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Objective: To examine antiseizure medication (ASM) prescription during pregnancy. Design: Population‐based drug utilisation study. Setting: UK primary and secondary care data, 1995–2018, from the Clinical Practice Research Datalink GOLD version. Population or Sample: 752 112 completed pregnancies among women registered for a minimum of 12 months with an 'up to standard' general practice prior to the estimated start of pregnancy and for the duration of their pregnancy. Methods: We described ASM prescription across the study period, overall and by ASM indication, examined patterns of prescription during pregnancy including continuous prescription and discontinuation, and used logistic regression to investigate factors associated with those ASM prescription patterns. Main Outcome Measures: Prescription of ASMs during pregnancy and discontinuation of ASMs before and during pregnancy. Results: ASM prescription during pregnancy increased from 0.6% of pregnancies in 1995 to 1.6% in 2018, driven largely by an increase in women with indications other than epilepsy. Epilepsy was an indication for 62.5% of pregnancies with an ASM prescription and non‐epilepsy indications were present for 66.6%. Continuous prescription of ASMs during pregnancy was more common in women with epilepsy (64.3%) than in women with other indications (25.3%). Switching ASMs was infrequent (0.8% of ASM users). Factors associated with discontinuation included age ≥35, higher social deprivation, more frequent contact with the GP and being prescribed antidepressants or antipsychotics. Conclusions: ASM prescription during pregnancy increased between 1995 and 2018 in the UK. Patterns of prescription around the pregnancy period vary by indication and are associated with several maternal characteristics. [ABSTRACT FROM AUTHOR]

While the concept of big data has emerged over the past decade as a hot topic in nearly all areas of scientific inquiry, it has rarely been discussed in the context of autism research. In this commentary we describe aspects of big data that are relevant to autism research and methodological issues such as confounding and data error that can hamper scientific investigation. Although big data studies can have transformative impact, bigger is not always better, and big data require the same methodological considerations and interdisciplinary collaboration as "small data" to extract useful scientific insight. Lay Summary: This commentary explains how big data can be used in autism research and the challenges that come with it, like confounding factors and data errors. Eventhough big data can have a big impact, it is not always better. Big data needs to be handled carefully and with collaboration from different fields to get the most out of it. [ABSTRACT FROM AUTHOR]

Purpose: Estimating causal effects in observational pharmacoepidemiology is a challenging task, as it is often plagued by confounding by indication. Restricting the sample to those with an indication for drug use is a commonly performed procedure; indication‐based sampling ensures that the exposed and unexposed are exchangeable on the indication—limiting the potential for confounding by indication. However, indication‐based sampling has received little scrutiny, despite the hazards of exposure‐related covariate control. Methods: Using simulations of varying levels of confounding and applied examples we describe bias amplification under indication‐based sampling. Results: We demonstrate that indication‐based sampling in the presence of unobserved confounding can give rise to bias amplification, a self‐inflicted phenomenon where one inflates pre‐existing bias through inappropriate covariate control. Additionally, we show that indication‐based sampling generally leads to a greater net bias than alternative approaches, such as regression adjustment. Finally, we expand on how bias amplification should be reasoned about when distinct clinically relevant effects on the outcome among those with an indication exist (effect‐heterogeneity). Conclusion: We conclude that studies using indication‐based sampling should have robust justification ‐ and that it should by no means be considered unbiased to adopt such approaches. As such, we suggest that future observational studies stay wary of bias amplification when considering drug indications. [ABSTRACT FROM AUTHOR]

Autism spectrum disorder (ASD) is highly heritable, yet how its familial risk and heritability may vary by cognitive ability is not well understood. In this population‐based cohort study, we examined the familial risk and heritability of ASD with and without co‐occurring intellectual disability (ID). We estimated odds ratios and heritability of ASD with ID (ASD+ID) and ASD without ID (ASD−ID) using register‐based diagnosis data of 567,436 index persons born in 1984–2009 in Stockholm County, Sweden, and their parents, siblings, cousins, aunts, and uncles. The familial risk profile exhibited differences between ASD−ID and ASD+ID, most notably for index persons with affected parents. For example, for an index person who had at least one parent with ASD, the child's odds of ASD−ID and ASD+ID (95% confidence interval (CI)) increased by 16.2 (14.2–18.6) and 7.4 (5.5–10.0) folds, respectively. The more closely related a family member with ASD was, the greater the observed risk was of ASD in the index person, especially for ASD−ID. The broad‐sense heritability (95% CI) for ASD − ID and ASD+ID were 64.6% (46.0–100.0%) and 33.4% (14.4–58.4%), respectively. Familial risk and heritability of ASD may vary by intellectual ability, which implies that risk factors between these ASD phenotypes may differ. Our findings from the heritability analysis and familial risk analysis suggest that ASD−ID may have a greater genetic basis than ASD+ID, although this should be verified in future studies. Lay Summary Autism spectrum disorder (ASD) is highly heritable, yet how its familial risk and heritability may vary by cognitive ability is not well‐understood. In a population‐based cohort study on families of 567,436 index persons using Swedish registers data, we found that the familial risk profile differed between ASD with and without intellectual disability. Our findings from the heritability analysis and familial risk analysis suggest that ASD−ID may have a greater genetic basis than ASD+ID, although this should be verified in future studies. [ABSTRACT FROM AUTHOR]

Prenatal maternal diet is a critical factor in offspring neurodevelopment. Emerging evidence suggests that prenatal diet may also play a role in the etiology autism spectrum disorder (ASD). This review summarizes studies published in English that examined prenatal nutrients or maternal diet in association with ASD from PubMed as of July 2020. Thiry‐six studies from nine countries were included in this systematic review; these focused on multivitamin (n = 5), prenatal vitamin (n = 3), folic acid (FA; n = 14), Vitamin D (n = 11), polyunsaturated fatty acid or fish/supplement intake (n = 7), iron (n = 3), Vitamin B12 (n = 1), calcium (n = 1), magnesium (n = 1), and broad maternal dietary habits (n = 3). Overall, higher or moderate intake of prenatal/multivitamin, FA, and Vitamin D was associated with reductions in odds of ASD, though results have not been uniform and there is a need to clarify differences in findings based on biomarkers versus reported intake. Evidence was inconclusive or insufficient for other nutrients. Differences in the timing and measurement of these dietary factors, as well as potential residual confounding, may contribute to existing discrepancies. Key areas for future research to better understand the role of maternal diet in ASD include the need to address potential critical windows, examine the combined effect of multiple nutrients, and consider interactions with genetic or environmental factors. Lay Summary: Maternal diet during pregnancy is important for child neurodevelopment. We reviewed 36 studies examining maternal diet and autism spectrum disorder (ASD) and found that prenatal vitamin/multivitamin use and adequate intake of folic acid and Vitamin D were each associated with lower likelihood of having a child with ASD. Future studies on these and other dietary factors are needed to better understand the role of maternal diet in the development of ASD. Autism Res 2020, 13: 1634–1658. © 2020 International Society for Autism Research and Wiley Periodicals LLC [ABSTRACT FROM AUTHOR]

Food allergies are frequently reported to co‐occur with autism spectrum disorder (ASD), but the prevalence of this co‐occurrence remains uncertain. In the present study, we examined parent‐reported prevalence of co‐occurring food allergy and ASD in a nationally representative sample of US children ages 2–17 in the National Health Interview Survey, study years 2011–2015. All analyses used survey weights to account for the complex sampling design. In the analytic sample of 53,365 children ages 2–17, there were 905 children with parent‐reported ASD (prevalence of 1.7%) and 2,977 children with parent‐reported food allergy (prevalence of 5.6%). Parent‐reported food allergies were nearly 2.5 times more common in children with ASD (prevalence of 13.1%) than in children without ASD (5.4%). These results indicate that food allergies commonly co‐occur with ASD, which may have etiological implications. Autism Research 2019, 12: 802–805. © 2019 International Society for Autism Research, Wiley Periodicals, Inc. Lay Summary: Food allergies are frequently reported to occur with autism spectrum disorder (ASD), but the prevalence of this co‐occurrence remains uncertain. In the present study, we examined parent‐reported prevalence of co‐occurring food allergy and ASD in a nationally representative sample of United States children. In the sample of 53,365 children ages 2–17, 1.7% of children were reported to have ASD, and 5.6% were reported to have food allergies. Parent‐reported food allergies were nearly 2.5 times more common in children with ASD (13.1%) than in children without ASD (5.4%). [ABSTRACT FROM AUTHOR]

Background: Preterm birth has been linked to increased risk of autism spectrum disorders (ASD), but how this risk changes with gestational age at birth has not been well characterised, especially with regard to co-occurring intellectual disability (ID).Methods: Register-based cohort study of singleton births in 1984-2007 in Stockholm County, Sweden (N total: 480 728; n ASD: 10 025). We assessed overall and sex-specific, gestational week-specific prevalence estimates and risk ratios of ASD with and without ID.Results: Preterm and postterm births were associated with elevated risk of ASD, and the relationship between gestational age at birth and ASD with and without ID differed in males and females. Risk of ASD without ID was higher in preterm births among both sexes and decreased continuously with increasing length of gestation. Risk of ASD with ID was higher in both preterm and postterm births among both sexes, with postterm birth in females being more highly associated with ASD with ID than that in males.Conclusions: The relationship between gestational age at birth and ASD differs by the presence/absence of co-occurring ID and fetal sex. Both preterm and postterm birth are associated with increased risk of ASD. Risk of ASD is not constant within conventionally defined gestational age at birth periods. Further research on mechanism underlying these associations is needed. [ABSTRACT FROM AUTHOR]

Aim: This study examined maternal and pregnancy risk factors for haemolytic and nonhaemolytic neonatal jaundice in a large population-based cohort study.Methods: We conducted a cohort study of 1 019 220 singleton live births from the Swedish medical birth register from 1987 to 2002, using information on neonatal jaundice and maternal and pregnancy characteristics. Diagnoses of gestational hypertensive disorders were obtained by linkage to the national inpatient register. Multivariate logistic regression analysis provided odds ratios for the risk factors of both forms of jaundice.Results: A total of 6057 (0.6%) births were affected by haemolytic jaundice and 36 869 (3.6%) by nonhaemolytic jaundice. The strongest risk factors for haemolytic jaundice were maternal alloimmunisation, blood group O and neonatal jaundice in older siblings. For nonhaemolytic jaundice, the strongest risk factors were preterm birth, neonatal jaundice in older siblings, maternal origin from East or South-East Asia and maternal obesity. We estimated that 13% of haemolytic jaundice was attributable to alloimmunisation and 39% of nonhaemolytic jaundice was attributable to preterm birth.Conclusion: Haemolytic and nonhaemolytic neonatal jaundice had different risk factor profiles. Interventions to reduce maternal alloimmunisation, preterm birth and maternal obesity may lower the prevalence of neonatal jaundice and the risk of consequent neurological complications. [ABSTRACT FROM AUTHOR]

In the era of globalization and with the emergence of autism spectrum disorder as a global concern, the landscape of autism research has expanded to encompass much of the world. Here, we seek to provide an overview of the world of autism research, by documenting collaboration underlying the International Meeting for Autism Research ( IMFAR), the pre-eminent annual scientific meeting devoted to the presentation of the latest autism research. We analyzed published abstracts presented at IMFAR meetings, between 2008 and 2013, to determine patterns of collaboration. We described collaboration networks on the individual, institutional, and international levels, and visually depicted these results on spatial network maps. Consistent with findings from other scientific disciplines, we found that collaboration is correlated with research productivity. Collaborative hotspots of autism research throughout the years were clustered on the East and West coasts of the U. S., Canada, and northern Europe. In years when conferences were held outside of North America, the proportion of abstracts from Europe and Asia increased. While IMFAR has traditionally been dominated by a large North American presence, greater global representation may be attained by shifting meeting locations to other regions of the world. Autism Res 2015, 8: 1-8. © 2014 International Society for Autism Research, Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Because animal and human studies indicate that androgen exposure can influence neurodevelopment, it has been hypothesized that prenatal exposure to excess androgens may predispose to disorders with male-skewed ratio such as autism spectrum disorders (ASD). Therefore, maternal conditions characterized by hyperandrogenism such as polycystic ovary syndrome (PCOS) or hirsutism may be relevant to child ASD. We previously found in a large Swedish case-control study of 23,748 ASD cases and 208,796 matched controls that PCOS in mothers is associated with increased offspring risk of ASD. In the same sample, we have now examined whether maternal diagnoses of hirsutism were associated with ASD. In both unadjusted logistic regression models and models adjusted for a variety of covariates, hirsutism was associated with higher odds of ASD. The most adjusted odds ratios for associations with ASD for hirsutism diagnosis before birth and lifetime diagnosis of hirsutism were 1.64 (95% CI: 0.94, 2.83) and 1.26 (95% CI: 1.01, 1.57), respectively. The presence of an association of maternal hirsutism with child ASD is consistent with the hypothesis that androgens may be involved in the etiology of ASD. Autism Res 2017, 10: 1544-1546. © 2017 International Society for Autism Research, Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Machine learning techniques such as classification and regression trees (CART) have been suggested as promising alternatives to logistic regression for the estimation of propensity scores. The authors examined the performance of various CART-based propensity score models using simulated data. Hypothetical studies of varying sample sizes ( n=500, 1000, 2000) with a binary exposure, continuous outcome, and 10 covariates were simulated under seven scenarios differing by degree of non-linear and non-additive associations between covariates and the exposure. Propensity score weights were estimated using logistic regression (all main effects), CART, pruned CART, and the ensemble methods of bagged CART, random forests, and boosted CART. Performance metrics included covariate balance, standard error, per cent absolute bias, and 95 per cent confidence interval (CI) coverage. All methods displayed generally acceptable performance under conditions of either non-linearity or non-additivity alone. However, under conditions of both moderate non-additivity and moderate non-linearity, logistic regression had subpar performance, whereas ensemble methods provided substantially better bias reduction and more consistent 95 per cent CI coverage. The results suggest that ensemble methods, especially boosted CART, may be useful for propensity score weighting. Copyright © 2009 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Patterns of seasonal variation in births in some neuropsychiatric conditions have been found in previous research; however, no study to date has examined these disorders for seasonal variation in singletons and multiple births separately. This study aimed to determine whether the birth date distribution for individuals with autism spectrum disorders (ASD), including singletons and multiple births, differed from the general population. Two ASD case groups were studied: 907 singletons and 161 multiple births concordant for ASD. Two control groups were obtained from registered births of singletons and multiples. Results of the non-parametric time-series analyses, where day of birth was used, suggested there were three peaks in ASD singletons and ASD concordant multiple births. Roughly, the peaks were in April, June and October for singletons and about 2–4 weeks earlier in multiples. Results from multivariable Poisson regression, where month of birth was used, indicated that ASD concordant multiple births in males tended to be higher than expected in March, May and September (with borderline statistical significance), but were 87% less in December ( P < 0.05), as compared with January. Overall, the patterns of relative risk estimates from Poisson regression are similar to findings from the non-parametric time-series approach, but are not exactly congruent. It is important to note that indications of seasonality may be sensitive to the selection of time cut-points and therefore an arbitrary binning of time can either mask existing trends or falsely indicate the presence of a trend. The presence of seasonal trends in ASD singletons and concordant multiple births suggests a role for non-heritable factors operating during the pre- or perinatal period, even among cases with a genetic susceptibility. [ABSTRACT FROM AUTHOR]

Objective: To examine antiseizure medication (ASM) prescription during pregnancy., Design: Population-based drug utilisation study., Setting: UK primary and secondary care data, 1995-2018, from the Clinical Practice Research Datalink GOLD version., Population or Sample: 752 112 completed pregnancies among women registered for a minimum of 12 months with an 'up to standard' general practice prior to the estimated start of pregnancy and for the duration of their pregnancy., Methods: We described ASM prescription across the study period, overall and by ASM indication, examined patterns of prescription during pregnancy including continuous prescription and discontinuation, and used logistic regression to investigate factors associated with those ASM prescription patterns., Main Outcome Measures: Prescription of ASMs during pregnancy and discontinuation of ASMs before and during pregnancy., Results: ASM prescription during pregnancy increased from 0.6% of pregnancies in 1995 to 1.6% in 2018, driven largely by an increase in women with indications other than epilepsy. Epilepsy was an indication for 62.5% of pregnancies with an ASM prescription and non-epilepsy indications were present for 66.6%. Continuous prescription of ASMs during pregnancy was more common in women with epilepsy (64.3%) than in women with other indications (25.3%). Switching ASMs was infrequent (0.8% of ASM users). Factors associated with discontinuation included age ≥35, higher social deprivation, more frequent contact with the GP and being prescribed antidepressants or antipsychotics., Conclusions: ASM prescription during pregnancy increased between 1995 and 2018 in the UK. Patterns of prescription around the pregnancy period vary by indication and are associated with several maternal characteristics., (© 2023 The Authors. BJOG: An International Journal of Obstetrics and Gynaecology published by John Wiley & Sons Ltd.)