Maternal and paternal age and risk of autism spectrum disorders.

OBJECTIVE: To explore the association between maternal and paternal age and risk of autism spectrum disorders (ASDs) in offspring. DESIGN: Historical birth cohort study. SETTING: Kaiser Permanente (KP) in Northern California. PARTICIPANTS: All singleton children born at KP from January 1, 1995, to December 31, 1999, were included in the study. We identified 593 children who had ASD diagnoses (International Classification of Diseases, Ninth Revision, Clinical Modification, code 299.0 or 299.8) recorded 2 or more times in KP outpatient databases before May 2005. These children were compared with all 132,251 remaining singleton KP births. Main Exposures Maternal and paternal age at birth of offspring. MAIN OUTCOME MEASURES: Relative risks (RRs) estimated from proportional hazards regression models. Risk of ASDs evaluated in relation to maternal and paternal age, adjusted for each other and for the sex, birth date, and birth order of the child, maternal and paternal educational level, and maternal and paternal race/ethnicity. RESULTS: Risk of ASDs increased significantly with each 10-year increase in maternal age (adjusted RR, 1.31; 95% confidence interval [CI], 1.07-1.62) and paternal age (RR, 1.28; 95% CI, 1.09-1.51). Adjusted RRs for both maternal and paternal age were elevated for children with autistic disorder (maternal age: RR, 1.18; 95% CI, 0.87-1.60; paternal age: RR, 1.34; 95% CI, 1.06-1.69) and children with Asperger disorder or pervasive developmental disorder not otherwise specified (maternal age: RR, 1.45; 95% CI, 1.09-1.93; paternal age: RR, 1.24; 95% CI, 0.99-1.55). Associations with parental age were somewhat stronger for girls than for boys, although sex differences were not statistically significant. CONCLUSION: Advanced maternal and paternal ages are independently associated with ASD risk.

Potential association between infertility and spinal neural tube defects in offspring.

BACKGROUND: We examined the possible association between infertility and spinal neural tube defects (NTDs). METHODS: This is a nested case-control study within the Kaiser Permanente Medical Care Program (KPMCP) in Northern California. Among a birth cohort of 110,624 singleton infants > or = 36 weeks gestation, 1994-1997, we electronically identified cases of spinal NTDs and confirmed the diagnosis by chart review. Controls (n = 1,608) were randomly selected from the birth population. History of infertility was defined as: (1) physician diagnosis of infertility; (2) prescription for an infertility medication noted in the KPMCP pharmacy; and/or (3) evaluation at 1 of 15 infertility clinics in Northern California. RESULTS: Eighteen infants diagnosed with spinal NTDs (prevalence 1.6/10,000) included 13 with spina bifida cystica and 5 with spina bifida occulta. Case mothers were more likely to have a history of infertility (4/18 vs. 96/1,608, OR 4.3, 95% CI 1.01-14.0), and to have been prescribed clomiphene citrate within the window spanning 60 days before to 15 days after conception (3/18 vs. 32/1,608, OR 11.7, 95% CI 2.0-44.8). CONCLUSION: This exploratory study suggests that infertility may be associated with an increased risk of spinal NTDs among liveborn, term infants.

A comparison of health care utilization and costs of children with and without autism spectrum disorders in a large group-model health plan.

OBJECTIVE: Data on the current costs of medical services for children with autism spectrum disorders are lacking. Our purpose for this study was to compare health care utilization and costs of children with and without autism spectrum disorders in the same health plan. PATIENTS AND METHODS: Participants included all 2- to 18-year-old children with autism spectrum disorders (n = 3053) and a random sample of children without autism spectrum disorders (n = 30529) who were continuously enrolled in the Kaiser Permanente Medical Care Program in northern California between July 1, 2003, and June 30, 2004. Data on health care utilization and costs were derived from health plan administrative databases. MAIN OUTCOME MEASURES: Outcome measures included mean annual utilization and costs of health services per child. RESULTS: Children with autism spectrum disorders had a higher annual mean number of total clinic (5.6 vs 2.8), pediatric (2.3 vs 1.6), and psychiatric (2.2 vs 0.3) outpatient visits. A higher percentage of children with autism spectrum disorders experienced inpatient (3% vs 1%) and outpatient (5% vs 2%) hospitalizations. Children with autism spectrum disorders were nearly 9 times more likely to use psychotherapeutic medications and twice as likely to use gastrointestinal agents than children without autism spectrum disorders. Mean annual member costs for hospitalizations (550 dollars vs 208 dollars), clinic visits (1373 dollars vs 540 dollars), and prescription medications (724 dollars vs 96 dollars) were more than double for children with autism spectrum disorders compared with children without autism spectrum disorders. The mean annual age- and gender-adjusted total cost per member was more than threefold higher for children with autism spectrum disorders (2757 dollars vs 892 dollars). Among the subgroup of children with other psychiatric conditions, total mean annual costs were 45% higher for children with autism spectrum disorders compared with children without autism spectrum disorders; excess costs were largely explained by the increased use of psychotherapeutic medications. CONCLUSIONS: The utilization and costs of health care are substantially higher for children with autism spectrum disorders compared with children without autism spectrum disorders. Research is needed to evaluate the impact of improvements in the management of children with autism spectrum disorders on health care utilization and costs.

Cerebral palsy in a term population: risk factors and neuroimaging findings.

OBJECTIVE: The purpose of this work was to study risk factors and neuroimaging characteristics of cerebral palsy in term and near-term infants. PATIENTS AND METHODS: Among a cohort of 334,339 infants > or = 36 weeks' gestation born at Kaiser Permanente Medical Care Program in northern California in 1991-2003, we identified infants with cerebral palsy and obtained clinical data from electronic and medical charts. Risk factors for cerebral palsy among infants with different brain abnormalities were compared using polytomous logistic regression. RESULTS: Of 377 infants with cerebral palsy (prevalence: 1.1 per 1000), 273 (72%) received a head computed tomography or MRI. Abnormalities included focal arterial infarction (22%), brain malformation (14%), and periventricular white matter abnormalities (12%). Independent risk factors for cerebral palsy were maternal age > 35, black race, and intrauterine growth restriction. Intrauterine growth restriction was more strongly associated with periventricular white matter injury than with other neuroimaging findings. Nighttime delivery was associated with cerebral palsy accompanied by generalized brain atrophy but not with cerebral palsy accompanied by other brain lesions. CONCLUSIONS: Cerebral palsy is a heterogeneous syndrome with focal arterial infarction and brain malformation representing the most common neuroimaging abnormalities in term and near-term infants. Risk factors for cerebral palsy differ depending on the type of underlying brain abnormality.