According to a new Kaiser Permanente study, second-born children who are conceived sooner than two years or later than six years after the arrival of their older sibling have a substantially increased risk of autism spectrum disorders. The study was recently published in the journal Pediatrics. The findings support the World Health Organization’s recommendation of spacing pregnancies a minimum of two years apart.
“Interpregnancy intervals – the time from the first birth to conception of the second child – may be a factor in autism risk,” said Ousseny Zerbo, PhD, research fellow with the Kaiser Permanente Division of Research and the study’s lead author. “And while additional research is needed, our study adds to the growing body of evidence about various risk factors for autism.”
This follows up on a longitudinal study, conducted between 1995 and 2009, by researchers at Kaiser Permanente Southern California, that found that children born to mothers who developed gestational diabetes before 26 weeks of pregnancy were at a 63 percent increased risk of being diagnosed with autism spectrum disorder. However, after controlling for maternal age, education, ethnicity, household income, the child’s sex and the mother’s pre-existing conditions, that risk did drop to 42 percent.
The study, which was published earlier this year in JAMA, found that while the overall rate of autism among study participants was 1 in 100 (mirroring national averages during the period of study), the rate of autism among children born to mothers with early pregnancy diabetes was 1 in 80. Because this is a longitudinal association study, researchers were not able to establish a cause for the autism diagnosis. However, the associations were strong enough to warrant at least two health applications for parents, according to study co-author Dr. Edward Curry.
First, the study’s results emphasize the importance of early prenatal care. The women whose children were most at risk for developing autism were not women with previously diagnosed type 2 diabetes (who were already managing the condition with insulin, medication and diet). Nor were they women who got gestational diabetes after 26 weeks. Instead, the link between early gestational diabetes and an increased likelihood of autism diagnosis could mean that a fetus’ early exposure to uncontrolled high blood sugar may somehow affect brain development.
“We want to get mothers in early to make sure they’re on their vitamins, folic acid and that they check blood sugar to make sure it’s under control early on,” said Curry. “I think that’s the real takeaway message from this study.”
The second application, according to Curry, is for moms who know they were diagnosed with gestational diabetes before 26 weeks. These moms should remain extra vigilant about their baby’s developmental milestones. Are they making eye contact, babbling and pointing? Parents should also tell their child’s pediatrician about the gestational diabetes diagnosis, and ensure that pediatricians screen for autism appropriately at 12, 18 or 24 months old.
“We as pediatricians are supposed to be screening [by at least] 18 and 24 months, but it never hurts for the parents to have increased vigilance,” explained Curry. He also emphasized that his finding needs to be confirmed with more studies, as well as a few that can find out the causal link between gestational diabetes and autism, if there is one.
Autism is a neurodevelopmental disorder defined by impairments in social interaction and communication, as well as restricted and repetitive patterns of behavior, which occurs in 1 in 68 children, according to the most recent data from the Centers for Disease Control and Prevention.
The cause of autism is unknown, but research has identified a number of different genetic and environmental factors that may play a role in its development. It’s known that autism tends to run in families and that having one child with autism increases the risk of subsequent siblings being diagnosed with the condition as well. Autism has also been linked in past studies to factors like air pollution, maternal obesity, periods of prenatal oxygen deprivation, exposure to pesticides and advanced parental age, according to the National Institutes of Health.
Previous studies have linked short pregnancy intervals with increased risk of psychiatric and neurodevelopmental disorders, including autism. Longer interpregnancy intervals (or IPI) have also been linked to adverse perinatal outcomes, including low birth weight, small for gestational age, and preterm birth, as well as increased autism risk. The recently published interpregnancy interval study reviewed the electronic medical records of about 45,000 children born between 2000 and 2009 in Kaiser Permanente’s Northern California hospitals.
Autism was diagnosed in 0.81 percent of second-born children following IPIs of three to four years. In second-born children with IPIs of less than six months, the prevalence of autism was 2.11 percent; for intervals of six to eight months, 1.74 percent; and for intervals of six years or more, 1.84 percent.
Unlike other studies, this one was able to rule out the possibility that several other autism risk factors explained the findings. These factors included ASD status, prematurity, low birth weight and C-section delivery of the first-born child; maternal weight changes between pregnancies; and maternal antidepressant use three months before the pregnancy of the second child.
To help determine how various autism risk factors may be linked to family genetics or environmental issues, a new effort is underway at Kaiser Permanente in Northern California called the Autism Family Biobank. The biobank will collect genetic information from 5,000 member families with a child on the autism spectrum.
“We don’t understand why factors such as interpregnancy interval may increase the risk of autism,” said Lisa A. Croen, PhD, research scientist with the Kaiser Permanente Division of Research, senior author of the study and director of Kaiser Permanente’s Autism Research Program. “We’re hoping that efforts like the new biobank can point us toward the answers.”
In addition to Croen and Zerbo, co-authors of the study were Cathleen Yoshida, MA, and Erica P. Gunderson, PhD, Kaiser Permanente Northern California Division of Research; and Kaht Dorward, MD, Kaiser Permanente Northern California Department of Obstetrics and Gynecology. This study was funded in part by the National Institute of Environmental Health Sciences.
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