Friday, January 27, 2023
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This activity is intended for psychiatrists, pediatricians, family medicine and primary care clinicians, neurologists, nurses, internists, and other members of the health care team who treat and manage patients with or at risk for autism spectrum disorder.
The goal of this activity is that learners will be better able to describe the association between ultrasonography fetal anomalies and autism spectrum disorder (ASD), based on a retrospective case-sibling-control study of children diagnosed with ASD in the National Autism Research Center of Israel database; their own typically developing, closest-in-age siblings; and typically developing children from the general population, matched by year of birth, sex and ethnicity.
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CME / ABIM MOC / CE Released: 4/29/2022
Valid for credit through: 4/29/2023
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Autism spectrum disorder (ASD) is a multifactorial, life-long neurodevelopmental disorder characterized by impaired social communication and restrictive-repetitive behaviors. Many people with ASD manifest additional comorbidities and congenital anatomical abnormalities that further complicate their clinical picture.
Accumulating evidence suggests that initial signs of autism spectrum disorder (ASD) emerge during early childhood and possibly even before birth. ASD may be associated with abnormal embryonic organogenesis of different body parts, causing postnatal malformations in some children with ASD.
Fetal abnormalities in the urinary system, heart, brain and elsewhere, detected via prenatal ultrasound, may signal ASD, new research suggests.
Results of a retrospective study showed that ultrasound in the second trimester identified ASD at a rate more than 3 times higher than that seen in typically developing children.
"This study shows some initial signs of autism are already detectable during the second trimester and we have this very effective tool--prenatal ultrasound surveys--to detect these signs," study investigator Idan Menashe, PhD, professor, Department of Public Health, Ben-Gurion University of the Negev, Beer Sheva, Israel, told Medscape Medical News.
The study was published online January 17 in Brain.
Registry DataASD is a neurodevelopmental disorder characterized by impaired social communication and restrictive-repetitive behaviors; diagnosis is based on symptoms that typically manifest in the second year of life.
Evidence shows that earlier detection and intervention improves long-term outcomes. In a bid to find ways to improve earlier diagnosis of ASD, the investigators conducted a retrospective study that included 229 children born between 2004 and 2018 registered in the National Autism Research Center of Israel database.
It also included 201 of their typically developing siblings (TDS) and 229 typically developing children from the general population (TDP), matched to ASD cases by year of birth, sex, and ethnicity.
There were no significant differences in clinical characteristics between groups, except the ASD group had more males than the TDS group (77.7% vs 56.7%; P<.001).
Prenatal ultrasound to survey fetal anatomy occurred at a mean gestational age of 22.85 weeks. The survey includes examination of anatomical landmarks in the head, brain, thorax, abdomen, spine, limbs, and umbilical cord.
In each organ, physicians classify abnormalities as either structural or "soft" markers. "Soft" markers indicate "something beyond the normal" but perhaps "not clear physiological abnormalities," said Dr Menashe, who is also scientific director of the Azrieli National Centre for Autism and Neurodevelopmental Research.
Biometric measures include head circumference, biparietal diameter, abdominal circumference, femur length, cisterna magna size, cerebellar diameter, lateral ventricle width, and ocular distance.
The study showed ultrasonography fetal anomalies (UFAs) in 29.3% of ASD cases, 15.9% of the TDS group, and 9.6% of the TDP group. After adjusting for sex, the ASD group was much more likely to have UFAs than the TDS group (adjusted odds ratio [aOR], 2.23; 95% confidence interval [CI], 1.32-3.78; P=.006) and the TDP group (aOR, 3.50; 95% CI, 2.07-5.91; P<.001).
Anatomical AnomaliesSignificantly more children with ASD had multiple anatomic anomalies (7%) compared with 2% for the TDS group and 0.9% for the TDP group.
In the ASD group, most UFAs were in the urinary system (12.8%), heart (12.1%), and head and brain (6.1% for combined UAFs).
Dilation of the renal pelvis was the most common urinary system UFA in ASD cases (11.5%), which was significantly higher than in the TDS (6.0%) and TDP (4.4%) controls.
One "soft" marker of a urinary UFA more prevalent in the ASD group was pyelectasis, a mild enlargement of part of the kidney caused by extra fluid, which has been linked to fetal genetic risk, said Dr Menashe. The authors note other examples of genetic syndromes associated with ASD that are characterized by renal abnormalities.
Heart-related anomalies included echogenic intracardiac focus, which is considered a "soft" marker associated with various genetic anomalies, and ventricular septal defect, a structural malformation that may progress to congenital heart disease after birth.
The most common head/brain UFAs were choroid plexus cysts, enlarged lateral ventricles, and mega cisterna magna, suggesting abnormal development of cerebrospinal fluid circulation in children with ASD compared with TDP controls.
ASD cases had significantly smaller head circumference and narrower biparietal diameter heads compared with TDP controls after adjusting for fetal sex and gestational age. This confirms findings of an earlier study by these investigators.
Earlier Intervention OpportunityInterestingly, the earlier research showed that typically developing siblings of children with ASD initially had the same smaller head, but "caught up" with the general population by the end of the pregnancy, said Dr Menashe.
In this new study, ocular distance relative to biparietal diameter was significantly larger in children with ASD, supporting previous evidence that children with ASD tend to have wide-set eyes.
"Children with autism have a narrower head compared to other children, so the distance between the eyes relative to the head width was much larger than other children without autism," said Dr Menashe.
ASD is 4 times more prevalent among males than females, but in this study, investigators found that UFAs were significantly more common in ASD females (43.1%) than males (25.3%). Female children with ASD also had a significantly higher prevalence of multiple co-occurring UFAs vs their male counterparts (15.7% vs. 4.5%). These results may indicate that the causes of ASD may differ in boys vs girls, said Dr Menashe.
These new findings provide further evidence that ASD starts before birth and should help stop the misconception that the disorder is linked to vaccines or other postnatal exposures, Dr Menashe added.
Identification of these markers at the earliest possible stage would allow for earlier intervention and ultimately may help improve outcomes in this patient population, he added.
He suggests that children with such markers be carefully monitored and interventions introduced as soon developmental delays or classic ASD behaviors present.
"Helpful Data"Commenting on the research for Medscape Medical News, Jeremy Veenstra-VanderWeele, MD, professor, Child and Adolescent Psychiatry, Columbia University, New York City, said the data from this study are "really helpful."
He noted that the authors applied "a careful design" and studied ultrasound fetal anomalies that are "quite common" but not usually associated with ASD or other neurodevelopmental problems.
He cautioned that although the study identifies increased rates of anomalies in ASD, particularly in girls, "the added risk is not enough to be useful in predicting autism at this point."
It would be "very interesting" to learn how these ultrasound findings relate to genetic or environmental risk factors in autism, Dr Veenstra-VanderWeele added.
The study was supported by a grant from the Israel Science Foundation. Dr Menashe and Dr Veenstra-VanderWeele have disclosed no relevant financial relationships.
Brain. Published online January 17, 2022.[1]
