We examined birth and diagnostic records for all children born in California between 1992 and 2000. Over the entire period, we analyzed 4906926 birth records. Of these, 18731 could be matched to children with a diagnosis of autism. To identify autism cases, we combined birth records obtained from the California Birth Master Files and the California Department of Developmental Services (DDS). The analysis began with the birth cohort of 1992, the first year the DDS began maintaining electronic records. To ensure that all children had ample time for case ascertainment, the analyses ended with the birth cohort of 2000. All children were followed from the time of birth until June 2006. Differential ascertainment times were allowed because the age of diagnosis for autism fell consistently from a mean of 5.9 years (±2.9) in the 1992 birth cohort to 3.8 years (±0.9) in the 2000 cohort.
The DDS coordinates diagnoses, services, and support for persons living in California with developmental disabilities, including mental retardation and autism. The agency provides services to patients with full syndrome autism (International Classification of Diseases, Ninth Revision, Clinical Modification
). Services are not available to persons diagnosed with Asperger disorder, childhood disintegrative disorder, Rett disorder, or pervasive developmental disorder-not otherwise specified. Although enrollment with the DDS is optional, it is estimated that 75% to 80% of persons with autism in California are enrolled,19
making the DDS the largest administrative source of autism diagnostic information.
To obtain demographic information for persons with and without autism, records from the DDS and Birth Master Files were electronically linked by using probabilistic and deterministic matching algorithms developed by Campbell.20
Matches were made on the basis of first, middle, and last name; date of birth; race; zip code at birth; and gender. Uncertain matches were manually reviewed. On average, 81% of the DDS files were linked to birth records. The linkage rate increased over time from 79% (1992) to 86% (2000). DDS files that could not be linked typically belonged to children who were born outside of California and later moved to the state.
Our primary variables of interest, maternal and paternal age at birth, were extracted from birth certificates. Data on paternal age for the entire population was missing from 8% of the birth records. Persons subsequently diagnosed with autism were more likely to have missing paternal age data, ranging from 8% to 10% depending on the birth cohort. Maternal age was rarely missing (<1%). We also obtained the following control variables from the birth certificates: child’s gender, race, birthweight, and duration of gestation; whether the child was a single or multiple-birth; and parity of the mother. Birthweight was examined categorically with birthweight less than 2500 grams considered low birthweight. Gestational age less than 35 weeks was considered premature. Whether the newborn was placed in a neonatal intensive care unit was extracted from the birth records as well. If a newborn had a birthweight greater than 2500 grams and a gestational age of more than 35 weeks but was admitted to the neonatal intensive care unit, this variable was set to 1. Otherwise, it was set to 0. Parity was used to generate a dummy variable for first birth. In addition to these variables, all analyses also included maternal and paternal education.
To examine the associations between maternal and paternal ages and autism, we conducted 3 sets of analyses. First, we ascertained the association between maternal and paternal age and autism for each birth cohort from 1992 to 2000. To do this, we ran logistic regressions treating parental age as a categorical variable (< 30, 30–34, 35–39, and ≥40 years). All of the control variables identified previously were included in the models.
Second, to observe the effect of pooling data, we cumulatively pooled across birth cohorts. Using a moving window for the 1995 birth cohort, we pooled data from the 1992, 1993, 1994, and 1995 birth cohorts; for the 1996 birth cohort, we pooled observations from the birth cohorts of 1992 to 1996, and so on. This allowed us to mimic the method used in most of the previous studies, which pooled data across birth cohorts.
Problems may arise from pooling data across birth cohorts. Categorical specifications are particularly prone to reversal paradoxes in contexts in which there are large differences by group in the denominators of a rate.21
To assess the effect these problems may have had on previous studies, we first examined whether there were large by-group differences in maternal and paternal age, as well as how these differences changed over time. Last, we conducted logistic regressions by using a decomposition strategy.
In this approach, maternal and paternal ages were considered in a continuous framework; that is, we did not treat age as a categorical variable. The decomposition was necessary to avoid the multicollinearity problems that arise when simultaneously including continuous maternal and paternal age in a regression. The decomposition enabled us to disentangle whether paternal or maternal age had a stronger association with autism while avoiding some of the problems generated by multicollinearity and categorical specifications. The decomposition was as follows:
is maternal age and Af
is paternal age. For instance, assume the case of a 32-year-old mother and a 35-year-old father. The sum of their ages, (Am
), is 67. The difference in their ages, (Am
), is −3. Following the decomposition, adding the sum, γ1
), and the difference, γ2
), gives us 64. This is twice the mother’s age. Similarly, the difference, (Am
) − (Am
)=70, is twice the father’s age. Using this approach, we can disentangle parental age effects without significant multicollinearity by including the sum and the difference of parental ages as separate terms and then rearranging the parameter estimates from the analysis to recover the parameters for maternal and paternal age. In the decomposition, β represents 2 parental years.