Link between fracking chemicals and immune system problems

Developmental Exposure to a Mixture of 23 Chemicals Associated With Unconventional Oil and Gas Operations Alters the Immune System of Mice

Chemicals commonly found in groundwater near fracked oil and gas wells appear to impair the proper functioning of the immune system, Environmental Health News reports.

The new study suggests that baby girls born to mothers near fracking wells may not fight diseases later in life as well as they could have with a pollution-free pregnancy.

2018 Study Abstract

Chemicals used in unconventional oil and gas (UOG) operations have the potential to cause adverse biological effects, but this has not been thoroughly evaluated. A notable knowledge gap is their impact on development and function of the immune system.

Herein, we report an investigation of whether developmental exposure to a mixture of chemicals associated with UOG operations affects the development and function of the immune system. We used a previously characterized mixture of 23 chemicals associated with UOG, and which was demonstrated to affect reproductive and developmental endpoints in mice. C57Bl/6 mice were maintained throughout pregnancy and during lactation on water containing two concentrations of this 23-chemical mixture, and the immune system of male and female adult offspring was assessed. We comprehensively examined the cellularity of primary and secondary immune organs, and used three different disease models to probe potential immune effects: house dust mite-induced allergic airway disease, influenza A virus infection, and experimental autoimmune encephalomyelitis (EAE). In all three disease models, developmental exposure altered frequencies of certain T cell sub-populations in female, but not male, offspring. Additionally, in the EAE model disease onset occurred earlier and was more severe in females.

Our findings indicate that developmental exposure to this mixture had persistent immunological effects that differed by sex, and exacerbated responses in an experimental model of autoimmune encephalitis. These observations suggest that developmental exposure to complex mixtures of water contaminants, such as those derived from UOG operations, could contribute to immune dysregulation and disease later in life.

Early exposure to BPA linked to increased hyperactivity

Prenatal exposure to bisphenol A and hyperactivity in children: a systematic review and meta-analysis

Bisphenol-A, widely used in plastics, receipt paper and canned food linings, is a culprit in some children developing hyperactivity : a July 2017 review, available online 7 March 2018, of more than 30 scientific studies, concludes early life exposure to the endocrine disrupting chemical BPA leaves children more susceptible to hyperactivity later in life.

Study Highlights

  • We used the OHAT systematic review framework to examine if early exposure to BPA has an effect on hyperactivity
  • We found that, in both rodents and humans, early exposure to BPA is linked to increased hyperactivity
  • Integration of animal and human evidence finds that BPA is a presumed hazard to human health
  • We suggest the development of clinical recommendations for avoiding BPA exposure, especially for pregnant women and children

2018 Study Abstract

Background
Attention-deficit hyperactivity disorder (ADHD) has increased in prevalence in the past decade. Studies attempting to identify a specific genetic component have not been able to account for much of the heritability of ADHD, indicating there may be gene-environment interactions underlying the disorder, including early exposure to environmental chemicals. Based on several relevant studies, we chose to examine bisphenol A (BPA) as a possible contributor to ADHD in humans. BPA is a widespread environmental chemical that has been shown to disrupt neurodevelopment in rodents and humans.

Objectives
Using the Office of Health Assessment and Translation (OHAT) framework, a systematic review and meta-analysis was designed to determine the relationship between early life exposure to BPA and hyperactivity, a key diagnostic criterion of ADHD.

Data sources
Searches of PubMed, Web of Science, and Toxline were completed for all literature to January 1, 2017.

Study eligibility criteria
For inclusion, the studies had to publish original data, be in the English language, include a measure of BPA exposure, and assess if BPA exposure affected hyperactive behaviors in mice, rats or humans. Exposure to BPA had to occur at <3 months of age for humans, up to postnatal day 35 for rats and up to postnatal day 40 for mice. Exposure could occur either gestationally (via maternal exposure) or directly to the offspring.

Study appraisal and synthesis methods
Studies were evaluated using the OHAT risk of bias tool. The effects in humans were assessed qualitatively. For rodents exposed to 20 μg/kg/day BPA, we evaluated the study findings in a random effects meta-analytical model.

Results
A review of the literature identified 29 rodent and 3 human studies. A random effects meta-analysis showed significantly increased hyperactivity in male rodents. In humans, early BPA exposure was associated with hyperactivity in boys and girls.

Limitations, conclusions, and implications of key findings
We concluded that early life BPA exposure is a presumed human hazard for the development of hyperactivity. Possible limitations of this systematic review include deficiencies in author reporting, exclusion of some literature based on language, and insufficient similarity between human studies. SRs that result in hazard-based conclusions are the first step in assessing and mitigating risks. Given the widespread exposure of BPA and increasing diagnoses of ADHD, we recommend immediate actions to complete such risk analyses and take next steps for the protection of human health. In the meantime, precautionary measures should be taken to reduce exposure in pregnant women, infants and children. The present analysis also discusses potential mechanisms by which BPA affects hyperactivity, and the most effective avenues for future research.

Sources and Press Releases

Toward Consistent Methodology to Quantify Populations in Proximity to Oil and Gas Development

Seventeen Million in U.S. Live Near Active Oil or Gas Wells

A number of studies indicate that there may be negative health outcomes associated with living in close proximity to oil and gas development. Degraded air quality; surface water, groundwater and soil contamination; and elevated noise and light pollution are exposure pathways that contribute to potential human health impacts.

Studies have identified multiple symptoms reported by residents living with oil and gas infrastructure in their communities, including respiratory symptoms, such as nose, eye, and throat irritation; headaches; and fatigue, among others.

One study has pointed to increased hospitalization rates for multiple medical categories, including cardiology, neurology, and oncology. Increased asthma incidence and severity has also been reported in Pennsylvania.

Preliminary epidemiological studies that use distance of oil and gas development as the exposure metric have found positive associations with adverse birth outcomes, including preterm birth, lower birth weight, and small for gestational age, as well as neural tube defects and congenital heart defects.

Studies also identified increased incidence of childhood hematologic cancer among children that live in close proximity to oil and gas development compared to those that live farther away.

While many findings in the public health literature on oil and gas development are sometimes inconsistent and studies often lack the designs to arrive at causal claims, the body of literature serves as an indication that proximity to oil and gas development is associated with adverse health risks and impacts.

Previous Population Proximity Studies

Public concern and the public health scientific literature to date has spurred interest in quantitative assessments of populations potentially at increased risk of health impacts from living in close proximity to oil and gas development. Four peer-reviewed studies were published in the last 2 y: two reporting population counts, and three reporting demographic subgroups. Three additional studies were identified in the gray literature. The earliest study we could identify was published in The Wall Street Journal. This early study has substantial methodological flaws, but is included in our review because it was the first published attempt to quantify populations near oil and gas wells.

2017 Study Abstract

BACKGROUND
Higher risk of exposure to environmental health hazards near oil and gas wells has spurred interest in quantifying populations that live in proximity to oil and gas development. The available studies on this topic lack consistent methodology and ignore aspects of oil and gas development of value to public health–relevant assessment and decision-making.

OBJECTIVES
We aim to present a methodological framework for oil and gas development proximity studies grounded in an understanding of hydrocarbon geology and development techniques.

METHODS
We geospatially overlay locations of active oil and gas wells in the conterminous United States and Census data to estimate the population living in proximity to hydrocarbon development at the national and state levels. We compare our methods and findings with existing proximity studies.

RESULTS
Nationally, we estimate that 17.6 million people live within 1,600 m (∼1 mi) of at least one active oil and/or gas well. Three of the eight studies overestimate populations at risk from actively producing oil and gas wells by including wells without evidence of production or drilling completion and/or using inappropriate population allocation methods. The remaining five studies, by omitting conventional wells in regions dominated by historical conventional development, significantly underestimate populations at risk.

CONCLUSIONS
The well inventory guidelines we present provide an improved methodology for hydrocarbon proximity studies by acknowledging the importance of both conventional and unconventional well counts as well as the relative exposure risks associated with different primary production categories (e.g., oil, wet gas, dry gas) and developmental stages of wells.

More Information

  • Toward Consistent Methodology to Quantify Populations in Proximity to Oil and Gas Development: A National Spatial Analysis and Review, Environmental Health Perspectives, DOI:10.1289/EHP1535, AUGUST 2017 | VOLUME 125 | ISSUE 8.
  • Seventeen Million in US Live Near Active Oil or Gas Wells, Truthout, September 06, 2017.
  • Featured image credit EHP : confirmed active well counts by U.S. county. Well data are from DrillingInfo. Administrative boundaries are from the U.S. Census Bureau.

Efficient technology to remove BPA and similar chemicals from water

A multidisciplinary investigation of the technical and environmental performances of TAML/peroxide elimination of Bisphenol A compounds from water

As water treatment plants struggle to keep up with the chemical cocktail heading into our pipes, researchers say they’ve come up with a solution to remove one of the most ubiquitous contaminants—BPA.

There now exists economically viable, efficient technology to remove bisphenol A (BPA) and a host of similar chemicals from water.

2017 Study Conclusion

In developing Green Chemistry, it is important that chemists come to understand the scope of the challenges posed by everyday-everywhere endocrine disruptors (EDs) to the sustainability of both the chemical enterprise and our complex global civilization. The most troubling such EDs, like BPA, invariably hold their protected positions in the economy because of seductive technical and cost performances that enable large, diverse, profitable markets. For sustainable chemicals, the health, environmental and fairness performances also have to be integral components of the value proposition. Understanding the negative performances of unsustainable chemicals helps in mapping the properties sustainable chemicals should not have. Key aspects of this understanding include the knowledge of which chemicals are and are not EDs and are and are not capable of eliciting low dose adverse effects by non-endocrine processes, the extent and routes by which the environment and people are exposed to commercial EDs, the environmental and human health consequences of ED exposures, the methods of assessment of endocrine activity including the TiPED, the mechanisms of the low dose adverse effects, the design approaches to attaining new and replacement chemicals free of such effects, and the stewardship methodologies that are currently deployed or might be deployed to better protect health and the environment from commercial EDs. This BPA case study traverses the appropriate multidisciplinary landscape with emphasis on the integration of chemistry and environmental health science in the development of endocrine disruption-free processes to aid the chemical enterprise and society in reducing BPA exposures. Importantly, the litany of unfortunate facts presented about BPA exposures and health and environmental performances is relieved to some extent by the possibility of reduced releases arising from the TAML/H2O2 technology mapped out in the empirical section.

This experimental component demonstrates that TAML/H2O2 provides simple, effective water treatment methodologies, which depending on the pH, either decompose BPA or isolate it in low solubility oligomers. Both processes require only very low concentrations of TAML activator and H2O2 in further reflection of the remarkable efficiencies of the peroxidase enzymes that are faithfully mimicked by TAML activator and in marked contrast with the much higher relative iron- and peroxide-requiring Fenton processes. It remains to be established whether the current laboratory studies project to real world scenarios. These may include treatment of BPA-contaminated landfill leachates and paper plant processing solutions where the concentrations are similar to those employed in this study. In such scenarios, TAML/H2O2 would present an enzyme-mimicking method which in the case of TAML activator is comprised exclusively of biochemically common elements and has passed multiple TiPED assays that, in contrast with existing real world processes, avoids generation of BPA-contaminated sludges and associated subsequent releases to soil, that does not generate a contaminated adsorbent which must be replaced or regenerated at elevated temperature, that does not generate chlorinated forms of BPA, that does not generate a concentrated retentate, and that is remarkably simple to deploy using very low and cheap chemical inputs with all the positive potential consequences thereof for capital and operating expenses.

Finally, in order to avoid the habit or perception of greenwashing, a realistic perspective is essential to the integrity of green chemistry. We view the sustainability challenges posed by BPA as enormous—the experimental work presented could evolve into a solution for some of these problems but is, by no means, a general quick fix. BPA markets large and small are expanding rapidly, especially as the industry has learned how to produce even more effective replacements for glass and metal products. Huge new markets are developing such as those of plastic glass houses, and even houses, and automobile body parts that are comprised primarily of BPA. In this build-up, BPA’s unfortunate health and environmental performances continue to be given short shrift. Continuation of the present BPA expansion trends without limits, technical corrections and more aggressive stewardship advances of multiple kinds will menace society with an ever increasing oestrogenization of the entire ecosphere.

Sources and More Information
  • BPA breakthrough: New treatment takes controversial chemical out of water, EHN, August 2, 2017.
  • Science: Pay attention to two other messages in the breakthrough BPA water treatment paper, EHN, August 8, 2017.
  • A multidisciplinary investigation of the technical and environmental performances of TAML/peroxide elimination of Bisphenol A compounds from water, pubs, 19th July 2017.
  • Feature image credit Leland Francisco.

The Florence Statement on Triclosan and Triclocarban

More than 200 scientists outline a broad range of concerns for triclosan and triclocarban and call for reduced use worldwide

Two ingredients used in thousands of products to kill bacteria, fungi and viruses linger in the environment and pose a risk to human health, according to a statement released today by more than 200 scientists and health professionals.

The scientists say the possible benefits in most uses of triclosan and triclocarban – used in some soaps, toothpastes, detergents, paints, carpets – are not worth the risk.

SUMMARY

“Triclosan and triclocarban have been permitted for years without definitive proof they’re providing benefits.”

Avery Lindeman, Green Policy Institute

The Florence Statement on Triclosan and Triclocarban documents a consensus of more than 200 scientists and medical professionals on the hazards of and lack of demonstrated benefit from common uses of triclosan and triclocarban.

These chemicals may be used in thousands of personal care and consumer products as well as in building materials. Based on extensive peer-reviewed research, this statement concludes that triclosan and triclocarban are environmentally persistent endocrine disruptors that bioaccumulate in and are toxic to aquatic and other organisms. Evidence of other hazards to humans and ecosystems from triclosan and triclocarban is presented along with recommendations intended to prevent future harm from triclosan, triclocarban, and antimicrobial substances with similar properties and effects.

Because antimicrobials can have unintended adverse health and environmental impacts, they should only be used when they provide an evidence-based health benefit. Greater transparency is needed in product formulations, and before an antimicrobial is incorporated into a product, the long-term health and ecological impacts should be evaluated.

Sources, Studies, Press Releases

  • The Florence Statement on Triclosan and Triclocarban, Environ Health Perspect; DOI:10.1289/EHP1788, JUNE 2017.
  • Patterns, Variability, and Predictors of Urinary Triclosan Concentrations during Pregnancy and Childhood, Environ. Sci. Technol., DOI: 10.1021/acs.est.7b00325, May 18, 2017
  • Hundreds of scientists call for caution on anti-microbial chemical use, EHN, June 20, 2017.
  • Hygiene leaves kids with loads of triclosan, EHN, June 1, 2017.
  • Image credit Mike Mozart.

BPF, BPS and other bisphenol analogues found more estrogenic than BPA

“BPA-free” may mean very little for consumers trying to protect their health from endocrine disrupting chemicals

Six popular BPA alternatives all mimic estrogen in breast cancer cells; three of them more so than BPA itself, according to new research.

2017 Study Abstract

Background
Plasticizers with estrogenic activity, such as bisphenol A (BPA), have been reported to have potential adverse health effects in humans. Due to mounting evidence of these health effects and public pressure, BPA is being phased out by the plastics manufacturing industry and replaced by other bisphenol variants in “BPA-free” products.

Objectives
We have compared estrogenic activity of BPA to 6 bisphenol analogues (bisphenol S, BPS; bisphenol F, BPF; bisphenol AP, BPAP; bisphenol AF, BPAF; bisphenol Z, BPZ; bisphenol B, BPB) in three human breast cancer cell lines.

Methods
Estrogenicity was assessed by cell growth in an estrogen receptor (ER)-mediated cell proliferation assay, and by the induction of estrogen response element (ERE)-mediated transcription in a luciferase assay. Gene expression profiles were determined in MCF-7 human breast cancer cells by microarray analysis and confirmed by Illumina-based RNA sequencing.

Results
All bisphenols showed estrogenic activity in promoting cell growth and inducing ERE-mediated transcription. BPAF was the most potent bisphenol, followed by BPB > BPZ ~ BPA > BPF ~ BPAP > BPS. The addition of ICI 182,780 antagonized the activation of ERs by bisphenols. Data mining of ToxCast high-throughput screening assays confirms our results but also shows divergence in the sensitivities of the assays. The comparison of transcriptome profile alterations resulting from BPA alternatives with an ERα gene expression biomarker further indicates that all BPA alternatives act as ERα agonists in MCF-7 cells. These results were confirmed by RNA sequencing.

Conclusion
In conclusion, BPA alternatives are not necessarily less estrogenic in a human breast cancer cell model. Three bisphenols (BPAF, BPB, and BPZ) were more estrogenic than BPA. The relevance of human exposure to BPA alternatives in hormone-dependent breast cancer risk should be investigated.

Sources and More Information
  • Transcriptome profiling reveals bisphenol A alternatives activate estrogen receptor alpha in human breast cancer cells, bioRxiv, Mar. 2, 2017.
  • BPA-free? Substitutions mimic hormones in breast cancer cells, environmentalhealthnews, March 16, 2017.
  • BPA Free by Mark Morgan.

High doses of pesticides can potentially impact DNA, triggering cancers later in life

Researchers find pesticide spills, accidents may alter farmworkers’ DNA

Farmworkers who have a high pesticide exposure event—such as a spill—are more likely to experience molecular changes on DNA that may lead to certain cancers, according to a large U.S. study of pesticide applicators in Iowa and North Carolina.

The research, part of the ongoing Agricultural Health Study that is monitoring the health of more than 57,000 private and commercial pesticide applicators in Iowa and North Carolina, adds to growing evidence that high exposure to certain pesticides may spur prostate and other cancers in people handling the chemicals.

2017 Study Abstract

High pesticide exposure events and DNA methylation among pesticide applicators in the agricultural health study, Environmental and molecular mutagenesis, NCBI PubMed PMID: 27996157, 2017 Jan.

Researchers find pesticide spills, accidents may alter farmworkers’ DNA, Environmental Health News , February 16, 2017.

Image credit Brad Covington.

Pesticide exposure has been associated with acute and chronic adverse health effects. DNA methylation (DNAm) may mediate these effects.

We evaluated the association between experiencing unusually high pesticide exposure events (HPEEs) and DNAm among pesticide applicators in the Agricultural Health Study (AHS), a prospective study of applicators from Iowa and North Carolina.

DNA was extracted from whole blood from male AHS pesticide applicators (n = 695). Questionnaire data were used to ascertain the occurrence of HPEEs over the participant’s lifetime. Pyrosequencing was used to quantify DNAm in CDH1, GSTp1, and MGMT promoters, and in the repetitive element, LINE-1. Linear and robust regression analyses evaluated adjusted associations between HPEE and DNAm. Ever having an HPEE (n = 142; 24%) was associated with elevated DNAm in the GSTp1 promoter at CpG7 (chr11:67,351,134; P < 0.01) and for the mean across the CpGs measured in the GSTp1 promoter (P < 0.01). In stratified analyses, elevated GSTP1 promoter DNAm associated with HPEE was more pronounced among applicators >59 years and those with plasma folate levels ≤16.56 ng/mL (p-interaction <0.01); HPEE was associated with reduced MGMT promoter DNAm at CpG2 (chr10:131,265,803; P = 0.03), CpG3 (chr10:131,265,810; P = 0.05), and the mean across CpGs measured in the MGMT promoter (P = 0.03) among applicators >59 years and reduced LINE-1 DNAm (P = 0.05) among applicators with ≤16.56 ng/mL plasma folate. Non-specific HPEEs may contribute to increased DNAm in GSTp1, and in some groups, reduced DNAm in MGMT and LINE-1.

The impacts of these alterations on disease development are unclear, but elevated GSTp1 promoter DNAm and subsequent gene inactivation has been consistently associated with prostate cancer.

Fluorinated Compounds in U.S. Fast Food Packaging

Fast food with a side of fluorinated chemicals

Fast food packaging from popular spots like McDonald’s and Starbucks contains a potentially harmful chemical that leaches into the food.

About one-third of containers, wrappers and boxes for fast food contain fluorine, which suggests the food may be exposing us to harmful chemicals that have been linked to cancer, development and immune system problems, low birth weights and decreased fertility.

2017 Study Abstract

Fluorinated Compounds in U.S. Fast Food Packaging, American Chemical Society, February 1, 2017.

Fast food with a side of fluorinated chemicals, environmentalhealthnews, February 1, 2017.

Per- and polyfluoroalkyl substances (PFASs) are highly persistent synthetic chemicals, some of which have been associated with cancer, developmental toxicity, immunotoxicity, and other health effects. PFASs in grease-resistant food packaging can leach into food and increase dietary exposure. We collected ∼400 samples of food contact papers, paperboard containers, and beverage containers from fast food restaurants throughout the United States and measured total fluorine using particle-induced γ-ray emission (PIGE) spectroscopy. PIGE can rapidly and inexpensively measure total fluorine in solid-phase samples. We found that 46% of food contact papers and 20% of paperboard samples contained detectable fluorine (>16 nmol/cm2). Liquid chromatography/high-resolution mass spectrometry analysis of a subset of 20 samples found perfluorocarboxylates, perfluorosulfonates, and other known PFASs and/or unidentified polyfluorinated compounds (based on nontargeted analysis). The total peak area for PFASs was higher in 70% of samples (10 of 14) with a total fluorine level of >200 nmol/cm2 compared to six samples with a total fluorine level of <16 nmol/cm2. Samples with high total fluorine levels but low levels of measured PFASs may contain volatile PFASs, PFAS polymers, newer replacement PFASs, or other fluorinated compounds. The prevalence of fluorinated chemicals in fast food packaging demonstrates their potentially significant contribution to dietary PFAS exposure and environmental contamination during production and disposal.

Bisphenol-A Concentrations among Workers in Industries that Manufacture and Use BPA

US workers making BPA have enormous loads of it in them

U.S. workers in industries that use or manufacture BPA have, on average, 70 times more of the chemical in their bodies than the general public—levels well above what has been shown to impact reproduction, according to a study published Wednesday.

Some workers’ contamination was more than a 1,000 times higher than the most exposed U.S. adults in the general population.

Abstract

Background
Bisphenol A (BPA) toxicity and exposure risk to humans has been the subject of considerable scientific debate; however, published occupational exposure data for BPA are limited.

Urinary Bisphenol A (BPA) Concentrations among Workers in Industries that Manufacture and Use BPA in the USA, The Annals of Occupational Hygiene, doi.org/10.1093/annweh/wxw021, 01 January 2017.

US workers making BPA have enormous loads of it in them, Environmental Health News, January 4, 2017.

Methods
In 2013–2014, 77 workers at six US companies making BPA, BPA-based resins, or BPA-filled wax provided seven urine samples over two consecutive work days (151 worker-days, 525 samples). Participant information included industry, job, tasks, personal protective equipment used, hygiene behaviors, and canned food/beverage consumption. Total (free plus conjugated) BPA, quantified in urine by mass spectrometry, was detected in all samples.

Results
The geometric mean (GM) creatinine-adjusted total BPA (total BPACR) concentration was 88.0 µg g−1 (range 0.78–18900 µg g−1), ~70 times higher than in US adults in 2013–2014 (1.27 µg g−1). GM total BPACR increased during Day 1 (26.6–127 µg g−1), decreased by pre-shift Day 2 (84.4 µg g−1) then increased during Day 2 to 178 µg g−1. By industry, baseline and post-baseline total BPACR was highest in BPA-filled wax manufacturing/reclaim (GM = 111 µg g−1) and lowest in phenolic resin manufacturing (GM = 6.56 µg g−1). By job, total BPACR was highest at baseline in maintenance workers (GM = 157 µg g−1) and post-baseline in those working with molten BPA-filled wax (GM = 441 µg g−1). Workers in the job of flaking a BPA-based resin had the lowest concentrations at baseline (GM = 4.81 µg g−1) and post-baseline (GM = 23.2 µg g−1). In multiple regression models, at baseline, industry significantly predicted increased total BPACR (P = 0.0248); post-baseline, handling BPA containers (P = 0.0035), taking ≥3 process/bulk samples with BPA (P = 0.0002) and wearing a Tyvek® coverall (P = 0.0042) significantly predicted increased total BPACR (after adjusting for total BPACR at baseline, time point, and body mass index).

Conclusion
Several work-related factors, including industry, job, and certain tasks performed, were associated with increased urinary total BPACR concentrations in this group of manufacturing workers. The potential for BPA-related health effects among these workers is unknown.

Acetaminophen use in pregnancy and risk of autism spectrum disorders in childhood

Popular painkiller like Tylenol linked to autism in boys

Acetaminophen during pregnancy linked to autism, environmentalhealthnews, July 6, 2016.
Image viaDaniel Lobo.

Boys exposed before birth to a popular pain reliever in many brands including Tylenol were more likely to have symptoms of autism during childhood, according to a new study of mothers and children in Spain.

Abstract

BACKGROUND
Acetaminophen is extensively used during pregnancy. But there is a lack of population-representative cohort studies evaluating its effects on a range of neuropsychological and behavioural endpoints. We aimed to assess whether prenatal exposure to acetaminophen is adversely associated with neurodevelopmental outcomes at 1 and 5 years of age.

Acetaminophen use in pregnancy and neurodevelopment: attention function and autism spectrum symptoms, NCBI PubMed PMID: 27353198, 2016 Jun 28.

METHODS
This Spanish birth cohort study included 2644 mother-child pairs recruited during pregnancy. The proportion of liveborn participants evaluated at 1 and 5 years was 88.8% and 79.9%, respectively. Use of acetaminophen was evaluated prospectively in two structured interviews. Ever/never use and frequency of use (never, sporadic, persistent) were measured. Main neurodevelopment outcomes were assessed using Childhood Autism Spectrum Test (CAST), Conner’s Kiddie Continuous Performance Test (K-CPT) and ADHD-DSM-IV form list. Regression models were adjusted for social determinants and co-morbidities.

RESULTS
Over 40% of mothers reported using acetaminophen. Ever-exposed offspring had higher risks of presenting more hyperactivity/impulsivity symptoms [incidence rate ratio (IRR) = 1.41, 95% confidence interval (CI) 1.01-1.98), K-CPT commission errors (IRR = 1.10, 1.03-1.17), and lower detectability scores (coefficient β = -0.75, -0.13–0.02). CAST scores were increased in ever-exposed males (β = 0.63, 0.09-1.18). Increased effect sizes of risks by frequency of use were observed for hyperactivity/impulsivity symptoms (IRR = 2.01, 0.95-4.24) in all children, K-CPT commission errors (IRR = 1.32, 1.05-1.66) and detectability (β = -0.18, -0.36-0.00) in females, and CAST scores in males (β = 1.91, 0.44-3.38).

CONCLUSIONS
Prenatal acetaminophen exposure was associated with a greater number of autism spectrum symptoms in males and showed adverse effects on attention-related outcomes for both genders. These associations seem to be dependent on the frequency of exposure.

Maternal use of acetaminophen during pregnancy and risk of autism spectrum disorders in childhood: A Danish national birth cohort study, NCBI PubMed PMID: 26688372, 2015 Dec 21.

And a much-publicized study last year found that women who reported using acetaminophen during pregnancy were about 50 percent more likely to have a child with autism and other behavioral issues such as hyperactivity and impulsivity.

Abstract

Acetaminophen (paracetamol) is the most commonly used pain and fever medication during pregnancy. Previously, a positive ecological correlation between acetaminophen use and autism spectrum disorders (ASD) has been reported but evidence from larger studies based on prospective data is lacking.

We followed 64,322 children and mothers enrolled in the Danish National Birth Cohort (DNBC; 1996-2002) for average 12.7 years to investigate whether acetaminophen use in pregnancy is associated with increased risk of ASD in the offspring. Information on acetaminophen use was collected prospectively from three computer-assisted telephone interviews. We used records from the Danish hospital and psychiatric registries to identify diagnoses of ASD. At the end of follow up, 1,027 (1.6%) children were diagnosed with ASD, 345 (0.5%) with infantile autism.

We found that 31% of ASD (26% of infantile autism) have also been diagnosed with hyperkinetic disorders. More than 50% women reported ever using acetaminophen in pregnancy. We used Cox proportional hazards model to estimate hazard ratio (HR) and 95% confident interval (CI). Prenatal use of acetaminophen was associated with an increased risk of ASD accompanied by hyperkinetic symptoms (HR = 1.51 95% CI 1.19-1.92), but not with other ASD cases (HR = 1.06 95% CI 0.92-1.24). Longer duration of use (i.e., use for >20 weeks in gestation) increased the risk of ASD or infantile autism with hyperkinetic symptoms almost twofold.

Maternal use of acetaminophen in pregnancy was associated with ASD with hyperkinetic symptoms only, suggesting acetaminophen exposure early in fetal life may specifically impact this hyperactive behavioral phenotype.