Long-term Effects of Indirect Hyperbilirubinemia on Auditory and Neurological Functions in Term Newborns

Abstract

Objective:The aim of this study was to investigate the long-term effects of hyperbilirubinemia on neurological and hearing function in otherwise healthy term newborns with neonatal indirect hyperbilirubinemia. Method: This study was performed prospectively in 41 term newborns hospitalized for indirect hyperbilirubinemia. Patients with no signs of hemolysis were categorized in 3 groups based on stabil levels as sTB <20 mg/dl, 20-24.9 mg/dl, and =>25 mg/dl. Patients with total bilirubin level =>20 mg/dl and hemolytic disease were classified as the fourth group. The relationship between maximum sTB level, duration of exposure to sTB levels >20 mg/dl and etiology of jaundice with neurological and auditory functions was investigated. Detailed neurological examination, Denver II developmental screening test and hearing tests (otoacoustic emissions, OAE and auditory brainstem responses, ABR) were performed to all patients between 18-24 months of age. Results: Neurodevelopmental disorder was found in 5 (12.2%) patients. Hemolytic disease was detected in two of these patients. Hearing loss was found in 4 (9.8%) of the patients. Two of these patients had auditory neuropathy spectrum disorder and the other two had cochlear hearing loss. The sTB levels of all these patients were above 25 mg/dl. No neurological disorder or hearing loss was found in the patients who had stabil of <25 mg/dl. Exposure time to sTB levels above 20 mg/dl was significantly longer in patients with neurological dysfunction and pathologic ABR results (p:0.007, p:0.007; p<0.05). Conclusion:This study demonstrates that kernicterus may develop in term newborns with severe hyperbilirubinemia (sTB>25 mg/dl) without any finding of significant hemolysis. Not only the bilirubin level but also the duration of exposure to high bilirubin levels may be effective in the development of bilirubin neurotoxicity. The high rate of hearing loss in our patients emphasizes the importance of screening for infants with severe hyperbilirubinemia using comprehensive auditory evaluation for early diagnosis of possible hearing loss. ÖZAmaç: Bu çalışmada, neonatal indirekt hiperbilirubinemi dışında başka sorunu olmayan term yenidoğanlarda, hiperbilirubineminin nörolojik gelişim ve işitme fonksiyonu üzerinde uzun dönem etkilerinin araştırılması amaçlanmıştır. Yöntem: Bu çalışma, indirekt hiperbilirubinemi nedeniyle yatırılarak tedavi edilen 41 term yenidoğanda ileriye dönük olarak gerçekleştirilmiştir. Hemoliz bulgusu saptanmayan hastalar sTB <20 mg/dl, 20-24.9 mg/dl, =>25 mg/dl olarak 3 gruba ayrılmıştır. Hemolitik hastalık saptanan ve sTB =>20 mg/dl olan hastalar 4. grup olarak belirlenmiştir. Maksimum sTB düzeyi, sTB >20 mg/dl üzerinde kalma süresi ve sarılık etyolojisi ile nörolojik ve işitsel fonksiyonlar arasındaki ilişki incelenmiştir. Tüm olgulara 18-24. aylar arasında ayrıntılı nörolojik muayene, Denver II gelişimsel tarama testi ve işitme testleri (otoakustik emisyon, OAE ve işitsel beyin sapı cevapları, ABR) incelemesi yapılmıştır. Bulgular: Hastaların 5'inde (%12,2) nö...

Neonatal hyperbilirubinemia and repercussions on neurodevelopment: A systematic review

“…Bilirubin above normal physiological parameters in infants born at term resulted in alterations in auditory development [nine (Agrawal et al, 1998;Bengtsson & Verneholt, 1974;Besli et al, 2020;Y. Chen & Kang, 1995;Grimmer et al, 1999;Gupta et al, 1990;Hung, 1989;Kahraman et al, 2021;Wong et al, 2006) of the 11 analysed studies presented low risk of bias, and eight (Agrawal et al, 1998;Besli et al, 2020;Y.…”

“…Only one study reported alterations in global development, specifically lower scores in the Denver Developmental Screening Test when comparing it with children with normal bilirubin levels(Agrawal et al, 1998).Finally, this review observed a large number of studies including a neurological evaluation. Specifically, nine studies assessed neurological function, with the most frequently used tool being the general neurological evaluation(Bengtsson & Verneholt, 1974;Besli et al, 2020;Özmert et al, 1996;Rubin et al, 1979;Wong et al, 2006), followed by the APGAR score(Gupta et al, 1990;Hokkanen et al, 2014;Lunsing et al, 2013;Rubin et al, 1979) and Prechtl's General movement assessment(Lunsing et al, 2013;Soorani-Lunsing et al, 2001), although other tests were also employed, including the Touwen's infant neurological examination(Grimmer et al, 1999), Hempel's neurologic examination(Lunsing et al, 2013), screening method of Amiel-Tison(Soorani-Lunsing et al, 2001) and Michelsson's Neurodevelopmental screening examinations(Hokkanen et al, 2014). Of note, four studies assessed the neurological risk in newborns via general movements evaluation(Kahraman et al, 2021;Lunsing et al, 2013;Soorani-Lunsing et al, 2001) or clinical risk index of babies for determining the mortality risk.…”

“…Behavioral aspects were evaluated via the Toddler Behavior Assessment Questionnaire in one study(Lunsing et al, 2013) and with a questionnaire for parents in another study(Soorani-Lunsing et al, 2001). Only one of the studies evaluating cognitive aspects found altered outcomes for this neurodevelopment area in the group of children affected by hyperbilirubinemia, where the subjects who had suffered hyperbilirubinemia obtained lower academic grades compared to the control group(Hokkanen et al, 2014).In addition to evaluating the different areas of development, six studies assessed the global development of children, mainly using the Denver Developmental Screening Test(Agrawal et al, 1998;Besli et al, 2020;Y. Chen & Kang, 1995) but also with other tools, such as the Brunet-Lezine scale(Sabatino et al, 1996), the development quotient(Deorari et al, 1994) and the Bayley Mental and Motor Scales of Infant Development(Rubin et al, 1979).…”

İndirekt Hiperbilirubinemide Exchange Transfüzyon Uygulanması: Tek Merkez Deneyimi

“…In order to reduce the risk of bilirubin encephalopathy and hospitalizations due to indirect hyperbilirubinemia, the American Academy of Pediatrics (AAP) recommends that health institutions should investigate the risk factors that may occur before the newborn discharge procedures, determine the rate of bilirubin increase, and establish a specific follow-up protocol in this regard (5). In our country, studies examining the risk factors that cause severe hyperbilirubinemia, possible outcomes after phototherapy and/or exchange transfusion therapy, and long-term neurodevelopmental follow-up of the cases are limited (6). In this study, it was aimed to evaluate the demographic characteristics, etiological causes, indirect hyperbilirubin levels and risk factors for the development of acute bilirubin encephalopathy in infants who underwent exchange transfusion for one year in the neonatal intensive care unit (NICU) due to indirect hyperbilirubinemia.…”

The Impact of Treatment Options on Neurodevelopmental Status of Neonates with Jaundice Requiring Exchange Transfusion

“…Gelişmekte olan ülkeler ve ülkemizde, ciddi hiperbilirubinemi riski yaratan durumlar, fototerapi ve/ veya kan değişimi ile tedavinin sonuçlarının incelendiği ve olguların uzun dönem nörogelişimsel izlemlerinin yapıldığı çalışmalar kısıtlıdır (5,6,9,12,13).…”