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Am J Perinatol 2019; 36(03): 252-257
DOI: 10.1055/s-0038-1667379
Review Article
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Side Effects of Phototherapy on Neonates

Fabrízia R. S. Faulhaber
1   Postgraduate Program in Child Health, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil
,
Renato S. Procianoy
1   Postgraduate Program in Child Health, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil
2   Department of Pediatrics, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil
3   Neonatal Section, Hospital de Clínicas de Porto Alegre, HCPA, Porto Alegre, Brazil
,
Rita C. Silveira
1   Postgraduate Program in Child Health, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil
2   Department of Pediatrics, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil
3   Neonatal Section, Hospital de Clínicas de Porto Alegre, HCPA, Porto Alegre, Brazil
› Author Affiliations
Further Information

Publication History

09 January 2018

02 July 2018

Publication Date:
06 August 2018 (online)

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Abstract

Phototherapy in neonates for treatment of pathological jaundice is an effective therapeutic tool that is widely used in neonatal units. Over the past years, a greater concern has emerged about the effects on the immune and inflammatory system and its potential genotoxic and side effects, especially the late ones, possibly associated with childhood diseases, showing that this treatment is not as harmless as previously believed. Numerous studies assessing these possible adverse effects of phototherapy on neonates have been published over the past years. Through this review, we seek to analyze what we know about the side effects of phototherapy in the neonatal period. The main causes of jaundice, phototherapy techniques, acute and late side effects, and effects on the immune and inflammatory system were reviewed. It was concluded that phototherapy is not a treatment free of side effects and further studies need to be conducted to elucidate its harmful effects on neonates.

Keywords

jaundice - hyperbilirubinemia - neonate - phototherapy - side effects
 

  • References

  • 1 Silva I, Luco M, Tapia JL. , et al. Single vs. double phototherapy in the treatment of full-term newborns with nonhemolytic hyperbilirubinemia. J Pediatr (Rio J) 2009; 85 (05) 455-458
    PubMedGoogle Scholar
  • 2 Bhutani VK, Vilms RJ, Hamerman-Johnson L. Universal bilirubin screening for severe neonatal hyperbilirubinemia. J Perinatol 2010; 30 (Suppl): S6-S15
    CrossrefPubMedGoogle Scholar
  • 3 Bhutani VK, Johnson LH, Keren R. Diagnosis and management of hyperbilirubinemia in the term neonate: for a safer first week. Pediatr Clin North Am 2004; 51 (04) 843-861
    CrossrefPubMedGoogle Scholar
  • 4 American Academy of Pediatrics Subcommittee on Hyperbilirubinemia. Management of hyperbilirubinemia in the newborn infant 35 or more weeks of gestation. Pediatrics 2004; 114 (01) 297-316
    CrossrefPubMedGoogle Scholar
  • 5 Dennery PA, Seidman DS, Stevenson DK. Neonatal hyperbilirubinemia. N Engl J Med 2001; 344 (08) 581-590
    CrossrefPubMedGoogle Scholar
  • 6 Bhutani VK. . Committee on Fetus and Newborn, American Academy of Pediatrics. Phototherapy to prevent severe neonatal hyperbilirubinemia in the newborn infant 35 or more weeks of gestation. Pediatric 2011; 128: e1046
    CrossrefPubMedGoogle Scholar
  • 7 Ennever JF, Costarino AT, Polin RA, Speck WT. Rapid clearance of a structural isomer of bilirubin during phototherapy. J Clin Invest 1987; 79 (06) 1674-1678
    CrossrefPubMedGoogle Scholar
  • 8 Vreman HJ, Wong RJ, Stevenson DK. Phototherapy: current methods and future directions. Semin Perinatol 2004; 28 (05) 326-333
    CrossrefPubMedGoogle Scholar
  • 9 Maisels MJ, Kring E. Rebound in serum bilirubin level following intensive phototherapy. Arch Pediatr Adolesc Med 2002; 156 (07) 669-672
    CrossrefPubMedGoogle Scholar
  • 10 Tridente A, De Luca D. Efficacy of light-emitting diode versus other light sources for treatment of neonatal hyperbilirubinemia: a systematic review and meta-analysis. Acta Paediatr 2012; 101 (05) 458-465
    CrossrefPubMedGoogle Scholar
  • 11 Holtrop PC, Madison K, Maisels MJ. A clinical trial of fiberoptic phototherapy vs conventional phototherapy. Am J Dis Child 1992; 146 (02) 235-237
    PubMedGoogle Scholar
  • 12 Kumar P, Chawla D, Deorari A. Light-emitting diode phototherapy for unconjugated hyperbilirubinaemia in neonates. Cochrane Database Syst Rev 2011; (12) CD007969
    PubMedGoogle Scholar
  • 13 Yahia S, Shabaan AE, Gouida M. , et al. Influence of hyperbilirubinemia and phototherapy on markers of genotoxicity and apoptosis in full-term infants. Eur J Pediatr 2015; 174 (04) 459-464
    CrossrefPubMedGoogle Scholar
  • 14 Aycicek A, Kocyigit A, Erel O, Senturk H. Phototherapy causes DNA damage in peripheral mononuclear leukocytes in term infants. J Pediatr (Rio J) 2008; 84 (02) 141-146
    PubMedGoogle Scholar
  • 15 El-Abdin MYZ, El-Salam MA, Ibrhim MY, Koraa SSM, Mahmoud E. Phototherapy and DNA changes in full term neonates with hyperbilirubinemia. Egypt J Med Hum Genet 2012; 13 (01) 29-35
    CrossrefPubMedGoogle Scholar
  • 16 Karakukcu C, Ustdal M, Ozturk A, Baskol G, Saraymen R. Assessment of DNA damage and plasma catalase activity in healthy term hyperbilirubinemic infants receiving phototherapy. Mutat Res 2009; 680 (1-2): 12-16
    PubMedGoogle Scholar
  • 17 Tatli MM, Minnet C, Kocyigit A, Karadag A. Phototherapy increases DNA damage in lymphocytes of hyperbilirubinemic neonates. Mutat Res 2008; 654 (01) 93-95
    PubMedGoogle Scholar
  • 18 Procianoy RS, Silveira RC, Fonseca LT, Heidemann LA, Neto EC. The influence of phototherapy on serum cytokine concentrations in newborn infants. Am J Perinatol 2010; 27 (05) 375-379
    Article in Thieme ConnectPubMedGoogle Scholar
  • 19 Sirota L, Straussberg R, Gurary N, Aloni D, Bessler H. Phototherapy for neonatal hyperbilirubinemia affects cytokine production by peripheral blood mononuclear cells. Eur J Pediatr 1999; 158 (11) 910-913
    CrossrefPubMedGoogle Scholar
  • 20 Zarkesh M, Dalili S, Fallah MJ, Heidarzadeh A, Rad AH. The effect of neonatal phototherapy on serum, level of interleukin-6 and white blood cell's count. J Clin Neonatol 2016; 5: 189-192
    CrossrefPubMedGoogle Scholar
  • 21 Rashedy FH, El-Hawy MA, Helwa MA, El-Shahat MI. Effect of phototherapy on CD4, CD8 and natural killer cells of full term neonates with indirect hyperbilirubinemia. Egypt J Immunol 2015; 22 (02) 23-29
    PubMedGoogle Scholar
  • 22 Eyada IK, El Saie AL, Ibrahem GA, Riad NM. Effect of phototherapy on B and T lymphocytes in Egyptian infants suffering from neonatal jaundice. Allergol Immunopathol (Madr) 2017; 45 (03) 290-296
    CrossrefPubMedGoogle Scholar
  • 23 Elfeky RAA, Fattah MAA, Gaafar DM, Afifi HA. The effect of phototherapy on lymphocyte subsets in newborn infants. J Allergy Clin Immunol 2012; 129 (02) AB12
    CrossrefPubMedGoogle Scholar
  • 24 Gathwala G, Sharma S. Phototherapy induces oxidative stress in premature neonates. Indian J Gastroenterol 2002; 21 (04) 153-154
    PubMedGoogle Scholar
  • 25 Kale Y, Aydemir O, Celik U. , et al. Effects of phototherapy using diferent light sources on oxidant and oxidant status of neonates with jaundice. Early Hum Dev 2013; 89 (12) 957-960
    CrossrefPubMedGoogle Scholar
  • 26 Demirel G, Uras N, Celik IH. , et al. Comparison of total oxidant/antioxidant status in unconjugated hyperbilirubinemia of newborn before and after conventional and LED phototherapy: a prospective randomized controlled trial. Clin Invest Med 2010; 33 (05) E335-E341
    CrossrefPubMedGoogle Scholar
  • 27 Gathwala G, Sharma S. Oxidative stress, phototherapy and the neonate. Indian J Pediatr 2000; 67 (11) 805-808
    CrossrefPubMedGoogle Scholar
  • 28 Yurdakok M. Phototherapy in the newborn: what's new?. J Pediatr Neonat Individual Med 2015; 4 (02) e040255
    PubMedGoogle Scholar
  • 29 Szucs KA, Rosenman MB. Family-centered, evidence-based phototherapy delivery. Pediatrics 2013; 131 (06) e1982-e1985
    CrossrefPubMedGoogle Scholar
  • 30 Green M, Solnit AJ. Reactions to the threatened loss of a child: a vulnerable child syndrome. Pediatric management of the dying child, part iii. Pediatrics 1964; 34: 58-66
    PubMedGoogle Scholar
  • 31 Xiong T, Qu Y, Cambier S, Mu D. The side effects of phototherapy for neonatal jaundice: what do we know? What should we do?. Eur J Pediatr 2011; 170 (10) 1247-1255
    CrossrefPubMedGoogle Scholar
  • 32 Maayan-Metzger A, Yosipovitch G, Hadad E, Sirota L. Transepidermal water loss and skin hydration in preterm infants during phototherapy. Am J Perinatol 2001; 18 (07) 393-396
    Article in Thieme ConnectPubMedGoogle Scholar
  • 33 Asl AS, Zarkeshl M, Heidarzadeh A, Maleknejad S, Hagikhani K. The effect of phototherapy on urinary calcium excretion in term neonates. Saudi J Kidney Dis Transpl 2016; 27 (03) 486-492
    CrossrefPubMedGoogle Scholar
  • 34 Karamifar H, Pishva N, Amirhakimi GH. Prevalence of phototherapy-induced hypocalcemia. Iran J Med Sci 2002; 27: 166-168
    PubMedGoogle Scholar
  • 35 Eghbalian F, Monsef A. Phototherapy-induced hypocalcemia in icteric newborns. Iran J Med Sci 2001; 27: 169-171
    PubMedGoogle Scholar
  • 36 Bertini G, Dani C, Fonda C, Zorzi C, Rubaltelli FF. Bronze baby syndrome and the risk of kernicterus. Acta Paediatr 2005; 94 (07) 968-971
    CrossrefPubMedGoogle Scholar
  • 37 Surmeli-Onay O, Korkmaz A, Yigit S, Yurdakok M. Phototherapy rash in newborn infants: does it differ between conventional and light emitting diode phototherapy?. Pediatr Dermatol 2013; 30 (05) 529-533
    CrossrefPubMedGoogle Scholar
  • 38 LaRusso J, Wilson J, Ceilley R. Phototherapy-induced purpuric eruption in a neonate. J Clin Aesthet Dermatol 2015; 8 (03) 46-48
    PubMedGoogle Scholar
  • 39 Jahanshahifard S, Ahmadpour-Kacho M, Pasha YZ. Effects of phototherapy on cytokines' levels and white blood cells in term neonate with hyperbilirubinemia. J Clin Neonatol 2012; 1 (03) 139-142
    CrossrefPubMedGoogle Scholar
  • 40 Mrkaić Lj, Kamenov B, Najman S, Dimitrijević H, Mitrović V, Maglajlić S. Neonatal immune system changes caused by phototherapy [Serbian]. Srp Arh Celok Lek 1994; 122 (Suppl 1): 36-37
    PubMedGoogle Scholar
  • 41 Bhargava O, Sutrakar SK, Ghanghoria P, Verma A. . Incidence of thrombocytopenia in hyperbilirubinemic neonates following phototherapy. Asian J Res Chem 2015; 8 (04) 221-230
    PubMedGoogle Scholar
  • 42 Khera S, Gupta R. Incidence of thrombocytopenia following phototherapy in hyperbilirubinemic neonates. Med J Armed Forces India 2011; 67 (04) 329-332
    CrossrefPubMedGoogle Scholar
  • 43 Kadalraja R, Patole SK, Muller R, Whitehall JS. Is mesenteric blood flow compromised during phototherapy in preterm neonates?. Arch Dis Child Fetal Neonatal Ed 2004; 89 (06) F564
    PubMedGoogle Scholar
  • 44 Raghavan K, Thomas E, Patole S, Muller R. Is phototherapy a risk factor for ileus in high-risk neonates?. J Matern Fetal Neonatal Med 2005; 18 (02) 129-131
    CrossrefPubMedGoogle Scholar
  • 45 Chen A, Du L, Xu Y, Chen L, Wu Y. The effect of blue light exposure on the expression of circadian genes: bmal1 and cryptochrome 1 in peripheral blood mononuclear cells of jaundiced neonates. Pediatr Res 2005; 58 (06) 1180-1184
    CrossrefPubMedGoogle Scholar
  • 46 Barefield ES, Dwyer MD, Cassady G. Association of ductus arteriosus and phototherapy in infants weighting less than 1000 grams. J Perinatol 1993; 13 (05) 376-380
    PubMedGoogle Scholar
  • 47 Benders MJ, Van Bel F, Van de Bor M. Cardiac output and ductal reopening during phototherapy in preterm infants. Acta Paediatr 1999; 88 (09) 1014-1019
    CrossrefPubMedGoogle Scholar
  • 48 Surmeli-Onay O, Yurdakok M, Karagoz T. , et al. A new approach to an old hypothesis; phototherapy does not affect ductal patency via PGE2 and PGI2. J Matern Fetal Neonatal Med 2015; 28 (01) 16-22
    CrossrefPubMedGoogle Scholar
  • 49 Grimm C, Wenzel A, Williams T, Rol P, Hafezi F, Remé C. Rhodopsin-mediated blue-light damage to the rat retina: effect of photoreversal of bleaching. Invest Ophthalmol Vis Sci 2001; 42 (02) 497-505
    PubMedGoogle Scholar
  • 50 Newman TB, Wickremasinghe AC, Walsh EM, Grimes BA, McCulloch CE, Kuzniewicz MW. Retrospective cohort study of phototherapy and childhood cancer in Northern California. Pediatrics 2016; 137 (06) e20151354
    CrossrefPubMedGoogle Scholar
  • 51 Wickremasinghe AC, Kuzniewicz MW, Grimes BA, McCulloch CE, Newman TB. Neonatal phototherapy and infantile cancer. Pediatrics 2016; 137 (06) e20151353
    CrossrefPubMedGoogle Scholar
  • 52 Cnattingius S, Zack M, Ekbom A, Gunnarskog J, Linet M, Adami HO. Prenatal and neonatal risk factors for childhood myeloid leukemia. Cancer Epidemiol Biomarkers Prev 1995; 4 (05) 441-445
    PubMedGoogle Scholar
  • 53 Brewster DH, Tucker JS, Fleming M. , et al. Risk of skin cancer after neonatal phototherapy: retrospective cohort study. Arch Dis Child 2010; 95 (10) 826-831
    CrossrefPubMedGoogle Scholar
  • 54 Berg P, Lindelöf B. Is phototherapy in neonates a risk factor for malignant melanoma development?. Arch Pediatr Adolesc Med 1997; 151 (12) 1185-1187
    CrossrefPubMedGoogle Scholar
  • 55 Wintermeier K, von Poblotzki M, Genzel-Boroviczény O. , et al. Neonatal blue light phototherapy increases café-au-lait macules in preschool children. Eur J Pediatr 2014; 173 (11) 1519-1525
    CrossrefPubMedGoogle Scholar
  • 56 Lai YC, Yew YW. Neonatal blue light phototherapy and melanocytic nevus count in children: a systematic review and meta-analysis of observational studies. Pediatr Dermatol 2016; 33 (01) 62-68
    CrossrefPubMedGoogle Scholar
  • 57 Mahé E, Beauchet A, Aegerter P, Saiag P. Neonatal blue-light phototherapy does not increase nevus count in 9-year-old children. Pediatrics 2009; 123 (05) e896-e900
    CrossrefPubMedGoogle Scholar
  • 58 Matichard E, Le Hénanff A, Sanders A, Leguyadec J, Crickx B, Descamps V. Effect of neonatal phototherapy on melanocytic nevus count in children. Arch Dermatol 2006; 142 (12) 1599-1604
    PubMedGoogle Scholar
  • 59 Csoma Z, Hencz P, Orvos H. , et al. Neonatal blue-light phototherapy could increase the risk of dysplastic nevus development. Pediatrics 2007; 119 (05) 1036-1037
    CrossrefPubMedGoogle Scholar
  • 60 Aspberg S, Dahlquist G, Kahan T, Källén B. Confirmed association between neonatal phototherapy or neonatal icterus and risk of childhood asthma. Pediatr Allergy Immunol 2010; 21 (4 Pt 2): e733-e739
    CrossrefPubMedGoogle Scholar
  • 61 Das RR, Naik SS. Neonatal hyperbilirubinemia and childhood allergic diseases: a systematic review. Pediatr Allergy Immunol 2015; 26 (01) 2-11
    CrossrefPubMedGoogle Scholar
  • 62 Beken S, Aydin B, Zenciroğğlu A. , et al. The effects of phototherapy on eosinophil and eosinophilic cationic protein in newborns with hyperbilirubinemia. Fetal Pediatr Pathol 2014; 33 (03) 151-156
    CrossrefPubMedGoogle Scholar
  • 63 Aydın B, Beken S, Zenciroğlu A, Dilli D, Okumuş N. Blood eosinophil levels in newborns with severe indirect hyperbilirubinemia treated with phototherapy. Iran J Pediatr 2014; 24 (03) 267-272
    PubMedGoogle Scholar
  • 64 Gloria-Bottini F, Bottini E. Is there a role of early neonatal events in susceptibility to allergy?. Int J Biomed Sci 2010; 6 (01) 8-12
    PubMedGoogle Scholar