PFAS levels and exposure determinants in sensitive population groups.

BACKGROUND: Per- and polyfluoroalkyl substances (PFAS) are persistent organic pollutants. The first exposure to PFAS occurs in utero, after birth it continues via breast milk, food intake, environment, and consumer products that contain these chemicals. Our aim was to identify determinants of PFAS concentrations in sensitive population subgroups- pregnant women and newborns. METHODS: Nine European birth cohorts provided exposure data on PFAS in pregnant women (INMA-Gipuzkoa, Sabadell, Valencia, ELFE and MoBa; total N = 5897) or newborns (3xG study, FLEHS 2, FLEHS 3 and PRENATAL; total N = 940). PFOS, PFOA, PFHxS and PFNA concentrations were measured in maternal or cord blood, depending on the cohort (FLEHS 2 measured only PFOS and PFOA). PFAS concentrations were analysed according to maternal characteristics (age, BMI, parity, previous breastfeeding, smoking, and food consumption during pregnancy) and parental educational level. The association between potential determinants and PFAS concentrations was evaluated using multiple linear regression models. RESULTS: We observed significant variations in PFAS concentrations among cohorts. Higher PFAS concentrations were associated with higher maternal age, primipara birth, and educational level, both for maternal blood and cord blood. Higher PFAS concentrations in maternal blood were associated with higher consumption of fish and seafood, meat, offal and eggs. In cord blood, higher PFHxS concentrations were associated with daily meat consumption and higher PFNA with offal consumption. Daily milk and dairy consumption were associated with lower concentrations of PFAS in both, pregnant women and newborns. CONCLUSION: High detection rates of the four most abundant PFAS demonstrate ubiquitous exposure of sensitive populations, which is of concern. This study identified several determinants of PFAS exposure in pregnant women and newborns, including dietary factors, and these findings can be used for proposing measures to reduce PFAS exposure, particularly from dietary sources.

Pre- and post-natal exposure of children to organophosphate flame retardants: A nationwide survey in France.

The use of organophosphate flame retardants (OPFRs) has been on the rise ever since many brominated flame retardants were banned, back in the 2000 s. The objectives of this study are to describe the pre- and post-natal exposure of children to OPFRs, and to explore their possible determinants. A total of 259 children aged 3.5 years and 388 mothers from the French ELFE mother-child cohort were included. Both pre- and post-natal exposure to OPFRs were assessed, using OPFR concentrations in the hair of pregnant women (in 2011) and their 3.5-year-old children (in 2014-2015) for 15 OPFRs, of which 9 were detected in > 20 % hair samples. The highest geometric means for pre-natal exposure were 272 ng/g for tris(1-chloro-2-propyl) phosphate (TCPP), 69.7 ng/g for ng/g for triphenyl phosphate (TPP) and 54.4 ng/g for tris(1,3-dichloro-2-propyl) phosphate (TDCPP). The highest geometric means for post-natal exposure were 249.6 ng/g for TCPP, 85.3 ng/g for TDCPP and 83.8 ng/g for 2-ethylhexyl diphenyl phosphate (EHDPP). Correlations were found between both pre-natal exposures, and between pre-and post-natal exposures. No correlation was however found between pre-and post-natal exposures for any given OPFR. Pre-natal exposure to the 9 OPFRs was associated with pre-natal exposure to polybrominated diphenyl ethers 209 (BDE209), and 47 (BDE47). Maternal BMI was associated with pre-natal exposure to OPFRs other than TBEP. Home renovation work prior to birth was also associated with pre-natal exposure to OPFRs, with the exception of EHDPP, tris(2-butoxyethyl) phosphate (TBEP) and triethyl phosphate (TEP). Determinants of post-natal exposure appeared more disparate across OPFRs; although both the type of flooring in children's rooms and pre-natal exposure to polybrominated diphenyl ethers seem to be associated with post-natal exposure. Lastly, higher socioeconomic status appeared to be associated with lower exposure for several (though not all) OPFRs. The high prevalence of exposure to OPFRs suggests the need for studies to assess the health effects of OPFRs exposure, particularly on children.

Maternal occupational exposures to nanoscale particles and small for gestational age outcome in the French Longitudinal Study of Children.

OBJECTIVES: To investigate the association between maternal occupational exposures to nanoscale particles (NPs) during pregnancy and small for gestational age (SGA). METHODS: This study included 11,224 mothers and singleton birth pairs from the French Longitudinal Study of Children (ELFE cohort), which included infants born after 33 weeks of gestation or more in continental France in 2011. Mothers who did not work during pregnancy were excluded from the analyses. Maternal occupational exposures to NPs was estimated using a job-exposure matrix for the probability (>50%: occupationally exposed group, n = 569; 0%: occupationally non-exposed group, n = 9113; between these two thresholds: uncertain group, n = 1542) and frequency of exposure. Associations were estimated from multivariate logistic regression models for occupationally exposed vs occupationally unexposed groups in a first analysis, and with the frequency-weighted duration of work for the occupationally exposed group only in a second analysis. RESULTS: Among working mothers, 5.1% were occupationally exposed to NPs. Maternal occupational exposures to NPs was associated with SGA (ORa = 1.63, 95% CI: 1.22, 2.18). The frequency-weighted duration of work for the occupationally exposed group (n = 569) was not associated with SGA (ORa = 1.02, 95% CI: 0.97, 1.08) in adjusted analyses. CONCLUSIONS: These results, showing a significant association between occupational exposures to NPs and SGA, should encourage further studies to examine the adverse effect of NPs exposure on fetal development.

Maternal cumulative exposure to extremely low frequency electromagnetic fields and pregnancy outcomes in the Elfe cohort.

OBJECTIVES: To study the relations between maternal cumulative exposure to extremely low frequency electromagnetic fields (ELF EMF) and the risk of moderate prematurity and small for gestational age within the Elfe cohort. METHODS: The Elfe study included 18,329 infants born at 33weeks of gestation or more in France in 2011 and was designed to follow the children until 20years of age. Gestational age and anthropometric data at birth were collected in medical records and small for gestational age was defined according to a French customized growth standard. During interviews, mothers were asked to report their job status during pregnancy. If employed, their occupation was coded according to the International Standard Classification of Occupations 1988 and the date on which they stopped their work was recorded. Cumulative exposure to ELF EMF during pregnancy was assessed, for both mothers who worked and those who did not during pregnancy, using a recently-updated job-exposure matrix (JEM). Cumulative exposure was considered as a categorical variable (<17.5, 17.5-23.8, 23.8-36.2, 36.2-61.6 or ≥61.6µT-days), a binary variable (<44.1 and ≥44.1µT-days) and a continuous variable. Associations were analyzed by logistic regression, adjusting for the mother's lifestyle factors, sociodemographic characteristics and some mother's medical history during and before pregnancy. Analyses were restricted to single births and to complete values for the pregnancy outcomes (n=16,733). RESULTS: Cumulative exposure was obtained for 96.0% of the mothers. Among them, 37.5% were classified in the 23.8-36.2µT-days category, but high exposures were rare: 1.3% in the ≥61.6µT-days category and 5.5% in the ≥44.1µT-days category. No significant association was observed between maternal cumulative exposure and moderate prematurity and small for gestational age in this exposure range. CONCLUSION: This large population-based study does not suggest that maternal exposure to ELF EMF during pregnancy is highly associated with risks of moderate prematurity or small for gestational age.

Microbiological characterization of 3193 French dwellings of Elfe cohort children.

Although exposure to indoor microorganisms in early life has already been associated with respiratory illness or allergy protection, only a few studies have performed standardized samplings and specific microbial analysis. Moreover, most do not target the different groups of microorganisms involved in respiratory diseases (fungi, bacteria, dust mites). In our study, ten specific qPCR targets (6 fungal species, 1 family and 2 genera of bacteria, 1 house dust mite) were used to analyze the microorganism composition of electrostatic dust fall collector (EDC) from 3193 dwellings of the Elfe French cohort study. Multivariate analyses allowed us to show that the microbial composition of dwellings, assessed with simultaneous analysis of 10 microorganisms, can be characterized by four entities: three bacteria, house dust mite Dermatophagoïdes pteronyssinus, fungi Alternaria alternata, and five other molds. Some dwellings' intrinsic characteristics (occupational ratio, type of dwelling and presence of pets) clearly influence microorganism distribution, and six different profiles of dwellings, characterized by their composition in microorganisms, have been described across France. The use of these clusters seems promising in the evaluation of allergic risk. Allergic respiratory diseases will develop in the near future in some children of the Elfe cohort and will indicate to what extent our approach can be predictive of respiratory disease.

Penetrance estimation of TTR familial amyloid polyneuropathy (type I) in Brazilian families.

BACKGROUND AND PURPOSE: Familial amyloid polyneuropathy (FAP) type I is a severe autosomal dominant inherited neuropathy associated with mutations in the transthyretin (TTR) gene. Significant phenotypic variability is seen amongst families with distinct geographic origin, especially regarding penetrance and age of onset. The aim of this study was to estimate the penetrance of FAP in Brazilian families. METHODS: Twenty-two distinct families were ascertained through genetically confirmed index cases and included in this study. Genealogical and clinical data were obtained from a total of 623 individuals, including 126 affected by FAP. In 15 families, TTR genotyping was performed in all available relatives (n = 86), after informed written consent. Seven families did not consent for genetic testing, but agreed to provide clinical and genealogical data. Penetrance was estimated using a previously described method based on survival analysis and corrected for ascertainment bias. RESULTS: Mean age of onset in our sample was 34.5 years, with a significant earlier onset in males (31.1 vs. 35.9, P < 0.0001). The penetrance of FAP in our sample was estimated as 83% (95% CI: 66-99) after 60 years. CONCLUSION: Our results provide new information on FAP in Brazilian patients and may be helpful in the genetic counseling of this population.

On the origin of the transthyretin Val30Met familial amyloid polyneuropathy.

Transthyretin (TTR) familial amyloid polyneuropathy is a severe autosomal dominant neuropathy of adulthood, frequently linked to the pathogenic Val30Met variant of the TTR gene. The condition was initially described in northern Portugal, which is the first focus of the disease. Other important clusters of families are found in Sweden, Japan and South America. The origin of the Val30Met mutation and its distribution through the populations remains unclear. In the present work, we aimed at refining the history of the Val30Met mutation in patients affected with TTR amyloid neuropathy from Portugal, Sweden and Brazil. The decay of haplotype sharing was studied in 60 patients to estimate the age of the Most Recent Common Ancestor (MRCA) of mutation carriers in these populations. Our results showed a common haplotype in Portuguese and Brazilian patients and an age estimate of the MRCA of 750 and 650 years, respectively. In contrast, a different haplotype was found in the Swedish Val30Met patients with a corresponding age estimate for the MRCA, of 375 years. This work strengthens the hypothesis of different founders in Portuguese and Swedish Val30Met carriers and suggested a Portuguese origin of the Brazilian mutation. The age estimates of the MRCA are in line with the current historical knowledge of these populations.

Diagnostic pitfalls in sporadic transthyretin familial amyloid polyneuropathy (TTR-FAP).

Transthyretin familial amyloid polyneuropathies (TTR-FAPs) are autosomal dominant neuropathies of fatal outcome within 10 years after inaugural symptoms. Late diagnosis in patients who present as nonfamilial cases delays adequate management and genetic counseling. Clinical data of the 90 patients who presented as nonfamilial cases of the 300 patients of our cohort of patients with TTR-FAP were reviewed. They were 21 women and 69 men with a mean age at onset of 61 (extremes: 38 to 78 years) and 17 different mutations of the TTR gene including Val30Met (38 cases), Ser77Tyr (16 cases), Ile107Val (15 cases), and Ser77Phe (5 cases). Initial manifestations included mainly limb paresthesias (49 patients) or pain (17 patients). Walking difficulty and weakness (five patients) and cardiac or gastrointestinal manifestations (five patients), were less common at onset. Mean interval to diagnosis was 4 years (range 1 to 10 years); 18 cases were mistaken for chronic inflammatory demyelinating polyneuropathy, which was the most common diagnostic error. At referral a length-dependent sensory loss affected the lower limbs in 2, all four limbs in 20, and four limbs and anterior trunk in 77 patients. All sensations were affected in 60 patients (67%), while small fiber dysfunction predominated in the others. Severe dysautonomia affected 80 patients (90%), with postural hypotension in 52, gastrointestinal dysfunction in 50, impotence in 58 of 69 men, and sphincter disturbance in 31. Twelve patients required a cardiac pacemaker. Nerve biopsy was diagnostic in 54 of 65 patients and salivary gland biopsy in 20 of 30. Decreased nerve conduction velocity, increased CSF protein, negative biopsy findings, and false immunolabeling of amyloid deposits were the main causes of diagnostic errors. We conclude that DNA testing, which is the most reliable test for TTR-FAP, should be performed in patients with a progressive length-dependent small fiber polyneuropathy of unknown origin, especially when associated with autonomic dysfunction.