patients struggle with the same issues; they were only tested on small groups, are difficult to apply or don\u2019t have a standardized definition or measurement method. The latter holds for PH on echocardiogram and the O\/E LHR, decreasing its reliability.\n\nIn Chapter 3 the Congenital Diaphragmatic Hernia Study Group prediction rule, an early model to predict mortality in CDH patients, is validated with a cohort of 343 CDH patients born in 4 large European centers. All centers use the same standardized CDH-EURO Consortium treatment protocol. In this group the rule shows a fair predictive performance. To further improve the rule, the pre- and postnatal parameters of 620 CDH patients are used to modify the rule. Interestingly, only liver herniation is of additional value to improve the rules ability to predict mortality in CDH patients. Also, the variable \u201cmissing Apgar score\u201d is taken out of the model as it is not of significant value in our population.\n\nIn addition to the discovery of novel early biomarkers SIGLEC-14, BCAM, and ANGPTLP to predict bronchopulmonary dysplasia in preterm infants, these biomarkers are tested in preterm infants, CDH patients and adults in Chapter 4. The role of these biomarkers in predicting BPD in preterm infants is validated and protein concentrations correlate with the duration of mechanical ventilation, oxygen supplementation and structural lung changes. Although chronic lung disease in CDH patients cannot be predicted, it does separate surviving from non-surviving CDH patients and SIGLEC-5\/14 seems to predict PH. In adults the biomarkers cannot separate patients from healthy controls.\n\nPART III Treatment\nIn Chapter 5 a novel, more individualized approach in the delivery room is described. In contrast to common practice, newborns with mild CDH, defined as isolated left-sided CDH, O\/E LHR \u226550% and intra-abdominal liver position, are not routinely intubated in the delivery room, but only when they develop respiratory failure. This approach is successful in 40% of the patients, decreasing possible iatrogenic complications of prompt intubation, while it does not seem to negatively affect outcomes in the patients who develop respiratory failure.\n\nTo develop an adequate dosing regimen of intravenous sildenafil in CDH patients, in Chapter 6 a pharmacokinetic model is developed, using samples from 23 infants with CDH. A two-compartment disposition model of sildenafil and a one-compartment disposition model of desmethyl sildenafil is observed. Only postnatal age increases sildenafil clearance and sildenafil is tolerated well in this relatively small group. The widely used loading dose of 0.4mg\/kg in 3 hours, followed by 1.6mg\/kg\/day continuous infusion, achieves appropriate sildenafil plasma levels in CDH patients.\n\nThe related trial protocol of the CoDiNOS trial is discussed in Chapter 7. The CoDiNOS trial is an international randomized controlled trial in which intravenous sildenafil is compared to inhaled nitric oxide for the first-step treatment of PH in neonates with CDH. We hypothesize that intravenous sildenafil is superior to inhaled nitric oxide. Primary outcome is the absence of pulmonary hypertension on echocardiography on day 14 without therapy and without treatment failure and\/or death within the first 28 days of life. With a sample size of 330 patients we will be able to detect a 25% relative difference in outcome between both drugs. Secondary outcome parameters are the need for ECMO, time on intervention drug, the incidence of chronic lung disease and the external validation of the pharmacokinetic model for sildenafil, among others.\n\nPART IV Discussion and\n\nThe general discussion in this thesis addresses the association of this research with the","auteur":"Suzan Cochius","auteur_slug":"suzan-cochius","publicatiedatum":"8 december 2020","taal":"EN","url_flipbook":"https:\/\/ebook.proefschriftmaken.nl\/ebook\/suzancochius?iframe=true","url_download_pdf":"","url_epub":"","ordernummer":"FTP-202604100916","isbn":"978-94-6380-994-8","doi_nummer":"","naam_universiteit":"Erasmus Universiteit Rotterdam","afbeeldingen":12360,"naam_student:":"","binnenwerk":"","universiteit":"Erasmus Universiteit Rotterdam","cover":"","afwerking":"","cover_afwerking":"","design":""},"_links":{"self":[{"href":"https:\/\/www.proefschriftmaken.nl\/en\/wp-json\/wp\/v2\/us_portfolio\/10927","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.proefschriftmaken.nl\/en\/wp-json\/wp\/v2\/us_portfolio"}],"about":[{"href":"https:\/\/www.proefschriftmaken.nl\/en\/wp-json\/wp\/v2\/types\/us_portfolio"}],"author":[{"embeddable":true,"href":"https:\/\/www.proefschriftmaken.nl\/en\/wp-json\/wp\/v2\/users\/8"}],"replies":[{"embeddable":true,"href":"https:\/\/www.proefschriftmaken.nl\/en\/wp-json\/wp\/v2\/comments?post=10927"}],"version-history":[{"count":1,"href":"https:\/\/www.proefschriftmaken.nl\/en\/wp-json\/wp\/v2\/us_portfolio\/10927\/revisions"}],"predecessor-version":[{"id":10928,"href":"https:\/\/www.proefschriftmaken.nl\/en\/wp-json\/wp\/v2\/us_portfolio\/10927\/revisions\/10928"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/www.proefschriftmaken.nl\/en\/wp-json\/wp\/v2\/media\/12360"}],"wp:attachment":[{"href":"https:\/\/www.proefschriftmaken.nl\/en\/wp-json\/wp\/v2\/media?parent=10927"}],"wp:term":[{"taxonomy":"us_portfolio_category","embeddable":true,"href":"https:\/\/www.proefschriftmaken.nl\/en\/wp-json\/wp\/v2\/us_portfolio_category?post=10927"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}