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Previous studies investigating the association between dysmorphology and cognitive, behavioral, and developmental outcomes among individuals with autism spectrum disorder (ASD) have been limited by the binary classification of dysmorphology and lack of comparison groups. We assessed the association using a continuous measure of dysmorphology severity (DS) in preschool children aged 2-5 years (322 with ASD and intellectual disability [ID], 188 with ASD without ID, and 371 without ASD from the general population [POP]). In bivariate analyses, an inverse association between DS and expressive language, receptive language, fine motor, and visual reception skills was observed in children with ASD and ID. An inverse association of DS with fine motor and visual reception skills, but not expressive language and receptive language, was found in children with ASD without ID. No associations were observed in POP children. These results persisted after exclusion of children with known genetic syndromes or major morphologic anomalies. Quantile regression models showed that the inverse relationships remained significant after adjustment for sex, race/ethnicity, maternal education, family income, study site, and preterm birth. DS was not associated with autistic traits or autism symptom severity, behaviors, or regression among children with ASD with or without ID. Thus, DS was associated with a global impairment of cognitive functioning in children with ASD and ID, but only with fine motor and visual reception deficits in children with ASD without ID. A better understanding is needed for mechanisms that explain the association between DS and cognitive impairment in children with different disorders. Autism Res 2020, 13: 1227-1238. © 2020 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: We examined whether having more dysmorphic features (DFs) was related to developmental problems among children with autism spectrum disorder (ASD) with or without intellectual disability (ID), and children without ASD from the general population (POP). Children with ASD and ID had more language, movement, and learning issues as the number of DFs increased. Children with ASD without ID had more movement and learning issues as the number of DFs increased. These relationships were not observed in the POP group. Implications are discussed.

Maternal infection and fever during pregnancy have been implicated in the etiology of autism spectrum disorder (ASD); however, studies have not been able to separate the effects of fever itself from the impact of a specific infectious organism on the developing brain. We utilized data from the Study to Explore Early Development (SEED), a case-control study among 2- to 5-year-old children born between 2003 and 2006 in the United States, to explore a possible association between maternal infection and fever during pregnancy and risk of ASD and other developmental disorders (DDs). Three groups of children were included: children with ASD (N = 606) and children with DDs (N = 856), ascertained from clinical and educational sources, and children from the general population (N = 796), randomly sampled from state birth records. Information about infection and fever during pregnancy was obtained from a telephone interview with the mother shortly after study enrollment and maternal prenatal and labor/delivery medical records. ASD and DD status was determined by an in-person standardized developmental assessment of the child at 3-5 years of age. After adjustment for covariates, maternal infection anytime during pregnancy was not associated with ASD or DDs. However, second trimester infection accompanied by fever elevated risk for ASD approximately twofold (aOR = 2.19, 95% confidence interval 1.14-4.23). These findings of an association between maternal infection with fever in the second trimester and increased risk of ASD in the offspring suggest that the inflammatory response to the infectious agent may be etiologically relevant. Autism Res 2019, 12: 1551-1561. © 2019 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: Using data from a large multisite study in the United States-the Study to Explore Early Development-we found that women who had an infection during the second trimester of pregnancy accompanied by a fever are more likely to have children with ASD. These findings suggest the possibility that only more severe infections accompanied by a robust inflammatory response increase the risk of ASD.

Previous studies have shown complications of pregnancy, often examined in aggregate, to be associated with autism spectrum disorder (ASD). Results for specific complications, such as maternal diabetes and hypertension, have not been uniformly consistent and should be investigated independently in relation to ASD in a large community-based sample. The Study to Explore Early Development (SEED), a US multisite case-control study, enrolled children born in 2003-2006 at 2-5 years of age. Children were classified into three groups based on confirmation of ASD (n = 698), non-ASD developmental delay (DD; n = 887), or controls drawn from the general population (POP; n = 979). Diagnoses of any diabetes or hypertensive disorder during pregnancy were identified from prenatal medical records and maternal self-report. Logistic regression models estimated adjusted odds ratios (aOR) and confidence intervals (CI) adjusting for maternal age, race/ethnicity, education, smoking during pregnancy, and study site. Models for hypertension were additionally adjusted for parity and plurality. Among 2,564 mothers, we identified 246 (9.6%) with any diabetes and 386 (15.1%) with any hypertension in pregnancy. After adjustment for covariates, any diabetes during pregnancy was not associated with ASD (aOR = 1.10 [95% CI 0.77, 1.56]), but any hypertension was associated with ASD (aOR = 1.69 [95% CI 1.26, 2.26]). Results were similar for DD, and any diabetes (aOR = 1.29 [95% CI 0.94, 1.78]) or any hypertension (aOR = 1.71 [95% CI 1.30, 2.25]). Some pregnancy complications, such as hypertension, may play a role in autism etiology and can possibly serve as a prompt for more vigilant ASD screening efforts. Autism Res 2019, 12: 967-975. © 2019 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: We studied if common complications in pregnancy are associated with autism spectrum disorder (ASD) in a large sample of mothers and children. Our results show an association between conditions marked by high blood pressure and ASD, but no association with conditions marked by high blood sugar and ASD. Associations were similar for children who had a developmental disorder that was not ASD, suggesting that this relationship may not be specific to ASD.

Studies report inconsistent findings on the relationship between ASD and breastfeeding. We explored associations between ASD and breastfeeding initiation (yes/no) and duration (months categorized in tertiles) in the Study to Explore Early Development, a community-based case-control study in six sites in the Unites States. We adjusted for various child and mother demographic and pregnancy factors. Breastfeeding initiation was reported in 85.7% of mothers of children with ASD and 90.6% of mothers of controls. After adjustment, we found no significant difference in breastfeeding initiation (adjusted odds-ratio [aOR]: 0.88 and 95% confidence interval (CI) 0.60-1.28). However, mothers of children with ASD were less likely to report duration of breastfeeding in the high (≥12 months) versus low tertile (

Most prior studies examining maternal pre-pregnancy body mass index (BMI) in relation to offspring autism spectrum disorders (ASD) have reported an association, though findings are not uniform and few have also examined gestational weight gain (GWG). Therefore, we examined both in the Study to Explore Early Development, a multi-site case-control study of children born in 2003-2006. Children identified from clinics, schools, and birth certificates were enrolled at ages 2-5 year and using standardized developmental evaluations, classified as: ASD, other developmental delays (DD), or population-based controls. Maternal height, weight, and GWG were self-reported during the telephone interview. Three primary weight risk factors were examined: (a) Pre-pregnancy BMI, classified as underweight to obese, (b) GWG continuous and categorized as quintiles, and (c) Institute of Medicine clinical weight-gain recommendations. Odds ratios adjusted (AOR) for sociodemographic and prenatal factors were calculated among term singletons, comparing the ASD (n = 540) or DD (n = 720) groups to the control group (n = 776). The AOR of ASD and maternal obesity was 1.37 (95%CI 0.98-1.92). Associations with higher GWG were stronger (Quintile5 vs. Quintile3 AOR = 1.58, 95%CI 1.08-2.31), and particularly so among overweight/obese women (AOR = 1.90, 95%CI 0.98-3.68). DD was associated with maternal overweight and obesity (obesity AOR = 1.48, 95%CI 1.08-2.02), but not with total GWG or clinical recommendations. High maternal BMI and GWG are risk factors for other pregnancy and child outcomes, and our results suggest they may also represent modifiable risk factors for neurodevelopmental outcomes. Autism Res 2019, 12: 316-327 © 2018 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: In a large, national study, we found that children with autism were more likely than unaffected children to have mothers with higher weight gain during pregnancy; risk of autism may be even stronger if mothers were also overweight before pregnancy. Children with other developmental delays were more likely to have mothers who were overweight or obese before pregnancy, but not who gained more weight during pregnancy. Overweight and weight gain may represent factors that could be modified.

Immune system abnormalities have been widely reported among children with autism spectrum disorder (ASD), which may increase the risk of childhood infections. The Study to Explore Early Development (SEED) is a multisite case-control study of children aged 30-69 months, born in 2003-2006. Cases are children previously diagnosed and newly identified with ASD enrolled from education and clinical settings. Children with a previously diagnosed non-ASD developmental condition were included in the developmental delay/disorder (DD) control group. The population (POP) control group included children randomly sampled from birth certificates. Clinical illness from infection during the first 28 days ("neonatal," from medical records) and first three years of life (caregiver report) in cases was compared to DD and POP controls; and between cases with and without regression. Children with ASD had greater odds of neonatal (OR = 1.8; 95%CI: 1.1, 2.9) and early childhood infection (OR = 1.7; 95%CI: 1.5, 1.9) compared to POP children, and greater odds of neonatal infection (OR = 1.5; 95%CI: 1.1, 2.0) compared to DD children. Cases with regression had 1.6 times the odds (95%CI: 1.1, 2.3) of caregiver-reported infection during the first year of life compared to cases without regression, but neonatal infection risk and overall early childhood infection risk did not differ. Our results support the hypothesis that children with ASD are more likely to have infection early in life compared to the general population and to children with other developmental conditions. Future studies should examine the contributions of different causes, timing, frequency, and severity of infection to ASD risk. Autism Research 2019, 12: 136-146. © 2018 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: We looked at infections during early childhood in relation to autism spectrum disorder (ASD). We found that children with ASD were more likely to have an infection in the first 28 days of life and before age three compared to children with typical development. Children with ASD were also more likely than children with other developmental delays or disorders to have an infection in the first 28 days of life.

Numerous studies have reported immune system disturbances in individuals with autism and their family members; however, there is considerable variability in findings with respect to the specific immune conditions involved, their timing, and the family members affected and little understanding of variation by autism subphenotype. Using data from the Study to Explore Early Development (SEED), a multi-site case-control study of children born 2003-2006 in the United States, we examined the role of family history of autoimmune diseases, asthma, and allergies in autism spectrum disorder (ASD) as well as other developmental disorders (DD). We investigated maternal immune conditions during the pregnancy period, as well as lifetime history of these conditions in several family members (mother, father, siblings, and study child). Logistic regression analyses included 663 children with ASD, 984 children with DD, and 915 controls ascertained from the general population (POP). Maternal history of eczema/psoriasis and asthma was associated with a 20%-40% increased odds of both ASD and DD. Risk estimates varied by specific ASD subphenotypes in association with these exposures. In addition, children with ASD were more likely to have a history of psoriasis/eczema or allergies than POP controls. No association was observed for paternal history or family history of these immune conditions for either ASD or DD. These data support a link between maternal and child immune conditions and adverse neurodevelopmental outcomes, and further suggest that associations may differ by ASD phenotype of the child. Autism Research 2019, 12: 123-135. © 2018 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: Using data from a large multi-site study in the US-the Study to Explore Early Development-we found that women with a history of eczema/psoriasis and asthma are more likely to have children with ASD or DD. In addition, children with ASD are more likely to have a history of psoriasis/eczema or allergies than typically developing children. These data support a link between maternal and child immune conditions and adverse neurodevelopmental outcomes.

Previous studies of autism spectrum disorder (ASD) and birth spacing had limitations; few examined phenotypic case subtypes or explored underlying mechanisms for associations and none assessed whether other (non-ASD) developmental disabilities (DDs) were associated with birth spacing. We assessed associations between inter-pregnancy interval (IPI) and both ASD and other DDs using data from the Study to Explore Early Development, a multi-site case-control study with rigorous case-finding and case-classification methods and detailed data collection on maternal reproductive history. Our sample included 356 ASD cases, 627 DD cases, and 524 population (POP) controls born in second or later births. ASD and DD cases were further sub-divided according to whether the child had intellectual disability (ID). ASD cases were also sub-divided by ASD symptom severity, and DD cases were subdivided by presence of some ASD symptoms (indicated on an autism screener). Odds ratios, adjusted for maternal-child sociodemographic factors, (aORs) and 95% confidence intervals were derived from logistic regression models. Among term births, ASD was associated with both IPI

Our objective was to estimate prevalence of current or ever use of a gluten free diet (GFD) in children aged 30-68 months with autism spectrum disorder (ASD) and population controls (POP); and to identify characteristics associated with ever having used GFD among children with ASD. We used data from the Study to Explore Early Development (SEED), a multi-site, case-control study of children with ASD. Caregivers reported GFD use by their children through structured questionnaires about diet patterns, gastrointestinal (GI) issues, and ASD-specific treatments. Prevalence was estimated and compared using log-Poisson regression, adjusting for confounders. In children with ASD, we examined whether child or mother's GI conditions or child's phenotypic traits were associated with ever trying a GFD. In SEED, 71 children with ASD (11.1% prevalence after adjustment) were on a GFD at time of the study and 130 (20.4%) had ever used a GFD, a greater percentage than in POP children (N = 11, 0.9% current use). Of current users with ASD, 50.7% had a dietary intervention that was prescribed by a medical professional. Among children with ASD, child GI conditions and developmental regression were positively and independently associated with having ever used a GFD. Current use and ever use of a GFD were prevalent in children with ASD identified in SEED. GFD usage was associated with GI issues and child phenotype. Clinicians may consider advising parents on how best to use these diets in the context of the child's GI presentation and current scientific knowledge about effectiveness in relation to ASD symptoms. Autism Res 2018, 11: 185-193. © 2017 International Society for Autism Research, Wiley Periodicals, Inc. Lay summary Gluten free diets (GFDs) are commonly used as an alternative therapy for autism spectrum disorder (ASD); however, the effectiveness is still uncertain which makes it important to know who tries this type of diet. We found that one in five preschool aged children with ASD had ever used a GFD. Children with gastrointestinal conditions and developmental regression were more likely to have tried a GFD.

Summary Information on gestational age for public health research and surveillance in the US is usually obtained from vital records and is primarily based on the first day of the woman's last menstrual period (LMP). However, using LMP as a marker of conception is subject to a variety of errors and results in misclassification of gestational age. Pregnancies conceived through assisted reproductive technology (ART) are unique in that the estimates of gestational age are not based on the LMP, but on the date when fertilisation actually occurred, and thus most gestational age errors are likely to be due to errors introduced in recording and data entry. The purpose of this paper was to examine the birthweight distribution by gestational age for ART singleton livebirths reported to a national ART surveillance system. Gestational age was categorised as 20–27, 28–31, 32–36 and 37–44 weeks; birthweight distributions were plotted for each category. The distributions of very-low-birthweight (VLBW

To examine associations of vaginal Ureaplasma urealyticum (UU) and bacterial vaginosis (BV) with preterm delivery (PTD), small for gestational age (SGA), and low birth weight (LBW).A population-based, prospective cohort study of 2,927 pregnancies. After exclusion of multiples and antibiotic use sample size was 2,662. BV (Amsel's criteria) and UU (culture) were assessed in week 17. Gestational age was determined by last menstrual period, confirmed by ultrasound measurement in 97.5%. SGA infants were calculated from intrauterine fetal growth measurements.There was no increased risk for spontaneous PTD among women with BV only (crude odds ratio 1.0, 95% CI 0.4-2.7), among women with UU only (1.3, 0.8-2.0), nor among women with UU + BV (0.9, 0.4-2.3) compared to women without UU and BV. However, there was a threefold increased risk of a LBW birth in women with UU + BV (3.1, 1.8-5.4), a twofold risk of a LBW birth among women with UU only (1.9, 1.3-2.9), but no increased risk among women with BV only (0.8, 0.3-2.2). Similarly, women with UU + BV had over a twofold increased risk of an SGA birth (2.3, 1.3-4.0), women with UU only had a 70% increase (1.7, 1.1-2.5), whereas a nonsignificant increase was found in women with BV only (1.3, 0.6-2.9). Adjustment by established confounders (smoking, previous PTD, previous LBW, and Escherichia coli) did not affect risk estimates.This analysis suggests that UU is independently associated with fetal growth and LBW and that BV with UU may enhance the risk of these outcomes.

On 1 March 1997, powerful tornadoes touched down in Arkansas (USA) on a Saturday afternoon. Twenty-six fatalities and 400 non-fatal injuries were reported. We performed a population-based cross-sectional study to determine factors associated with appropriate responses to tornado warnings. Of 146 survey participants, 140 (96 per cent) knew the difference between 'tornado watch' and 'tornado warning' and were aware of when the warning was announced. Of those 140 participants, 64 (45.7 per cent) responded to the warning by seeking shelter, and 58 (90.6 per cent) of those 64 acted within five minutes of hearing the warning. Four factors were positively associated with those seeking shelter: having graduated from high school (OR = 4.2, 95 per cent CI = 1.1-15.5); having a basement in one's house (OR = 3.8, 95 per cent exact CI = 1.1-17.1); hearing a siren (OR = 4.4, 95 per cent CI = 1.3-18.9); and having prepared a household plan of response when tornadoes occur (OR = 2.6, 95 per cent CI = 1.1-6.3). On the basis of these findings, we recommend: first, that people who live in tornadoprone areas have a personal plan of action to help them respond immediately to warnings; second, public-health education officials in areas with frequent tornadic activity should do more to educate the public about what they can do to protect themselves from a tornado; and third, that emergency-management officials planning protection measures for vulnerable communities should consider that most people have limited time (our study documented five minutes) in which to respond to a tornado warning. Thus, shelters in tornado-prone areas should be quickly accessible by residents. Language: en