Association of Autism with Maternal Infections, Perinatal and Other Risk Factors: A Case-Control Study
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.
KeywordsAutism Risk factors Maternal infections Perinatal factors Consanguinity
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).
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.
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 was obtained from all individual participants included in the study.
- American Psychiatric Association. (1993). DSM-IV draft criteria: Amer Psychiatric Pub Incorporated.Google Scholar
- American Psychiatric Association. (2013). Diagnostic and statistical manual of mental disorders (DSM-5®): American Psychiatric Pub.Google Scholar
- 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
- 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
- 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
- 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
- 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
- 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/.
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- Rizk, F., Salameh, P., & Hamadé, A. (2014). Congenital anomalies: Prevalence and risk factors. Universal Journal of Public Health, 2(2), 58–63.Google Scholar
- 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