Autism Speaks’ Alycia Halladay, Ph.D., will be live online this afternoon (4 pm EDT, 1 pm PDT) to answer your questions on the just released study showing a high risk of autism among the younger siblings of children on the spectrum. Dr. Halladay organized and continues to help lead the High-Risk Baby Siblings Research Consortium that conducted the research and which continues to study the factors that predispose some families to autism recurrence. Please join us and bring your questions. Meanwhile, please see our news item and a special commentary from Autism Speaks’ Chief Science Officer Geri Dawson, Ph.D.
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To read the entire transcript from this chat, please visit here.
Parents of a child with autism are understandably concerned about the likelihood that their subsequent children will be affected. Autism Speaks and its legacy organization, the National Alliance for Autism Research, have been funding research on younger siblings for nearly 15 years– to help us better understand their development.
In 2003, we began organizing and co-funding a very special collaboration—the High Risk Baby Siblings Research Consortium—in partnership with Eunice Kennedy Shriver National Institute for Child Health Development.
This week, we announced the results of the consortium’s largest ever siblings study. The researchers followed younger brothers and sisters from infancy through the preschool period, when autism diagnosis becomes possible. The study revealed a markedly higher risk among younger siblings than had been previously reported.
As the autism community absorbs the news, let me give you some background on the quality and importance of this research—and what it means for parents.
Our “Baby Sibs” researchers are an international network of clinical researchers who have been pooling information from studies of affected families in 21 sites in the US, Canada, Israel and the UK. Alycia Halladay, Autism Speaks director of research for environmental sciences, and Andy Shih, vice president of scientific affairs, have led the consortium from the start and continue to coordinate its activities.
In the study making headlines this week, the consortium researchers assessed 664 infants. Each had at least one older sibling diagnosed with an autism spectrum disorder (ASD). They found that 1 in 5 babies with an older sibling on the spectrum will likewise be affected—more than double previous estimates. The rate was higher among younger brothers—1 in 4, versus 1 in 9 for younger sisters. And autism affected nearly 1 in 3 infants with more than one older sibling on the spectrum. (Previous estimates came out of much smaller and sometimes less reliably conducted studies.)
So what does this mean for parents?
If you have an older child on the spectrum and you are concerned about your infant, talk to your pediatrician about your baby’s risk and your desire for close monitoring. And if you have any concerns about your child’s development, don’t wait. Speak with your doctor about screening.
Here are links to a number of helpful resources:
* Recent research funded by Autism Speaks shows that a one-page baby-toddler checklist can be used effectively as early as 12 months as an initial screen for autism and other developmental disorders. The screener is available here.
* As a parent or caregiver, one of the most important things you can do is learn the early signs of autism and understand the developmental milestones your child should be reaching. You can see the Learn the Signs guidelines on our website, here.
* Finally, families with one or more children on the spectrum can contact their nearest “Baby Sibs” consortium researcher if they would like to participate in this important research. The list is on our website, here.
By monitoring your infant closely and promptly beginning intervention if signs of autism appear, you can ensure that your child will have the best possible outcome.
Autism risk ‘high’ for kids with older sibling with the disorder. Autism Speaks’ Alycia Halladay, Ph.D., provides perspective of NPR’s All Things Considered. To listen to the segment, visit here.
Posted by Alycia Halladay, PhD, director of research for environmental science, Autism Speaks
For over four decades, autism researchers have been combing through birth records to look for events that might increase the risk that a newborn goes on to develop an autism spectrum disorder (ASD). Many clues have emerged regarding the influence of such factors as prematurity, low birth weight, method of delivery, or even the season in which conception or delivery occurs. But no one study was large enough to provide definitive answers, and inconsistent results between studies have caused confusion among scientists as well as parents trying to follow the science.
Today, the respected journal Pediatrics publishes a study that goes far in cutting through the confusion. Researchers from Harvard and Brown universities reviewed and analyzed the combined results of 40 studies that looked at potential autism risk factors during the birth (perinatal) and newborn (neonatal) period.
Such a “meta-analysis” study is a powerful tool in science, as it allows researchers to combine and compare findings from different sources to get a clearer, more reliable picture of the associations between potential risks and conditions such as autism. Importantly, the study confirmed an association between autism and such conditions as abnormal fetal presentation during delivery (for example, breech), fetal respiratory distress (breathing difficulties), birth injury or trauma, low 5-minute APGAR score (a 1-10 score for assessing newborn health after delivery), newborn seizures, low birth weight, multiple births (twins, triplets, etc.), anemia (low blood iron, and being born in the summer.
Of note, preterm birth was not found to be associated with ASD, of particular interest because there had been considerable differences on this count across earlier studies. Most importantly, perhaps, the researchers concluded that the evidence did not implicate any one perinatal or neonatal factor as causing autism by itself. Rather, the evidence suggests that a combination of these factors—reflecting generally poor conditions during and immediately after birth–may increase the risk that a child with an underlying genetic disposition will develop autism.
One common thread across several of these risk factors is that they result in a lack of adequate blood flow to the brain during the birth process. One hypothesis is that, when combined with a genetic predisposition, oxygen deprivation to the brain worsens abnormal brain development. Studying these and other environmental (versus genetic) risk factors for autism is important to increase our understanding of the biology of ASD and to provide practical guidance for physicians and parents on how to avoid or modify those risk factors that can be changed.
In addition, this meta-analysis strongly suggests that pediatricians and parents should closely monitor the development of babies born in difficult situations so that early intervention can be offered should developmental issues such as autism arise. What this study does not say is that difficult birth means a baby will go on to develop autism. Rather, these conditions and complications may increase the risk of autism among those who have a genetic predisposition for developing it.
As in my last post, I want to invite readers to explore the many environmental risk studies that Autism Speaks is supporting with donor dollars, scientific resources, and the participation of autism families in clinical studies. Please see our Grants Search and Participate gateways at www.autismspeaks.org. Thanks for being a vital part of our mission to improve the lives of all who struggle with autism. For more on the Pediatrics meta-analysis study, also see Autism Speaks news.
As reported last week, a large twin study supported by Autism Speaks compared the frequency with which identical and fraternal twins both share a diagnosis of autism. This approach enabled the investigators to use statistical techniques to calculate the degree to which environmental factors shared by twins contribute to their risk of developing autism. Such factors include conditions in the womb and during birth.
The results of the California Autism Twin study were game-changing because they revealed a much larger environmental influence than had previously been estimated—accounting for about 58% of the risk of developing autism. By contrast, much smaller twin studies had previously suggested that genes largely accounted for a child’s risk of autism.
The results underscore the need to investigate the role that non-inherited risk factors play in the development of autism spectrum disorders (ASD). So what’s being done to help speed this research? And what role are Autism Speaks and its donor dollars playing in this effort?
Autism Speaks has funded over $21 million in the study of environmental risk factors, an initiative we call (obviously enough) the Environmental Factors of Autism Initiative. Already, we have a large body of evidence suggesting that it is not any one environmental factor, but many different factors working together, that elevate the risk and severity of autism in individuals with a genetic predisposition for this condition. In other words, autism is seldom caused by any one thing and neither is it an “all or nothing” condition. Furthermore, different combinations of genetic and environmental risk factors contribute to individual cases of autism.
Within the Environmental Factors of Autism Initiative are ongoing studies focusing on environmental exposures that occur before and during pregnancy and throughout the first year of life—crucial periods for human brain development. These studies look at such possible risk factors as maternal and paternal age, socioeconomic status, season of birth, exposure to chemicals or toxic agents, nutrition and exposure to various pharmaceutical drugs during pregnancy, the difficulty of labor and delivery, and various other forms of prenatal stress. The researchers we support are also investigating the mechanisms by which genes and the environment may interact (so-called epigenetics) and the role of the immune system. We are also supporting large scale epidemiological studies that focus on pregnancy and the first year of life. These include the EARLI study and the IBIS study.
Are you interested in learning more about the studies Autism Speaks is funding with donor dollars? We are proud to debut the new Grant Search function on our website. Please use it to explore past and present research studies by topic or location. And if you or your family is affected by autism, please consider participating in one of our clinical studies.
by Alycia Halladay, Ph.D, Director of Environmental Science
Research using identical and fraternal twins is typically used to identify genetic influences on the development of ASD. This year, researchers studied a large group of twins and examined the concordance of different types of symptoms (1). Using this approach, the researchers found that the concordance of severe autism between identical twins and fraternal twins was about the same, indicating a strong environmental component to ASD severity. But what are those environmental factors? Epidemiological studies are providing clues.
At this year’s IMFAR, new data was presented that focused on studying groups of people and their exposures to a number of environmental factors. Each used different designs with their own unique advantages. For example, at UC Davis, the CHARGE study (www.beincharge.ucdavis.edu) examined the risk of developing autism following exposure to a number of factors that were identified through self report or medical records. Those that showed an association were antidepressant SSRI use (2) and metabolic disorders including hypertension and diabetes (3). On the other hand, a previously identified factor, maternal infection, was not associated (4). Why not? The researchers suggested that fever, not infection per se, may be a factor. Using self-report and medical records obtained prior to study entry may not accurately capture all relevant information, and an infection or fever may be missed in some reports. However, other types of information, such as method of birth, is easier to gather accurately. An analysis revealed that non-emergency or elective c-section deliveries did not show a significant association with autism, addressing a concern that many public and community stakeholders have expressed (5).
As an alternative to retrospective reports, the Early Markers of Autism Study in California is obtaining samples of blood from pregnant women by obtaining extra blood taken during the alpha-fetal protein screen that is banked. Not all states bank these samples for research, so this is a unique resource. By examining the levels of mercury in blood taken during pregnancy together with newborn blood spots, the researchers can get a more comprehensive picture of the prenatal environment. They reported no difference in mercury levels compared to those of non-affected children during gestation, and also reported no difference in thyroid hormone levels (6,7). Examination of subgroups of autism with regression did not change the results. While these data are incredibly novel and valuable, these studies were not designed to capture information throughout the entire pregnancy nor capture factors after birth
Another way to study exposures during pregnancy is through birth certificate data. In some states, the birth certificate contains information such as the place of birth and the occupation of the mother and the father. Using this information, scientists found that occupational exposures in mothers to certain chemicals resulted in an increased risk of ASD in offspring (8).
While each approach brings unique strengths, all researchers agree that the most comprehensive way to capture all information accurately, is a prospective design. This means identifying children as soon as possible and following them from that point on to gather every piece of relevant information from medical reports to blood samples. Autism Speaks is proud to co-sponsor such a study: the Early Autism Risk Longitudinal Investigation (EARLI). This groundbreaking project will provide even more answers to what causes autism, and needs the help of the community to do so.
So how can researchers blend or expand their research if they are using only one type of design? Autism Speaks and the National Institutes for Environmental Health Sciences are sponsoring a network of projects called the Environmental Epidemiology of Autism Research Network (EEARN). The goal of this network is to improve communication among researchers in this field, identify opportunities for collaborative projects and improve research tools for both existing, and new projects. Over 20 studies from 8 countries are represented in the network. We will keep you updated on the activity of the network, and we hope you will keep checking in for updates.
1. Understanding Clinical Variability In Autism: Results From a California Twin Study. W. Froehlich*1, S.
Cleveland1, A. Torres1, J. M. Phillips1, B. Cohen2, A. Fedele3, T. Torigoe2, J. Collins4, K. S. Smith5, L. Lotspeich1, L. A. Croen4, S. Ozonoff6, C. Lajonchere7, J. K. Grether5, N. Risch8 and J. Hallmayer1, (1)Stanford University, Stanford, CA, (2)Autism Genetic ResourceExchange, Los Angeles, CA, (3)Autism Speaks, Westmont, NJ,
United States, (4)Kaiser Permanente, Division of Research, Oakland, CA, (5)California Department of Public Health, Richmond , CA, (6)UC Davis MIND Institute, Sacramento, CA, (7)Autism Speaks, Los Angeles, CA, United States, (8)University of California San Francisco, San Francisco, CA
2. SSRI Use During Pregnancy and Risk of ASD or Developmental Delay In Children. R. A. Harrington*1,L. C. Lee1, C. K. Walker2, R. L. Hansen3, S. Ozonoff3 and I. Hertz-Picciotto4, (1)Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, (2)Department of Public Health Sciences, University of California at Davis, Davis, CA, (3)MIND Institute, University of California at Davis, Sacramento, CA, (4)Department of Public Health Sciences, University of California Davis, Davis, CA
3. The Role of Maternal Diabetes and Related Conditions In Autism and Other Developmental Delays. P. Krakowiak*1,2, A. A. Bremer3, A. S. Baker1, C. K. Walker1,4, R. L. Hansen2,3 and I. Hertz-Picciotto1,2, (1)Public Health Sciences, University of California, Davis, Davis, CA, (2)M.I.N.D. Institute, Sacramento, CA, (3)Pediatrics, University of California, Davis, Sacramento, CA, (4)Obstetrics & Gynecology, University of California, Davis, Sacramento, CA
4. Prenatal Influenza or Fever and Risk of Autism/Autism Spectrum Disorders. O. Zerbo*1, I. Hertz- Picciotto2,3, A. M. Iosif4, R. L. Hansen5,6,7 and C. K. Walker8, (1)Sacramento, CA, (2)University of California, Davis, Davis, CA, (3)Department of Public Health Sciences, University of California Davis, Davis, CA, (4)UC Davis, Davis, CA, (5)University of California, Davis, MIND Institute, Sacramento, CA, (6)MIND Institute, University of California at Davis, Sacramento, CA, (7)MIND Institute and Dept. of Pediatrics, University of California Davis, Davis, CA, (8)Department of Public Health Sciences, University of California at Davis, Davis, CA
5. Cesarean Birth and Autism Spectrum Disorder. C. K. Walker*1, P. Krakiowiak2, A. S. Baker3, R. L. Hansen4, S. Ozonoff5 and I. Hertz-Picciotto6, (1)Obstetrics & Gynecology, UC Davis, Sacramento, CA, (2)Public Health Sciences, UC Davis, Sacramento, CA, (3)Public Health Sciences, UC Davis, Davis, CA, (4)Pediatrics, M.I.N.D. Institute, UC Davis, Sacramento, CA, (5)Psychiatry and Behavioral Sciences, M.I.N.D. Institute, UC Davis, Sacramento, CA, (6)Public Health Sciences, M.I.N.D. Institute, UC Davis, Davis, CA
6. Prenatal and Neonatal Peripheral Blood Mercury Levels and Autism Spectrum Disorders. L. A. Croen*1, M. A. Lutsky1, C. Yoshida1, C. P. Alaimo2, M. Kharrazi3, J. K. Grether4 and P. Green2, (1)Kaiser Permanente Division of Research, Oakland, CA, (2)Civil and Environmental Engineering, Univ. of California Davis, Davis, CA, (3)Genetic Disease Screening Program, California Department of Public Health, Richmond, CA, (4)California Department of Public Health, Richmond, CA
7. Prenatal and Neonatal Thyroid Stimulating Hormone Levels and Autism Spectrum Disorder. M. A. Lutsky*1, C. Yoshida1, B. Lasley2, M. Kharrazi3, J. K. Grether4, G. Windham4 and L. A. Croen1, (1)Kaiser Permanente Division of Research, Oakland, CA, (2)Department of Population Health and Reproduction, UC Davis, Davis, CA, (3)Genetic Disease Screening Program, California Department of Public Health, Richmond, CA, (4)California Department of Public Health, Richmond, CA
8. Autism Spectrum Disorders In Relation to Parental Occupational Exposures During Pregnancy. G. Windham*1, J. K. Grether2, A. Sumner3, S. Li4, E. Katz5 and L. A. Croen6, (1)California Department of Public Health, Richmond, CA, (2)California Department of Public Health, Richmond, CA, (3)Vermont Department of Health, Burlington, VT, (4)Kaiser Permanente Divison of Research, Oakland, CA, (5)Occupational Health Branch, CA Department of Public Health, Richmond, CA, (6)Kaiser Permanente Division of Research, Oakland, CA
This is a guest post by Alycia Halladay, Ph.D. and Leanne Chukoskie, Ph.D. Dr. Halladay is Autism Speaks’ Director, Research for Enivronmental Services. Leanne earned her Ph.D. at NYU’s Center for Neural Science studying the neural mechanisms that mediate vision during eye movements. During her postdoctoral training at the Salk Institute she studied search behavior in both humans and animals. A family connection as well as the curious manner in which people with autism tend to scan a visual scene led her to work for Autism Speaks as the Assistant Director of Science Communication and Special Projects. Leanne also continues her research as a Project Scientist at UCSD.
This is a guest post by Alycia Halladay, Ph.D. Dr. Halladay is Autism Speaks’ Director, Research for Enivronmental Services.
Instead of focusing on just genetics or just environmental factors, autism researchers have been studying gene-environment interactions as possible risk factors of the disorder. A next series of posts will begin to try and explain why this is an important concept, and how it is changing the way scientists think about causes.
Why is this concept important?
First, in the context of risk factors, if only the separate contributions of genetics and environmental influences is calculated without considering the interaction, the proportion of the disorder that is attributable to both is underestimated. For example, environmental factors may play an important role in the development of some diseases. However, in others, the effect is only seen in susceptible individuals. Studies that examine gene-environment interactions can do the following (taken from Hunter, 2005)
- Obtain a better estimate of the risk associated with genetic and environmental risk factors
- Strengthen the association between environmental risk factors and disease
- Help researchers understand the biological mechanism of disease
- Determine which environmental factors produce risk
- Lead to new prevention and therapeutic strategies
What does it mean?
As most people know, genetics typically refers to the stable sequence of nucleotides on DNA strands in every cell of the human body. The nucleotides are translated to amino acids, which in turn create proteins. The amino acid sequence determines how proteins are configured, which may affect their function. Put in an oversimplistic fashion, these proteins are what affect cell function. Some of the genetic code is inherited from both parents, and will be conferred to their children; another, more recently studied type of genetics, called epigenetics, refers to a change in protein synthesis that is not due to alterations in the DNA code. In other words, the DNA code stays the same but the way it is expressed changes. These concepts will also be discussed in a later chapter. With regards to the term “environment”, this is a term that can refer to many “non-genetic” influences on biology and behavior. Typically when they hear “environment” people think of one of the hundreds of thousands of potential chemicals and toxins that are present in food, air and water. However, environment can also include some demographic characteristics like socioeconomic status, nutritional status and education, as well as medical procedures and illnesses, and exposure to vitamins, pharmaceuticals and/or alternative medicines. It can even refer to exposures that we may not be thinking about every day, like UV sunlight, cosmetics, food additives, and ventilation in the home. While most people think of gene-environment interactions as an environmental risk factor producing more profound effects in a susceptible individuals, some genes may offer protection against deleterious environmental effects. Other genes may promote healthy development and their effects stifled, or even enhanced, in different environments. These concepts will be explored further in a different chapter.
How are these interactions determined and studied?
The best way to determine whether an interaction exists in a human population is an epidemiologic study. One of the biggest challenges is the need for large samples, or many individuals to enroll and participate. Typically, self-report measures are obtained from all participants and family members, and DNA and other biologicals are included to study DNA/RNA and level of exposure. If other measures are available such as medical records, these are also collected throughout the study. Genetic and environmental factors, and their interaction, can be studied retrospectively (after the disease has developed) or prospectively (prior to when the disease appears). Each design has strengths and weaknesses, and in many cases both approaches are taken to identify and then replicate findings. Other study designs include case-control vs. case-case. Case-control refers to studying both individuals with and without the disease. Case-case refers to studying cases (in this case individuals with autism only) both with and without different exposure levels and/or genotypes.
The NCS, or National Children’s Study, was authorized by Congress in 2000 as part of the Children’s Health Act. This study, unprecendented in size and scope in the United States, will seek to recruit hundreds of thousands of pregnant women to ultimately enroll and follow 100,000 children from gestation through adulthood. During the course of the study, parents and children will be studied carefully, with measures of behavioral, psychosocial and medical development tracked. This includes autism and autism spectrum disorders. Recent prevalence estimates suggest that around 1,000 children born to mothers enrolled in the study will develop ASD.
The overarching goal of the study is to examine how genetic and environmental factors affect child health and development. In addition to screening for autism spectrum disorders at 18 and 24 months, the current study protocol will collect multiple measures of genetic factors and environmental exposures, including specimens from mother, father and child at multiple times during development and adolescence, examination of environmental exposures, as well as medical information and medical events. The term environment is used broadly, and the study is very comprehensive in the frequency and specificity of examinations, as well as keeping in mind the magnitude and duration of a variety of exposures (medical, chemical, behavioral, psychosocial, demographic). Autism Speaks is currently working with the NCS to create a more developed and enhanced autism screening and diagnosis protocol, and identify solutions to clinical and ethical questions. This means that the NCS will be an instrumental tool for examining the relationship between genes and the environment and their relation to developmental disorders, including autism.
Because of the comprehensive nature of the study, families are expected to contribute a great deal. However, being enrolled in the NCS also provides an opportunity to contribute to a rich database of health information. This health information will be used to make policies on a statewide and federal level, identify possible intervention and treatment strategies for those enrolled, and provide participants with in depth evaluation and long-term follow up that they might not have received elsewhere. For the study to be successful, families should be willing to participate. Recruitment has already begun, and the study looks forward to talking to families who may be eligible to join – not just from those affected by autism, but those who are not affected. That means that your friends, family and neighbors could enroll even if you do not participate!!