Otizm Spektrum Bozukluğu Tanılı Olgularda Prenatal ve Perinatal Özelliklerin Değerlendirilmesi: Cinsiyet Farklılığı Var Mı?

Amaç: Bu çalışmada, otizm spektrum bozukluğu (OSB) tanılı çocuklarda prenatal ve perinatal özelliklerin geriye dönük olarak değerlendirilmesi amaçlanmıştır. Gereç ve Yöntem: 01.01.2018-31.12.2019 tarihleri arasında kliniğimize başvurmuş, yaşları 12-72 ay arasında olan ve OSB tanısı almış olgular ile aynı zaman aralığında polikliniğimize başvurup herhangi bir nörogelişimsel bozukluk tanısı almamış olan olguların (kontrol grubu) dosya verileri geriye dönük olarak incelenmiş, pre/perinatal özellikler açısından karşılaştırılmıştır.Bulgular: Prenatal özelliklerden; gebelik sırasında anne yaşı ve baba yaşı, anne-baba yaşı arasındaki fark, gebelik sırasında annede tıbbi hastalık varlığı, düşük tehdidi, annenin gebelikte maruz kaldığı olumsuz yaşam olayları ve gebelikte sigara/ilaç kullanımı OSB grubunda anlamlı yüksek saptanmıştır. Perinatal özellikler arasında; düşük doğum ağırlığı, preterm doğum, zor doğum öyküsü, sezaryen doğum, hipoksi/asfiksi öyküsü, kuvöz/yoğun bakım öyküsü oranı OSB grubunda kontrol grubuna göre anlamlı yüksek bulunmuştur. OSB grubunda cinsiyete göre yapılan analizlerde, prenatal etmenlerden anne ve baba yaşı, erkek OSB’lilerde kızlara göre anlamlı yüksek saptanmıştır. Perinatal etmenlerden ise; zor doğum öyküsü, hipoksi/asfiksi öyküsü ve kuvöz/yoğun bakım öyküsü yine erkek OSB’lilerde kızlara göre anlamlı yüksek saptanmıştır.Sonuç: Çalışmamızda, otizm olgularında otizm olmayan olgulara göre daha fazla prenatal ve perinatal güçlük olduğu saptanmıştır. İleri anne-baba yaşı dışında, anne-baba yaşı arasındaki farkın da otizmli grupta anlamlı yüksek bulunması dikkat çekicidir. Ek olarak, bazı pre/perinatal özelliklerin, özellikle erkek otizmli olgularda anlamlı fazla olması da mevcut literatür bulgularıyla birlikte yorumlandığında araştırılmaya değer görülmektedir.

Evaluation of Prenatal and Perinatal Features in Children Diagnosed with Autism Spectrum Disorder: Is There a Gender Difference?

Objectives: In this study, it was aimed to retrospectively evaluate prenatal and perinatal features in children with autism spectrum disorder (ASD).Materials and Methods: The data of the children who applied to our outpatient clinic between 01.01.2018 and 31.12.2019 and who were between the ages of 12 and 72 months were examined retrospectively. The children who were diagnosed with ASD and the children who were not diagnosed with neurodevelopmental disorder (control group) were compared in terms of pre/perinatal features.Results: From prenatal features; maternal and paternal age during pregnancy, difference between the age of parents, maternal medical illness during pregnancy, threatened abortion, negative life events and maternal smoking/medication during pregnancy were significantly higher in children with ASD. From perinatal features; low birth weight, preterm delivery, labor difficulties, cesarean section, hypoxia/asphyxia, and incubator/intensive care history were significantly higher in ASD than in the control group. In the analysis conducted considering gender in the ASD group; maternal and paternal age, labor difficulties, hypoxia/asphyxia history and incubator/intensive care history were significantly higher in boys than in girls.Conclusion: In our study, it was found that there were more prenatal and perinatal difficulties in children with autism than in those without autism. It is noteworthy that apart from the advanced age of parents, the difference in the ages of parents was significantly higher in the group with autism. In addition, it appears to be worth investigating when interpreted in conjunction with current literature findings that some pre/perinatal features are significantly higher in boys than in girls in ASD.

Kaynakça

1. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders Fifth Edition (DSM-5). Washington DC; ABD; American Psychiatric Publishing; 2013.

2. Baio J, Wiggins L, Christensen DL, Maenner MJ, Daniels J, Warren Z, Kurzius-Spencer M, Zahorodny W, Robinson Rosenberg C, White T, Durkin MS, Imm P, Nikolaou L, Yeargin-Allsopp M, Lee LS, Harrington R, Lopez M, Fitzgerald RT, Hewitt A, Pettygrove S, Constantino JN, Vehorn A, Shenouda J, Hall-Lande J, Van Naarden Braun K, Dowling NF. Prevalence of autism spectrum disorder among children aged 8 years - Autism and developmental disabilities monitoring network, 11 sites, United States. MMWR Surveill Summ. 2018;67:1-23.

3. Dietert RR, Dietert JM, Dewitt JC. Environmental risk factors for autism. Emerg Health Threats J. 2011;4:7111.

4. King M, Bearman P. Diagnostic change and the increased prevalence of autism. Int J Epidemiol. 2009;38:1224-1234.

5. Engel SM, Daniels JL. On the complex relationship between genes and environment in the etiology of autism. Epidemiology. 2011;22:486-488.

6. Duan G, Yao M, Ma Y, Zhang W. Perinatal and background risk factors for childhood autism in central China. Psychiatry Res. 2014;220:410- 417.

7. Tanıdır C, Mukaddes NM. Otizm spektrum bozuklukları. Çocuk ve Ergen Ruh Sağlığı ve Hastalıkları içinde. Eds. Pekcanlar A, Ercan ES. Ankara; Hekimler Yayın Birliği; 2016:126-150.

8. Siu MT, Weksberg R. Epigenetics of Autism Spectrum Disorder. Adv Exp Med Biol. 2017;978:63‐90.

9. Hallmayer J, Cleveland S, Torres A, Phillips J, Cohen B, Torigoe T, Miller J, Fedele A, Collins J, Smith K, Lotspeich L, Croen LA, Ozonoff S, Lajonchere C, Grether JK, Risch N. Genetic heritability and shared environmental factors among twin pairs with autism. Arch Gen Psychiatry. 2011;68:1095‐1102.

10. Lyall K, Schmidt RJ, Hertz-Picciotto I. Maternal lifestyle and environmental risk factors for autism spectrum disorders. International journal of epidemiology. 2014;43;443-464.

11. Mamidala MP, Polinedi A, P T V PK, Rajesh N, Vallamkonda OR, Udani V, Singhal N, Rajesh V. Prenatal, perinatal and neonatal risk factors of Autism Spectrum Disorder: a comprehensive epidemiological assessment from India. Res Dev Disabil. 2013;34:3004-3013.

12. Sandin S, Schendel D, Magnusson P, Hultman C, Surén P, Susser E, Grønborg T, Gissler M, Gunnes N, Gross R, Henning M, Bresnahan M, Sourander A, Hornig M, Carter K, Francis R, Parner E, Leonard H, Rosanoff M, Stoltenberg C, Reichenberg A. Autism risk associated with parental age and with increasing difference in age between the parents. Mol Psychiatry. 2016;21:693-700.

13. Karakoç Demirkaya S. Otizm spektrum bozukluklarında etiyopatogenez. Nörogelişimsel Bozukluklar içinde. Motavalli Mukaddes N, Ercan ES, Editörler. İstanbul; Nobel Tıp Kitabevleri; 2018:317-334.

14. Wu S, Wu F, Ding Y, Hou J, Bi J, Zhang Z. Advanced parental age and autism risk in children: a systematic review and meta-analysis. Acta Psychiatr Scand. 2017;135:29-41.

15. Gao Y, Yu Y, Xiao J, Luo J, Zhang Y, Tian Y, Zhang J, Olsen J, Li J, Liew Z. Association of Grandparental and Parental Age at Childbirth With Autism Spectrum Disorder in Children. JAMA Netw Open. 2020;3:e202868.

16. Frans EM, Sandin S, Reichenberg A, Långström N, Lichtenstein P, McGrath JJ, Hultman CM. Autism risk across generations: a population-based study of advancing grandpaternal and paternal age. JAMA Psychiatry. 2013;70:516-521.

17. Malaspina D. Paternal factors and schizophrenia risk: de novo mutations and imprinting. Schizophr Bull. 2001;27:379-393.

18. Iossifov I, Ronemus M, Levy D, Wang Z, Hakker I, Rosenbaum J, Yamrom B, Lee YH, Narzisi G, Leotta A, Kendall J, Grabowska E, Ma B, Marks S, Rodgers L, Stepansky A, Troge J, Andrews P, Bekritsky M, Pradhan K, Ghiban E, Kramer M, Parla J, Demeter R, Fulton LL, Fulton RS, Magrini VJ, Ye K, Darnell JC, Darnell RB, Mardis ER, Wilson RK, Schatz MC, McCombie WR, Wigler M. De novo gene disruptions in children on the autistic spectrum. Neuron. 2012;74:285-299.

19. Croen LA, Najjar DV, Fireman B, Grether JK. Maternal and paternal age and risk of autism spectrum disorders. Arch Pediatr Adolesc Med. 2007;161:334-340.

20. Byars SG, Boomsma JJ. Opposite differential risks for autism and schizophrenia based on maternal age, paternal age, and parental age differences. Evol Med Public Health. 2016;2016:286-298.

21. Williams G, King J, Cunningham M, Stephan M, Kerr B, Hersh JH. Fetal valproate syndrome and autism: additional evidence of an association. Dev Med Child Neurol. 2001;43:202-206.

22. Gidaya NB, Lee BK, Burstyn I, Michael Y, Newschaffer CJ, Mortensen EL. In utero Exposure to β-2-Adrenergic Receptor Agonist Drugs and Risk for Autism Spectrum Disorders. Pediatrics. 2016;137:e20151316.

23. Ornoy A, Weinstein-Fudim L, Ergaz Z. Prenatal factors associated with autism spectrum disorder (ASD). Reprod Toxicol. 2015;56:155-169.

24. Hultman CM, Sparén P, Cnattingius S. Perinatal risk factors for infantile autism. Epidemiology. 2002;13:417-423.

25. Lyall K, Pauls DL, Spiegelman D, Ascherio A, Santangelo SL. Pregnancy complications and obstetric suboptimality in association with autism spectrum disorders in children of the Nurses’ Health Study II. Autism Res. 2012;5:21-30.

26. Li M, Fallin MD, Riley A, Landa R, Walker SO, Silverstein M, Caruso D, Pearson C, Kiang S, Dahm JL, Hong X, Wang G, Wang MC, Zuckerman B, Wang X. The Association of Maternal Obesity and Diabetes With Autism and Other Developmental Disabilities. Pediatrics. 2016;137:e20152206.

27. Gardener H, Spiegelman D, Buka SL. Prenatal risk factors for autism: comprehensive meta-analysis. Br J Psychiatry. 2009;195:7-14.

28. Wang C, Geng H, Liu W, Zhang G. Prenatal, perinatal, and postnatal factors associated with autism: A meta-analysis. Medicine (Baltimore). 2017;96:e6696.

29. Larsson M, Weiss B, Janson S, Sundell J, Bornehag CG. Associations between indoor environmental factors and parental-reported autistic spectrum disorders in children 6-8 years of age. Neurotoxicology. 2009;30:822-831.

30. Lee BK, Gardner RM, Dal H, Svensson A, Galanti MR, Rai D, Dalman C, Magnusson C. Brief report: maternal smoking during pregnancy and autism spectrum disorders. J Autism Dev Disord. 2012;42:2000- 2005.

31. Kalkbrenner AE, Braun JM, Durkin MS, Maenner MJ, Cunniff C, Lee LC, Pettygrove S, Nicholas JS, Daniels JL. Maternal smoking during pregnancy and the prevalence of autism spectrum disorders, using data from the autism and developmental disabilities monitoring network. Environ Health Perspect. 2012;120:1042-1048.

32. Aronson M, Hagberg B, Gillberg C. Attention deficits and autistic spectrum problems in children exposed to alcohol during gestation: a follow-up study. Dev Med Child Neurol. 1997;39:583-587.

33. Eliasen M, Tolstrup JS, Nybo Andersen AM, Grønbaek M, Olsen J, Strandberg-Larsen K. Prenatal alcohol exposure and autistic spectrum disorders--a population-based prospective study of 80,552 children and their mothers. Int J Epidemiol. 2010;39:1074- 1081.

34. Gallagher C, McCarthy FP, Ryan RM, Khashan AS. Maternal Alcohol Consumption During Pregnancy and the Risk of Autism Spectrum Disorders in Offspring: A Retrospective Analysis of the Millennium Cohort Study. J Autism Dev Disord. 2018;48:3773-3782.

35. Elazığ İli Sosyal Analiz Çalışması. Adem Solak, editor. Ankara; Hermes Ofset; 2017.

36. Şahin B, Bozkurt A, Karabekiroğlu K. Perinatal and Medical Risk Factors in Children with Attention Deficit Hyperactivity Disorder, Autism Spectrum Disorder or Specific Learning Disorder: Comparison Between Diagnostic Groups. Istanbul Tip Dergisi. 2019; 20;502-507.

37. Li J, Vestergaard M, Obel C, Christensen J, Precht DH, Lu M, Olsen J. A nationwide study on the risk of autism after prenatal stress exposure to maternal bereavement. Pediatrics. 2009;123:1102- 1107.

38. Rai D, Golding J, Magnusson C, Steer C, Lewis G, Dalman C. Prenatal and early life exposure to stressful life events and risk of autism spectrum disorders: population-based studies in Sweden and England. PLoS One. 2012;7:e38893.

39. Maimburg RD, Vaeth M. Perinatal risk factors and infantile autism. Acta Psychiatr Scand. 2006;114:257-264.

40. Fitzallen GC, Taylor HG, Bora S. What do we know about the preterm behavioral phenotype? A Narrative Review. Front Psychiatry. 2020;11:154.

41. Talmi Z, Mankuta D, Raz R. Birth weight and autism spectrum disorder: A population-based nested case-control study. Autism Res. 2020;13:655-665.

42. Larsson HJ, Eaton WW, Madsen KM, Vestergaard M, Olesen AV, Agerbo E, Schendel D, Thorsen P, Mortensen PB. Risk factors for autism: perinatal factors, parental psychiatric history, and socioeconomic status. Am J Epidemiol. 2005;161:916-928.

43. Modabbernia A, Velthorst E, Reichenberg A. Environmental risk factors for autism: an evidence-based review of systematic reviews and meta-analyses. Mol Autism. 2017;8:13.

44. Hebert KJ, Miller LL, Joinson CJ. Association of autistic spectrum disorder with season of birth and conception in a UK cohort. Autism Res. 2010;3:185-190.

45. Mouridsen SE, Nielsen S, Rich B, Isager T. Season of birth in infantile autism and other types of childhood psychoses. Child Psychiatry Hum Dev. 1994;25:31-43.

46. Stevens MC, Fein DH, Waterhouse LH. Season of birth effects in autism. J Clin Exp Neuropsychol. 2000;22:399-407.

47. Lee BK, Gross R, Francis RW, Karlsson H, Schendel DE, Sourander A, Reichenberg A, Parner ET, Hornig M, Yaniv A, Leonard H, Sandin S. Birth seasonality and risk of autism spectrum disorder. Eur J Epidemiol. 2019;34:785-792.

48. Shalev H, Solt I, Chodick G. Month of birth and risk of autism spectrum disorder: a retrospective cohort of male children born in Israel. BMJ Open. 2017;7:e014606.

49. Kolevzon A, Weiser M, Gross R, Lubin G, Konobler HY, Schmeidler J, Siverman JM, Reichenberg A. Effects of season of birth on autism spectrum disorders: fact or fiction? Am J Psychiatry. 2006;163:1288- 1290.

50. Atladóttir HO, Parner ET, Schendel D, Dalsgaard S, Thomsen PH, Thorsen P. Variation in incidence of neurodevelopmental disorders with season of birth. Epidemiology. 2007;18:240-245.

51. Demirkaya SK, Aksu H, Taş K, Özgür BG. Nörogelişimsel psikiyatrik bozukluklarin doğum mevsimi ile ilişkisinin incelenmesi. Sdü Tıp Fakültesi Dergisi. 2016;23.

52. Jenabi E, Bashirian S, Khazaei S. Association between neonatal jaundice and autism spectrum disorders among children: a metaanalysis. Clin Exp Pediatr. 2020;63:8-13.

53. Croen LA, Yoshida CK, Odouli R, Newman TB. Neonatal hyperbilirubinemia and risk of autism spectrum disorders. Pediatrics. 2005;115:e135-138.

54. Mandy W, Chilvers R, Chowdhury U, Salter G, Seigal A, Skuse D. Sex differences in autism spectrum disorder: evidence from a large sample of children and adolescents. J Autism Dev Disord. 2012;42:1304-1313.

55. Bloss CS, Courchesne E. MRI neuroanatomy in young girls with autism: a preliminary study. J Am Acad Child Adolesc Psychiatry. 2007;46:515-523.

56. Schumann CM, Barnes CC, Lord C, Courchesne E. Amygdala enlargement in toddlers with autism related to severity of social and communication impairments. Biol Psychiatry. 2009;66:942-949.

57. Lai MC, Lombardo MV, Suckling J, Ruigrok AN, Chakrabarti B, Ecker C, Deoni SC, Craig MC, Murphy DG, Bullmore ET; MRC AIMS Consortium, Baron-Cohen S. Biological sex affects the neurobiology of autism. Brain. 2013;136:2799-2815.

58. Ardalan M, Chumak T, Vexler Z, Mallard C. Sex-Dependent Effects of Perinatal Inflammation on the Brain: Implication for Neuro- Psychiatric Disorders. Int J Mol Sci. 2019;20:2270.

59. Werling DM, Geschwind DH. Sex differences in autism spectrum disorders. Curr Opin Neurol. 2013;26:146-153.

60. Ferri SL, Abel T, Brodkin ES. Sex Differences in Autism Spectrum Disorder: a Review. Curr Psychiatry Rep. 2018;20:9.

61. May T, Adesina I, McGillivray J, Rinehart NJ. Sex differences in neurodevelopmental disorders. Curr Opin Neurol. 2019;32:622-626.

62. Bale TL. The placenta and neurodevelopment: sex differences in prenatal vulnerability. Dialogues Clin Neurosci. 2016;18:459-464.

63. McCarthy MM. Sex differences in the developing brain as a source of inherent risk. Dialogues Clin Neurosci. 2016;18:361-372.

Kaynak Göster