Little is understood about the causal mechanisms underlying autism spectrum disorders (ASD). Prenatal risk factors, including maternal obstetric characteristics, labor and delivery complications, and neonatal problems have all been associated significantly with autism.
Objectives:
1. To define the prevalence rates of in vitro fertilization (IVF) and prematurity in a cohort with ASD and compare them to the general Israeli population rates
2. To examine possible relationships between prenatal IVF and prematurity to autism severity, adaptive skills and developmental trajectories (regression/no regression)
Methods:
The study included 564 children who came to a tertiary autism center in Israel for a comprehensive evaluation. A pediatric neurologist obtained birth and developmental histories and performed a neurological examination. Evaluations of autism severity and of adaptive skills were performed using standardized tests [Autism Diagnosis Interview (ADI-R), Autism Diagnosis Observation Schedule (ADOS, the new ADOS severity scale and Vineland Adaptive Behavior Scales].
Results:
Of the 564 participants, 461 (81%) children, (M=39.8 months, SD=26.3) were diagnosed with ASD. IVF was present in 10.2% (47/438) which was significantly higher than the rate in the general Israeli population (3.5%) (χ2=73.5, p<0.001). Maternal age (M=32.6y, SD=4.8) in the IVF group was significantly higher than in the non-IVF group (M=30.8y, SD=5.6) [F(1,425)=4.9, p<.05, h2=.011]. Paternal ages in the two groups were not significantly different. There were no significant differences between the IVF and the non-IVF groups in mean age (months) at evaluation (M=43 vs 40), ADOS mean severity score (M=7.6, SD=1.7 vs 7.5, SD=2.1), mean Vineland composite scores (M=71.8, SD=11.2 vs M=71.9, SD=15.3), and history of regression [8/47 (17%) vs 99/381 (26%)].
Prematurity: Of the ASD cohort, the birthweight of 17/354 (4.8%) was below 1500 gr. (low birthweight=LBW), which was significantly higher than the 1% in the general Israeli population (χ2= 37.3, p<0.001). There was no difference in the ADOS severity score between the LBW group (M=7.3, SD=2) and the >1500 gr. group (M=7.5, SD=2). The LBW group had significantly lower adaptive composite scores (M=62.3, SD=18.7) than the >1500 gr. group (M=72.1, SD=14) [F(1,264)=4.4, p<.05, h2=.016]. When looking at the Vineland specific domains, the LBW group had significantly lower scores than the >1500 gr. group in daily living skills (DLS), socialization and motor scores (p<0.5).
Gestational age: Of 417 participants, 16 (3.8%) had gestational age (GA) <32 weeks. There was no difference in the ADOS severity score between GA <32 w (7.1, SD=1.9) and GA >32 w (M=7.5, SD=2.1). However, the GA <32 w had significantly lower adaptive composite scores (M=55.0, DS=1.9) than the GA >32 w (M=67.0, SD=9.6) [F(1,277)=12.9, p<.001, h2=.044]. Specifically, the GA <32 w group had lower DLS and motor skills scores than the GA >32 w (p<0.01) but did not significantly differ in communication and socialization scores.
Conclusions:
Prevalence rates of IVF and LBW were significantly higher in the ASD cohort than in the general population, adding to previous reports on birth risk factors in autism. These birth risk factors are not associated with autism severity and do not suggest a specific clinical subtype, but add to the severity of the child's general functioning.