Abstract
BackgroundAutism spectrum disorders (ASD) are associated with complications of pregnancy that implicate fetal hypoxia (FH); the excess of ASD in male gender is poorly understood. We tested the hypothesis that risk of ASD is related to fetal hypoxia and investigated whether this effect is greater among males.MethodsProvincial delivery records (PDR) identified the cohort of all 218,890 singleton live births in the province of Alberta, Canada, between 01-01-98 and 12-31-04. These were followed-up for ASD via ICD-9 diagnostic codes assigned by physician billing until 03-31-08. Maternal and obstetric risk factors, including FH determined from blood tests of acidity (pH), were extracted from PDR. The binary FH status was missing in approximately half of subjects. Assuming that characteristics of mothers and pregnancies would be correlated with FH, we used an Estimation-Maximization algorithm to estimate HF-ASD association, allowing for both missing-at-random (MAR) and specific not-missing-at-random (NMAR) mechanisms.ResultsData indicated that there was excess risk of ASD among males who were hypoxic at birth, not materially affected by adjustment for potential confounding due to birth year and socio-economic status: OR 1.13, 95%CI: 0.96, 1.33 (MAR assumption). Limiting analysis to full-term males, the adjusted OR under specific NMAR assumptions spanned 95%CI of 1.0 to 1.6.ConclusionOur results are consistent with a weak effect of fetal hypoxia on risk of ASD among males. E-M algorithm is an efficient and flexible tool for modeling missing data in the studied setting.
Highlights
Autism spectrum disorders (ASD) are associated with complications of pregnancy that implicate fetal hypoxia (FH); the excess of ASD in male gender is poorly understood
If fetal hypoxia were likely among boys and girls, but boys were more susceptible to its effect on ASD risk, this would contribute to explaining male predominance among ASD patients
There were 273,343 singleton live births in Alberta according to Alberta Perinatal Health Program (APHP) records between 1998 and 2004, among whom 25,970 children could not be identified by AHW and 28,421 either died, or lost residence during follow-up; a further 62 had missing gender, leaving 218,890 children for analysis
Summary
Autism spectrum disorders (ASD) are associated with complications of pregnancy that implicate fetal hypoxia (FH); the excess of ASD in male gender is poorly understood. We tested the hypothesis that risk of ASD is related to fetal hypoxia and investigated whether this effect is greater among males. While some genetic risk factors juvenile mice following prenatal hypoxic insults, that males are more susceptible to development of maladaptive stress responses associated with many neurodevelopmental disorders such as ASD. They suggested that this vulnerability is determined by sex-specific differences in placental physiology[14]. If fetal hypoxia were likely among boys and girls, but boys were more susceptible to its effect on ASD risk, this would contribute to explaining male predominance among ASD patients
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