Developmental origins of the Autism Spectrum Disorder in the Middle East and North Africa Region: A Systematic Review and Meta-Analysis of adjusted risk factors

Background and ObjectivesThe etiology of autism spectrum disorder (ASD) is poorly understood, with sparse data from the Middle East and North Africa (MENA) region, which has a unique climate and socio-epidemiological setting. This research investigated the developmental (early life) risk factors associated with ASD in the MENA region. MethodsIn this systematic review and meta-analysis, we searched for observational studies, which carried out adjusted analyses for ASD risk factors in the MENA region, in PubMed, Embase, Scopus, and CINAHL databases. We analyzed associations between ASD and factors related to conception, inheritance, maternal morbidity during pregnancy and adverse pregnancy outcomes. After study quality assessment, meta-analyses for each risk factor were carried out using the bias-adjusted inverse variance heterogeneity model. Heterogeneity was assessed using I2 and publication bias using Doi and funnel plots. ResultsThe systematic review included 19 case control studies from eight countries within the MENA region. In overall synthesis, male sex (OR=3.27, 95% CI: 2.39-4.48, I2 = 40.9%), family history of ASD (OR=2.98, 95% CI: 0.51-17.31, I2 = 85.0%), and consanguinity (OR= 1.77, 95% CI: 1.38-2.28, I2 = 57.1%) were associated with ASD. Although with limited studies, a review of the literature showed some possible associations between ASD and gestational diabetes, gestational hypertension, macrosomia, NICU admission, respiratory distress syndrome, cesarean delivery, gestational age, and older maternal age. ConclusionThese findings confirm the association between male sex, family history of ASD and consanguinity with ASD, potentially suggesting some inherited mechanism in the etiology of ASD in the MENA region. Some maternal co-morbidities during pregnancy and adverse pregnancy outcomes may contribute to ASD risk in the MENA region, although more studies are needed in the region. RegistrationThe protocol for this systematic review and meta-analysis is registered on the International Prospective Register of Systematic Reviews (PROSPERO) with registration ID CRD42024499837.