ÇOK DÜŞÜK DOĞUM AĞIRLIKLI YENİDOĞANLARDA KONJENİTAL HİPOTİROİDİ VE PREMATÜRE RETİNOPATİSİ İLİŞKİSİNİN ARAŞTIRILMASI

Abstract

Amaç: Prematüre retinopatisi (PR), çocukluk çağında körlüğe neden olabilen başlıca prematürelerin retinasında meydana gelen vazoproliferatif bir hastalıktır. Çalışmamızda çok düşük doğum ağırlıklı (ÇDDA) prematürelerde konjenital hipotiroidinin (KH) PR’si üzerine etkisi ve PR için risk faktörlerine bakılması amaçlanmıştır.

Gereç ve Yöntem: Çalışma 51 aylık dönem boyunca yatan ÇDDA bebeklerde geriye dönük tıbbi kayıtların değerlendirilmesi neticesinde gerçekleştirildi. Hastalar KH tanısı ve lazer fotokoagülasyon tedavisi gerektiren PR olmasına göre gruplara ayrıldı.

Bulgular: Çalışmaya 621 hasta dahil edildi. Bunlar arasında, 5. gün tiroid fonksiyon testi (TFT) sonucu olan, postnatal 1. ayda hem sağ kalan hem TFT sonucu olan hem de PR muayenesi yapılabilen 534 hasta ile çalışma sonlandırıldı. Konjenital hipotiroidi olan grupta (n=23) PR oranı %26,1 (n=6), KH olmayan grupta (n=511) PR oranı %10,9 (n=56) olarak tespit edildi.

Konjenital hipotiroidi olan ve olmayan gruplar arasında PR açısından anlamlı fark tespit edilmedi (p=0.077). Prematüre retinopatisi için risk faktörleri başlıca, düşük gebelik haftası, doğum ağırlığı, düşük 1. ve 5. dakika Apgar skoru, uzun mekanik ventilasyon ve oksijen destek süresi, respiratuvar distres sendromu, intraventriküler kanama, bronkopulmoner displazi, hemodinamik anlamlı patent duktus arteriosus ve geç neonatal sepsis olarak bulunmuştur. PR’i olan grupta serbest tiroksin (sT4) düzeyi daha düşük, tiroid stimülan hormon (TSH) düzeyi daha yüksek bulunmuştur (sırasıyla, p=0.002; 0.047).

Sonuç: KH’nin PR üzerine etkisi bulunmamıştır. Ancak, PR’si üzerine prematüreliğin getirdiği diğer riskler daha etkili bulunmuştur. PR’si olan infantlarda sT4 daha düşük, TSH daha yüksek bulunmuştur. Tiroid hormonlarının anjiyogenezis üzerine etkisi olduğundan, PR ve tiroid hormonları ilişkisi açısından daha başka çalışmalara ihtiyaç vardır.

Keywords

• konjenital hipotiroidi,prematüre,prematüre retinopatisi,Çok düşük doğum ağırlığı,tiroid disfonksiyonu

Evaluation of the Relationship Between Congenital Hypothyroidism and Retinopathy of Prematurity in Very Low Birth Weight Newborns

Abstract

Objective: Retinopathy of prematurity (ROP) is a vasoproliferative disease that mainly occurs in retinas of premature infants, and causes blindness in childhood. The aim of this study was to evaluate the risk factors for PR and the effect of congenital hypothyroidism (CH) on PR in very low birth weight infants (VLBW) (birth weight <1500 g).

Material and Method: The retrospective study was conducted by the evaluation of medical records of hospitalized VLBW infants during the 51 months of follow-up. Patients were divided into groups according to diagnosed CH, and according to ROP requiring laser photocoagulation therapy.

Results: There were 570 patients of 621 patients of whom we were able to obtain TFT results on the 5th day of the study. A total of 534 patients who survived the postnatal 1st month, and on whom we were able to perform both TFT and ROP examinations were included in the study. The PR rate was 26.1%(n=6) in the group with congenital hypothyroidism (n=23) and the ROP rate was 10.9%(n=56) in the non-CH group (n=511). However, there was no statistically significant difference between the groups in terms of ROP (p=0.077). The risk factors for premature retinopathy were mainly including low gestational age/birth weight, low 1st and 5th minute Apgar score, longer duration of mechanical ventilation and oxygen support, respiratory distress syndrome, intraventricular hemorrhage, bronchopulmonary dysplasia, hemodynamically significant patent ductus arteriosus and late neonatalsepsis. In infants with ROP, the levels of free thyroxine (sT4) were lower and the levels of thyroid stimulating hormone (TSH) were higher (p=0.002, 0.047, respectively).

Conclusion: CH had no effect on ROP. However, other risks of prematurity on ROP were found to be more effective. In infants with ROP, sT4 was lower and TSH was higher. Since thyroid hormones have an effect on angiogenesis, further studies on the relation between ROP and thyroid hormones are warranted.

Keywords

• Very low birth weight,congenital hypothyroidism,premature,retinopathy of prematurity,thyroid dysfunction

References

1. 1. Mookadam M, Leske DA, Fautsch MP, Lanier WL, Holmes JM. Anti-thyroid methimazole in an acidosis-induced retinopathy rat model of retinopathy of prematurity. Mol Vis. 2005;11:909-15.
2. 2. Shah PK, Prabhu V, Karandikar SS, Ranjan R, Narendran V, Kalpana N. Retinopathy of prematurity: Past, present and future. World J Clin Pediatr. 2016;5(1):35-46.
3. 3. Rivera JC, Holm M, Austeng D, Morken TS, Zhou TE, Beaudry-Richard A et al. Retinopathy of prematurity: inflammation, choroidal degeneration, and novel promising therapeutic strategies. J Neuroinflammation. 2017;14(1):165.
4. 4. Asano MK, Dray PB. Retinopathy of prematurity. Dis Mon. 2014;60(6):282-91.
5. 5. Silva RA, Moshfeghi DM. Interventions in retinopathy of prematurity. Neoreviews. 2012;13:476-85.
6. 6. Chen J, Joyal JS, Hatton CJ, Juan AM, Pei DT, Hurst CG et al. Propranolol inhibition of β-adrenergic receptor does not suppress pathologic neovascularization in oxygen-induced retinopathy. Invest Ophthalmol Vis Sci. 2012;53(6):2968-77.
7. 7. Italiano JE Jr, Richardson JL, Patel-Hett S, Battinelli E, Zaslavsky A, Short S et al. Angiogenesis is regulated by a novel mechanism: pro-and antiangiogenic proteins are organized into separate platelet alpha granules and differentially released. Blood. 2008;111(3):1227-33.
8. 8. Sapieha P, Joyal JS, Rivera JC, Kermorvant-Duchemin E, Sennlaub F, Hardy P et al. Retinopathy of prematurity: understanding ischemic retinal vasculopathies at an extreme of life. J Clin Invest. 2010;120(9):3022-32.

9. 9. Carmona-Cortés J, Rodríguez-Gómez I, Wangensteen R, Banegas I, García-Lora ÁM, Quesada A et al. Effect of thyroid hormone-nitric oxide interaction on tumor growth, angiogenesis, and aminopeptidase activity in mice. Tumour Biol. 2014;35(6):5519-26.
10. 10. Liu X, Zheng N, Shi YN, Yuan J, Li L. Thyroid hormone induced angiogenesis through the integrin αvβ3/protein kinase D/histone deacetylase 5 signaling pathway. J Mol Endocrinol. 2014;52(3):245-54.
11. 11. Mousa SA, Lin HY, Tang HY, Hercbergs A, Luidens MK, Davis PJ. Modulation of angiogenesis by thyroid hormone and hormone analogues: implications for cancer management. Angiogenesis. 2014;17(3):463-9.
12. 12. Li J, Teng L, Jiang H. Relationship between preoperative serum TSH levels and expression of VEGF in papillary thyroid carcinoma. Asia Pac J Clin Oncol. 2014;10(2):149-52.
13. 13. Silva JF, Ocarino NM, Vieira AL, Nascimento EF, Serakides R. Effects of hypo- and hyperthyroidism on proliferation, angiogenesis, apoptosis and expression of COX-2 in the corpus luteum of female rats. Reprod Domest Anim. 2013;48(4):691-8.
14. 14. Mutapcic L, Wren SM, Leske DA, Fautsch MP, Holmes JM. The effect of L-thyroxine supplementation on retinal vascular development in neonatal rats. Curr Eye Res. 2005;30(12):1035-40.
15. 15. Osborn DA, Hunt RW. Prophylactic postnatal thyroid hormones for prevention of morbidity and mortality in preterm infants. Cochrane Database Syst Rev. 2007;(1):CD005948.
16. 16. Chiesa A, Prieto L, Mendez V, Papendieck P, Calcagno Mde L, Gruñeiro-Papendieck L. Prevalence and etiology of congenital hypothyroidism detected through an argentine neonatal screening program (1997-2010). Horm Res Paediatr. 2013;80(3):185-92.
17. 17. Olivieri A, Fazzini C, Medda E; Collaborators. Multiple factors influencing the incidence of congenital hypothyroidism detected by neonatal screening. Horm Res Paediatr. 2015;83:86-93.
18. 18. Section on Ophthalmology American Academy of Pediatrics; American Academy of Ophthalmology, American Association for Pediatric Ophthalmology and Strabismus. Screening examination of premature infants for retinopathy of prematurity. Pediatrics. 2006;117(2):572-6.
19. 19. International Committee for the Classification of Retinopathy of Prematurity. The international classification of retinopathy of prematurity revisited. Arch Ophthalmol. 2005;123(7):991-9.
20. 20. Paysse EA. Retinopathy of prematurity. Accessed date: 30 November 2018: https://www.uptodate.com/contents/retinopathy-of-prematurity-treatment-and-prognosis?search=etrop&source=search_result&selectedTitle=1~1&usage_type=default&display_rank=1
21. 21. Fenton TR. A new growth chart for preterm babies: Babson and Benda's chart updated with recent data and new format. BMC Pediatr. 2003;16:3-13.
22. 22. Dargaville PA, Gerber A, Johansson S, De Paoli AG, Kamlin CO, Orsini F et al. Australian and New Zealand Neonatal Network. Incidence and outcome of CPAP failure in preterm infants. Pediatrics. 2016;138(1). Doi: 10.1542/peds.2015-3985.
23. 23. Northway Jr WH, Rosan RC, Porter DY. Pulmonary disease following respirator therapy of hyaline-membrane disease. Bronchopulmonary dysplasia. N Engl J Med. 1967;276:357e68.
24. 24. Papile LA, Burstein J, Burstein R, Koffler H. Incidence and evolution of subependymal and intraventricular hemorrhage: a study of infants with birth weights less than 1500 gm. J Pediatr. 1978;92:529e34.
25. 25. Bell MJ, Ternberg JL, Feigin RD, Keating JP, Marshall R, Barton L et al. Neonatal necrotizing enterocolitis. Therapeutic decision based upon clinical staging. An Surg. 1978;187:1-7.
26. 26. Terrin G, Conte F, Scipione A, Bacchio E, Conti MG, Ferro R et al. Efficacy of paracetamol for the treatment of patent ductus arteriosus in preterm neonates. Ital J Pediatr. 2014;40(1):21.
27. 27. Lee JH, Kim SW, Jeon GW, Sin JB. Thyroid dysfunction in very low birth weight preterm infants. Korean J Pediatr. 2015;58(6):224-9.
28. 28. Korkmaz L, Bastug O, Daar G, Korkut S, Ozdemir A, Adnan Ozturk M et al. The effects of thyroid function on retinopathy of prematurity. J Neonatal Perinatal Med. 2016;9(4):349-56.
29. 29. Mookadam M, Leske DA, Fautsch MP, Lanier WL, Holmes JM. The anti-thyroid drug methimazole induces neovascularization in the neonatal rat analogous to ROP. Invest Ophthalmol Vis Sci. 2004;45(11):4145-50. 30. Dogra MR, Katoch D, Dogra M. An Update on Retinopathy of Prematurity (ROP). Indian J Pediatr. 2017;84(12):930-6.
30. 31. Bas AY, Demirel N, Koc E, Ulubas Isik D, Hirfanoglu İM, Tunc T; TR-ROP Study Group. Incidence, risk factors and severity of retinopathy of prematurity in Turkey (TR-ROP study): a prospective, multicentre study in 69 neonatal intensive care units. Br J Ophthalmol. 2018;102(12):1711-16. Doi: 10.1136/bjophthalmol-2017-311789.
31. 32. Darlow BA, Hutchinson JL, Henderson-Smart DJ, Donoghue DA, Simpson JM, Evans NJ; Australian and New Zealand Neonatal Network. Prenatal risk factors for severe retinopathy of prematurity among very preterm infants of the Australian and New Zealand Neonatal Network. Pediatrics. 2005;115(4):990-6.
32. 33. Freeman CI, Hezelgrave NL, Shennan AH. Antenatal steroids for fetal lung maturity: Time to target more frequent doses to fewer women? Obstet Med. 2015;8(4):172-6.
33. 34. Männistö T, Mendola P, Reddy U, Laughon SK. Neonatal outcomes and birth weight in pregnancies complicated by maternal thyroid disease. Am J Epidemiol. 2013;178(5):731-40.
34. 35. Leviton A, Dammann O, Engelke S, Allred E, Kuban KC, O'Shea TM. ELGAN study investigators. The clustering of disorders in infants born before the 28th week of gestation. Acta Paediatr. 2010;99(12):1795-800.