Neurodevelopmental outcomes of infants who underwent therapeutic hypothermia due to hypoxic ischemic encephalopathy

Abstract

Objective: Hypoxic ischemic encephalopathy (HIE), is one of the most important causes of neurodevelopmental problems in our country as well as in the world. We aimed to evaluate the neurodevelopmental outcomes of children who underwent therapeutic hypothermia.

Material and Methods: Medical records of 47 children who were followed up in the Developmental Pediatrics Outpatient Clinic for HIE between January 2017-August 2019 and underwent therapeutic hypothermia were retrospectively reviewed. Neurodevelopmental assessment was performed with the Bayley Scales of Infant and Toddler Development 2nd Edition (BSID-II).

Results: Moderate and severe HIE were in 39 (83%) and 8 (17%) patients. Patients with moderate HIE had higher median mental developmental index (MDI) and psychomotor developmental index (PDI) scores than patients with severe HIE (median MDI 95 vs 49, p=0.007; PDI 89 vs 49, p=0.013, respectively). Cognitive delay, motor delay, cerebral palsy and severe neurodevelopmental disability were found in 42.6%, 42.5%, 19.1% and 17% of patients, respectively. Bayley-II scores were normal in only 44.6% of patients. Severe cognitive delay (MDI≤69), severe motor delay (PDI≤69), cerebral palsy and severe neurodevelopmental disability were more common in patients with severe HIE (p=0.001, p=0.020, p=0.004 and p=0.002, respectively). Epilepsy, microcephaly, hearing impairment, blindness and swallowing problems were more frequent in patients with severe HIE but not statistically significant (p>0.05). Special education, physiotherapy and language therapy were found statistically higher in patients with severe HIE (p=0.001, p=0.028 and p=0.033, respectively). Patients with seizures in the neonatal period had lower median MDI scores than patients without seizures (79.6 vs 93.8, p=0.020).

Conclusion: Although therapeutic hypothermia reduces the mortality or major disability in children with HIE, about half of the survivors have neurodevelopmental problems. Neurodevelopmental monitoring, support, timely and appropriate intervention are important to improve long-term outcomes of these patients.

Keywords

• hypoxic ischemic encephalopathy
• therapeutic hypothermia
• neurodevelopmental outcomes

Hipoksik İskemik Ensefalopati Nedeniyle Terapötik Hipotermi Uygulanan Bebeklerin Nörogelişimsel Sonuçları

Abstract

Amaç: Hipoksik iskemik ensefalopati (HİE) dünyada olduğu gibi ülkemizde de gelişimsel sorunların önemli nedenlerinden biridir. Çalışmamızda terapötik hipotermi uygulanan bebeklerin nörogelişimsel sonuçlarının değerlendirilmesi amaçlandı.

Gereç ve Yöntemler: Ocak 2017-Ağustos 2019 tarihleri arasında Gelişimsel Pediatri Polikliniği’nde HİE nedeniyle izlenen ve yenidoğan döneminde terapötik hipotermi uygulanan 47 hastanın tıbbi kayıtları retrospektif olarak incelendi. Gelişimsel değerlendirmede Bayley Bebek ve Çocuklar için Gelişimsel Değerlendirme Ölçeği II (Bayley-II) kullanıldı.

Bulgular: Otuz dokuz (%83) hastada orta HİE; 8 (%17) hastada ağır HİE saptandı. Orta HİE’li hastaların, Bilişsel Gelişim İndeksi (MDI) ve Psikomotor Gelişim İndeksi (PDI) skorları ağır HİE’li hastalardan daha yüksekti (ortanca MDI sırasıyla 95 ve 49, p=0.007; PDI sırasıyla 89 ve 49, p=0.013). Bilişsel gelişimde gecikme, hareket gelişiminde gecikme, serebral palsi ve ciddi nörogelişimsel sorun sırasıyla hastaların %42.6, %42.5, %19.1 ve %17’sinde saptandı. Bayley-II skorları hastaların sadece %44.6’sında normaldi. Ağır HİE’li hastalarda bilişsel gelişimde belirgin gecikme (MDI≤69), hareket gelişiminde belirgin gecikme (PDI≤69), serebral palsi ve ciddi nörogelişimsel sorun daha sıktı (sırasıyla p=0.001, p=0.020, p=0.004 ve p=0.002). Epilepsi, mikrosefali, işitme kaybı, görme kaybı ve yutma sorunu ağır HİE’li hastalarda daha sık görülmesine rağmen istatistiksel anlamlı fark saptanmadı (p>0.05). Özel eğitim, fizyoterapi ve dil terapisi gereksinimi ağır HİE’li hastalarda daha sıktı (sırasıyla p=0.001, p=0.028 ve p=0.033). Yenidoğan döneminde nöbet geçiren hastaların ortanca MDI skorları, geçirmeyenlerden düşüktü (sırasıyla 79.6 ve 93.8, p=0.020).

Sonuç: Terapötik hipotermi, HİE’li bebeklerde ölüm ya da ağır engel gelişme riskini azaltsa da hayatta kalanların yaklaşık yarısında nörogelişimsel sorunlar görülmektedir. Bu bebeklerde gelişimin izlenmesi, desteklenmesi, zamanında ve uygun sağaltımı uzun vadeli sonuçların iyileştirilmesi bakımından önemlidir.

Keywords

• hipoksik iskemik ensefalopati
• gelişimsel sonuçlar
• terapötik hipotermi

References

1. Referans 1. Sarnat HB, Sarnat MS. Neonatal encephalopathy following fetal distress. A clinical and electroencephalographic study. Arch Neurol 1976; 33: 696-705.
2. Referans 2. Lawn JE, Kerber K, Enweronu-Laryea C, Cousens S. 3.6 million neonatal deaths--what is progressing and what is not? Semin Perinatol 2010; 34: 371-86.
3. Referans 3. Finder M, Boylan GB, Twomey D, Ahearne C, Murray DM, Hallberg B. Two-Year Neurodevelopmental Outcomes After Mild Hypoxic Ischemic Encephalopathy in the Era of Therapeutic Hypothermia. JAMA Pediatr 2019; 174: 48-55.
4. Referans 4. Wyatt JS, Gluckman PD, Liu PY, Azzopardi D, Ballard R, Edwards AD, et al. Determinants of outcomes after head cooling for neonatal encephalopathy. Pediatrics 2007; 119: 912-21.
5. Referans 5. Shankaran S, Laptook AR, Ehrenkranz RA, Tyson JE, McDonald SA, Donovan EF, et al. Whole-body hypothermia for neonates with hypoxic-ischemic encephalopathy. N Engl J Med 2005; 353: 1574-84.
6. Referans 6. Azzopardi DV, Strohm B, Edwards AD, Dyet L, Halliday HL, Juszczak E, et al. Moderate hypothermia to treat perinatal asphyxial encephalopathy. N Engl J Med 2009; 361: 1349-58.
7. Referans 7. Jacobs SE, Morley CJ, Inder TE, Stewart MJ, Smith KR, McNamara PJ, et al. Whole-body hypothermia for term and near-term newborns with hypoxic-ischemic encephalopathy: a randomized controlled trial. Arch Pediatr Adolesc Med 2011; 165: 692-700.
8. Referans 8. Jacobs SE, Berg M, Hunt R, Tarnow-Mordi WO, Inder TE, Davis PG. Cooling for newborns with hypoxic ischaemic encephalopathy. Cochrane Database Syst Rev 2013: CD003311.

9. Referans 9. Moster D, Lie RT, Markestad T. Joint association of Apgar scores and early neonatal symptoms with minor disabilities at school age. Arch Dis Child Fetal Neonatal Ed 2002; 86: F16-21.
10. Referans 10. Marlow N, Rose AS, Rands CE, Draper ES. Neuropsychological and educational problems at school age associated with neonatal encephalopathy. Arch Dis Child Fetal Neonatal Ed 2005; 90: F380-7.
11. Referans 11. van Handel M, de Sonneville L, de Vries LS, Jongmans MJ, Swaab H. Specific memory impairment following neonatal encephalopathy in term-born children. Dev Neuropsychol 2012; 37: 30-50.
12. Referans 12. Gonzalez FF, Miller SP. Does perinatal asphyxia impair cognitive function without cerebral palsy? Arch Dis Child Fetal Neonatal Ed 2006; 91: F454-9.
13. Referans 13. Akar M, Aydemir Ö, Oğuz ŞS, Erdeve Ö, Aydemir C, Gökmen T, et al. Tüm vücut soğutma yöntemi ile hipotermi uygulanan hipoksik iskemik ansefalopatili yenidoğanların değerlendirilmesi. Türk Ped Arş 2011; 46: 286-91. Referans 14. Akisu M, Kumral A, Canpolat FE. Turkish Neonatal Society Guideline on neonatal encephalopathy. Turk Pediatri Ars 2018; 53: S32-S44.
14. Referans 15. Bayley N. Bayley Scales of Infant Development. Second ed. San Antonio: Tx: The Psychological Corporation; 1993.
15. Referans 16. Swedo SE. Neurodevelopmental Disorders. In: Kupfer DJ, Regier DAR, editors. American Psychiatric Association: Diagnostic and statistical manual of mental disorders. 5th ed. Arlington, VA: American Psychiatric Association; 2013.
16. Referans 17. Shankaran S, Pappas A, McDonald SA, Vohr BR, Hintz SR, Yolton K, et al. Childhood outcomes after hypothermia for neonatal encephalopathy. N Engl J Med 2012; 366: 2085-92.
17. Referans 18. Tagin MA, Woolcott CG, Vincer MJ, Whyte RK, Stinson DA. Hypothermia for neonatal hypoxic ischemic encephalopathy: an updated systematic review and meta-analysis. Arch Pediatr Adolesc Med 2012; 166: 558-66.
18. Referans 19. Martinello K, Hart AR, Yap S, Mitra S, Robertson NJ. Management and investigation of neonatal encephalopathy: 2017 update. Arch Dis Child Fetal Neonatal Ed 2017; 102: F346-F58.
19. Referans 20. Pappas A, Shankaran S, McDonald SA, Vohr BR, Hintz SR, Ehrenkranz RA, et al. Cognitive outcomes after neonatal encephalopathy. Pediatrics 2015; 135: e624-34.
20. Referans 21. Lee-Kelland R, Jary S, Tonks J, Cowan FM, Thoresen M, Chakkarapani E. School-age outcomes of children without cerebral palsy cooled for neonatal hypoxic-ischaemic encephalopathy in 2008-2010. Arch Dis Child Fetal Neonatal Ed 2020; 105: 8-13.
21. Referans 22. Azzopardi D, Strohm B, Marlow N, Brocklehurst P, Deierl A, Eddama O, et al. Effects of hypothermia for perinatal asphyxia on childhood outcomes. N Engl J Med 2014; 371: 140-9.
22. Referans 23. Glass HC, Hong KJ, Rogers EE, Jeremy RJ, Bonifacio SL, Sullivan JE, et al. Risk factors for epilepsy in children with neonatal encephalopathy. Pediatr Res 2011; 70: 535-40.
23. Referans 24. Kwon JM, Guillet R, Shankaran S, Laptook AR, McDonald SA, Ehrenkranz RA, et al. Clinical seizures in neonatal hypoxic-ischemic encephalopathy have no independent impact on neurodevelopmental outcome: secondary analyses of data from the neonatal research network hypothermia trial. J Child Neurol 2011; 26: 322-8.