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Autistic children vary in symptoms, co-morbidities, and response to interventions. This study aimed to identify clusters of autistic children with a distinct pattern of attaining early developmental milestones (EDMs). The clustering of 5836 autistic children was based on the attainment of 43 gross motor, fine motor, language, and social developmental milestones during the first 3 years of life as recorded in baby wellness visits. K-means cluster analysis detected four EDM clusters: mild (n = 1686); moderate (n = 1691); severe (n = 2265); and global (n = 194). The most prominent cluster differences were in the language domain. The global cluster showed earlier and greater developmental delay across domains, unique early gross motor delays, and more were born preterm via cesarean section. The severe cluster had poor language development prominently in the second year of life, and later fine motor delays. Moderate cluster had mainly language delays in the third year of life. The mild cluster mostly passed milestones. EDM clusters differed demographically, with higher socioeconomic status in mild cluster and lowest in global cluster. However, the severe cluster had more immigrant and non-Jewish mothers followed by the moderate cluster. The rates of parental concerns and provider developmental referrals were significantly higher in the global, followed by the severe, moderate, and mild EDM clusters. Autistic children's language and motor delay in the first 3 years can be grouped by common magnitude and onset profiles as distinct groups that may link to specific etiologies (like prematurity or genetics) and specific intervention programs. Early autism screening should be tailored to these different developmental profiles.
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LAY ABSTRACT: Timely identification of autism spectrum conditions is a necessity to enable children to receive the most benefit from early interventions. Emerging technological advancements provide avenues for detecting subtle, early indicators of autism from routinely collected health information. This study tested a model that provides a likelihood score for autism diagnosis from baby wellness visit records collected during the first 2 years of life. It included records of 591,989 non-autistic children and 12,846 children with autism. The model identified two-thirds of the autism spectrum condition group (boys 63% and girls 66%). Sex-specific models had several predictive features in common. These included language development, fine motor skills, and social milestones from visits at 12-24 months, mother's age, and lower initial growth but higher last growth measurements. Parental concerns about development or hearing impairment were other predictors. The models differed in other growth measurements and birth parameters. These models can support the detection of early signs of autism in girls and boys by using information routinely recorded during the first 2 years of life.
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Early detection of autism spectrum disorder (ASD) is crucial for timely intervention, yet diagnosis typically occurs after age three. This study aimed to develop a machine learning model to predict ASD diagnosis using infants' electronic health records obtained through a national screening program and evaluate its accuracy. A retrospective cohort study analyzed health records of 780,610 children, including 1163 with ASD diagnoses. Data encompassed birth parameters, growth metrics, developmental milestones, and familial and post-natal variables from routine wellness visits within the first two years. Using a gradient boosting model with 3-fold cross-validation, 100 parameters predicted ASD diagnosis with an average area under the ROC curve of 0.86 (SD < 0.002). Feature importance was quantified using the Shapley Additive explanation tool. The model identified a high-risk group with a 4.3-fold higher ASD incidence (0.006) compared to the cohort (0.001). Key predictors included failing six milestones in language, social, and fine motor domains during the second year, male gender, parental developmental concerns, non-nursing, older maternal age, lower gestational age, and atypical growth percentiles. Machine learning algorithms capitalizing on preventative care electronic health records can facilitate ASD screening considering complex relations between familial and birth factors, post-natal growth, developmental parameters, and parent concern.
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BACKGROUND: Structural differences exist in the brains of autistic individuals. To date only a few studies have explored the relationship between fetal brain growth and later infant autistic traits, and some have used fetal head circumference (HC) as a proxy for brain development. These findings have been inconsistent. Here we investigate whether fetal subregional brain measurements correlate with autistic traits in toddlers. METHODS: A total of 219 singleton pregnancies (104 males and 115 females) were recruited at the Rosie Hospital, Cambridge, UK. 2D ultrasound was performed at 12-, 20- and between 26 and 30 weeks of pregnancy, measuring head circumference (HC), ventricular atrium (VA) and transcerebellar diameter (TCD). A total of 179 infants were followed up at 18-20 months of age and completed the quantitative checklist for autism in toddlers (Q-CHAT) to measure autistic traits. RESULTS: Q-CHAT scores at 18-20 months of age were positively associated with TCD size at 20 weeks and with HC at 28 weeks, in univariate analyses, and in multiple regression models which controlled for sex, maternal age and birth weight. LIMITATIONS: Due to the nature and location of the study, ascertainment bias could also have contributed to the recruitment of volunteer mothers with a higher than typical range of autistic traits and/or with a significant interest in the neurodevelopment of their children. CONCLUSION: Prenatal brain growth is associated with toddler autistic traits and this can be ascertained via ultrasound starting at 20 weeks gestation.
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Autistic Disorder , Male , Infant , Pregnancy , Female , Humans , Autistic Disorder/diagnostic imaging , Brain/diagnostic imaging , Gestational AgeABSTRACT
The premutation of the fragile X messenger ribonucleoprotein 1 (FMR1) gene is characterized by an expansion of the CGG trinucleotide repeats (55 to 200 CGGs) in the 5' untranslated region and increased levels of FMR1 mRNA. Molecular mechanisms leading to fragile X-premutation-associated conditions (FXPAC) include cotranscriptional R-loop formations, FMR1 mRNA toxicity through both RNA gelation into nuclear foci and sequestration of various CGG-repeat-binding proteins, and the repeat-associated non-AUG (RAN)-initiated translation of potentially toxic proteins. Such molecular mechanisms contribute to subsequent consequences, including mitochondrial dysfunction and neuronal death. Clinically, premutation carriers may exhibit a wide range of symptoms and phenotypes. Any of the problems associated with the premutation can appropriately be called FXPAC. Fragile X-associated tremor/ataxia syndrome (FXTAS), fragile X-associated primary ovarian insufficiency (FXPOI), and fragile X-associated neuropsychiatric disorders (FXAND) can fall under FXPAC. Understanding the molecular and clinical aspects of the premutation of the FMR1 gene is crucial for the accurate diagnosis, genetic counseling, and appropriate management of affected individuals and families. This paper summarizes all the known problems associated with the premutation and documents the presentations and discussions that occurred at the International Premutation Conference, which took place in New Zealand in 2023.
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Fragile X Mental Retardation Protein , Fragile X Syndrome , Humans , Fragile X Mental Retardation Protein/genetics , Fragile X Mental Retardation Protein/metabolism , Mutation/genetics , RNA, Messenger/metabolism , Trinucleotide Repeat Expansion/genetics , Fragile X Syndrome/diagnosis , Fragile X Syndrome/genetics , Fragile X Syndrome/therapyABSTRACT
Objective: Carriers of Fragile X premutation may have associated medical comorbidities, such as Fragile X-associated tremor and ataxia (FXTAS) and Fragile X-associated premature ovarian insufficiency (FXPOI). We examined the Fragile X premutation effect on cognition, and we assumed that there is a direct correlation between the continuous spectrum of specific learning and attention deficits to the number of CGG repeats on the FMR1 gene. Methods: A total of 108 women were referred to our center due to a related Fragile X syndrome (FXS) patient, 79 women carried a premutation of 56-199 repeats, and 19 women carried a full mutation of more than 200 CGG repeats on FMR1 gene. Genetic results of CGG repeats, demographic information, structured questionnaires for ADHD, learning disabilities of language and mathematics, and independence level were analyzed in women carrying the FMR1 premutation and compared to the group carrying the full mutation. Women with FXS and FXTAS were excluded. Results: When analyzed as a continuum, there was a significant increase in the following complaints which were associated with a higher number of repeats: specific daily function skills such as driving a car, writing checks, disorientation in directions, and also specific learning difficulties such as spelling and math difficulties. Additionally, when tested as a categorical independent variable, we observe that women with the full mutation were more likely to have ADHD or other learning disability diagnoses in the past than during premutation (<200 CGG repetitions). Conclusion: Specific learning and attention difficulties and resulting daily function difficulties correlate with an increased number of CGG repeats and are more likely to be associated as a common feature of premutation and full mutation in a female premutation carrier. Despite evidence of learning and attention difficulties, it is encouraging that most female carriers of the premutation and full mutation function well in most areas. Nevertheless, they face significant difficulties in specific areas of functioning such as driving, and confusion in times and schedules. Those daily function skills are mostly impacted by dyscalculia, right and left disorientation, and attention difficulties. This may aid to design specific interventions to address specific learning deficits in order to improve daily function skills and quality of life.
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The Fragile X premutation is a genetic instability of the FMR1 gene caused by 55-199 recurrences of the CGG sequence, whereas there are only 7-54 repeats of the CGG sequence in the normal condition. While males with the premutation of Fragile X were found to have difficulties in executive functions and working memory, little data have been collected on females. This study is among the first to address executive functions and phonological memory in females with the Fragile X premutation. Twenty-three female carriers aged 20-55 years and twelve non carrier females matched in age and levels of education (in years) participated in this study. Executive functions and phonological memory were assessed using the self-report questionnaire The Behavior Rating Inventory of Executive Function (BRIEF) and behavioral measures (nonword repetitions, forward and backward digit span). Females who were carriers of the premutation of the FMR1 gene reported less efficient executive functions in the BRIEF questionnaire compared to the control group. In addition, a relationship was found between the number of repetitions on the CGG sequence of nucleotides, nonword repetitions, and forward digit span. The findings suggest that the premutation of Fragile X in females affects their performance of executive functions and may have impact on everyday functioning.
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Hemangioma, Capillary , Hemangioma , Skin Neoplasms , Humans , Child , Infant , Atenolol , Case-Control Studies , Cohort Studies , Skin Neoplasms/therapy , Treatment OutcomeABSTRACT
INTRODUCTION: Missed appointments (MAs) at child development centres (ChDCs) cause multiple problems: they preclude timely diagnosis and treatment of both the invited child and children whose appointment was delayed due to overbooking, as well as disrupting efficient organisational management. The aim of this study was to assess the rate and describe the reasons for missed appointments at Israeli ChDCs, and to evaluate the association of socio-demographic, clinical, and administrative variables with MA rates. METHODS: This nested case-control study included all children scheduled for initial appointments (N = 1143) at three centres during 1 year. Parents of children who missed their appointment and a sample of those who attended were interviewed by telephone. RESULTS: The rate of missed appointments was 26.6%, and the most frequent reasons were unexpected events (26.0%) and lack of insurance coverage (23.4%). Variables associated with lower MA rates were: having had ≥3 types of rehabilitative interventions (odds ratios (OR) = 0.26; 95% confidence interval [CI] 0.16-0.44), detailed referral letter (OR = 0.48; 95%CI 0.30-0.75), telephone reminder (OR = 0.37; 95%CI 0.24-0.57) and health maintenance organisations or private insurance coverage (OR = 0.12; 95%CI 0.06-0.17 and OR = 0.56; 95% CI 0.38-0.89, respectively). CONCLUSION: Encouraging physician's referral letters and personal-contact reminders can reduce missed appointments. Understanding the family's and the child's personal characteristics, and the organisational/administrative aspects of missed appointments may guide efforts to ensure timely care for every child.
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Child Development , Reminder Systems , Appointments and Schedules , Case-Control Studies , Child , Humans , IsraelABSTRACT
Background: Studies have reported that Covid-19 home-quarantine periods have had mostly negative psychological impact on children with ASD and their families. Here we examined parent perceived impact of a 6-week quarantine period imposed in Israel at the beginning of the Covid-19 outbreak, in mid-March 2020. Methods: An anonymous online questionnaire was completed by parents of 268 children with ASD. Parents rated deterioration/improvement in their child's behaviors, abilities, mood, sleep, and anxiety along with changes in their own mood, sleep, parenting skills, and family relationships. We performed t-tests and ANOVA analyses to assess the significance of perceived impact on each domain and potential differences in the impact across families with children of different ages, genders, and levels of required support as well as families that experienced different magnitudes of economic hardships. Results: Parents reported significant deterioration in their mood and sleep along with significant improvements in relationships with their spouse and child with ASD, and in their parenting skills. Parents also reported significant increases in the severity of tantrums, anxiety, and restricted and repetitive behavior symptoms along with significant improvements in social and communication abilities of their child with ASD. Ratings were significantly lower in families of ASD children who regularly require more support and in families that experienced economic hardships. Conclusions: While periods of home-quarantine create numerous hardships for families of children with ASD, they may also offer an opportunity for improving parenting skills, family relationships, and children's social communication abilities with potential relevance for improving remote services.
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BACKGROUND: Among all of the studied potential causes of autism, vaccines have received some of the most scrutiny and have been the topic of many evidence-based studies. These efforts have led the great majority of scientists, physicians, and public health researchers to refute causation between vaccines and autism. RATIONALE: This presumed association and concern has been a major contributor to parents' refusal to immunize their children and has become a major threat to public health in secluded populations over the last two decades, even prior to the COVID-19 pandemic. With the emergence of COVID-19 immunizations, sentiments towards this topic were addressed as a public health concern that may influence the ability to overcome the Corona virus worldwide. SCIENTIFIC REVIEW OF DATA: Despite the overwhelming data demonstrating that there is no link between vaccines and autism, many parents are hesitant to immunize their children because of the alleged association. Other contributing factors to the myths and conspiracy theories surrounding the association between vaccines and autism include the fact that the diagnosis of autism is typically made after the age of receiving the main childhood immunizations, as well as the occasional occurrence of regression after the age of first year vaccinations. In spite of vast evidence that the main contribution to the increase in incidence is from improvement of the diagnostic process, this rapid and publicized rise in autism diagnoses feeds parental concerns regarding any medical intervention that may be associated with the health of their children. RECOMMENDATIONS: It is plausible that with more evidence-based studies linking autism to specific etiologies the myth will diminish and disappear eventually. In an era where conspiracy theories are prevalent on social media, it is critical that evidence-based studies relating autism to specific etiologies be made public, and that information concerning autism diagnosis and causes be made more readily available through social media and parental organizations.
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Autistic Disorder , COVID-19 , Autistic Disorder/epidemiology , Autistic Disorder/etiology , Child , Humans , Pandemics , Parents , SARS-CoV-2 , Vaccination/adverse effectsABSTRACT
Background: Fragile X syndrome (FXS), the most common single-gene cause of intellectual disability and autism spectrum disorder (ASD), is caused by a >200-trinucleotide repeat expansion in the 5' untranslated region of the fragile X mental retardation 1 (FMR1) gene. Individuals with FXS can present with a range of neurobehavioral impairments including, but not limited to: cognitive, language, and adaptive deficits; ASD; anxiety; social withdrawal and avoidance; and aggression. Decreased expression of the γ-aminobutyric acid type A (GABAA) receptor δ subunit and deficient GABAergic tonic inhibition could be associated with symptoms of FXS. Gaboxadol (OV101) is a δ-subunit-selective, extrasynaptic GABAA receptor agonist that enhances GABAergic tonic inhibition, providing the rationale for assessment of OV101 as a potential targeted treatment of FXS. No drug is approved in the United States for the treatment of FXS. Methods: This 12-weeks, randomized (1:1:1), double-blind, parallel-group, phase 2a study was designed to assess the safety, tolerability, efficacy, and optimal daily dose of OV101 5 mg [once (QD), twice (BID), or three-times daily (TID)] when administered for 12 weeks to adolescent and adult men with FXS. Safety was the primary study objective, with key assessments including treatment-emergent adverse events (TEAEs), treatment-related adverse events leading to study discontinuation, and serious adverse events (SAEs). The secondary study objective was to evaluate the effect of OV101 on a variety of problem behaviors. Results: A total of 23 participants with FXS (13 adolescents, 10 adults) with moderate-to-severe neurobehavioral phenotypes (Full Scale Intelligence Quotient, 41.5 ± 3.29; ASD, 82.6%) were randomized to OV101 5 mg QD (n = 8), 5 mg BID (n = 8), or 5 mg TID (n = 7) for 12 weeks. OV101 was well tolerated across all 3 treatment regimens. The most common TEAEs were upper respiratory tract infection (n = 4), headache (n = 3), diarrhea (n = 2), and irritability (n = 2). No SAEs were reported. Improvements from baseline to end-of-treatment were observed on several efficacy endpoints, and 60% of participants were identified as treatment responders based on Clinical Global Impressions-Improvement. Conclusions: Overall, OV101 was safe and well tolerated. Efficacy results demonstrate an initial signal for OV101 in individuals with FXS. These results need to be confirmed in a larger, randomized, placebo-controlled study with optimal outcomes and in the most appropriate age group. Clinical Trial Registration: www.ClinicalTrials.gov, identifier: NCT03697161.
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Exome sequencing (ES) is an important diagnostic tool for individuals with neurodevelopmental disorders (NDD) and/or multiple congenital anomalies (MCA). However, the cost of ES limits the test's accessibility for many patients. We evaluated the yield of publicly funded clinical ES, performed at a tertiary center in Israel, over a 3-year period (2018-2020). Probands presented with (1) moderate-to-profound global developmental delay (GDD)/intellectual disability (ID); or (2) mild GDD/ID with epilepsy or congenital anomaly; and/or (3) MCA. Subjects with normal chromosomal microarray analysis who met inclusion criteria were included, totaling 280 consecutive cases. Trio ES (proband and parents) was the default option. In 252 cases (90.0%), indication of NDD was noted. Most probands were males (62.9%), and their mean age at ES submission was 9.3 years (range 1 month to 51 years). Molecular diagnosis was reached in 109 probands (38.9%), mainly due to de novo variants (91/109, 83.5%). Disease-causing variants were identified in 92 genes, 15 of which were implicated in more than a single case. Male sex, families with multiple-affected members and premature birth were significantly associated with lower ES yield (p < 0.05). Other factors, including MCA and coexistence of epilepsy, autism spectrum disorder, microcephaly or abnormal brain magnetic resonance imaging findings, were not associated with the yield. To conclude, our findings support the utility of clinical ES in a real-world setting, as part of a publicly funded genetic workup for individuals with GDD/ID and/or MCA.
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Abnormalities, Multiple/diagnosis , Exome Sequencing/economics , Financing, Government , Genetic Testing/economics , Neurodevelopmental Disorders/diagnosis , Abnormalities, Multiple/economics , Abnormalities, Multiple/genetics , Adolescent , Adult , Child , Child, Preschool , Cost-Benefit Analysis , Feasibility Studies , Female , Genetic Counseling/economics , Genetic Counseling/methods , Genetic Counseling/statistics & numerical data , Genetic Testing/methods , Genetic Testing/statistics & numerical data , Humans , Infant , Infant, Newborn , Israel , Male , Maternal Age , Neurodevelopmental Disorders/economics , Neurodevelopmental Disorders/genetics , Paternal Age , Pregnancy , Prenatal Diagnosis/economics , Prenatal Diagnosis/methods , Program Evaluation , Retrospective Studies , Tertiary Care Centers/economics , Tertiary Care Centers/statistics & numerical data , Exome Sequencing/statistics & numerical data , Young AdultABSTRACT
Background: Presenting symptoms and age specific differential diagnosis of Autism Spectrum Disorder (ASD), determine the age of initial assessment and the age of a definite diagnosis. The AAP recommends screening all children for ASD at 18 and 24 months followed by a comprehensive evaluation for children with developmental concerns. More recently it has been recommended that the evaluation should be performed at a younger age, with a diagnosis being made as early as the beginning of the second year of life resulting in earlier intensive intervention. Objective: To assess early developmental milestones in a cohort of children diagnosed with Autism Spectrum Disorder (ASD) in order to find an objective and reliable early marker. We suggest that low muscle tone- hypotonia, is a sign that meets the above criteria of consistency and reliability and may be related to early diagnosis. Methods: We compared age distributions of ASD diagnosis in the presence of hypotonia in a dataset of 5,205 children diagnosed at Keshet Center. One thousand, one hundred eighty-two children (953 males) were diagnosed with ASD and compared to other developmental diagnoses. Within the ASD cohort we further analyzed for gender and pre-maturity differences. Results: In the presence of hypotonia, the mean age for ASD diagnosis was significantly lower (by 1.5 years for males and females) and this effect increased in children born at term as compared to pre-maturity. Conclusions: Hypotonia is a recognizable marker of ASD and may serve as a "red flag" to prompt earlier recognition and neurodevelopmental evaluation toward an autism diagnosis.
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BACKGROUND: While assisted reproductive technology is increasingly prevalent, there is concern amid conflicting findings reported regarding the long-term outcomes of children born following these treatments. The aim of this research was to investigate aspects of cognitive development in early school-age Israeli children born following assisted reproductive technology (ART) treatments, compared to those spontaneously conceived (SC). METHOD: This prospective follow-up study was based on an Israeli cohort recruited from June 2006 to December 2008, that included 561 women whose pregnancies were achieved by ART treatments and 600 women whose pregnancies were SC. When the children were 7-8 years old, 759 of their mothers were interviewed by telephone, and 294 were came for developmental assessment. The examination included: Kaufman Brief Intelligence Test; Kaufman Assessment Battery for Children (arithmetic only); Test of Everyday Attention for Children; Beery-Buktenica Developmental Test of Visual-Motor Integration and Supplemental Test for Visual Perception; Rey-Osterrieth Complex Figure Test; Aleph-ad-Tav Hebrew reading and writing; Tavor Picture Naming Expressive Vocabulary Test. Multivariable analyses were adjusted for maternal years of education (≤12, 13+) at child's birth and child's sex. RESULTS: Cognitive function, visual-motor ability, attention, and verbal skills of children born after ART treatments were similar to those of SC children, upon both univariate and multivariable analysis. CONCLUSION AND IMPLICATIONS: No significant differences were found between the ART and SC groups on any of the measures examined. This finding offers couples seeking ART treatments improved information regarding child development during the important and formative school years. WHAT THIS PAPER ADDS: Increasing rates of ART treatments arouse concern about long-term outcomes for offspring, and conflicting findings have been reported with respect to the skills necessary to their academic success. This prospective follow-up study compared school-age children born following ART with spontaneously-conceived children. Children were examined by developmental psychologists, and cognitive function, visual-motor, attention, verbal, and performance skills were similar in both groups.
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Reproductive Techniques, Assisted , Schools , Child , Cognition , Female , Follow-Up Studies , Humans , Pregnancy , Prospective Studies , Reproductive Techniques, Assisted/adverse effectsABSTRACT
OBJECTIVE: The purpose of this study was to assess major neurodevelopmental aspects of children conceived by assisted reproductive treatments compared to spontaneously conceived children during the early school years. MATERIAL & METHODS: In this follow-up study, mothers of 358 children born following assisted reproductive treatments and 401 spontaneously-conceived children were interviewed by telephone regarding their children's health and development, when the children were 7-8 years old. The main outcomes were maternal responses to 4 questionnaires: Developmental Coordination Disorder Questionnaire, Short Sensory Profile, Autism Spectrum Screening Questionnaire, and the Attention-deficit hyperactive disorder (ADHD) Child Symptom Inventory-4 subscale. Mothers reported diagnoses of ADHD and autism spectrum disorder. RESULTS: No significant differences were found between the groups in Developmental Coordination Disorder Questionnaire or Short Sensory Profile scores upon univariate or multivariable analyses. There was a slightly higher but nonsignificant rate of diagnosed ADHD among children in the assisted reproductive treatment group (9.6% vs 5.5%; P = .18); on multivariable analysis, a nonsignificant increase in ADHD was also found for assisted reproductive treatment children (hazard ratio 1.45, 95% confidence interval 0.81-2.61). Regarding the Child Symptom Inventory-4 criteria for ADHD among the children who had never been diagnosed, there was also a slightly higher but nonsignificant rate among the assisted reproductive treatments compared to spontaneously-conceived children on univariate (2.4% vs 1.8%; P = .50) and multivariable analysis (odds ratio 0.88, 95% confidence interval 0.27-2.86). Autism spectrum disorder diagnosis or Autism Spectrum Screening Questionnaire scores were not significantly different; however, 5 of the 6 children with autism spectrum disorder diagnoses were in the assisted reproductive treatment group. CONCLUSIONS: Neurodevelopmental measures were similar in both groups, although nonconclusive regarding ADHD and autism spectrum disorder risk. These findings contribute to the knowledge regarding long-term assisted reproductive treatment outcomes.
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Neurodevelopmental Disorders/epidemiology , Reproductive Techniques, Assisted , Adolescent , Adult , Case-Control Studies , Child , Cohort Studies , Educational Status , Female , Humans , Male , Maternal Age , Neurodevelopmental Disorders/diagnosis , Odds Ratio , Proportional Hazards Models , Surveys and Questionnaires , Young AdultABSTRACT
INTRODUCTION: Prematurity has been identified as a risk factor for Autism Spectrum Disorder (ASD). The link between Autism Spectrum Disorder (ASD) and birth-week has not been strongly evidenced. We evaluated the correlation between the degree of prematurity and the incidence of autism in a cohort of 871 children born prematurely and followed from birth. The cohort was reduced to 416 premature infants born between 2011-2017 who were followed for 2-14 years, and analyzed according to birth week (degree of prematurity), and according to gender. RESULTS: 43 children (10.3%) received a definite diagnosis of ASD. There was a significant correlation between birth week and the risk of ASD, with 22.6% of children diagnosed with ASD when born at 25 weeks, versus 6% of ASD diagnoses at 31 weeks of prematurity. For children born after 32 weeks, the incidence decreased to 8-12.5%. A strong link was found between earlier birth week and increased autism risk; the risk remained elevated during near-term prematurity in boys. A correlation between early birth week and an elevated risk for ASD was seen in all children, but accentuated in females, gradually decreasing as birth week progresses; in males the risk for ASD remains elevated for any birth week. CONCLUSION: A statistically significant increase in rates of autism was found with each additional week of prematurity. Females drove this direct risk related to degree of prematurity, while males had an elevated risk throughout prematurity weeks, even at near-term. We recommend including ASD screening in follow up of infants born prematurely, at all levels of prematurity.