A large longitudinal study challenged longstanding assumptions about the gender prevalence of autism spectrum disorder (ASD).

Among 2.7 million people born in Sweden between 1985 and 2022 and followed from birth up to age 37, 2.8% were diagnosed with autism at a mean age of 14.3 years, reported Caroline Fyfe, PhD, of the Karolinska Institutet in Solna, and co-authors.

Diagnosis rates increased steadily throughout childhood, peaking at 645.5 per 100,000 person-years for males ages 10-14 and 602.6 per 100,000 person-years for females ages 15-19, the researchers wrote in The BMJ.

While the prevalence of ASD was higher among males during early childhood, a marked female catch-up pattern was noted during adolescence, leading to a nearly 1:1 male-to-female diagnosis ratio by age 20.

“These findings indicate that the male-to-female ratio for autism has decreased over time and with increasing age at diagnosis. This male-to-female ratio may therefore be substantially lower than previously thought, to the extent that, in Sweden, it may no longer be distinguishable by adulthood,” Fyfe and colleagues wrote.

“These observations highlight the need to investigate why female individuals receive diagnoses later than male individuals,” they added.

Historically, autism has been considered a condition predominantly diagnosed in males, with a reported male-to-female diagnosis ratio of approximately 4:1. The most recent U.S. report, based on data from the CDC’s Autism and Developmental Disabilities Monitoring (ADDM) network, showed that autism prevalence among 8-year-old children was 3.4 times higher in boys than in girls.

Higher male-to-female ratios have been ascribed to gender differences in social and communication skills, potentially delaying recognition in females, among other factors, Fyfe and colleagues said.

The findings in Sweden are not surprising, noted Diana Schendel, PhD, of the A.J. Drexel Autism Institute at Drexel University in Philadelphia, who wasn’t involved with the study.

“We’ve seen that same kind of pattern, in terms of age-specific rates between males and females, in Denmark — another Scandinavian country with large national registries where you can track the whole country over time,” Schendel told MedPage Today.

There isn’t any large longitudinal U.S. analysis similar to the Swedish study, she said. In the ADDM network, “we only have 4-year-olds and 8-year-olds,” she pointed out. To detect the kind of changes seen in Sweden, “you have to follow individuals into adolescence or adulthood.”

But even among children, male-to-female ratios can vary, Schendel added. “The sex ratio varies from site to site across the ADDM network … in 8-year-olds, it varies enormously,” she said.

“The fact that you see these huge differences in the sex ratio across different areas of the United States indicates there are a lot of local factors going on that impact who’s being referred, and who’s being diagnosed and reported with autism,” Schendel observed.

The findings in Sweden support the argument that current practices may be failing to recognize autism in females until later in life, noted Anne Cary of Boulder, Colorado, a patient and patient advocate, in an accompanying editorial.

“The harms of underdiagnosis and misdiagnosis of autism in women — harms that are infrequently reported in medical research but are often discussed in the autistic community — extend beyond barriers to appropriate interventions, supports, and accommodations afforded to correctly diagnosed autism in women,” Cary wrote.

Some females are “likely to be (mis)diagnosed with psychiatric conditions, especially mood and personality disorders, and they are forced to self-advocate to be seen and treated appropriately: as autistic patients, just as autistic as their male counterparts,” she concluded.

Fyfe and colleagues conducted a population-based, prospectively collected birth cohort study to investigate the influence of age at diagnosis, calendar period, and birth cohort on male-to-female ratios in autism diagnoses. Age-specific incidence of autism increased for each calendar period and birth cohort between 1985 and 2020.

Autism diagnoses were based on ICD-9 and ICD-10 codes in national patient records. The process for diagnosing autism in Sweden evolved over the course of the study period in line with changes in the Diagnostic and Statistical Manual of Mental Disorders.

The study had several limitations, the researchers acknowledged. It did not address other conditions associated with autism, such as intellectual disability or attention deficit-hyperactivity disorder (ADHD).

“We also did not consider potential modifiers of the male-to-female ratio, such as preterm birth,” they noted. “These conditions and variables require specific studies that were beyond the scope of our current research.”