Acetaminophen Use During Pregnancy and Children's Risk of Autism, ADHD, and Intellectual Disability.

Importance: Several studies suggest that acetaminophen (paracetamol) use during pregnancy may increase risk of neurodevelopmental disorders in children. If true, this would have substantial implications for management of pain and fever during pregnancy. Objective: To examine the associations of acetaminophen use during pregnancy with children's risk of autism, attention-deficit/hyperactivity disorder (ADHD), and intellectual disability. Design, Setting, and Participants: This nationwide cohort study with sibling control analysis included a population-based sample of 2 480 797 children born in 1995 to 2019 in Sweden, with follow-up through December 31, 2021. Exposure: Use of acetaminophen during pregnancy prospectively recorded from antenatal and prescription records. Main Outcomes and Measures: Autism, ADHD, and intellectual disability based on International Classification of Diseases, Ninth Revision and International Classification of Diseases, Tenth Revision codes in health registers. Results: In total, 185 909 children (7.49%) were exposed to acetaminophen during pregnancy. Crude absolute risks at 10 years of age for those not exposed vs those exposed to acetaminophen were 1.33% vs 1.53% for autism, 2.46% vs 2.87% for ADHD, and 0.70% vs 0.82% for intellectual disability. In models without sibling control, ever-use vs no use of acetaminophen during pregnancy was associated with marginally increased risk of autism (hazard ratio [HR], 1.05 [95% CI, 1.02-1.08]; risk difference [RD] at 10 years of age, 0.09% [95% CI, -0.01% to 0.20%]), ADHD (HR, 1.07 [95% CI, 1.05-1.10]; RD, 0.21% [95% CI, 0.08%-0.34%]), and intellectual disability (HR, 1.05 [95% CI, 1.00-1.10]; RD, 0.04% [95% CI, -0.04% to 0.12%]). To address unobserved confounding, matched full sibling pairs were also analyzed. Sibling control analyses found no evidence that acetaminophen use during pregnancy was associated with autism (HR, 0.98 [95% CI, 0.93-1.04]; RD, 0.02% [95% CI, -0.14% to 0.18%]), ADHD (HR, 0.98 [95% CI, 0.94-1.02]; RD, -0.02% [95% CI, -0.21% to 0.15%]), or intellectual disability (HR, 1.01 [95% CI, 0.92-1.10]; RD, 0% [95% CI, -0.10% to 0.13%]). Similarly, there was no evidence of a dose-response pattern in sibling control analyses. For example, for autism, compared with no use of acetaminophen, persons with low (<25th percentile), medium (25th-75th percentile), and high (>75th percentile) mean daily acetaminophen use had HRs of 0.85, 0.96, and 0.88, respectively. Conclusions and Relevance: Acetaminophen use during pregnancy was not associated with children's risk of autism, ADHD, or intellectual disability in sibling control analysis. This suggests that associations observed in other models may have been attributable to familial confounding.

The burden of mild intellectual disability attributed to prenatal exposure to methylmercury in China, 2017.

Methylmercury (MeHg) is a neurodevelopmental toxicant that is widespread in the environment and food. Considering the presence of multiple sources of MeHg exposure in the environment, the burden attributable to different exposure sources needs to be determined. This study aimed to estimate the burden of mild intellectual disability (MID) caused by in-utero exposure to MeHg and identify the attributable burden related to MeHg exposure from different sources in China. We applied the hair mercury concentrations from studies to evaluate the burden of MID associated with maternal MeHg exposure and quantify it by disability-adjusted life years (DALYs). The DALYs attributable to MeHg exposure sources were calculated by combining the total DALYs and the contribution rates of various sources of MeHg exposure. The maternal MeHg exposure resulted in 6504 MID cases and a loss of 63,354 DALYs in China in 2017. The contribution rates of aquatic products and rice were 52.2% and 27.1%, respectively, leading to health losses of 28,115 and 18,011 DALYs. The burden of MeHg-induced MID associated with aquatic products was high in coastal areas. Several sites such as Zhejiang, Hunan, and Guangxi had high DALYs caused by rice MeHg exposure. Regions with high DALYs of MID related to MeHg exposure require more attention. Local governments should establish targeted measures to reduce MeHg exposure, thus preventing health loss.

Trimester-specific ambient PM2.5 exposures and risk of intellectual disability in Utah.

Prenatal fine particulate matter (PM2.5) exposure is an understudied risk factor for neurodevelopmental outcomes, including intellectual disability (ID). Associations among prenatal exposures and neurodevelopmental outcomes may vary depending on the timing of exposure. Limited numbers of studies examining PM2.5 and neurodevelopmental outcomes have considered exposures occurring during the preconception period. To address these gaps, we conducted a case-control study of children born in Utah between 2002 and 2008 (n = 1032). Cases were identified using methods developed by the Centers for Disease Control and Prevention's Autism and Developmental Disabilities Monitoring Network and matched with controls on birth year, sex, and birth county. We estimated the daily average PM2.5 concentration during a period spanning 12 weeks before the estimated conception date, as well as during each of the three trimesters at the maternal residential address listed on the child's birth certificate. In a multivariable model, the third (OR: 2.119, CI: 1.123-3.998, p = .021) and fourth (OR: 2.631, CI: 1.750-3.956, p < .001) quartiles for preconception average PM2.5 demonstrated significantly increased risk of ID relative to the first quartile. Second quartile preconception exposure was also associated with increased risk, though it did not reach significance (OR: 1.385, CI: 0.979-1.959, p = .07). The fourth quartile of first trimester average PM2.5 was positive and significant (OR: 2.278, CI: 1.522-3.411, p < .001); the third quartile was positive, but not significant (OR: 1.159, CI: 0.870-1.544, p = .312). Quartiles of second and third trimester were not associated with higher risk of ID. These findings from Utah, which were robust to a variety of sensitivity analyses, provide initial evidence that preconception and prenatal PM2.5 exposure may be associated with ID. Future studies are needed across other geographic locations and populations.

Top-Up Clozapine for Risperidone LAI-Related Acute Dystonia and TR Bipolar in an Adolescent with ID-Putting the Cart before the Horse?

Objectives: Young patients with intellectual disability (ID) have both diagnostic and therapeutic challenges. These include, inter alia, diagnostic overshadowing, diagnostic slippage and heightened vulnerability to adverse drug reactions. These would portent a generally poor prognostication. Methods: This is a case-study of an adolescent with intellectual disability long-hospitalized for co-morbid treatment-resistant bipolar mood disorder that failed to respond to ECT. Patient partially responded to LAI risperidone with repeated ADRs. Top-up with low-dose clozapine (100 mg/d) was pursued. Results: Low-dose clozapine top-up complemented therapeutic response (mood lability and paranoia) and strikingly safeguarded effectively against risperidone-related extrapyramidal side effects. Conclusions: Add-on clozapine remains a viable option, albeit off-label, in young patients with ID and treatment-resistant affective/schizophreniform psychoses. Clozapine has an edge over other agents in the setting of dyskinesias.

Trends in neurodevelopmental disability burden due to early life chemical exposure in the USA from 2001 to 2016: A population-based disease burden and cost analysis.

Endocrine disrupting chemicals are known to cause neurodevelopmental toxicity through direct and indirect pathways. In this study we used data from the National Health and Nutrition Examination Surveys, along with known exposure-disease relationships, to quantify the intellectual disability burden attributable to in utero exposure to polybrominated diphenyl ethers (PBDEs), organophosphates, and methylmercury and early life exposure to lead. We also estimated the cost of the IQ points lost and cases of intellectual disability. PBDE exposure was the greatest contributor to intellectual disability burden, resulting in a total of 162 million IQ points lost and over 738,000 cases of intellectual disability. This was followed by lead, organophosphates, and methylmercury. From 2001 to 2016, IQ loss from PBDEs, methylmercury, and lead have decreased or remained stagnant. Organophosphate exposure measurements were only available up to 2008 but did show an increase in organophosphate-attributable IQ loss. Although most of these trends show benefit for children's neurodevelopmental health, they may also point towards the use of potentially harmful substitutions for chemicals that are being phased out.

Association of Drug Burden Index with grip strength, timed up and go and Barthel index activities of daily living in older adults with intellectual disabilities: an observational cross-sectional study.

BACKGROUND: Drug Burden Index (DBI), a measure of exposure to medications with anticholinergic and sedative activity, has been associated with poorer physical function in older adults in the general population. While extensive study has been conducted on associations between DBI and physical function in older adults in the general population, little is known about associations in older adults with intellectual disabilities (ID). This is the first study which aims to examine the association between DBI score and its two sub-scores, anticholinergic and sedative burden, with two objective measures of physical performance, grip strength and timed up and go, and a measure of dependency, Barthel Index activities of daily living, in older adults with ID. METHODS: Data from Wave 2 (2013/2014) of the Intellectual Disability Supplement to the Irish Longitudinal Study on Ageing (IDS-TILDA) was analysed. Analysis of Covariance (ANCOVA) was used to detect associations and produce adjusted means for the physical function and dependency measures with respect to categorical DBI scores and the anticholinergic and sedative sub-scores (DBA and DBS). RESULTS: After adjusting for confounders (age, level of ID, history of falls, comorbidities and number of non-DBI medications, Down syndrome (grip strength only) and gender (timed up and go and Barthel Index)), neither grip strength nor timed up and go were significantly associated with DBI, DBA or DBS score > 0 (p > 0.05). Higher dependency in Barthel Index was associated with DBS exposure (p < 0.001). CONCLUSIONS: DBI, DBA or DBS scores were not significantly associated with grip strength or timed up and go. This could be as a result of established limitations in physical function in this cohort, long-term exposure to these types of medications or lifelong sedentary lifestyles. Higher dependency in Barthel Index activities of daily living was associated with sedative drug burden, which is an area which can be examined further for review.

Neurodevelopmental retardation in a baby born to a multiple sclerosis patient being treated with fingolimod.

This report is about a female child born to a multiple sclerosis mother who continued fingolimod during her first trimester of pregnancy. The child was born with normal full-term delivery but showed neurodevelopmental retardation in the following years. it is recommended that multiple sclerosis patients undergoing treatment with fingolimod use contraceptive methods for at least two months after discontinuation of the medication.

Intellectual Disability After Gestational Exposure to Antidepressant Drugs: The Confidence Interval as a Compatibility Interval.

There is growing concern among statisticians that the use of P value dichotomization into significant and nonsignificant outcomes does not appropriately describe research findings; in fact, misconceptions about the very meaning of the P value abound. Many alternate approaches to interpreting data have been suggested. The use of the 95% confidence interval (CI) as a compatibility interval is one such approach. By this approach, the study estimate for an outcome is considered to be the most compatible with the population value for that outcome, and all the values in the 95% CI around that estimate are also considered to be compatible with the population value with decreasing likelihood of compatibility the greater the distance of the value from the study estimate. This concept is explained with the help of a study that examined the risk of intellectual disability (ID) in children who had been gestationally exposed to antidepressant drugs (ADs). A conventional interpretation of the study findings is that, after adjustment for confounders, AD exposure was not associated with an increased risk of ID; this, in fact, is also how the authors expressed their conclusions. However, when the 95% CI in the main analyses, subgroup analyses, and sensitivity analyses in this study are examined as compatibility intervals, it becomes apparent that, even after adjustment for confounders, a very sizeable range of values indicating increased risk is compatible with the population value. In contrast, the range of values indicating decreased or no risk is very small. The implication, therefore, is that adjustment for confounding attenuates the risk, but the risk probably remains elevated. There is uncertainty in this subjective conclusion, but this conclusion is more truthful than a conclusion that a significant risk was rendered nonsignificant by adjustment for confounding.

Prenatal and infant exposure to ambient pesticides and autism spectrum disorder in children: population based case-control study.

OBJECTIVE: To examine associations between early developmental exposure to ambient pesticides and autism spectrum disorder. DESIGN: Population based case-control study. SETTING: California's main agricultural region, Central Valley, using 1998-2010 birth data from the Office of Vital Statistics. POPULATION: 2961 individuals with a diagnosis of autism spectrum disorder based on the Diagnostic and Statistical Manual of Mental Disorders, fourth edition, revised (up to 31 December 2013), including 445 with intellectual disability comorbidity, were identified through records maintained at the California Department of Developmental Services and linked to their birth records. Controls derived from birth records were matched to cases 10:1 by sex and birth year. EXPOSURE: Data from California state mandated Pesticide Use Reporting were integrated into a geographic information system tool to estimate prenatal and infant exposures to pesticides (measured as pounds of pesticides applied per acre/month within 2000 m from the maternal residence). 11 high use pesticides were selected for examination a priori according to previous evidence of neurodevelopmental toxicity in vivo or in vitro (exposure defined as ever v never for each pesticide during specific developmental periods). MAIN OUTCOME MEASURE: Odds ratios and 95% confidence intervals using multivariable logistic regression were used to assess associations between pesticide exposure and autism spectrum disorder (with or without intellectual disabilities) in offspring, adjusting for confounders. RESULTS: Risk of autism spectrum disorder was associated with prenatal exposure to glyphosate (odds ratio 1.16, 95% confidence interval 1.06 to 1.27), chlorpyrifos (1.13, 1.05 to 1.23), diazinon (1.11, 1.01 to 1.21), malathion (1.11, 1.01 to 1.22), avermectin (1.12, 1.04 to 1.22), and permethrin (1.10, 1.01 to 1.20). For autism spectrum disorder with intellectual disability, estimated odds ratios were higher (by about 30%) for prenatal exposure to glyphosate (1.33, 1.05 to 1.69), chlorpyrifos (1.27, 1.04 to 1.56), diazinon (1.41, 1.15 to 1.73), permethrin (1.46, 1.20 to 1.78), methyl bromide (1.33, 1.07 to 1.64), and myclobutanil (1.32, 1.09 to 1.60); exposure in the first year of life increased the odds for the disorder with comorbid intellectual disability by up to 50% for some pesticide substances. CONCLUSION: Findings suggest that an offspring's risk of autism spectrum disorder increases following prenatal exposure to ambient pesticides within 2000 m of their mother's residence during pregnancy, compared with offspring of women from the same agricultural region without such exposure. Infant exposure could further increase risks for autism spectrum disorder with comorbid intellectual disability.

Global burden of intellectual disability resulting from dietary exposure to lead, 2015.

Lead is a ubiquitous dietary contaminant that occurs in food because of natural and anthropogenic sources and pathways of exposure. Lead adversely affects a number of tissues and organ systems and the severity of effect on each is dependent on the level and duration of exposure. The most sensitive and notable effects are those that occur on the nervous system. This is particularly the case in the exposure to the fetus, infant and child. Infants and children generally have higher lead exposures on a body weight basis. While lead exposure can come from many sources, a major source of exposure for at least some individuals comes from food. Estimates for the impact of dietary lead on IQ were developed from published total diet studies. While most of these were designed to characterize intake of chemical contaminants on a national basis, some sampled market baskets from a single city. To develop global estimates, default ranges were created for countries with no data which encompassed the values encountered elsewhere. Blood lead levels and IQ decrements were estimated using functions previously developed by the WHO Joint Expert Committee for Food Additives. Since both the exposure and dose response components were variable and uncertain, a two dimensional Monte-Carlo simulation was used to develop the estimates for the impact of dietary lead on IQ. In addition to estimating blood lead and IQ decrements attributable to dietary lead from those countries with published market basket data, simulations were also run for WHO regions that sampled in the variability dimension based on the population size of the individual countries in each region. Dietary exposure to lead occurs throughout the world. The global average IQ decrement attributable to dietary lead was 1.1. The total number of Disability-Adjusted Life Years (DALYs) arising from those IQ decrements were estimated to be 5.2 million DALYs, with an uncertainty range of 0-31 million DALYs. Significant uncertainties regarding exposure and dose-response relationships, however, warrant continued investigation.

Prenatal Exposure to Endocrine-disrupting Chemicals in Relation to Autism Spectrum Disorder and Intellectual Disability.

BACKGROUND: Exposure to endocrine disruptors is unavoidable. Many such compounds are suspected to impact neurologic development of children, but most studies conducted have considered effects of individual chemicals in isolation. Because exposures co-occur, it is important to consider their health impacts in a single regression framework. METHODS: We applied Bayesian statistical tools (including shared mean and mixture priors for 25 unique chemicals) to study independent associations of endocrine disruptor biomarkers with autism spectrum disorder (ASD) (n = 491) and intellectual disability (n = 155), compared with 373 general population controls, in the Early Markers for Autism study. We measured biomarkers in maternal serum collected and stored from midpregnancy and considered them individually or as a class (i.e., summed polychlorinated biphenyls). We adjusted all models for original matching factors (child sex and month and year of birth), maternal age, maternal race/ethnicity, parity, and maternal education at the time samples were collected. We estimated the change in the odds of ASD or intellectual disability per 1 SD increase in the z-score of measured biomarker concentration for each chemical. RESULTS: Odds of ASD and intellectual disability did not change with increasing concentration for any specific endocrine disruptor. The effect estimates for each chemical were centered on or near an odds ratio of 1.00 in both models where we applied a shared mean or a mixture prior. CONCLUSION: Our mixtures analyses do not suggest an independent relationship with ASD or intellectual disability with any of the 25 chemicals examined together in this mixtures analysis.

Intellectual functioning in clinically confirmed fetal valproate syndrome.

BACKGROUND: An increased risk of impaired intelligence (IQ) has been documented in valproate-exposed children, but investigations have not previously focused on those with a clinical diagnosis of Fetal Valproate Syndrome (FVS). METHODS: This cross sectional observational study recruited individuals with a diagnosis of FVS and completed standardized assessments of intellectual abilities making comparisons to a normative comparison group. Both mean difference (MD) and prevalence of scores below the lower average range were analyzed. RESULTS: The mean full-scale IQ in 31 individuals with FVS (mean age 14.97; range 6-27 years) was 19 points lower (19.55, 95% CI -24.94 to 14.15), and IQ scores <70 were present in 26%. The mean differences for verbal comprehension (21.07, 95% CI -25.84 to -16.29), working memory (19.77, 95% CI -25.00 to -14.55) and processing speed (16.87, 95% CI -22.24 to -11.50) performances were poorer than expected with the mean differences over one standard deviation from the comparison group. Sixty one percent of cases demonstrated disproportionately lower verbal comprehension ability. There were no significant group differences for IQ in high vs. moderate dose valproate or mono vs. polytherapy. There were no differences in IQ between those with and those without a major congenital malformation. The requirement for educational intervention was high at 74%. CONCLUSION: Intellectual difficulties are a central feature of FVS and are more severe in their presentation in individuals with a diagnosis of valproate embryopathy. Individuals with FVS who present with the characteristic facial presentation should be considered at high risk of cognitive difficulties regardless of the dose of valproate exposure or the presence of a major congenital malformation.

Association of Maternal Insecticide Levels With Autism in Offspring From a National Birth Cohort.

OBJECTIVE: Autism is a complex neurodevelopmental disorder with a largely unknown etiology. To date, few studies have investigated prenatal exposure to toxins and risk of autism by using maternal biomarkers of exposure. Persistent organic pollutants are lipophilic halogenated organic compounds and include the insecticide dichlorodiphenyltrichloroethane (DDT), as well as its metabolite p,p'-dichlorodiphenyl dichloroethylene (p,p'-DDE), and polychlorinated biphenyls (PCBs). The objective of this study was to test whether elevated maternal levels of persistent organic pollutants are associated with autism among offspring. METHOD: The investigation was derived from the Finnish Prenatal Study of Autism, a national birth cohort study based on a nested case-control design. Cases of autism among children born between 1987 and 2005 were ascertained by national registry linkages. In cases of childhood autism and matched control subjects (778 matched case-control pairs), maternal serum specimens from early pregnancy were assayed for levels of p,p'-DDE and total levels of PCBs. RESULTS: The odds of autism among offspring were significantly increased with maternal p,p'-DDE levels that were in the highest 75th percentile, with adjustment for maternal age, parity, and history of psychiatric disorders (odds ratio=1.32, 95% CI=1.02, 1.71). The odds of autism with intellectual disability were increased by greater than twofold with maternal p,p'-DDE levels above this threshold (odds ratio=2.21, 95% CI=1.32, 3.69). There was no association between total levels of maternal PCBs and autism. CONCLUSIONS: These findings provide the first biomarker-based evidence that maternal exposure to insecticides is associated with autism among offspring. Although further research is necessary to replicate this finding, this study has implications for the prevention of autism and may provide a better understanding of its pathogenesis.

Developmental neurotoxicity in the progeny after maternal gavage with chlorpyrifos.

Today, developmental intellectual disorders affect one out of six children in industrialised countries. Intensively used in agriculture, the neurotoxicant pesticide chlorpyrifos (CPF) is known for its environmental persistence and bioaccumulation. Its role has not yet been established in the aetiology of intellectual impairments. Here we assessed whether maternal ingestion of low CPF dose in rats could impair the cerebral function of their progeny. Rat dams received daily CPF exposures (1 mg/kg, per os) during gestation and lactation. Behaviours relevant to mental retardation were measured in the surface righting, negative geotaxis and grip strength at post-natal days (PND) 3 and 7. Open field tests were performed at PND 16, 18 and 20. Fear conditioning was assessed at PND 34. Startle inhibition was tested at PND 31 and 60. According to the results, the progeny of CPF-treated dams showed slower negative geotaxis as neonates, lower novelty exploration as juveniles and faster startle reflex as adolescents and adults. This data suggests that developmental CPF relevant to human exposure may impair novelty-related activity and sensori-motor functions, thus adaptability to the environment. This data supports the hypothesis that CPF may contribute to behavioural disorders including acquisition retardation and consequences as an adult.

Disease burden of methylmercury in the German birth cohort 2014.

This study aimed to estimate the disease burden of methylmercury for children born in Germany in the year 2014. Humans are mainly exposed to methylmercury when they eat fish or seafood. Prenatal methylmercury exposure is associated with IQ loss. To quantify this disease burden, we used Monte Carlo simulation to estimate the incidence of mild and severe mental retardation in children born to mothers who consume fish based on empirical data. Subsequently, we calculated the disease burden with the disability-adjusted life years (DALY)-method. DALYs combine mortality and morbidity in one measure and quantify the gap between an ideal situation, where the entire population experiences the standard life expectancy without disease and disability, and the actual situation. Thus, one DALY corresponds to the loss of one year of life in good health. The methylmercury-induced burden of disease for the German birth cohort 2014 was an average of 14,186 DALY (95% CI 12,915-15,440 DALY). A large majority of the DALYs was attributed to morbidity as compared to mortality. Of the total disease burden, 98% were attributed to mild mental retardation, which only leads to morbidity. The remaining disease burden was a result of severe mental retardation with equal proportions of premature death and morbidity.

Data relating to prenatal lead exposure and child IQ at 4 and 8 years old in the Avon Longitudinal Study of Parents and Children.

As part of the Avon Longitudinal Study of Parents and Children (ALSPAC), measures of child IQ were collected by trained psychologists. The Wechsler Pre-school and Primary Scale of Intelligence - Revised UK edition (WPPSI) was used at age 4 years in a subsample of children enrolled in ALSPAC (the Children in Focus cohort), chosen at random from the last 6 months of ALSPAC births (about 10% of the participants). At age 8 years all children enrolled in the main cohort were invited to complete a short form of the Wechsler Intelligence Scale for Children (WISC)-III UK. Prenatal blood lead (B-Pb) concentrations were measured by inductively-couple plasma mass spectrometry in samples from women at a median gestation age of 11 weeks. Child blood lead was measured by atomic absorption spectrometry in samples from children attending the Children in Focus clinic at age 30 months. Maternal reports at 32 weeks' gestation were used to generate data on a range of potential confounders. The data were used to determine the associations between prenatal exposure to lead and child IQ at 4 and 8 years. The effect of child B-Pb at 3 years as a moderator of these associations was tested. (For results, please see doi:10.1016/j.neuro.2017.07.003 Taylor et al., (2017)).

Human cost burden of exposure to endocrine disrupting chemicals. A critical review.

Recently published papers have alleged that exposures to endocrine disrupting chemicals (EDCs) are causing substantial disease burdens in the EU and US and are consequently costing society hundreds of billions of dollars annually. To date, these cost estimates have not undergone adequate scientific scrutiny, but nevertheless are being used aggressively in advocacy campaigns in an attempt to fundamentally change how chemicals are tested, evaluated and regulated. Consequently, we critically evaluated the underlying methodology and assumptions employed by the chief architects of the disease burden cost estimates. Since the vast majority of their assigned disease burden costs are driven by the assumption that "loss of IQ" and "increased prevalence of intellectual disability" are caused by exposures to organophosphate pesticides (OPPs) and brominated flame retardants (PBDEs), we have taken special care in describing and evaluating the underlying toxicology and epidemiology evidence that was relied upon. Unfortunately, our review uncovered substantial flaws in the approach taken and the conclusions that were drawn. Indeed, the authors of these papers assumed causal relationships between putative exposures to EDCs and selected diseases, i.e., "loss of IQ" and "increased prevalence of intellectual disability", despite not having established them via a thorough evaluation of the strengths and weaknesses of the underlying animal toxicology and human epidemiology evidence. Consequently, the assigned disease burden costs are highly speculative and should not be considered in the weight of evidence approach underlying any serious policy discussions serving to protect the public and regulate chemicals considered as EDCs.

A Systematized Review of Atypical Antipsychotics in Pregnant Women: Balancing Between Risks of Untreated Illness and Risks of Drug-Related Adverse Effects.

OBJECTIVE: To summarize risks related to (1) illness and (2) second-generation antipsychotic (SGA) treatment in pregnant women and their offspring. Concerning illness-related risks, we focused on bipolar disorder and schizophrenia, psychiatric disorders for which SGAs are preferentially prescribed. DATA SOURCES: PubMed, Ovid, Scopus, PsycINFO, and Cochrane Library were searched from the date of the first available article to October 2015 using the following key terms: pregnancy OR gestation OR bipolar disorder OR schizophrenia. We also included cross-references from identified articles. STUDY SELECTION: We included 49 English-language articles regarding illness-related and SGA-related risks in bipolar disorder and schizophrenia. First, searches were done for epidemiologic or experimental studies (from January 2000 to October 2015), then for systematic reviews and meta-analyses. DATA EXTRACTION: Data were extracted independently, after removing duplicates and studies that were not relevant or not pertinent. RESULTS: Abrupt discontinuation of treatment-exposed mothers with bipolar disorder or schizophrenia led to a high risk of relapses during pregnancy. Both bipolar disorder and schizophrenia were linked to a slightly increased risk of obstetric complications for mothers (schizophrenia) and the newborn (bipolar disorder and schizophrenia), although data on drug exposure during pregnancy were not given in the majority of studies. Maternal morbidity (schizophrenia but not bipolar disorder) may be associated with the worst neonatal outcomes (stillbirth, neonatal or infant deaths, and intellectual disability). Untreated bipolar disorder and schizophrenia may be considered independent risk factors for congenital malformations, while SGAs were not associated with increased recurring defects in fetuses. Evidence regarding the potential effects of SGAs on child neurodevelopment remains reassuring. CONCLUSION: After taking into account the parents' will and after they provide informed consent, the most reasonable and less harmful choice for treating future mothers with bipolar disorder or schizophrenia appears to be maintaining them at the safest minimum dosage.

False Balance in Public Health Reporting? Michele Bachmann, the HPV Vaccine, and "Mental Retardation".

This content analysis of media coverage of Michele Bachmann's erroneous comments that the HPV vaccine causes mental retardation explores the relationship between truth-telling (the presentation of accurate information) and balance (presenting opposing perspectives of an issue equally and legitimately) in public health reporting. Of 200 articles analyzed, about 50% provided correction and about 40% provided a counterpoint. We also found that health reporters tended to engage in truth-telling and balance more than political reporters. Implications for theory and practice are discussed.