Next-generation biomonitoring of the early-life chemical exposome in neonatal and infant development

2022 ◽  
Author(s):  
Thomas Jamnik ◽  
Mira Flasch ◽  
Dominik Braun ◽  
Yasmin Fareed ◽  
Daniel Wasinger ◽  
...  
Keyword(s):  
Breast Milk ◽  
Early Life ◽  
Large Scale ◽  
Infant Development ◽  
Association Studies ◽  
Post Partum ◽  
Tropane Alkaloids ◽  
Human Biomonitoring ◽  
Chemical Exposure ◽  
Liquid Chromatography Tandem Mass

Exposure to man-made and natural chemicals is a major, yet not sufficiently considered, environmental risk factor in the etiology of chronic diseases. Current human biomonitoring approaches typically measure a limited number of exposures rather than investigating complex mixtures. The latter would be fundamental and necessary for a holistic assessment of chemical exposure in exposome-wide association studies. In this work, an highly-sensitive liquid chromatography-tandem mass spectrometry approach was developed and thoroughly-validated. The assay enables the simultaneous and targeted assessment of more than 80 highly-diverse xenobiotics in the investigated body fluids of urine, serum/plasma, and breast milk; the detection limit for most toxicants are in the pg-ng/mL range. In the plasma of extremely-premature infants (gestational age <28 weeks, birth weight <1 kg) a total of 27 different xenobiotics are identified; including severe contamination with synthetic plasticizers, perfluorinated alkylated substances and parabens. In an independent sample set of breast milk that was longitudinally collected over the first 211 days post-partum, a total of 29 analytes is detected, including the first-ever identification of pyrrolizidine- and tropane alkaloids in this matrix. Based on the generated data, a preliminary estimation of daily toxicant intake via breast milk is conducted. In conclusion, our proof-of-principle experiments show significant early-life co-exposure to multiple toxicants, and demonstrate the method’s applicability in future large-scale exposomics-type cohort studies in vulnerable populations.

scholarly journals Biphasic Glucocorticoid Rhythm in One-Month-Old Infants: Reflection of a Developing HPA-Axis?

2019 ◽  
Vol 105 (3) ◽  
pp. e544-e554 ◽  
Author(s):  
Jonneke J Hollanders ◽  
Bibian van der Voorn ◽  
Paul de Goede ◽  
Alyssa A Toorop ◽  
Lisette R Dijkstra ◽  
...  
Keyword(s):  
Breast Milk ◽  
Hpa Axis ◽  
Early Life ◽  
Medical Center ◽  
Depression Scale ◽  
Area Under The Curve ◽  
San Jose ◽  
Liquid Chromatography Tandem Mass ◽  
The Mean ◽  
Hpa Axis Activity

Abstract Context The hypothalamus-pituitary-adrenal (HPA) axis displays a diurnal rhythm. However, little is known about its development in early life. Objective To describe HPA-axis activity and study possible influencing factors in 1-month-old infants. Design Observational. Setting Amsterdam University Medical Center, location VU University Medical Center (VUMC), and Onze Lieve Vrouwe Gasthuis (OLVG), Amsterdam. Participants Fifty-five mother-infant pairs. Interventions Collection of breast milk and infants’ saliva 1 month postpartum for analysis of glucocorticoids (GCs; ie, cortisol and cortisone) using liquid chromatography– tandem mass spectrometry. Main Outcome Measure GC rhythm in infants’ saliva and associations with vulnerability for maternal psychological distress (increased Hospital Anxiety and Depression Scale [HADS] score) or consultation at the Psychiatric Obstetric Pediatric (POP clinic), season at sampling, sex, and breast milk GC rhythmicity analyzed with SigmaPlot 14.0 software (Systat Software, San Jose, CA, USA) and regression analyses. Results A significant biphasic GC rhythm was detected in infants, with mean peaks [standard error of the mean, SEM] at 6:53 am [1:01] and 18:36 pm [1:49] for cortisol, and at 8:50 am [1:11] and 19:57 pm [1:13] for cortisone. HADS score, POP consultation, season at sampling, and sex were not associated with the infants’ GC rhythm. Breast milk cortisol maximum was positively associated with infants’ cortisol area-under-the-curve (AUC) increase and maximum. Higher breast milk cortisone AUC increase, AUC ground, and maximum were associated with an earlier maximum in infants. Breast milk and infant GC concentrations were associated between 6:00 am and 9:00 am. Conclusions A biphasic GC rhythm, peaking in the morning and evening, was seen in 1-month-old infants at a group level. Breast milk GC parameters might be associated with the infants’ GC rhythm, possibly caused by a signaling effect of breast milk GCs, or as an associative effect of increased mother-infant synchrony. These results contribute to an increased understanding of early life HPA-axis development.

scholarly journals Optimized permutation testing for information theoretic measures of multi-gene interactions

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
James M. Kunert-Graf ◽  
Nikita A. Sakhanenko ◽  
David J. Galas
Keyword(s):  
Large Scale ◽  
Permutation Test ◽  
Association Studies ◽  
Genome Wide Association Studies ◽  
Permutation Testing ◽  
Exact Test ◽  
Information Theoretic ◽  
Information Theoretic Measures ◽  
Full Analysis ◽  
Computational Bottleneck

Abstract Background Permutation testing is often considered the “gold standard” for multi-test significance analysis, as it is an exact test requiring few assumptions about the distribution being computed. However, it can be computationally very expensive, particularly in its naive form in which the full analysis pipeline is re-run after permuting the phenotype labels. This can become intractable in multi-locus genome-wide association studies (GWAS), in which the number of potential interactions to be tested is combinatorially large. Results In this paper, we develop an approach for permutation testing in multi-locus GWAS, specifically focusing on SNP–SNP-phenotype interactions using multivariable measures that can be computed from frequency count tables, such as those based in Information Theory. We find that the computational bottleneck in this process is the construction of the count tables themselves, and that this step can be eliminated at each iteration of the permutation testing by transforming the count tables directly. This leads to a speed-up by a factor of over 103 for a typical permutation test compared to the naive approach. Additionally, this approach is insensitive to the number of samples making it suitable for datasets with large number of samples. Conclusions The proliferation of large-scale datasets with genotype data for hundreds of thousands of individuals enables new and more powerful approaches for the detection of multi-locus genotype-phenotype interactions. Our approach significantly improves the computational tractability of permutation testing for these studies. Moreover, our approach is insensitive to the large number of samples in these modern datasets. The code for performing these computations and replicating the figures in this paper is freely available at https://github.com/kunert/permute-counts.

scholarly journals Calcium isotopic patterns in enamel reflect different nursing behaviors among South African early hominins

2019 ◽  
Vol 5 (8) ◽  
pp. eaax3250 ◽  
Author(s):  
Théo Tacail ◽  
Jeremy E. Martin ◽  
Florent Arnaud-Godet ◽  
J. Francis Thackeray ◽  
Thure E. Cerling ◽  
...  
Keyword(s):  
Breast Milk ◽  
South African ◽  
Early Life ◽  
Tooth Enamel ◽  
Biological Evolution ◽  
Milk Consumption ◽  
Interbirth Interval ◽  
Australopithecus Africanus ◽  
The Social ◽  
Life Behavior

Nursing is pivotal in the social and biological evolution of hominins, but to date, early-life behavior among hominin lineages is a matter of debate. The calcium isotopic compositions (δ44/42Ca) of tooth enamel can provide dietary information on this period. Here, we measure the δ44/42Ca values in spatially located microsized regions in tooth enamel of 37 South African hominins to reconstruct early-life dietary-specific variability in Australopithecus africanus, Paranthropus robustus, and early Homo. Very low δ44/42Ca values (<−1.4‰), indicative of milk consumption, are measured in early Homo but not in A. africanus and P. robustus. In these latter taxa, transitional or adult nonmilk foods must have been provided in substantial quantities relative to breast milk rapidly after birth. The results suggest that early Homo have continued a predominantly breast milk–based nursing period for longer than A. africanus and P. robustus and have consequently more prolonged interbirth interval.

scholarly journals Chemical Exposure: European Citizens’ Perspectives, Trust, and Concerns on Human Biomonitoring Initiatives, Information Needs, and Scientific Results

2021 ◽  
Vol 18 (4) ◽  
pp. 1532
Author(s):  
Maria Uhl ◽  
Ricardo R. Santos ◽  
Joana Costa ◽  
Osvaldo Santos ◽  
Ana Virgolino ◽  
...  
Keyword(s):  
Decision Making ◽  
Policy Development ◽  
Information Needs ◽  
Policy Decision ◽  
Human Biomonitoring ◽  
Chemical Exposure ◽  
The European Union ◽  
Cross Sectional ◽  
The United Kingdom ◽  
Scientific Results

Over the last few decades, citizen awareness and perception of chemical products has been a topic of interest, particularly concerning national and international policy decision makers, expert/scientific platforms, and the European Union itself. To date, few qualitative studies on human biomonitoring have analysed communication materials, made recommendations in terms of biomonitoring surveillance, or asked for feedback in terms of specific biomonitoring methods. This paper provides in-depth insight on citizens’ perceptions of knowledge of biomonitoring, impact of chemical exposure on daily life, and claims on how results of research should be used. Four semi-structured focus groups were held in Austria, Portugal, Ireland, and the United Kingdom (UK). The cross-sectional observational qualitative design of this study allows for better understanding of public concern regarding chemicals, application, and use of human biomonitoring. The main findings of this study include citizens’ clear articulation on pathways of exposure, the demand on stakeholders for transparent decision-making, and sensitivity in communication of results to the public. Validated and trustful communication is perceived as key to empowering citizens to take action. The results can be used to facilitate decision-making and policy development, and feeds into the awareness needs of similar and future projects in human biomonitoring. Furthermore, it also brings to light ideas and concepts of citizens’ in shaping collaborative knowledge between citizens’, experts, scientists, and policy makers on equal terms.

scholarly journals Pilot study testing a European human biomonitoring framework for biomarkers of chemical exposure in children and their mothers: experiences in the UK

2015 ◽  
Vol 22 (20) ◽  
pp. 15821-15834 ◽  
Author(s):  
Karen Exley ◽  
Dominique Aerts ◽  
Pierre Biot ◽  
Ludwine Casteleyn ◽  
Marike Kolossa-Gehring ◽  
...  
Keyword(s):  
Pilot Study ◽  
Human Biomonitoring ◽  
Chemical Exposure ◽  
The Uk ◽  
Mothers Experiences

Power comparison of Cochran-Armitage trend test against allelic and genotypic tests in large-scale case-control genetic association studies

2016 ◽  
Vol 27 (9) ◽  
pp. 2657-2673 ◽  
Author(s):  
Mathieu Emily
Keyword(s):  
Large Scale ◽  
Association Studies ◽  
Disease Model ◽  
Trend Test ◽  
Genome Wide Association Studies ◽  
Power Functions ◽  
Power Comparison ◽  
Powerful Test ◽  
Armitage Trend Test ◽  
Mode Of Inheritance

The Cochran-Armitage trend test (CA) has become a standard procedure for association testing in large-scale genome-wide association studies (GWAS). However, when the disease model is unknown, there is no consensus on the most powerful test to be used between CA, allelic, and genotypic tests. In this article, we tackle the question of whether CA is best suited to single-locus scanning in GWAS and propose a power comparison of CA against allelic and genotypic tests. Our approach relies on the evaluation of the Taylor decompositions of non-centrality parameters, thus allowing an analytical comparison of the power functions of the tests. Compared to simulation-based comparison, our approach offers the advantage of simultaneously accounting for the multidimensionality of the set of features involved in power functions. Although power for CA depends on the sample size, the case-to-control ratio and the minor allelic frequency (MAF), our results first show that it is largely influenced by the mode of inheritance and a deviation from Hardy–Weinberg Equilibrium (HWE). Furthermore, when compared to other tests, CA is shown to be the most powerful test under a multiplicative disease model or when the single-nucleotide polymorphism largely deviates from HWE. In all other situations, CA lacks in power and differences can be substantial, especially for the recessive mode of inheritance. Finally, our results are illustrated by the comparison of the performances of the statistics in two genome scans.

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