Search

Objective: To investigate whether maternal paracetamol use in early pregnancy is associated with cerebral palsy (CP) in offspring., Study Design: We conducted a registry and biobank-based case-control study with mother-child pairs. We identified CP cases (n = 322) born between 1995 and 2014 from a nationwide CP-registry. Randomly selected controls (n = 343) and extra preterm controls (n = 258) were obtained from a birth registry. For each mother, a single serum sample from early pregnancy (gestation weeks 10-14) was retrieved from a biobank and analyzed for serum concentrations of paracetamol, categorized into unexposed (<1 ng/ml), mildly exposed (1-100 ng/ml), and highly exposed (>100 ng/ml), and in quartiles. Analyses were performed using logistic regression and adjusted for potential confounders. Separate analyses were conducted including only those children born preterm and only those born term., Results: Of the 923 participants, 36.8% were unexposed, 53.2% mildly exposed, and 10% highly exposed to paracetamol. Overall, prenatal exposure to paracetamol was not associated with CP. Sensitivity and subgroup analyses showed no clear associations between paracetamol and CP across strata of term/preterm birth as well as subtypes of CP., Conclusions: The present study does not support an association between intrauterine exposure to paracetamol in early pregnancy and the risk of CP. However, it is important to stress that the exposure estimate is based on a single serum sample., Competing Interests: Declaration of Competing Interest This study is part of the ReproUnion collaborative study, cofinanced by the European Union, Interreg V Öresund-Kattegat-Skagerrak (NYPS 20200407). The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Aims: The aims were to investigate the association between maternal serum levels of perfluorooctane sulfonate (PFOS), perfluorooctanoic acid (PFOA), perfluorohexane sulfonate (PFHxS) and perfluorononanoic acid (PFNA) in early pregnancy and overweight in the child at 4 years and to assess potential heterogeneity in exposure effect between strata with different levels of other risk factors for overweight., Methods: We used a case-control design and included 354 cases (ISO-BMI ≥ 18 kg/m2) and 2 controls per case (ISO-BMI ≤17 kg/m2) from child health care centers in Malmö, Sweden. Controls were selected stratified on risk scores for overweight in a propensity score framework. Maternal serum levels were analyzed in biobanked samples collected by routine around gestational week 14. Logistic regression was used to estimate odds ratios between quartiles of maternal serum levels and child overweight at age 4., Results: There were no consistent monotonic exposure-response relationships. We found some significant odds ratios in specific quartiles but these were regarded as spurious findings. The absence of an effect was consistent over risk strata., Conclusions: We did not find evidence of an association between maternal serum levels of PFOS, PFOA, PFHxS and PFNA in early pregnancy and child overweight at age 4. The level of other risk factors for overweight did not affect children's susceptibility to prenatal PFAS exposure., Competing Interests: The authors have declared that no competing interests exist.

Background: Maternal smoking during pregnancy has repeatedly been associated with decreased sperm counts in sons. Nevertheless, our team recently detected a lower total sperm count in the sons of smoking fathers as compared to sons of non-smoking fathers. Since paternal and maternal tobacco smoking often coincide, it is difficult to discriminate whether effects are mediated paternally or maternally when using questionnaire- or register-based studies. Therefore, getting an objective measure of the maternal nicotine exposure level during pregnancy might help disentangling the impact of paternally and maternally derived exposure., Objectives: Our aim was to study how paternal smoking at the time of the pregnancy was associated with semen quality in the sons after adjusting for the maternal levels of nicotine exposure during pregnancy., Methods: We recruited 104 men (17-20 years old) from the general Swedish population. The participants answered a questionnaire about paternal smoking. Associations between smoking and semen volume, total sperm count, sperm concentration, morphology and motility were adjusted for levels of the nicotine metabolite cotinine in stored maternal serum samples obtained from rubella screening between the 6th and 35th week of pregnancy. We additionally adjusted for the estimated socioeconomic status., Results: After adjusting for the maternal cotinine, the men of smoking fathers had 41% lower sperm concentration and 51% lower total sperm count than the men of non-smoking fathers (p = 0.02 and 0.003, respectively). This was robust to the additional adjustment., Conclusions: Our results suggest a negative association between paternal smoking and sperm counts in the sons, independent of the level maternal nicotine exposure during the pregnancy., Competing Interests: The authors have declared that no competing interests exist.

Background: More than 20 years ago, it was hypothesized that exposure to prenatal and early postnatal environmental xenobiotics with the potential to disrupt endogenous hormone signaling might be on the causal path to cryptorchidism, hypospadias, low sperm count and testicular cancer. Several consensus statements and narrative reviews in recent years have divided the scientific community and have elicited a call for systematic transparent reviews. We aimed to fill this gap in knowledge in the field of male reproductive disorders., Objective and Rationale: The aim of this study was to systematically synthesize published data on the risk of cryptorchidism, hypospadias, low sperm counts and testicular cancer following in utero or infant exposure to chemicals that have been included on the European Commission's list of Category 1 endocrine disrupting chemicals defined as having documented adverse effects due to endocrine disruption in at least one intact organism., Search Methods: A systematic literature search for original peer reviewed papers was performed in the databases PubMed and Embase to identify epidemiological studies reporting associations between the outcomes of interest and exposures documented by biochemical analyses of biospecimens including maternal blood or urine, placenta or fat tissue as well as amnion fluid, cord blood or breast milk; this was followed by meta-analysis of quantitative data., Outcomes: The literature search resulted in 1314 references among which we identified 33 papers(28 study populations) fulfilling the eligibility criteria. These provided 85 risk estimates of links between persistent organic pollutants and rapidly metabolized compounds (phthalates and Bisphenol A) and male reproductive disorders. The overall odds ratio (OR) across all exposures and outcomes was 1.11 (95% CI 0.91-1.35). When assessing four specific chemical subgroups with sufficient data for meta-analysis for all outcomes, we found that exposure to one of the four compounds, p,p'-DDE, was related to an elevated risk: OR 1.35 (95% CI 1.04-1.74). The data did not indicate that this increased risk was driven by any specific disorder., Wider Implications: The current epidemiological evidence is compatible with a small increased risk of male reproductive disorders following prenatal and postnatal exposure to some persistent environmental chemicals classified as endocrine disruptors but the evidence is limited. Future epidemiological studies may change the weight of the evidence in either direction. No evidence of distortion due to publication bias was found, but exposure-response relationships are not evident. There are insufficient data on rapidly metabolized endocrine disruptors and on specific exposure-outcome relations. A particular data gap is evident with respect to delayed effects on semen quality and testicular cancer. Although high quality epidemiological studies are still sparse, future systematic and transparent reviews may provide pieces of evidence contributing to the narrative and weight of the evidence assessments in the field., (© The Author 2016. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology.)

Background: Many women of childbearing age are occupationally active, which leads to a large number of pregnancies potentially exposed to occupational exposures. Occupational noise has been identified as a risk factor for hearing impairment in adults. However, very few studies have assessed the effect of occupational noise on the fetus., Objectives: The aim of this study was to investigate whether occupational exposure to noise during pregnancy is associated with hearing dysfunction in children., Methods: This population based cohort study included 1,422,333 single births in Sweden 1986-2008. Data on mothers' occupation, smoking habits, age, ethnicity, body mass index, leave of absence, and socioeconomic factors were obtained from interviews performed by prenatal care unit staff at approximately 10 weeks of gestation and from national registers. Occupational noise exposure was classified by a job-exposure-matrix as < 75, 75-84, or ≥ 85 dBLAeq,8h. Diagnosed cases of hearing dysfunction (ICD-10 codes H90.3-7, 91.0, 91.2-3, 91.8, 93.1-2) were identified from a register of specialized medical care. Cox proportional hazards models were used to estimate associations., Results: In the full sample, containing a mixture of part-time and full-time workers during pregnancy, the adjusted HR for hearing dysfunction associated with maternal occupational noise exposure ≥ 85 vs. < 75 dBLAeq,8h was 1.27 (95% CI: 0.99, 1.64; 60 exposed cases). When restricted to children whose mothers worked full-time and had < 20 days leave of absence during pregnancy, the corresponding HR was 1.82 (95% CI: 1.08, 3.08; 14 exposed cases)., Conclusions: This study showed an association between occupational noise exposure during pregnancy and hearing dysfunction in children. In view of mechanistic evidence and earlier indicative epidemiological and experimental findings, the results support that pregnant women should not be exposed to high levels of noise at work., Citation: Selander J, Albin M, Rosenhall U, Rylander L, Lewné M, Gustavsson P. 2016. Maternal occupational exposure to noise during pregnancy and hearing dysfunction in children: a nationwide prospective cohort study in Sweden. Environ Health Perspect 124:855-860; http://dx.doi.org/10.1289/ehp.1509874.

Background: Some legacy and emerging environmental contaminants are suspected risk factors for intrauterine growth restriction. However, the evidence is equivocal, in part due to difficulties in disentangling the effects of mixtures., Objectives: We assessed associations between multiple correlated biomarkers of environmental exposure and birth weight., Methods: We evaluated a cohort of 1,250 term (≥ 37 weeks gestation) singleton infants, born to 513 mothers from Greenland, 180 from Poland, and 557 from Ukraine, who were recruited during antenatal care visits in 2002-2004. Secondary metabolites of diethylhexyl and diisononyl phthalates (DEHP, DiNP), eight perfluoroalkyl acids, and organochlorines (PCB-153 and p,p´-DDE) were quantifiable in 72-100% of maternal serum samples. We assessed associations between exposures and term birth weight, adjusting for co-exposures and covariates, including prepregnancy body mass index. To identify independent associations, we applied the elastic net penalty to linear regression models., Results: Two phthalate metabolites (MEHHP, MOiNP), perfluorooctanoic acid (PFOA), and p,p´-DDE were most consistently predictive of term birth weight based on elastic net penalty regression. In an adjusted, unpenalized regression model of the four exposures, 2-SD increases in natural log-transformed MEHHP, PFOA, and p,p´-DDE were associated with lower birth weight: -87 g (95% CI: -137, -340 per 1.70 ng/mL), -43 g (95% CI: -108, 23 per 1.18 ng/mL), and -135 g (95% CI: -192, -78 per 1.82 ng/g lipid), respectively; and MOiNP was associated with higher birth weight (46 g; 95% CI: -5, 97 per 2.22 ng/mL)., Conclusions: This study suggests that several of the environmental contaminants, belonging to three chemical classes, may be independently associated with impaired fetal growth. These results warrant follow-up in other cohorts.

Background: Genetic and non-genetic factors probably act together to initiate and accelerate development of type 1 diabetes [T1D]. One suggested risk factor contributing to development of T1D is air pollution., Objective: The aim of the study was to investigate whether maternal exposure during pregnancy to air pollution, measured as nitrogen oxides [NOx] and ozone, in a low-dose exposure area was associated with the child developing T1D., Method: In Scania (Skåne), the most southern county in Sweden, 84,039 infants were born during the period 1999-2005. By the end of April 2013, 324 of those children had been diagnosed with T1D. For each of those T1D children three control children were randomly selected and matched for HLA genotype and birth year. Individually modelled exposure data at residence during pregnancy were assessed for nitrogen oxides [NOx], traffic density and ozone., Results: Ozone as well as NOx exposures were associated with T1D. When the highest exposure group was compared to the lowest group an odds ratios of 1.62 (95% confidence interval [CI] 0.99-2.65) was observed for ozone in the second trimester and 1.58 (95% CI 1.06-2.35) for NOx in the third trimester., Conclusion: This study indicates that living in an area with elevated levels of air pollution during pregnancy may be a risk factor for offspring T1D., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: Prenatal exposure to phthalates is suggested to negatively impact male reproductive function, but human data are lacking., Objectives: To study associations between prenatal exposure to diethylhexyl phthalate (DEHP) and diisononyl phthalate (DiNP), and reproductive parameters of adolescent men., Methods: Using linear regression models adjusted for potential confounders, we studied associations between levels of DEHP- and DiNP metabolites in maternal sera from mean 12 weeks of pregnancy, and testicular size, semen quality and reproductive hormones in 112 adolescent sons, recruited from the general population., Results: Men in the highest exposure tertile of one DiNP metabolite [mono-(carboxy-iso-octyl) phthalate], compared with men in the lowest tertile had: 4.3mL (95% CI: 0.89, 7.6mL; p<0.001) lower total testicular volume; 30% (95% CI: 3.6, 63%; p=0.02) higher levels of follicle-stimulating hormone; and 0.87mL (95% CI: 0.28, 1.5mL; p=0.004) lower semen volume. Men in the highest exposure tertile of one DEHP metabolite [mono-(2-ethyl-5-hydroxylhexyl) phthalate] had 0.70mL (95% CI: 0.090, 1.3mL; p=0.03) lower semen volume than men in the lowest exposure tertile. The levels of two DiNP metabolites [mono-(hydroxy-iso-nonyl) phthalate and mono-(oxo-iso-nonyl) phthalate] were linearly associated with luteinizing hormone (p<0.01)., Conclusion: Prenatal levels of some metabolites of DEHP and DiNP seemed negatively associated with reproductive function of adolescent men., (Copyright © 2015 Elsevier Inc. All rights reserved.)

The main objective of this study was to investigate the risk of type 1 diabetes mellitus (T1D) in children exposed to tobacco smoking in utero, also taking genetic predisposition as expressed by HLA haplotype into account. In Skåne, the southernmost county of Sweden, all children born 1999-2005 who developed T1D were registered, resulting in 344 cases. For each child with T1D, three control children, matched for HLA haplotype and birthyear, were selected. Information on prenatal smoking exposure was retrieved from a regional birth register. Conditional logistic regressions were used to evaluate T1D risk following prenatal smoking exposure. In these data, maternal smoking in early pregnancy was associated with a higher risk of her child developing T1D [odds ratio (OR) 2.83; 95% confidence interval (CI) 1.67-4.80 for 1-9 cigarettes/day, and OR 3.91; 95% CI 1.22-12.51 for >9 cigarettes/day]. Results remained through all adjustments and sensitivity analyses. When genetic predisposition in terms of HLA haplotype was taken into account, we found that children exposed to smoking during fetal life were at higher risk of developing T1D in childhood.

Existing evidence on the effects of manganese and selenium during fetal life on neurodevelopmental disorders is inadequate. This study aims to investigate the hypothesized relationship between fetal exposure to manganese and selenium and attention deficit hyperactivity disorder (ADHD) diagnosis in childhood. Children born between 1978 and 2000 with ADHD (n=166) were identified at the Department of Child and Adolescent Psychiatry in Malmö, Sweden. Controls from the same region (n=166) were selected from the Medical Birth Register and were matched for year of birth and maternal country of birth. Manganese and selenium were measured in umbilical cord serum. The median cord serum concentrations of manganese were 4.3μg/L in the cases and 4.1μg/L in the controls. The corresponding concentrations of selenium were 47 and 48μg/L. When the exposures were analyzed as continuous variables no associations between cord manganese or selenium concentration and ADHD were observed. However, children with selenium concentrations above the 90th percentile had 2.5 times higher odds (95% confidence interval 1.3-5.1) of having ADHD compared to those with concentrations between the 10th and 90th percentiles. There was no significant interaction between manganese and selenium exposure (p=0.08). This study showed no association between manganese concentrations in umbilical cord serum and ADHD. The association between ADHD diagnoses in children with relatively high cord selenium was unexpected and should be interpreted with caution., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: In animal studies, perfluorinated alkyl substances affect growth and neuro-behavioural outcomes. Human epidemiological studies are sparse. The aim was to investigate the association between pregnancy serum concentrations of perfluorooctanoate (PFOA) and perfluorooctane sulfonate (PFOS) and offspring behaviour and motor development at 5-9 years of age., Methods: Maternal sera from the INUENDO cohort (2002-2004) comprising 1,106 mother-child pairs from Greenland, Kharkiv (Ukraine) and Warsaw (Poland) were analysed for PFOS and PFOA, using liquid-chromatography-tandem-mass-spectrometry. Exposures were grouped into country specific as well as pooled tertiles as well as being used as continuous variables for statistical analyses. Child motor development and behaviour at follow-up (2010-2012) were measured by the Developmental Coordination Disorder Questionnaire 2007 (DCDQ) and Strength and Difficulties Questionnaire (SDQ), respectively. Exposure-outcome associations were analysed by multiple logistic and linear regression analyses., Results: In the pooled analysis, odds ratio (OR) (95% confidence interval (CI)) for hyperactivity was 3.1 (1.3, 7.2) comparing children prenatally exposed to the highest PFOA tertile with those exposed to the lowest PFOA tertile. Comparing children in the highest PFOS tertile with those in the lowest PFOS tertile showed elevated but statistically non-significant OR of hyperactivity (OR (95% CI) 1.7 (0.9, 3.2)). In Greenland, elevated PFOS was associated with higher SDQ-total scores indicating more behavioural problems (β (95% CI)=1.0 (0.1, 2.0)) and elevated PFOA was associated with higher hyperactivity sub-scale scores indicating more hyperactive behaviour (β (95% CI)=0.5 (0.1, 0.9)). Prenatal PFOS and PFOA exposures were not associated with motor difficulties., Conclusions: Prenatal exposure to PFOS and PFOA may have a small to moderate effect on children's neuro-behavioural development, specifically in terms of hyperactive behaviour. The associations were strongest in Greenland where exposure contrast is largest.

Background: Maternal smoking during pregnancy has been reported to negatively impact sperm counts of the sons. Sufficient data on the effect of paternal smoking is lacking., Objectives: We wished to elucidate the impact of maternal and paternal smoking during pregnancy and current own smoking on reproductive function of the male offspring., Methods: Semen parameters including sperm DNA integrity were analyzed in 295 adolescents from the general population close to Malmö, Sweden, recruited for the study during 2008-2010. Information on maternal smoking was obtained from the Swedish Medical Birth Register, and regarding own and paternal smoking from questionnaires. The impacts of maternal, paternal and own smoking were evaluated in a multivariate regression model and by use of models including interaction terms. Totally, three exposures and five outcomes were evaluated., Results: In maternally unexposed men, paternal smoking was associated with 46% lower total sperm count (95%CI: 21%, 64%) in maternally unexposed men. Both paternal and maternal smoking were associated with a lower sperm concentration (mean differences: 35%; 95%CI: 8.1%, 55% and 36%; 95%CI: 3.9%, 57%, respectively) if the other parent was a non-smoker. No statistically significant impact of own smoking on semen parameters was seen., Conclusions: Prenatal both maternal and paternal smoking were separately associated with some decrease in sperm count in men of whom the other parent was not reported to smoke.

Background: The incidence of type 1 diabetes in Europe is increasing at a rate of about 3% per year and there is also an increasing incidence throughout the world. Type 1 diabetes is a complex disease caused by multiple genetic and environmental factors. Persistent organochlorine pollutants (POPs) have been suggested as a triggering factor for developing childhood type 1 diabetes. The aim of this case-control study was to assess possible impacts of in utero exposure to POPs on type 1 diabetes., Methodology/ Principal Findings: The study was performed as a case-control study within a biobank in Malmö, a city located in the Southern part of Sweden. The study included 150 cases (children who had their diagnosis mostly before 18 years of age) and 150 controls, matched for gender and day of birth. 2,2',4,4',5,5'-hexachlorobiphenyl (PCB-153) and the major DDT metabolite 1,1-dichloro-2,2-bis (p-chlorophenyl)-ethylene (p,p'-DDE) were used as a biomarkers for POP exposure. When comparing the quartile with the highest maternal serum concentrations of PCB-153 with the other quartiles, an odds ratio (OR) of 0.73 (95% confidence interval [CI] 0.42, 1.27) was obtained. Similar results was obtained for p,p'-DDE (OR 0.56, 95% CI 0.29, 1.08)., Conclusions: The hypothesis that in utero exposure to POPs will trigger the risk for developing type 1 diabetes was not supported by the results. The risk estimates did, although not statistically significant, go in the opposite direction. However, it is not reasonable to believe that exposure to POPs should protect against type 1 diabetes.

In Sweden the main exposure route for persistent organochlorine pollutants (POP) is through consumption of fatty fish from the Baltic Sea (off the eastern coast). The present study aimed to investigate whether intrauterine exposure for POP may have negative impact on children's weight and height at 4 and 7 years of age, respectively. The study included 174 fishermen's wives from the Swedish east coast who had given birth to an infant with either low (n=55) or normal (n=119) birth weight, and 88 and 206 corresponding women from the Swedish west coast (where the fish is less polluted). Comparisons between the east and west coast cohorts were performed. In addition, blood samples were collected among the east coast women and the concentrations of 2,2',4,4',5,5'-hexachlorobiphenyl (CB-153) in plasma was analyzed and estimated for the year of childbirth. There were no significant differences between the east and west coast cohorts regarding weight and height at 4 and 7 years of age. There were, however, significant negative associations between the estimated plasma concentrations of CB-153 during year of childbirth and weight at 4 and 7 years of age, respectively, among the normal birth weight children. The study gives only very weak support for the hypothesized association.

Objectives: The present study aimed to investigate whether boys who had been pre- and postnatally exposed to persistent organochlorine compounds through the consumption of contaminated fatty fish from the Baltic Sea (on the east coast of Sweden) had medical or psychometric impairments in the compulsory conscript examination at 18 years of age., Methods: Boys born in 1973 to 1975 to fishermen's wives and fishermen's sisters from the Swedish east coast were examined at 18 years of age. For relevant comparisons a corresponding group from the Swedish west coast, where the fish are less contaminated, were used. In addition, comparisons were made with expected values based on conscript examination data for the general population in the same geographic areas., Results: The boys in the 2 cohorts did not, during the conscript testing, significantly differ in the results of the psychometric tests. On the other hand, the boys from the eastcoast cohort were somewhat shorter and had more visual and hearing impairments than the boys from the west coast. However, the eastcoast boys did not differ from the regional reference population with respect to visual and hearing ability., Conclusions: Although no individual exposure data were available, the present results do not support any harmful long-term impact of pre- and postnatal exposure to persistent organochlorine compounds from mothers' fish consumption on the psychometric functions of boys in their conscript examinations.

Background: Epidemiological studies on the association between maternal exposure to persistent organic pollutants (POPs) and fetal growth alteration report inconsistent findings which weights in favor of additional studies.Methods: Blood samples were collected from interviewed pregnant women in Greenland (572), Kharkiv (611) and Warsaw (258) and were analyzed for CB-153 and p,p'-DDE by gas chromatography-mass spectrometry. Data on birth weight, gestational age and preterm birth were obtained for 1322 singleton live births. We examined the association between natural log-transformed serum POPs concentration and birth weight and gestational age using multiple linear regression and the association with prematurity using logistic regression controlling for potential confounding factors.Results: The median serum concentrations of CB-153 and p,p'-DDE were for Inuit mothers 105.6 and 298.9, for Kharkiv mothers 27.0 and 645.4 and for Warsaw mothers 10.7 and 365.2 ng/g lipids, respectively. Increase in CB-153 concentration by one unit on the log scale in Inuit mothers serum was associated with significant decrease in infant birth weight of -59 g and gestational age by -0.2 week. Decreases observed in the cohorts in Kharkiv (-10 g and -0.1 week) and in Warsaw (-49 g and -0.2 week) were not statistically significant. Increase in p,p'-DDE concentration by one unit on the log scale was associated with a statistically significant decrease in infant birth weight of -39.4 g and -104.3 g and shortening of gestational age of -0.2 week and -0.6 week in the Inuit and Warsaw cohorts, respectively. In the Kharkiv cohort decrease in birth weight (-30.5 g) was not significant, however a shortening of gestational age of -0.2 week per increase in p,p'-DDE concentration by one unit on the log scale was of the borderline significance. There was no significant association between CB-153 and p,p'-DDE concentrations and risk of preterm birth however, in all cohorts the odds ratio was above 1.Conclusions: In utero exposure to POPs may reduce birth weight and gestational age of newborns however, new insights as to why results vary across studies were not apparent. [ABSTRACT FROM AUTHOR]