İleri Ebeveyn Yaşının Çocuklarda Otizm Spektrum Bozukluğu Gelişimi ile İlişkisi: Meta-Analiz

Year 2024, Volume: 7 Issue: 1, 29 - 41, 31.12.2024

Iman Ali Jama , Cüneyd Yavaş , Lütfiye Karcıoğlu Batur , Nermin Akçalı , Sajjad Eslamkhah , Ahmet Köseoğlu , Elif Aslan

Abstract

Arka Plan: Otizm Spektrum Bozukluğu (OSB), bebeklik döneminde en sık görülen nörolojik durumlardan biridir ve her 36 çocuktan yaklaşık 1'ini etkiler. Erkek/kız oranı 4,5:1’dir. OSB'li çocuklar genellikle iletişim, sosyal ilişkiler, ani değişimlere uyum sağlama, sınırlı ve tekrarlayıcı davranış, ilgi alanları ve/veya aktivitelerle mücadele ederler. Bu sistematik derleme ve meta-analizin amacı, ileri ebeveyn yaşı risk faktörleri ile otizm spektrum bozukluklarının (OSB'ler) çocuklarda gelişimi arasındaki bağlantıyı araştırmaktır.

Yöntemler: Web of Science, PubMed, EMBASE, Medline, Scopus, CINAHL ve Cochrane Library gibi birden fazla veri tabanını taradık ve bu meta-analize dahil edilecek ilgili çalışmaları Haziran 2022'ye kadar çapraz referansladık. İstatistiksel analiz, Review Manager Versiyon 5.4 yazılımı kullanılarak gerçekleştirildi ve risk tahminleri rastgele etki modelleriyle birleştirildi. Heterojenliği ölçmek için I2 testleri kullanıldı.

Sonuçlar: Arama, meta-analize dahil edilen 21 çalışmayı ortaya çıkardı. Referans noktalarıyla karşılaştırıldığında, ileri ebeveyn yaşı, çocuklarda otizm spektrum bozuklukları riskinde %59'luk bir artışla ilişkiliydi ve bu durum OR (olasılık oranı) = 1,59 ve %95 GA (güven aralığı) (1,45-1,74) olarak belirlendi. Meta-regresyon analizi ayrıca anne ve baba yaşında 10 yıllık bir artışın sırasıyla %35 ve %29 daha yüksek otizm riskiyle ilişkili olduğunu gösterdi.

Sonuç: İleri ebeveyn yaşı, çocuklarda otizm spektrum bozukluğu gelişimi ile anlamlı şekilde ilişkili bulunmuştur. Bu pozitif ilişkiyi daha fazla açıklığa kavuşturmak için daha fazla mekanistik çalışmaya ihtiyaç vardır.

Keywords

Otizm Spektrum Bozukluğu, İleri Ebeveyn Yaşları, Meta-analiz.

Advanced Parental Age Association with the Development of Autism Spectrum Disorder: Meta-analysis

Abstract

Background: Autism Spectrum Disorder (ASD) is one of the most frequent neurological conditions in infancy, afflicting about 1 in 36 children, with a male-to-female ratio of 4:5:1. Children with autism spectrum disorder often struggle with communication, social relationships, adjusting to rapid changes, as well as, confined repetitive modes of behavior, pursuits, and/or activities. This systematic review and meta-analysis was aimed to explore the link between advanced parental age risk factors and the development of autism spectrum disorders (ASDs) in youngsters. Methods: We searched and cross-referenced multiple databases, including Web of Science, PubMed, EMBASE, Medline, Scopus, CINAHL, and Cochrane Library, to find relevant studies to incorporate in this review and meta-analysis until June 2022. Statistical analysis was performed on Review Manager Version 5.4 software, and the risk estimates were pooled using random effect models. I2 tests were used to measure the heterogeneity. Results: The search yielded twenty-one studies that were included in the meta-analysis. Advanced parental age, compared to the reference points, was associated with a 59% surge in the development of risk of autism spectrum disorders in children with an OR (odds ratio) = 1.59 with 95% CI (1.45-1.74). Meta-regression analysis also demonstrated that an increase of 10 years in maternal and paternal age was associated with a 35% and 29% higher risk of autism, respectively. Conclusion: Advanced parental age was significantly associated with the development of autism spectrum disorder in children. More mechanistic studies are required to clarify this positive association further.

Keywords

Autism Spectrum Disorder, Advanced parental ages, Meta-analysis.

Ethical Statement

Since it is a meta-analysis study, there is no need for ethical approval.

Supporting Institution

No support was received. The article is derived from the first author's thesis.

References

• Al-Mamari, W., Idris, A. B., Al-Zadjali, A. A., Jalees, S., Murthi, S., Al-Jabri, M., Gabr, A., & Fombonne, E. (2021). Parental Age and the Risk of Autism Spectrum Disorder in Oman. Sultan Qaboos University Medical Journal [SQUMJ], 21(3), 465–471. https://doi.org/10.18295/squmj.4.2021.024.
• American Psychiatric Association. Diagnostic and statistical manual of mental disorders: DSM-III. 3rd ed. Washington, DC: American Psychiatric Association; 1980.
• American Psychiatric Association. Diagnostic and statistical manual of mental disorders: DSM-III-R. 3rd ed. Washington, DC: American Psychiatric Association; 1987
• American Psychiatric Association. Diagnostic and statistical manual of mental disorders: DSM-IV. 4th ed. Washington, DC: American Psychiatric Association; 1994. 10.
• American Psychiatric Association. Diagnostic and statistical manual of mental disorders: DSM-IV-R. 4th ed. Washington, DC: American Psychiatric Association; 2000.
• Andreas Stang (2010). Critical evaluation of the Newcastle-Ottawa scale for the assessment of the quality of nonrandomized studies in meta-analyses. , 25(9), 603–605. doi:10.1007/s10654-010-9491-z.
• Bilder, D.; Pinborough-Zimmerman, J.; Miller, J.; McMahon, W. (2009). Prenatal, Perinatal, and Neonatal Factors Associated With Autism Spectrum Disorders. PEDIATRICS, 123(5), 1293–1300. doi:10.1542/peds.2008-0927.
• Bishop, Somer L.; Havdahl, Karoline Alexandra; Huerta, Marisela; Lord, Catherine (2016). Subdimensions of social-communication impairment in autism spectrum disorder. Journal of Child Psychology and Psychiatry, (), n/a–n/a. doi:10.1111/jcpp.12510.
• Bölte, Sven; Girdler, Sonya; Marschik, Peter B. (2018). The contribution of environmental exposure to the etiology of autism spectrum disorder. Cellular and Molecular Life Sciences, (), –. doi:10.1007/s00018-018-2988-4
• Boyle, C. A.; Boulet, S.; Schieve, L. A.; Cohen, R. A.; Blumberg, S. J.; Yeargin-Allsopp, M.; Visser, S.; Kogan, M. D. (2011). Trends in the Prevalence of Developmental Disabilities in US Children, 1997-2008. PEDIATRICS, 127(6), 1034–1042. doi:10.1542/peds.2010-2989.
• Burstyn I, Sithole F, Zwaigenbaum L. Autism spectrum disorders, maternal characteristics and obstetric complications among singletons born in Alberta, Canada. Chronic Diseases in Canada. 2010 Sep;30(4):125-134. PMID: 20946713.
• Croen, L. A., Najjar, D. V., Fireman, B., & Grether, J. K. (2007). Maternal and Paternal Age and Risk of Autism Spectrum Disorders. Archives of Pediatrics & Adolescent Medicine, 161(4), 334. https://doi.org/10.1001/archpedi.161.4.334.
• Durkin, M. S., Maenner, M. J., Newschaffer, C. J., Lee, L.-C. ., Cunniff, C. M., Daniels, J. L., Kirby, R. S., Leavitt, L., Miller, L., Zahorodny, W., & Schieve, L. A. (2008). Advanced Parental Age and the Risk of Autism Spectrum Disorder. American Journal of Epidemiology, 168(11), 1268–1276. https://doi.org/10.1093/aje/kwn250.
• Eapen, Valsamma (2011). Autism - A Neurodevelopmental Journey from Genes to Behaviour || Genome-Wide Association Studies of Copy Number Variation in Autism Spectrum Disorder. , 10.5772/974(Chapter 9), –. doi:10.5772/22207.
• Erik Thorlund Parner, Baron-Cohen, S., Lauritsen, M. B., Jørgensen, M., Schieve, L. A., Yeargin-Allsopp, M., & Obel, C. (2012). Parental age and autism spectrum disorders. Annals of Epidemiology, 22(3), 143–150. https://doi.org/10.1016/j.annepidem.2011.12.006.
• Erin Rotheram-Fuller; Connie Kasari; Brandt Chamberlain; Jill Locke (2010). Social involvement of children with autism spectrum disorders in elementary school classrooms. Journal of Child Psychology and Psychiatry 51(11), 1227–1234. doi:10.1111/j.1469-7610.2010.02289.x
• Fajardo, J., Albores-Gallo, L., Genis-Mendoza, A. D., Martnez-Magaa, J. J., & Nicolini, H. (2020). Advanced paternal age as a risk factor for autism spectrum disorder in a Mexican population. Salud Mental, 43(3), 113–118. https://www.medigraphic.com/cgi-bin/new/resumenI.cgi?IDARTICULO=95278.
• Faraone, Stephen V.; Larsson, Henrik (2018). Genetics of attention deficit hyperactivity disorder. Molecular Psychiatry, (), –. doi:10.1038/s41380-018-0070-0.
• Franz L, Chambers N, von Isenburg M, de Vries PJ (2017) Autism spectrum disorder in sub-Saharan Africa: A comprehensive scoping review. Autism Research. 10,723-749. doi: 10.1002/aur.1766.
• Frazier, Thomas W.; Youngstrom, Eric A.; Speer, Leslie; Embacher, Rebecca; Law, Paul; Constantino, John; Findling, Robert L.; Hardan, Antonio Y.; Eng, Charis (2012). Validation of Proposed DSM-5 Criteria for Autism Spectrum Disorder. Journal of the American Academy of Child & Adolescent Psychiatry, 51(1), 28–40.e3. doi:10.1016/j.jaac.2011.09.021
• Gao, Y., Yu, Y., Xiao, J., Luo, J., Zhang, Y., Tian, Y., Zhang, J., Olsen, J., Li, J., & Liew, Z. (2020). Association of Grandparental and Parental Age at Childbirth With Autism Spectrum Disorder in Children. JAMA Network Open, 3(4), e202868. https://doi.org/10.1001/jamanetworkopen.2020.2868.
• Grether, J. K., Anderson, M. C., Croen, L. A., Smith, D., & Windham, G. C. (2009). Risk of Autism and Increasing Maternal and Paternal Age in a Large North American Population. American Journal of Epidemiology, 170(9), 1118–1126. https://doi.org/10.1093/aje/kwp247
• Hahler, Eva-Maria; Elsabbagh, Mayada (2015). Autism: A Global Perspective. Current Developmental Disorders Reports, 2(1), 58–64. doi:10.1007/s40474-014-0033-3.
• Hallmayer J, Cleveland S, Torres A, Phillips J, Cohen B, Torigoe T, et al. Genetic heritability and shared environmental factors among twin pairs with autism. Arch Gen Psychiatry (2011) 68(11):1095–102. doi:10.1001/archgenpsychiatry. 2011.76.
• Hultman, C M; Sandin, S; Levine, S Z; Lichtenstein, P; Reichenberg, A (2010). Advancing paternal age and risk of autism: new evidence from a population-based study and a meta-analysis of epidemiological studies. , 16(12), 1203–1212. doi:10.1038/mp.2010.121.
• Hultman, C. M. (2013). Autism Risk Across Generations. JAMA Psychiatry, 70(5), 516. https://doi.org/10.1001/jamapsychiatry.2013.1180.
• Hultman, C. M., Sandin, S., Levine, S. Z., Lichtenstein, P., & Reichenberg, A. (2010). Advancing paternal age and risk of autism: new evidence from a population-based study and a meta-analysis of epidemiological studies. Molecular Psychiatry, 16(12), 1203–1212. https://doi.org/10.1038/mp.2010.121
• Hultman, C. M., Sparén, P., & Cnattingius, S. (2002). Perinatal Risk Factors for Infantile Autism. Epidemiology, 13(4), 417–423. https://doi.org/10.1097/00001648-200207000-00009
• Hyman SL, Levy SE and Myers SM. Identification, evaluation and management of children with autism spectrum disorder. Pediatrics 2020; 145: e20193447.
• Jacobine E. Buizer-Voskamp; Wijnand Laan; Wouter G. Staal; Eric A.M. Hennekam; Maartje F. Aukes; Fabian Termorshuizen; René S. Kahn; Marco P.M. Boks; Roel A. Ophoff (2011). Paternal age and psychiatric disorders: Findings from a Dutch population registry. , 129(2-3), 128–132. doi:10.1016/j.schres.2011.03.021.
• Lampi, K. M., Hinkka-Yli-Salomäki, S., Lehti, V., Helenius, H., Gissler, M., Brown, A. S., & Sourander, A. (2013). Parental Age and Risk of Autism Spectrum Disorders in a Finnish National Birth Cohort. Journal of Autism and Developmental Disorders, 43(11), 2526–2535. https://doi.org/10.1007/s10803-013-1801-3
• Larsson, H. J., Eaton, W. W., Madsen, K. M., Vestergaard, M., Olesen, A. V., Agerbo, E., Schendel, D., Thorsen, P., & Mortensen, P. B. (2005). Risk Factors for Autism: Perinatal Factors, Parental Psychiatric History, and Socioeconomic Status. American Journal of Epidemiology, 161(10), 916–925. https://doi.org/10.1093/aje/kwi123
• Lauritsen, M. B., Pedersen, C. B., & Mortensen, P. B. (2005). Effects of familial risk factors and place of birth on the risk of autism: a nationwide register-based study. Journal of Child Psychology and Psychiatry, 46(9), 963–971. https://doi.org/10.1111/j.1469-7610.2004.00391.x.
• Leppa, Virpi M.; Kravitz, Stephanie N.; Martin, Christa Lese; Andrieux, Joris; Le Caignec, Cedric; Martin-Coignard, Dominique; DyBuncio, Christina; Sanders, Stephan J.; Lowe, Jennifer K.; Cantor, Rita M.; Geschwind, Daniel H. (2016). Rare Inherited and De Novo CNVs Reveal Complex Contributions to ASD Risk in Multiplex Families. The American Journal of Human Genetics, 99(3), 540–554. doi:10.1016/j.ajhg.2016.06.036
• Lyall, K., Croen, L., Daniels, J., Fallin, M. D., Ladd-Acosta, C., Lee, B. K., Park, B. Y., Snyder, N. W., Schendel, D., Volk, H., Windham, G. C., & Newschaffer, C. (2017). The Changing Epidemiology of Autism Spectrum Disorders. Annual Review of Public Health, 38(1), 81–102. https://doi.org/10.1146/annurev-publhealth-031816-044318
• Lyall, K., Song, L., Botteron, K., Croen, L. A., Dager, S. R., Fallin, M. D., Hazlett, H. C., Kauffman, E., Landa, R., Ladd‐Acosta, C., Messinger, D. S., Ozonoff, S., Pandey, J., Piven, J., Schmidt, R. J., Schultz, R. T., Stone, W. L., Newschaffer, C. J., & Volk, H. E. (2020). The Association Between Parental Age and Autism‐Related Outcomes in Children at High Familial Risk for Autism. Autism Research, 13(6), 998–1010. https://doi.org/10.1002/aur.2303.
• McGrath, J. J., Petersen, L., Agerbo, E., Mors, O., Mortensen, P. B., & Pedersen, C. B. (2014). A Comprehensive Assessment of Parental Age and Psychiatric Disorders. JAMA Psychiatry, 71(3), 301. https://doi.org/10.1001/jamapsychiatry.2013.4081.
• Modabbernia, Amirhossein; Velthorst, Eva; Reichenberg, Abraham (2017). Environmental risk factors for autism: an evidence-based review of systematic reviews and meta-analyses. Molecular Autism, 8(1), 13–. doi:10.1186/s13229-017-0121-4.
• Moher, D., Liberati, A., Tetzlaff, J., Altman, D. G., & The PRISMA Group. (2009). Preferred Reporting Items for Systematic Reviews and Meta-Analyses: the PRISMA Statement. PLoS Medicine, 6(7), e1000097. https://doi.org/10.1371/journal.pmed.1000097.
• Myers, Scott M.; Voigt, Robert G.; Colligan, Robert C.; Weaver, Amy L.; Storlie, Curtis B.; Stoeckel, Ruth E.; Port, John D.; Katusic, Slavica K. (2018). Autism Spectrum Disorder: Incidence and Time Trends Over Two Decades in a Population-Based Birth Cohort. Journal of Autism and Developmental Disorders, (), –. doi:10.1007/s10803-018-3834-0
• P. Bolton; H. Macdonald; A. Pickles; P. Rios; S. Goode; M. Crowson; A. Bailey; M. Rutter (1994). A Case-Control Family History Study of Autism, 35(5), 877–900. doi:10.1111/j.1469-7610.1994.tb02300.x.
• Reichenberg, A., Gross, R., Weiser, M., Bresnahan, M., Silverman, J., Harlap, S., Rabinowitz, J., Shulman, C., Malaspina, D., Lubin, G., Knobler, H. Y., Davidson, M., & Susser, E. (2006). Advancing Paternal Age and Autism. Archives of General Psychiatry, 63(9), 1026. https://doi.org/10.1001/archpsyc.63.9.1026.
• Rice, C. E., Rosanoff, M., Dawson, G., Durkin, M. S., Croen, L. A., Singer, A., & Yeargin-Allsopp, M. (2012). Evaluating Changes in the Prevalence of the Autism Spectrum Disorders (ASDs). Public Health Reviews, 34(2). doi:10.1007/bf03391685.
• Sandin, S., Hultman, C. M., Kolevzon, A., Gross, R., MacCabe, J. H., & Reichenberg, A. (2012). Advancing Maternal Age Is Associated With Increasing Risk for Autism: A Review and Meta-Analysis. Journal of the American Academy of Child & Adolescent Psychiatry, 51(5), 477-486.e1. https://doi.org/10.1016/j.jaac.2012.02.018
• 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. (2015). Autism risk associated with parental age and with increasing difference in age between the parents. Molecular Psychiatry, 21(5), 693–700. https://doi.org/10.1038/mp.2015.70.
• Sasanfar, R., Haddad, S. A., Tolouei, A., Ghadami, M., Yu, D., & Santangelo, S. L. (2010). Paternal age increases the risk for autism in an Iranian population sample. Molecular Autism, 1(1), 2. https://doi.org/10.1186/2040-2392-1-2.
• Schaaf CP, Zoghbi HY. Solving the autism puzzle a few pieces at a time. Neuron. 2011;70:806–8.
• Schaefer GB, Mendelsohn NJ, Professional P, Guidelines C. Clinical genetics evaluation in identifying the etiology of autism spectrum disorders: 2013 guideline revisions. Genet Med 2013; 15: 399407.
• Schaefer, G. (2016). Clinical Genetic Aspects of Autism Spectrum Disorders. International Journal of Molecular Sciences, 17(2), 180–. doi:10.3390/ijms17020180
• Sebastian Lundström; Claire M.A. Haworth; Eva Carlström; Christopher Gillberg; Jonathan Mill; Maria Råstam; Christina M. Hultman; Angelica Ronald; Henrik Anckarsäter; Robert Plomin; Paul Lichtenstein; Abraham Reichenberg (2010). Trajectories leading to autism spectrum disorders are affected by paternal age: findings from two nationally representative twin studies. , 51(7), 850–856. doi:10.1111/j.1469-7610.2010.02223.x.
• Shelton, J. F., Tancredi, D. J., & Hertz-Picciotto, I. (2010). Independent and dependent contributions of advanced maternal and paternal ages to autism risk. Autism Research, n/a-n/a. https://doi.org/10.1002/aur.116.
• Tsuchiya, K. J., Matsumoto, K., Miyachi, T., Tsujii, M., Nakamura, K., Takagai, S., Kawai, M., Yagi, A., Iwaki, K., Suda, S., Sugihara, G., Iwata, Y., Matsuzaki, H., Sekine, Y., Suzuki, K., Sugiyama, T., Mori, N., & Takei, N. (2008). Paternal age at birth and high-functioning autistic-spectrum disorder in offspring. British Journal of Psychiatry, 193(4), 316–321. https://doi.org/10.1192/bjp.bp.107.045120.
• Turkheimer E, Waldron M. Nonshared environment: a theoretical, methodological, and quantitative review. Psychol Bull. 2000;126:78–108.
• Van Balkom, Ingrid D. C.; Bresnahan, Michaeline; Vuijk, Pieter Jelle; Hubert, Jan; Susser, Ezra; Hoek, Hans W.; Burne, Thomas (2012). Paternal Age and Risk of Autism in an Ethnically Diverse, Non-Industrialized Setting: Aruba. PLoS ONE, 7(9), e45090–. doi:10.1371/journal.pone.0045090.
• Wu, S., Ding, Y., Wu, F., Li, R., Xie, G., Hou, J., & Mao, P. (2015). Family history of autoimmune diseases is associated with an increased risk of autism in children: A systematic review and meta-analysis. Neuroscience & Biobehavioral Reviews, 55(322-32), 322–332. https://doi.org/10.1016/j.neubiorev.2015.05.004.
• Wu, S., Wu, F., Ding, Y., Hou, J., Bi, J., & Zhang, Z. (2016). Advanced parental age and autism risk in children: a systematic review and meta-analysis. Acta Psychiatrica Scandinavica, 135(1), 29–41. https://doi.org/10.1111/acps.12666.