Turkiye Klinikleri Journal of Pediatrics

.: REVIEW
Prematüre Apnesinde Kafein Tedavisi: Geleneksel Derleme
Caffeine Therapy in Apnea of Prematurity: Traditional Review
Özmert Muhammet Ali ÖZDEMİRa
aPamukkale Üniversitesi Tıp Fakültesi, Neonatoloji BD, Denizli, Türkiye
Turkiye Klinikleri J Pediatr. 2023;32(1):56-65
doi: 10.5336/pediatr.2022-92416
Article Language: TR
Full Text
ÖZET
Prematüre apnesi, yenidoğan yoğun bakım ünitelerinde prematüre bebeklerde sıklıkla karşılaşılan bir durum olup, solunumun 15-20 sn'den daha fazla durması ya da daha kısa süreli solunum kesintisine oksijen satürasyon düşüklüğü ve/veya bradikardinin eşlik etmesi olarak tanımlanır. Gebelik haftası 28'in altında doğan bebeklerin hemen tümünde apne görülürken, gebelik haftası büyüdükçe apne sıklığı azalmaktadır. Prematüre doğumun getirdiği nörolojik immatürite ile birlikte apne nedeniyle araya giren hipoksemi ve bradikardi atakları, bu bebeklerde nörolojik hasarlanma riskini artırmakta ve uzun dönemde; serebral palsi, gelişimsel koordinasyon bozukluğu, bilişsel ve davranışsal bozukluklar, bronkopulmoner displazi ve prematüre retinopatisi gibi önemli morbiditelere neden olabilmektedir. Bu nedenle prematüre bebeklerde apne tanısı ve tedavisi önem arz etmekte, apnenin farmakolojik tedavisinde de ilk tercih olarak bir metilksantin türevi olan kafein yer almaktadır. Kafein, yapısal olarak adenozine benzemekte ve etkisi doza bağımlı olarak başlıca adenozin reseptörleri üzerinden olmaktadır. Kafein, prematüre apnesinde adenozin ile baskılanmış medüller solunum merkezi inhibisyonunu ortadan kaldırmakta, gama aminobütirik asit salınımını önleyerek sinirsel uyarılmayı artırmakta, santral sinir sisteminin kan karbondioksit düzeylerine hassasiyeti artırmakta, böylece apneli bebeklerde solunumu uyarmakta ve devamlılığını sağlamaktadır. Bu derlemede, prematüre bebeklerde apne tedavisinde ilk tercih olan kafeinin etkisi, kimlere, ne zaman, hangi dozda ve ne kadar süre kullanmamız gerektiğiyle ilgili bilgiler, son literatür bilgileri ışığında verilmeye çalışılmıştır.

Anahtar Kelimeler: Kafein; prematüre bebek; apne
ABSTRACT
Apnea of prematurity is a frequently encountered condition in premature infants in the neonatal-intensive-care-units and is defined as respiratory arrest for more than 15-20 seconds or short-term respiratory interruption accompanied by low oxygen-saturation and/or bradycardia. While apnea is observed in almost all babies born below 28 weeks of gestation, the frequency of apnea decreases as the gestational week gets older. Hypoxemia and bradycardia attacks intervening due to apnea together with the neurological immaturity caused by premature-birth increase the risk of neurological damage in these babies and in the long term; it can cause significant morbidities such as cerebral palsy, developmental coordination disorder, cognitive and behavioral disorders, bronchopulmonary dysplasia, and retinopathy of prematurity. For this reason, the diagnosis and treatment of apnea in premature infants is important, and caffeine, a methylxanthine derivative, is the first choice in the pharmacological treatment of apnea. Caffeine is structurally similar to adenosine and its effect is dose-dependent mainly on adenosine receptors. Caffeine eliminates the inhibition of the medullary-respiratory-center suppressed by adenosine in apnea of prematurity, increases neural excitation by preventing gammaaminobutyric acid release, increases the sensitivity of the central nervous system to blood carbon-dioxide levels, thus it stimulates and maintains respiration in infants with apnea. In this review, the effect of caffeine, which is the first choice in the treatment of apnea in premature infants, information about who, when, in which dose, and for how long we should use it, has been tried to be given in the light of the recent literature data.

Keywords: Caffeine; premature infant; apnea
REFERENCES:
  1. Patrinos ME. Neonatal apnea and the foundation of respiratory control. In: Martin RJ, Fanaroff AA, Walsh MC, eds. Fanaroff & Martin's Neonatal-Perinatal-Medicine: Diseases of the Fetus and Infant. 11th ed. Philadelphia: Elsevier; 2020. p.1231-43.
  2. Vergales BD. Apnea. In: Gomella TL, Eyal FG, Bany-Mohammed F, eds. Gomella's Neonatology: Management, Procedures, on-call Problems, Diseases, and Drugs. 8th ed. New York: Mc Graw Hill; 2020. p.823-7.
  3. Vegales BD. Apnea and bradycardia (A's and B's): On call. In: Gomella TL, Eyal FG, Bany-Mohammed F, eds. Gomella's Neonatology: Management, Procedures, on-call Problems, Diseases, and Drugs. 8th ed. New York: Mc Graw Hill; 2020. p.442-59.
  4. Özdemir ÖMA. Prematüre apnesi. Klinik Tıp Pediatri Dergisi. 2021:13(3):171-6. [Link] 
  5. Eichenwald EC; Committee on Fetus and Newborn, American Academy of Pediatrics. Apnea of Prematurity. Pediatrics. 2016;137(1). [Crossref]  [PubMed] 
  6. Moschino L, Zivanovic S, Hartley C, Trevisanuto D, Baraldi E, Roehr CC. Caffeine in preterm infants: where are we in 2020? ERJ Open Res. 2020;6(1):00330-2019. [Crossref]  [PubMed]  [PMC] 
  7. Williamson M, Poorun R, Hartley C. Apnoea of prematurity and neurodevelopmental outcomes: current understanding and future prospects for research. Front Pediatr. 2021;9:755677. [Crossref]  [PubMed]  [PMC] 
  8. Kumar VHS, Lipshultz SE. Caffeine and clinical outcomes in premature neonates. Children (Basel). 2019;6(11):118. [Crossref]  [PubMed]  [PMC] 
  9. Aranda JV, Beharry KD. Pharmacokinetics, pharmacodynamics and metabolism of caffeine in newborns. Semin Fetal Neonatal Med. 2020;25(6):101183. [Crossref]  [PubMed] 
  10. Long JY, Guo HL, He X, Hu YH, Xia Y, Cheng R, et al. Caffeine for the pharmacological treatment of apnea of prematurity in the NICU: dose selection conundrum, therapeutic drug monitoring and genetic factors. Front Pharmacol. 2021;12:681842. [Crossref]  [PubMed]  [PMC] 
  11. Yang L, Yu X, Zhang Y, Liu N, Xue X, Fu J. Encephalopathy in preterm infants: advances in neuroprotection with caffeine. Front Pediatr. 2021;9:724161. [Crossref]  [PubMed]  [PMC] 
  12. Jensen EA. What is bronchopulmonary dysplasia and does caffeine prevent it? Semin Fetal Neonatal Med. 2020;25(6):101176. [Crossref]  [PubMed] 
  13. Aranda JV, Gorman W, Bergsteinsson H, Gunn T. Efficacy of caffeine in treatment of apnea in the low-birth-weight infant. J Pediatr. 1977;90(3):467-72. [Crossref]  [PubMed] 
  14. Schmidt B, Roberts RS, Davis P, Doyle LW, Barrington KJ, Ohlsson A, et al; Caffeine for Apnea of Prematurity Trial Group. Caffeine therapy for apnea of prematurity. N Engl J Med. 2006;354(20):2112-21. [Crossref]  [PubMed] 
  15. Eichenwald EC. National and international guidelines for neonatal caffeine use: are they evidenced-based? Semin Fetal Neonatal Med. 2020;25(6):101177. [Crossref]  [PubMed] 
  16. Schmidt B, Roberts RS, Davis P, Doyle LW, Barrington KJ, Ohlsson A, et al; Caffeine for Apnea of Prematurity Trial Group. Long-term effects of caffeine therapy for apnea of prematurity. N Engl J Med. 2007;357(19):1893-902. [Crossref]  [PubMed] 
  17. Schmidt B, Anderson PJ, Doyle LW, Dewey D, Grunau RE, Asztalos EV, et al; Caffeine for Apnea of Prematurity (CAP) Trial Investigators. Survival without disability to age 5 years after neonatal caffeine therapy for apnea of prematurity. JAMA. 2012;307(3):275-82. [Crossref]  [PubMed] 
  18. Mürner-Lavanchy IM, Doyle LW, Schmidt B, Roberts RS, Asztalos EV, Costantini L, et al; Caffeine for Apnea of Prematurity (CAP) Trial Group. Neurobehavioral outcomes 11 years after neonatal caffeine therapy for apnea of prematurity. Pediatrics. 2018;141(5):e20174047. [Crossref]  [PubMed] 
  19. Henderson-Smart DJ, Steer PA. Caffeine versus theophylline for apnea in preterm infants. Cochrane Database Syst Rev. 2010;(1):CD000273. [Crossref]  [PubMed] 
  20. Alhersh E, Abushanab D, Al-Shaibi S, Al-Badriyeh D. Caffeine for the treatment of apnea in the neonatal intensive care unit: a systematic overview of meta-analyses. Paediatr Drugs. 2020;22(4):399-408. [Crossref]  [PubMed]  [PMC] 
  21. Özkan H, Erdeve Ö, Kutman GK. Türk Neonatoloji Derneği Respiratuvar Distres Sendromu ve Sürfaktan Tedavi Rehberi 2018 Güncellemesi. [Link] 
  22. Acunaş B, Baş AY, Uslu S. Türk Neonatoloji Derneği Yüksek Riskli Bebek İzlem Rehberi 2018 Güncellemesi. [Link] 
  23. Sweet DG, Carnielli V, Greisen G, Hallman M, Ozek E, Te Pas A, et al. European Consensus Guidelines on the Management of Respiratory Distress Syndrome-2019 Update. Neonatology. 2019;115(4):432-50. [Crossref]  [PubMed]  [PMC] 
  24. NICE Guideline. Specialist neonatal respiratory care for babies born preterm. Published: 3 April 2019. Available from: [Link] 
  25. Ji D, Smith PB, Clark RH, Zimmerman KO, Laughon M, Ku L, et al. Wide variation in caffeine discontinuation timing in premature infants. J Perinatol. 2020;40(2):288-93. [Crossref]  [PubMed]  [PMC] 
  26. Davis PG. When to start and stop caffeine and why respiratory status matters. Semin Fetal Neonatal Med. 2020;25(6):101175. [Crossref]  [PubMed] 
  27. Prakash R, Pournami F, Prabhakar J, Nandakumar A, Nair PMC, Jain N. Duration of caffeine for apnea of prematurity-a randomized controlled trial. Indian J Pediatr. 2021;88(12):1174-9. [Crossref]  [PubMed] 
  28. Chung J, Tran Lopez K, Amendolia B, Bhat V, Nakhla T, Slater-Myer L, et al. Stopping caffeine in premature neonates: how long does it take for the level of caffeine to fall below the therapeutic range? J Matern Fetal Neonatal Med. 2022;35(3):551-5. [Crossref]  [PubMed] 
  29. Ma C, Broadbent D, Levin G, Panda S, Sambalingam D, Garcia N, et al. Discharging preterm infants home on caffeine, a single center experience. Children (Basel). 2020;7(9):114. [Crossref]  [PubMed]  [PMC] 
  30. Drugs.com [Internet]. © 2000-2022 Drugs.com. [Cited: September 29, 2020]. Caffeine citrate. Available from: [Link] 
  31. European Medicines Agency [Internet]. © 1995-2022 European Medicines Agency. [Cited: October 10, 2020]. Peyona (Previously Nymus). Available from: [Link] 
  32. Saroha V, Patel RM. Caffeine for preterm infants: fixed standard dose, adjustments for age or high dose? Semin Fetal Neonatal Med. 2020;25(6):101178. [Crossref]  [PubMed]  [PMC] 
  33. Pakvasa MA, Saroha V, Patel RM. Optimizing caffeine use and risk of bronchopulmonary dysplasia in preterm infants: a systematic review, meta-analysis, and application of grading of recommendations assessment, development, and evaluation methodology. Clin Perinatol. 2018;45(2):273-91. [Crossref]  [PubMed] 
  34. Vliegenthart R, Miedema M, Hutten GJ, van Kaam AH, Onland W. High versus standard dose caffeine for apnoea: a systematic review. Arch Dis Child Fetal Neonatal Ed. 2018;103(6):F523-9. [Crossref]  [PubMed] 
  35. Brattström P, Russo C, Ley D, Bruschettini M. High-versus low-dose caffeine in preterm infants: a systematic review and meta-analysis. Acta Paediatr. 2019;108(3):401-10. [Crossref]  [PubMed] 
  36. Chen J, Jin L, Chen X. Efficacy and safety of different maintenance doses of caffeine citrate for treatment of apnea in premature infants: a systematic review and meta-analysis. Biomed Res Int. 2018;2018:9061234. [Crossref]  [PubMed]  [PMC] 
  37. Park HW, Lim G, Chung SH, Chung S, Kim KS, Kim SN. Early caffeine use in very low birth weight infants and neonatal outcomes: a systematic review and meta-analysis. J Korean Med Sci. 2015;30(12):1828-35. [Crossref]  [PubMed]  [PMC] 
  38. Kua KP, Lee SW. Systematic review and meta-analysis of clinical outcomes of early caffeine therapy in preterm neonates. Br J Clin Pharmacol. 2017;83(1):180-91. [Crossref]  [PubMed]  [PMC] 
  39. Nylander Vujovic S, Nava C, Johansson M, Bruschettini M. Confounding biases in studies on early- versus late-caffeine in preterm infants: a systematic review. Pediatr Res. 2020;88(3):357-64. [Crossref]  [PubMed] 
  40. Henderson-Smart DJ, De Paoli AG. Prophylactic methylxanthine for prevention of apnoea in preterm infants. Cochrane Database Syst Rev. 2010;2010(12):CD000432. [Crossref]  [PubMed]  [PMC] 
  41. Henderson-Smart DJ, Davis PG. Prophylactic methylxanthines for endotracheal extubation in preterm infants. Cochrane Database Syst Rev. 2010;(12):CD000139. [Crossref]  [PubMed] 
  42. Lodha A, Seshia M, McMillan DD, Barrington K, Yang J, Lee SK, et al; Canadian Neonatal Network. Association of early caffeine administration and neonatal outcomes in very preterm neonates. JAMA Pediatr. 2015;169(1):33-8. [Crossref]  [PubMed] 
  43. Jain VG, Saroha V, Patel RM, Jobe A. Is early caffeine therapy safe and effective for ventilated preterm infants? J Perinatol. 2019;39(5):754-7. [Crossref]  [PubMed] 
  44. Elmowafi M, Mohsen N, Nour I, Nasef N. Prophylactic versus therapeutic caffeine for apnea of prematurity: a randomized controlled trial. J Matern Fetal Neonatal Med. 2021:1-9. [PubMed] 

.: Up To Date

Login



Contact


Ortadoğu Reklam Tanıtım Yayıncılık Turizm Eğitim İnşaat Sanayi ve Ticaret A.Ş.

.: Address

Turkocagi Caddesi No:30 06520 Balgat / ANKARA
Phone: +90 312 286 56 56
Fax: +90 312 220 04 70
E-mail: info@turkiyeklinikleri.com

.: Manuscript Editing Department

Phone: +90 312 286 56 56/ 2
E-mail: yaziisleri@turkiyeklinikleri.com

.: English Language Redaction

Phone: +90 312 286 56 56/ 145
E-mail: tkyayindestek@turkiyeklinikleri.com

.: Marketing Sales-Project Department

Phone: +90 312 286 56 56/ 142
E-mail: reklam@turkiyeklinikleri.com

.: Subscription and Public Relations Department

Phone: +90 312 286 56 56/ 118
E-mail: abone@turkiyeklinikleri.com

.: Customer Services

Phone: +90 312 286 56 56/ 118
E-mail: satisdestek@turkiyeklinikleri.com

1. TERMS OF USE

1.1. To use the web pages with http://www.turkiyeklinikleri.com domain name or the websites reached through the sub domain names attached to the domain name (They will be collectively referred as "SITE"), please read the conditions below. If you do not accept these terms, please cease to use the "SITE." "SITE" owner reserves the right to change the information on the website, forms, contents, the "SITE," "SITE" terms of use anytime they want.

1.2. The owner of the "SITE" is Ortadoğu Advertisement Presentation Publishing Tourism Education Architecture Industry and Trade Inc. (From now on it is going to be referred as "Turkiye Klinikleri", shortly) and it resides at Turkocagi cad. No:30, 06520 Balgat Ankara. The services in the "SITE" are provided by "Turkiye Klinikleri."

1.3. Anyone accessing the "SITE" with or without a fee whether they are a natural person or a legal identity is considered to agree these terms of use. In this contract hereby, "Turkiye Klinikleri" may change the stated terms anytime. These changes will be published in the "SITE" periodically and they will be valid when they are published. Any natural person or legal identity benefiting from and reaching to the "SITE" are considered to be agreed to any change on hereby contract terms done by "Turkiye Klinikleri."

1.4. The "Terms of Use" hereby is published in the website with the last change on March 30th 2014 and the "SITE" is activated by enabling the access to everyone. The "Terms of Use" hereby is also a part of the any "USER Contract" was and/or will be done with the users using "Turkiye Klinikleri" services with or without a fee an inseparable.

2. DEFINITIONS

2.1. "SITE": A website offering different kind of services and context with a certain frame determined by "Turkiye Klinikleri" and it is accessible on-line on http://www.turkiyeklinikleri.com domain name and/or subdomains connected to the domain name.

2.2. USER: A natural person or a legal identity accessing to the "SITE" through online settings.

2.3. LINK: A link enabling to access to another website through the "SITE", the files, the context or through another website to the "SITE", the files and the context.

2.4. CONTEXT: Any visual, literary and auditory images published in the "Turkiye Klinikleri", "SITE" and/or any website or any accessible information, file, picture, number/figures, price, etc.

2.5. "USER CONTRACT": An electronically signed contract between a natural or a legal identity benefiting from special services "Turkiye Klinikleri" will provide and "Turkiye Klinikleri".

3. SCOPE OF THE SERVICES

3.1. "Turkiye Klinikleri" is completely free to determine the scope and quality of the services via the "SITE".

3.2. To benefit the services of "Turkiye Klinikleri" "SITE", the "USER" must deliver the features that will be specified by "Turkiye Klinikleri". "Turkiye Klinikleri" may change this necessity any time single-sided.

3.3. Not for a limited number, the services "Turkiye Klinikleri" will provide through the "SITE" for a certain price or for free are;

- Providing scientific articles, books and informative publications for health industry.

- Providing structural, statistical and editorial support to article preparation stage for scientific journals.

4. GENERAL PROVISIONS

4.1. "Turkiye Klinikleri" is completely free to determine which of the services and contents provided in the "SITE" will be charged.

4.2. People benefiting from the services provided by "Turkiye Klinikleri" and using the website can use the "SITE" only according to the law and only for personal reasons. Users have the criminal and civil liability for every process and action they take in the "SITE". Every USER agrees, declares and undertakes that they will not proceed by any function or action infringement of rights of "Turkiye Klinikleri"s and/or other third parties', they are the exclusive right holder on usage, processing, storage, made public and revealing any written, visual or auditory information reported to Turkiye Klinikleri" and/or "SITE" to the third parties. "USER" agrees and undertakes that s/he will not duplicate, copy, distribute, process, the pictures, text, visual and auditory images, video clips, files, databases, catalogs and lists within the "SITE", s/he will not be using these actions or with other ways to compete with "Turkiye Klinikleri", directly or indirectly.

4.3. The services provided and the context published within the "SITE" by third parties is not under the responsibility of "Turkiye Klinikleri", institutions collaborated with "Turkiye Klinikleri", "Turkiye Klinikleri" employee and directors, "Turkiye Klinikleri" authorized salespeople. Commitment to accuracy and legality of the published information, context, visual and auditory images provided by any third party are under the full responsibility of the third party. "Turkiye Klinikleri" does not promise and guarantee the safety, accuracy and legality of the services and context provided by a third party.

4.4. "USER"s cannot act against "Turkiye Klinikleri", other "USER"s and third parties by using the "SITE". "Turkiye Klinikleri" has no direct and/or indirect responsibility for any damage a third party suffered or will suffer regarding "USER"s actions on the "SITE" against the rules of the hereby "Terms of Use" and the law.

4.5. "USER"s accept and undertake that the information and context they provided to the "SITE" are accurate and legal. "Turkiye Klinikleri" is not liable and responsible for promising and guaranteeing the verification of the information and context transmitted to "Turkiye Klinikleri" by the "USER"s, or uploaded, changed and provided through the "SITE" by them and whether these information are safe, accurate and legal.

4.6. "USER"s agree and undertake that they will not perform any action leading to unfair competition, weakening the personal and commercial credit of "Turkiye Klinikleri" and a third party,  encroaching and attacking on personal rights within the "SITE" in accordance with the Turkish Commercial Code Law.

4.7. "Turkiye Klinikleri" reserves the right to change the services and the context within the "SITE"  anytime. "Turkiye Klinikleri" may use this right without any notification and timelessly. "USER"s have to make the changes and/or corrections "Turkiye Klinikleri" required immediately. Any changes and/or corrections that are required by "Turkiye Klinikleri", may be made by "Turkiye Klinikleri" when needed. Any harm, criminal and civil liability resulted or will result from changes and/or corrections required by "Turkiye Klinikleri" and were not made on time by the "USER"s belongs completely to the users.

4.8. "Turkiye Klinikleri" may give links through the "SITE" to other websites and/or "CONTEXT"s and/or folders that are outside of their control and owned and run by third parties. These links are provided for ease of reference only and do not hold qualification for support the respective web SITE or the admin or declaration or guarantee for the information inside. "Turkiye Klinikleri" does not hold any responsibility over the web-sites connected through the links on the "SITE", folders and context, the services or products on the websites provided through these links or their context.

4.9. "Turkiye Klinikleri" may use the information provided to them by the "USERS" through the "SITE" in line with the terms of the "PRIVACY POLICY" and "USER CONTRACT". It may process the information or classify and save them on a database. "Turkiye Klinikleri" may also use the USER's or visitor's identity, address, e-mail address, phone number, IP number, which sections of the "SITE" they visited, domain type, browser type, date and time information to provide statistical evaluation and customized services.

5. PROPRIETARY RIGHTS

5.1. The information accessed through this "SITE" or provided by the users legally and all the elements (including but not limited to design, text, image, html code and other codes) of the "SITE" (all of them will be called as studies tied to "Turkiye Klinikleri"s copyrights) belongs to "Turkiye Klinikleri". Users do not have the right to resell, process, share, distribute, display or give someone permission to access or to use the "Turkiye Klinikleri" services, "Turkiye Klinikleri" information and the products under copyright protection by "Turkiye Klinikleri". Within hereby "Terms of Use" unless explicitly permitted by "Turkiye Klinikleri" nobody can reproduce, process, distribute or produce or prepare any study from those under "Turkiye Klinikleri" copyright protection.

5.2. Within hereby "Terms of Use", "Turkiye Klinikleri" reserves the rights for "Turkiye Klinikleri" services, "Turkiye Klinikleri" information, the products associated with "Turkiye Klinikleri" copyrights, "Turkiye Klinikleri" trademarks, "Turkiye Klinikleri" trade looks or its all rights for other entity and information it has through this website unless it is explicitly authorized by "Turkiye Klinikleri".

6. CHANGES IN THE TERMS OF USE

"Turkiye Klinikleri" in its sole discretion may change the hereby "Terms of Use" anytime announcing within the "SITE". The changed terms of the hereby "Terms of Use" will become valid when they are announced. Hereby "Terms of Use" cannot be changed by unilateral declarations of users.

7. FORCE MAJEURE

"Turkiye Klinikleri" is not responsible for executing late or never of this hereby "Terms of Use", privacy policy and "USER Contract" in any situation legally taken into account as force majeure. Being late or failure of performance or non-defaulting of this and similar cases like this will not be the case from the viewpoint of "Turkiye Klinikleri", and "Turkiye Klinikleri" will not have any damage liability for these situations. "Force majeure" term will be regarded as outside of the concerned party's reasonable control and any situation that "Turkiye Klinikleri" cannot prevent even though it shows due diligence. Also, force majeure situations include but not limited to natural disasters, rebellion, war, strike, communication problems, infrastructure and internet failure, power cut and bad weather conditions.

8. LAW AND AUTHORISATION TO FOLLOW

Turkish Law will be applied in practicing, interpreting the hereby "Terms of Use" and managing the emerging legal relationships within this "Terms of Use" in case of finding element of foreignness, except for the rules of Turkish conflict of laws. Ankara Courts and Enforcement Offices are entitled in any controversy happened or may happen due to hereby contract.

9. CLOSING AND AGREEMENT

Hereby "Terms of Use" come into force when announced in the "SITE" by "Turkiye Klinikleri". The users are regarded to agree to hereby contract terms by using the "SITE". "Turkiye Klinikleri" may change the contract terms and the changes will be come into force by specifying the version number and the date of change on time it is published in the "SITE".

 

30.03.2014

Privacy Policy

We recommend you to read the terms of use below before you visit our website. In case you agree these terms, following our rules will be to your favor. Please read our Terms of Use thoroughly.

www.turkiyeklinikleri.com website belongs to Ortadoğu Advertisement Presentation Publishing Tourism Education Architecture Industry and Trade Inc. and is designed in order to inform physicians in the field of health

www.turkiyeklinikleri.com cannot reach to user’s identity, address, service providers or other information. The users may send this information to the website through forms if they would like to. However, www.turkiyeklinikleri.com may collect your hardware and software information. The information consists of your IP address, browser type, operating system, domain name, access time, and related websites. www.turkiyeklinikleri.com cannot sell the provided user information (your name, e-mail address, home and work address, phone number) to the third parties, publish it publicly, or keep it in the website. Gathered information has a directing feature to be a source for the website’s visitor profile, reporting and promotion of the services.

www.turkiyeklinikleri.com uses the taken information:

-To enhance, improve and maintain the quality of the website

-To generate visitor’s profile and statistical data

-To determine the tendency of the visitors on using our website

-To send print publications/correspondences

-To send press releases or notifications through e-mail

-To generate a list for an event or competition

By using www.turkiyeklinikleri.com you are considered to agree that;

-Ortadoğu Advertisement Presentation Publishing Tourism Education Architecture Industry and Trade Inc. cannot be hold responsible for any user’s illegal and immoral behavior,

-Terms of use may change from time to time,

-It is not responsible for other websites’ contents it cannot control or the harms they may cause although it uses the connection they provided.

Ortadoğu Advertisement Presentation Publishing Tourism Education Architecture Industry and Trade Inc. may block the website to users in the following events:

-Information with wrong, incomplete, deceiving or immoral expressions is recorded to the website,

-Proclamation, advertisement, announcement, libelous expressions are used against natural person or legal identity,

-During various attacks to the website,

-Disruption of the website because of a virus.

Written, visual and audible materials of the website, including the code and the software are under protection by legal legislation.

Without the written consent of Ortadoğu Advertisement Presentation Publishing Tourism Education Architecture Industry and Trade Inc. the information on the website cannot be downloaded, changed, reproduced, copied, republished, posted or distributed.

All rights of the software and the design of the website belong to Ortadoğu Advertisement Presentation Publishing Tourism Education Architecture Industry and Trade Inc.

Ortadoğu Advertisement Presentation Publishing Tourism Education Architecture Industry and Trade Inc. will be pleased to hear your comments about our terms of use. Please share the subjects you think may enrich our website or if there is any problem regarding our website.

info@turkiyeklinikleri.com