Association of Autism with Maternal Infections, Perinatal and Other Risk Factors: A Case-Control Study

  • Dikran Richard Guisso
  • Fadi S. Saadeh
  • Dahlia Saab
  • Joud El Deek
  • Sarah Chamseddine
  • Hadi Abou El Hassan
  • Ghidaa Majari
  • Rose-Mary Boustany
Original Paper

Abstract

This case-control study explores the association between pregnancy/birth complications and other factors with Autism Spectrum Disorder (ASD) in Lebanese subjects aged 2–18 years. Researchers interviewed 136 ASD cases from the American University of Beirut Medical Center Special Kids Clinic, and 178 controls selected by systematic digit dialing in the Greater-Beirut area. Male gender (Adjusted Odds Ratio [95% CI]: 3.9 [2.2–7.0]); postpartum feeding difficulties (2.5 [1.2–5.4]); maternal infections/complications during pregnancy (2.9 [1.5–5.5], 2.1 [1.1–3.9]); consanguinity (2.5 [1.0–6.0]); family history of psychiatric disorders (2.2 [1.1–4.4]) were risk factors for ASD. Being born first/second (0.52 [0.28–0.95]) and maternal psychological support during pregnancy (0.49 [0.27–0.89]) were negatively associated with ASD. Identifying ASD correlates is crucial for instigating timely screening and subsequent early intervention.

Keywords

Autism Risk factors Maternal infections Perinatal factors Consanguinity 

Notes

Acknowledgments

The authors would like to acknowledge the efforts of Mr. Chris Kaspar for his assistance in data collection. This study was funded by OpenMinds (private foundation/NGO).

Author Contributions

DRG conceived of the study, participated in its design, data collection and interpretation, performed statistical analysis and drafted the manuscript; FSS conceived of the study, participated in its design, data collection and interpretation and drafted the manuscript; DS conceived of the study, participated in its design and coordination, performed statistical analysis and data interpretation and drafted the manuscript; JED, SC, HAEH and GM conceived of the study, participated in its design, data collection and interpretation, and assisted in drafting the manuscript; RMB conceived of the study, participated in its design and coordination, interpreted the data and drafted the manuscript. All authors read and approved the final manuscript.

Compliance with Ethical Standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study.

Supplementary material

10803_2017_3449_MOESM1_ESM.docx (12 kb)
Supplementary material 1 (DOCX 12 KB)
10803_2017_3449_MOESM2_ESM.docx (31 kb)
Supplementary material 2 (DOCX 30 KB)
10803_2017_3449_MOESM3_ESM.docx (56 kb)
Supplementary material 3 (DOCX 56 KB)

References

  1. American Psychiatric Association. (1993). DSM-IV draft criteria: Amer Psychiatric Pub Incorporated.Google Scholar
  2. American Psychiatric Association. (2013). Diagnostic and statistical manual of mental disorders (DSM-5®): American Psychiatric Pub.Google Scholar
  3. Atladottir, H. O., Thorsen, P., Ostergaard, L., Schendel, D. E., Lemcke, S., Abdallah, M., et al. (2010). Maternal infection requiring hospitalization during pregnancy and autism spectrum disorders. Journal of Autism and Developmental Disorders, 40(12), 1423–1430.  https://doi.org/10.1007/s10803-010-1006-y.CrossRefPubMedGoogle Scholar
  4. Barbour, B., & Salameh, P. (2009). Consanguinity in Lebanon: Prevalence, distribution and determinants. Journal of Biosocial Science, 41(4), 505–517.  https://doi.org/10.1017/S0021932009003290.CrossRefPubMedGoogle Scholar
  5. Blake, N. M., Kirk, R. L., McDermid, E. M., Case, J., & Bashir, H. (1973). The distribution of blood, serum protein and enzyme groups in a series of Lebanese in Australia. The Australian Journal of Experimental Biology and Medical Science, 51(2), 209–220.CrossRefPubMedGoogle Scholar
  6. Burstyn, I., Wang, X., Yasui, Y., Sithole, F., & Zwaigenbaum, L. (2011). Autism spectrum disorders and fetal hypoxia in a population-based cohort: Accounting for missing exposures via estimation-maximization algorithm. BMC Medical Research Methodology, 11(1), 2.CrossRefPubMedPubMedCentralGoogle Scholar
  7. Chaaya, M., Saab, D., Maalouf, F. T., & Boustany, R. M. (2016). Prevalence of autism spectrum disorder in nurseries in Lebanon: A Cross Sectional Study. Journal of Autism and Developmental Disorders, 46(2), 514–522.  https://doi.org/10.1007/s10803-015-2590-7.CrossRefPubMedGoogle Scholar
  8. Chaste, P., & Leboyer, M. (2012). Autism risk factors: Genes, environment, and gene-environment interactions. Dialogues in Clinical Neuroscience, 14(3), 281.PubMedPubMedCentralGoogle Scholar
  9. Christensen, D. L., Baio, J., Van Naarden Braun, K., Bilder, D., Charles, J., Constantino, J. N., et al. (2016). Prevalence and characteristics of autism spectrum disorder among children aged 8 years–autism and developmental disabilities monitoring Network, 11 Sites, United States, 2012. Morbidity and Mortality Weekly Report. Surveillance Summaries, 65(3), 1–23.  https://doi.org/10.15585/mmwr.ss6503a1.PubMedGoogle Scholar
  10. Collier, S. A., Rasmussen, S. A., Feldkamp, M. L., & Honein, M. A., & National Birth Defects Prevention, S (2009).Prevalence of self-reported infection during pregnancy among control mothers in the National Birth Defects Prevention Study. Birth Defects Research. Part A, Clinical and Molecular Teratology, 85(3), 193–201.  https://doi.org/10.1002/bdra.20540.CrossRefPubMedGoogle Scholar
  11. Deykin, E. Y., & MacMahon, B. (1979). Viral exposure and autism. American Journal of Epidemiology, 109(6), 628–638.CrossRefPubMedGoogle Scholar
  12. El Rafei, R., Abbas, H. A., Charafeddine, L., Nakad, P., Al Bizri, A., Hamod, D., et al. (2016). Association of pre-pregnancy body mass index and gestational weight gain with preterm births and fetal size: An observational study from Lebanon. Paediatric and Perinatal Epidemiology, 30(1), 38–45.CrossRefPubMedGoogle Scholar
  13. El-Fishawy, P., & State, M. W. (2010). The genetics of autism: Key issues, recent findings, and clinical implications. Psychiatric Clinics of North America, 33(1), 83–105.  https://doi.org/10.1016/j.psc.2009.12.002.CrossRefPubMedPubMedCentralGoogle Scholar
  14. Frazier, T. W., Georgiades, S., Bishop, S. L., & Hardan, A. Y. (2014). Behavioral and cognitive characteristics of females and males with autism in the Simons Simplex Collection. Journal of the American Academy of Child & Adolescent Psychiatry, 53(3), 329–340.CrossRefGoogle Scholar
  15. Furfaro, H. (2017). Doctors twice as likely to miss girls as boys on autism screen Spectrum. Retrieved from https://spectrumnews.org/news/doctors-twice-likely-miss-girls-boys-autism-screen/.
  16. Gardener, H., Spiegelman, D., & Buka, S. L. (2009). Prenatal risk factors for autism: Comprehensive meta-analysis. The British Journal of Psychiatry, 195(1), 7–14.CrossRefPubMedPubMedCentralGoogle Scholar
  17. Goldin, R. L., & Matson, J. L. (2016). Premature birth as a risk factor for autism spectrum disorder. Developmental Neurorehabilitation, 19(3), 203–206.  https://doi.org/10.3109/17518423.2015.1044132.PubMedGoogle Scholar
  18. Guy, A., Seaton, S. E., Boyle, E. M., Draper, E. S., Field, D. J., Manktelow, B. N., et al. (2015). Infants born late/moderately preterm are at increased risk for a positive autism screen at 2 years of age. Journal of Pediatrics, 166(2), 269–275 e263.  https://doi.org/10.1016/j.jpeds.2014.10.053.CrossRefPubMedGoogle Scholar
  19. Hamade, A., Salameh, P., Medlej-Hashim, M., Hajj-Moussa, E., Saadallah-Zeidan, N., & Rizk, F. (2013). Autism in children and correlates in Lebanon: A pilot case-control study. Journal of Research in Health Sciences, 13(2), 119–124.PubMedGoogle Scholar
  20. Hiller, R. M., Young, R. L., & Weber, N. (2014). Sex differences in autism spectrum disorder based on DSM-5 criteria: Evidence from clinician and teacher reporting. Journal of Abnormal Child Psychology, 42(8), 1381–1393.CrossRefPubMedGoogle Scholar
  21. Hultman, C. M., Sparén, P., & Cnattingius, S. (2002). Perinatal risk factors for infantile autism. Epidemiology, 13(4), 417–423.CrossRefPubMedGoogle Scholar
  22. Hussein, H., Taha, G. R., & Almanasef, A. (2011). Characteristics of autism spectrum disorders in a sample of egyptian and saudi patients: Transcultural cross sectional study. Child and Adolescent Psychiatry and Mental Health, 5, 34.  https://doi.org/10.1186/1753-2000-5-34.CrossRefPubMedPubMedCentralGoogle Scholar
  23. Kerstjens, J. M., de Winter, A. F., Bocca-Tjeertes, I. F., Bos, A. F., & Reijneveld, S. A. (2012). Risk of developmental delay increases exponentially as gestational age of preterm infants decreases: A cohort study at age 4 years. Developmental Medicine and Child Neurology, 54(12), 1096–1101.  https://doi.org/10.1111/j.1469-8749.2012.04423.x.CrossRefPubMedGoogle Scholar
  24. Kim, Y. S., & Leventhal, B. L. (2015). Genetic epidemiology and insights into interactive genetic and environmental effects in autism spectrum disorders. Biological Psychiatry, 77(1), 66–74.CrossRefPubMedGoogle Scholar
  25. Kim, Y. S., Leventhal, B. L., Koh, Y.-J., Fombonne, E., Laska, E., Lim, E.-C., et al. (2011). Prevalence of autism spectrum disorders in a total population sample. American Journal of Psychiatry, 168(9), 904–912.CrossRefPubMedGoogle Scholar
  26. Kogan, M. D., Blumberg, S. J., Schieve, L. A., Boyle, C. A., Perrin, J. M., Ghandour, R. M., et al. (2009). Prevalence of parent-reported diagnosis of autism spectrum disorder among children in the US, 2007. Pediatrics, 124(5), 1395–1403.  https://doi.org/10.1542/peds.2009-1522.CrossRefPubMedGoogle Scholar
  27. Kolevzon, A., Gross, R., & Reichenberg, A. (2007). Prenatal and perinatal risk factors for autism: A review and integration of findings. Archives of Pediatrics & Adolescent Medicine, 161(4), 326–333.CrossRefGoogle Scholar
  28. Kuzniewicz, M. W., Wi, S., Qian, Y., Walsh, E. M., Armstrong, M. A., & Croen, L. A. (2014). Prevalence and neonatal factors associated with autism spectrum disorders in preterm infants. The Journal of Pediatrics, 164(1), 20–25.CrossRefPubMedGoogle Scholar
  29. Lampi, K. M., Lehtonen, L., Tran, P. L., Suominen, A., Lehti, V., Banerjee, P. N., et al. (2012). Risk of autism spectrum disorders in low birth weight and small for gestational age infants. The Journal of Pediatrics, 161(5), 830–836.CrossRefPubMedPubMedCentralGoogle Scholar
  30. Larsson, H. J., Eaton, W. W., Madsen, K. M., Vestergaard, M., Olesen, A. V., Agerbo, E., et al. (2005). Risk factors for autism: Perinatal factors, parental psychiatric history, and socioeconomic status. American Journal of Epidemiology, 161(10), 916–925.CrossRefPubMedGoogle Scholar
  31. Lavelle, T. A., Weinstein, M. C., Newhouse, J. P., Munir, K., Kuhlthau, K. A., & Prosser, L. A. (2014). Economic burden of childhood autism spectrum disorders. Pediatrics, 133(3), e520–e529.  https://doi.org/10.1542/peds.2013-0763.CrossRefPubMedGoogle Scholar
  32. Lee, B. K., Magnusson, C., Gardner, R. M., Blomstrom, A., Newschaffer, C. J., Burstyn, I., et al. (2015). Maternal hospitalization with infection during pregnancy and risk of autism spectrum disorders. Brain, Behavior, and Immunity, 44, 100–105.  https://doi.org/10.1016/j.bbi.2014.09.001.CrossRefPubMedGoogle Scholar
  33. Limperopoulos, C., Bassan, H., Sullivan, N. R., Soul, J. S., Robertson, R. L. Jr., Moore, M., et al. (2008). Positive screening for autism in ex-preterm infants: Prevalence and risk factors. Pediatrics, 121(4), 758–765.  https://doi.org/10.1542/peds.2007-2158.CrossRefPubMedPubMedCentralGoogle Scholar
  34. Mazina, V., Gerdts, J., Trinh, S., Ankenman, K., Ward, T., Dennis, M. Y., et al. (2015). Epigenetics of autism-related impairment: Copy number variation and maternal infection. Journal of Developmental and Behavioral Pediatrics, 36(2), 61–67.  https://doi.org/10.1097/DBP.0000000000000126.CrossRefPubMedPubMedCentralGoogle Scholar
  35. McGinnis, W. R., Audhya, T., & Edelson, S. M. (2013). Proposed toxic and hypoxic impairment of a brainstem locus in autism. International Journal of Environmental Research and Public Health, 10(12), 6955–7000.CrossRefPubMedPubMedCentralGoogle Scholar
  36. Moore, G. S., Kneitel, A. W., Walker, C. K., Gilbert, W. M., & Xing, G. (2012). Autism risk in small- and large-for-gestational-age infants. American Journal of Obstetrics & Gynecology, 206(4), 314.  https://doi.org/10.1016/j.ajog.2012.01.044.Google Scholar
  37. Newschaffer, C. J., Fallin, D., & Lee, N. L. (2002). Heritable and nonheritable risk factors for autism spectrum disorders. Epidemiologic Reviews, 24(2), 137–153.CrossRefPubMedGoogle Scholar
  38. Rizk, F., Salameh, P., & Hamadé, A. (2014). Congenital anomalies: Prevalence and risk factors. Universal Journal of Public Health, 2(2), 58–63.Google Scholar
  39. Salhia, H. O., Al-Nasser, L. A., Taher, L. S., Al-Khathaami, A. M., & El-Metwally, A. A. (2014). Systemic review of the epidemiology of autism in Arab Gulf countries. Neurosciences, 19(4), 291–296.PubMedPubMedCentralGoogle Scholar
  40. Soueid, J., Kourtian, S., Makhoul, N. J., Makoukji, J., Haddad, S., Ghanem, S. S., et al. (2016). RYR2, PTDSS1 and AREG genes are implicated in a Lebanese population-based study of copy number variation in autism. Scientific Reports, 6, 19088.  https://doi.org/10.1038/srep19088.CrossRefPubMedPubMedCentralGoogle Scholar
  41. Tordjman, S., Somogyi, E., Coulon, N., Kermarrec, S., Cohen, D., Bronsard, G., et al. (2014). Gene × Environment interactions in autism spectrum disorders: Role of epigenetic mechanisms. Frontiers in Psychiatry, 5, e53.CrossRefGoogle Scholar
  42. Volpe, J. J. (2009). Brain injury in premature infants: A complex amalgam of destructive and developmental disturbances. The Lancet Neurology, 8(1), 110–124.  https://doi.org/10.1016/S1474-4422(08)70294-1.CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Faculty of MedicineAmerican University of BeirutBeirutLebanon
  2. 2.Department of Biochemistry and Molecular GeneticsAmerican University of BeirutBeirutLebanon
  3. 3.Department of Pediatrics and Adolescent MedicineAmerican University of BeirutBeirutLebanon

Personalised recommendations