In utero exposure to perfluoroalkyl and polyfluoroalkyl substances and attention and executive function in the offspring: A study in the Danish National Birth Cohort.

Background: Perfluoroalkyl and polyfluoroalkyl substances (PFAS) are ubiquitous in the environment and accumulate in humans. PFAS are suspected to affect the neuropsychological function of children, but only few studies have evaluated the association with childhood attention and executive function.

Objectives: To investigate the association between intrauterine exposure to PFAS and offspring attention and executive function.

Early Life Exposure to Perfluoroalkyl Substances (PFAS) and ADHD: A Meta-Analysis of Nine European Population-Based Studies.

Introduction: To date, the evidence for an association between perfluoroalkyl substances (PFAS) exposure and attention deficit and hyperactivity disorder (ADHD) is inconclusive.

Objective: We investigated the association between early life exposure to perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA), and ADHD in a collaborative study including nine European population-based studies, encompassing 4,826 mother-child pairs.

Methods: Concentrations of PFOS and PFOA were measured in maternal serum/plasma during pregnancy, or in breast milk, with different timing of sample collection in each cohort.

Head circumference at birth and school performance: a nationwide cohort study of 536,921 children.

Background: Early measures of cognitive function are of great public health interest. We aimed to estimate the association between head circumference at birth, a measure of cerebral size, and school performance.

Methods: We conducted a nationwide cohort study of all liveborn singletons in Denmark, 1997-2005.

Head circumference at birth and intellectual disability: a nationwide cohort study.

Background: Intellectual disability (ID) is a prevalent chronic disability affecting up to 1-3% of the general population. Small head circumference at birth, a surrogate measure of foetal cerebral growth, may be a risk factor for ID. We aimed to investigate the association between the full distribution of head circumference at birth and ID.

Associations of Fetal Growth Outcomes with Measures of the Combined Xenoestrogenic Activity of Maternal Serum Perfluorinated Alkyl Acids in Danish Pregnant Women.

Background: Higher concentrations of single perfluorinated alkyl acids (PFAAs) have been associated with lower birth weight (BW), but few studies have examined the combined effects of PFAA mixtures. PFAAs have been reported to induce estrogen receptor (ER) transactivity, and estrogens may influence human fetal growth. We hypothesize that mixtures of PFAAs may affect human fetal growth by disrupting the ER.

Conditioning on Parity in Studies of Perfluoroalkyl Acids and Time to Pregnancy: An Example from the Danish National Birth Cohort.

Background: Previous studies have investigated the associations between perfluoroalkyl acids (PFAAs) in women and time to pregnancy (TTP). Inconsistent results may be explained by differences in conditioning on parity.

Objectives: We used causal directed acyclic graphs to illustrate potential confounding related to previous pregnancies and exposure measurement error due to differences in the interpregnancy interval in pregnancy-based studies that include parous women.

Directed acyclic graphs: a tool for causal studies in paediatrics.

Many paediatric clinical research studies, whether observational or interventional, have as an eventual aim the identification or quantification of causal relationships. One might ask: does screen time influence childhood obesity? Could overuse of paracetamol in infancy cause wheeze? How does breastfeeding affect later cognitive outcomes? In this review, we present causal directed acyclic graphs (DAGs) to a paediatric audience. DAGs are a graphical tool which provide a way to visually represent and better understand the key concepts of exposure, outcome, causation, confounding, and bias.

Prenatal Exposure to Perfluoroalkyl Substances and IQ Scores at Age 5; a Study in the Danish National Birth Cohort.

Background: Perfluoroalkyl substances (PFASs) are widespread persistent organic compounds that have been suggested to affect neurodevelopment.

Objective: We aimed to evaluate whether prenatal exposure to PFASs is associated with IQ in children.

Methods: We studied 1,592 pregnancies enrolled in the Danish National Birth Cohort (DNBC) during 1996-2002.

Head circumference at birth and childhood developmental disorders in a nationwide cohort in Denmark.

Background: Early markers of Attention Deficit Hyperactivity Disorder (ADHD) and Autism Spectrum Disorder (ASD) may improve the understanding and early recognition of these disorders. We aimed to estimate the association between head circumference at birth, a measure of cerebral size at birth, and the risk of ADHD and ASD.

Methods: We present a register-based cohort study of all Danish singletons born alive between 1997 and 2013.

Congenital Heart Defects and Measures of Prenatal Brain Growth: A Systematic Review.

Background: We summarize the evidence for an association between congenital heart defects and prenatal brain growth through a systematic literature review. Congenital heart defects are among the most common malformations, affecting approximately six per 1000 live births. The association between congenital heart defects and long-term neurodevelopmental disorders is well established.

Paracetamol use during pregnancy and attention and executive function in offspring at age 5 years.

Methods: We studied 1491 mothers and children enrolled in the Danish National Birth Cohort (DNBC; 1996-2002). Prenatal paracetamol use was prospectively recorded in three telephone interviews. Trained psychologists assessed child's attention function using the Test of Everyday Attention for Children at Five (TEACh-5).

Determinants of serum levels of perfluorinated alkyl acids in Danish pregnant women.

Humans are exposed to perfluorinated alkyl acids (PFAAs) from food, drinking water, air, dust, and consumer products. PFAAs are persistent and bio-accumulative. In the present study, we aimed to establish how the serum levels of PFAAs differ according to age, pre-pregnancy body mass index (BMI), previous miscarriages, educational level, country of birth, smoking, and alcohol intake.

Congenital Heart Defects and Indices of Placental and Fetal Growth in a Nationwide Study of 924 422 Liveborn Infants.

Background: Congenital heart defects (CHDs) have been associated with placental anomalies. The nature and the consequences of this association remain poorly understood. We aimed to estimate the associations between all major subtypes of CHD and placental weight at birth, and the association between placental weight and measures of both overall and cerebral growth in fetuses with CHD, as well.

Microarray-Based Analysis of Methylation of 1st Trimester Trisomic Placentas from Down Syndrome, Edwards Syndrome and Patau Syndrome.

Methylation-based non-invasive prenatal testing of fetal aneuploidies is an alternative method that could possibly improve fetal aneuploidy diagnosis, especially for trisomy 13(T13) and trisomy 18(T18). Our aim was to study the methylation landscape in placenta DNA from trisomy 13, 18 and 21 pregnancies in an attempt to find trisomy-specific methylation differences better suited for non-invasive prenatal diagnosis. We have conducted high-resolution methylation specific bead chip microarray analyses assessing more than 450,000 CpGs analyzing placentas from 12 T21 pregnancies, 12 T18 pregnancies and 6 T13 pregnancies.

Perfluoroalkyl and polyfluoroalkyl substances and measures of human fertility: a systematic review.

Perfluoroalkyl and polyfluoroalkyl substances (PFASs) are found widespread in the environment and humans. The relation of PFASs to fertility has now been examined in a relatively large number of epidemiologic studies and a synthesis is in order. The aim of this study was to assess the current human epidemiologic evidence on the association between exposure to PFASs and measures of human fertility, with particular emphasis on perfluorooctane sulfonate (PFOS) and perfluorooctanoate (PFOA).

Congenital Heart Defects and Measures of Fetal Growth in Newborns with Down Syndrome or 22q11.2 Deletion Syndrome.

Objectives: To estimate the association between congenital heart defects (CHD) and indices of fetal growth in Down and 22q11.2 deletion syndromes.

Study Design: We established 2 Danish nationwide cohorts of newborn singletons with either Down syndrome (n = 670) or 22q11.

Time trends of perfluorinated alkyl acids in serum from Danish pregnant women 2008-2013.

We aimed to estimate the levels and time trends of perfluorinated alkyl acids (PFAAs) in serum of 1533 Danish pregnant nulliparous women between 2008 and 2013. The selection criterion of only including nulliparous women was chosen to avoid confounding from parity. The serum samples were analyzed for sixteen PFAAs using solid phase extraction and liquid chromatography tandem mass spectrometry (LC-MS/MS).

Congenital Heart Defects and Indices of Fetal Cerebral Growth in a Nationwide Cohort of 924 422 Liveborn Infants.

Background: Neurodevelopmental disorders are the most common and distressful comorbidities associated with congenital heart defects (CHD). Head circumference at birth (HC), a proxy for prenatal cerebral growth, is an established risk factor for neurodevelopmental disorders.

Methods And Results: In a nationwide cohort, we included all 924 422 liveborn Danish singletons, 1997 to 2011.

Perfluoroalkyl Acids in Maternal Serum and Indices of Fetal Growth: The Aarhus Birth Cohort.

Background: Previous studies indicated an association between intrauterine exposure to perfluorooctane sulfonate (PFOS) or perfluorooctanoate (PFOA) and lower birth weight. However, these perfluoroalkyl acids (PFAAs) have to some extent been substituted by other compounds on which little is known.

Objectives: We investigated the association between specific PFAAs and birth weight, birth length, and head circumference at birth.

Perfluoroalkyl Acid Concentrations in Blood Samples Subjected to Transportation and Processing Delay.

Background: In studies of perfluoroalkyl acids, the validity and comparability of measured concentrations may be affected by differences in the handling of biospecimens. We aimed to investigate whether measured plasma levels of perfluoroalkyl acids differed between blood samples subjected to delay and transportation prior to processing and samples with immediate processing and freezing.

Methods: Pregnant women recruited at Aarhus University Hospital, Denmark, (n = 88) provided paired blood samples.

Serum perfluoroalkyl acids and time to pregnancy in nulliparous women.

Background: Previous studies on the exposure to perfluoroalkyl acids (PFAAs) and female fertility have provided conflicting results. We aimed to investigate the association between several PFAAs and time to pregnancy among nulliparous women.

Methods: From 2008 to 2013, we included 1372 women from the Aarhus Birth Cohort, Aarhus University Hospital, Denmark, who provided data on time to pregnancy and a blood sample before 20 gestational weeks.

Microarray-Based Analysis of Methylation Status of CpGs in Placental DNA and Maternal Blood DNA--Potential New Epigenetic Biomarkers for Cell Free Fetal DNA-Based Diagnosis.

Epigenetic markers for cell free fetal DNA in the maternal blood circulation are highly interesting in the field of non-invasive prenatal testing since such markers will offer a possibility to quantify the amount of fetal DNA derived from different chromosomes in a maternal blood sample. The aim of the present study was to define new fetal specific epigenetic markers present in placental DNA that can be utilized in non-invasive prenatal diagnosis. We have conducted a high-resolution methylation specific beadchip microarray study assessing more than 450.

Perfluoroalkyl acids and time to pregnancy revisited: An update from the Danish National Birth Cohort.

Background: We previously demonstrated an association between plasma perfluorooctane sulfonate (PFOS) and perfluorooctanoate (PFOA) and longer time to pregnancy (TTP) in a sample from the Danish National Birth Cohort (DNBC, 1996-2002). In this study we investigated this association in a new sample from the same cohort.

Methods: Sample 1 consisted of 440 women, and Sample 2 consisted of 1161 women from whom we previously published the associations between PFOS or PFOA and TTP.

Perfluoroalkyl substances and time to pregnancy in couples from Greenland, Poland and Ukraine.

Background: Perfluoroalkyl substances (PFAS) are suggested to affect human fecundity through longer time to pregnancy (TTP). We studied the relationship between four abundant PFAS and TTP in pregnant women from Greenland, Poland and Ukraine representing varying PFAS exposures and pregnancy planning behaviors.

Methods: We measured serum levels of perfluorooctanoic acid (PFOA), perfluorooctane sulfonate (PFOS), perfluorohexane sulfonic acid (PFHxS) and perfluorononanoic acid (PFNA) in 938 women from Greenland (448 women), Poland (203 women) and Ukraine (287 women).