EDC mixtures during pregnancy and body fat at 7 years of age in a Swedish cohort, the SELMA study.

BACKGROUND: Some endocrine disrupting chemicals (EDC), are "obesogens" and have been associated with overweight and obesity in children. Daily exposure to different classes of EDCs demands for research with mixtures approach. OBJECTIVES: This study evaluates the association, considering sex-specific effects, between prenatal exposure to EDC mixture and children's body fat at seven years of age. METHODS: A total of 26 EDCs were assessed in prenatal urine and serum samples from first trimester in pregnancy from 737 mother-child pairs participating in the Swedish Environmental Longitudinal, Mother and child, Asthma and allergy (SELMA) study. An indicator for children's "overall body fat" was calculated, using principal component analysis (PCA), based on BMI, percent body fat, waist, and skinfolds measured at seven years of age. Weighted quantile sum (WQS) regression was used to assess associations between EDC mixture and children's body fat. RESULTS: Principal component (PC1) represented 83.6 % of the variance, suitable as indicator for children's "overall body fat", with positive loadings of 0.40-0.42 for each body fat measure. A significant interaction term, WQS*sex, confirmed associations in the opposite direction for boys and girls. Higher prenatal exposure to EDC mixture was borderline significant with more "overall body fat" for boys (Mean ß = 0.20; 95 % CI: -0.13, 0.53) and less for girls (Mean ß = -0.23; 95 % CI: -0.58, 0.13). Also, higher prenatal exposure to EDC mixture was borderline significant with more percent body fat (standardized score) for boys (Mean ß = 0.09; 95 % CI: -0.04, 0.21) and less for girls (Mean ß = -0.10 (-0.26, 0.05). The chemicals of concern included bisphenols, phthalates, PFAS, PAH, and pesticides with different patterns for boys and girls. DISCUSSION: Borderline significant associations were found between prenatal exposure to a mixture of EDCs and children's body fat. The associations in opposite directions suggests that prenatal exposure to EDCs may present sex-specific effects on children's body fat.

Unpredictable supplementation of vitamin D to infants in the neonatal intensive care unit: An experimental study.

AIM: Extremely premature infants receive nutrition and medication through nasogastric tubes. Breastmilk given accordingly is subject to fat loss. This study aimed to investigate whether this could also apply to vitamin D. METHODS: A questionnaire investigated vitamin D administration at a level III neonatal intensive care unit in Sweden in 2021. Feeding simulations with breastmilk and various vitamin D mixtures were done accordingly. After administration, vitamin D3 concentration was analysed using chromatography with mass spectrometry, followed by repeated simulations with vitamin D mixtures without breastmilk in 2023. RESULTS: The questionnaire was completed by 10 persons. Vitamin D was administered as drops using an enteral syringe and a nasogastric tube in conjunction with a breastmilk meal. In the feeding simulations, vitamin D3 concentration after administration was significantly higher using a syringe alone compared to standard administration. When vitamins were administered according to standard but without breastmilk, 100% of the vitamin D and 40% of the multivitamins were lost. The vitamins adhered to the material, mainly in the nasogastric tube. CONCLUSION: Our findings indicate that standard vitamin D supplementation in the neonatal intensive care unit may be unpredictable when administered by enteral syringe and nasogastric tube. We suggest using direct oral administration whenever possible.

Maternal nutrition during mid-pregnancy and children's body composition at 7 years of age in the SELMA study.

Optimal nutrition during pregnancy is vital for both maternal and child health. Our objective was to explore if prenatal diet is associated with children's height and body fat. Nutrient intake was assessed through a FFQ from 808 pregnant women and summarised to a nutrition index, 'My Nutrition Index' (MNI). The association with children's height and body fat (bioimpedance) was assessed with linear regression models. Secondary analysis was performed with BMI, trunk fat and skinfolds. Overall, higher MNI score was associated with greater height (ß = 0·47; (95 % CI 0·00, 0·94), among both sexes. Among boys, higher MNI was associated with 0·15 higher BMI z-scores, 0·12 body fat z-scores, 0·11 trunk fat z-scores, and larger triceps, and triceps + subscapular skinfolds (ß = 0·05 and ß = 0·06; on the log2 scale) (P-value < 0·05). Among girls, the opposite associations were found with 0·12 lower trunk fat z-scores, and smaller subscapular and suprailiac skinfolds (ß = -0·07 and ß = -0·10; on the log2 scale) (P-value < 0·05). For skinfold measures, this would represent a ± 1·0 millimetres difference. Unexpectedly, a prenatal diet in line with recommended nutrient intake was associated with higher measures of body fat for boys and opposite to girls at a pre-pubertal stage of development.

Study protocol for a randomized controlled trial with rituximab for psychotic disorder in adults (RCT-Rits).

BACKGROUND: The role of inflammation in the aetiology of schizophrenia has gained wide attention and research on the association shows an exponential growth in the last 15 years. Autoimmune diseases and severe infections are risk factors for the later development of schizophrenia, elevated inflammatory markers in childhood or adolescence are associated with a greater risk of schizophrenia in adulthood, individuals with schizophrenia have increased levels of pro-inflammatory cytokines compared to healthy controls, and autoimmune diseases are overrepresented in schizophrenia. However, treatments with anti-inflammatory agents are so far of doubtful clinical relevance. The primary objective of this study is to test whether the monoclonal antibody rituximab, directed against the B-cell antigen CD20 ameliorates psychotic symptoms in adults with schizophrenia or schizoaffective disorder and to examine potential mechanisms. A secondary objective is to examine characteristics of inflammation-associated psychosis and to identify pre-treatment biochemical characteristics of rituximab responders. A third objective is to interview a subset of patients and informants on their experiences of the trial to obtain insights that rating scales may not capture. METHODS: A proof-of-concept study employing a randomised, parallel-group, double-blind, placebo-controlled design testing the effect of B-cell depletion in patients with psychosis. 120 participants with a diagnosis of schizophrenia spectrum disorders (SSD) (ICD-10 codes F20, F25) will receive either one intravenous infusion of rituximab (1000 mg) or saline. Psychiatric measures and blood samples will be collected at baseline, week 12, and week 24 post-infusion. Brief assessments will also be made in weeks 2 and 7. Neuroimaging and lumbar puncture, both optional, will be performed at baseline and endpoints. Approximately 40 of the patients and their informants will be interviewed for qualitative analyses on the perceived changes in well-being and emotional qualities, in addition to their views on the research. DISCUSSION: This is the first RCT investigating add-on treatment with rituximab in unselected SSD patients. If the treatment is helpful, it may transform the treatment of patients with psychotic disorders. It may also heighten the awareness of immune-psychiatric disorders and reduce stigma. TRIAL REGISTRATION: NCT05622201, EudraCT-nr 2022-000220-37 version 2.1. registered 14th of October 2022.

Anthropometric measures do not explain the 2D:4D ratio sexual dimorphism in 7-year-old children.

OBJECTIVES: Digit ratio (2D:4D) might reflect prenatal testosterone exposure and has been used as a putative marker for androgen related outcomes. However, such associations might be inflicted by confounders. Application of 2D:4D in epidemiological research motivate identification of biological background determinants. We examined sex, anthropometric measures, and maternal factors as determinants of 2D:4D in Swedish 7-year-old children. METHODS: The study was embedded in the Swedish Environmental, Longitudinal, Mother and Child, Asthma and Allergy (SELMA) pregnancy cohort. A total of 870 pre-pubertal children, median 7.5 years of age, were studied. A single assessor performed digit measurements from scanned photocopies using computer software. Child anthropometric measurements investigated were hand size, birthweight, recumbent birth length, standing height, weight, BMI, body fat percentage, and waist/hip circumference. Maternal factors included age, pregnancy length, parity, and education. RESULTS: We found a significant sexual dimorphism regarding digit lengths and 2D:4D, boys on average presenting a lower 2D:4D than girls also after adjustment for summed finger lengths and body fatness. In crude analyses, maternal age correlated with 2D:4D across the whole population and in females but not in adjusted models. No other study variables were associated with 2D:4D. CONCLUSION: Digit ratio showed sexual dimorphism at the age of seven and seems to represent a true sex difference rather than an artifact and bias from hand size, body size or body fat content. Among the rest of our investigated variables, we found no determinants constituting important confounders in future research on 2D:4D ratio.

Maternal serum levels of perfluoroalkyl substances in early pregnancy and offspring birth weight.

BACKGROUND: Perfluoroalkyl substances (PFASs) are widespread, bioaccumulating, and persistent and show placental transfer. Emerging research indicates associations between prenatal exposure and low birth weight. The aim of this study was to assess the associations between first trimester exposure to PFASs and birth weight (BW) in the Swedish Environmental, Longitudinal, Mother and child, Asthma and allergy (SELMA) study and examine whether associations differ between girls and boys. METHODS: Eight PFASs were analyzed in maternal serum (median: 10 weeks of pregnancy). Associations between prenatal PFAS exposure and birth outcomes with BW, BW for gestational age, and birth small for gestational age (SGA) were assessed in 1533 infants, adjusted for potential confounders and stratified by sex. RESULTS: Increased maternal perfluorooctane sulfonate (PFOS), perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDA), and perfluoroundecanoic acid (PFUnDA) were associated with lower BW, lower BW for gestational age, and SGA birth. Associations were significant only in girls, where prenatal exposure in the upper quartile was associated with a 93-142-g lower BW when compared with that of the lowest quartile exposure. The associations were not mediated by effects on gestational age. CONCLUSIONS: We found associations between prenatal exposure for five different PFASs and birth weight, with more pronounced associations in girls than in boys.

Prenatal phthalate exposure was associated with croup in Swedish infants.

AIM: This study examined whether prenatal phthalate exposure was associated with lower or upper airway inflammation in infants. METHODS: From 2007 to 2010, we used liquid chromatography-tandem mass spectrometry, adjusted for creatinine, to analyse 14 phthalate metabolites and one phthalate replacement in the urine of 1062 Swedish mothers at a median of 10 weeks of pregnancy. This was used to determine any associations between prenatal phthalate exposure and croup, wheezing or otitis in their offspring until 12 months of age, using logistic regression, adjusted for potential confounders. RESULTS: There were significant associations between phthalate metabolites of butyl-benzyl phthalate (BBzP) and di-ethyl-hexyl phthalate (DEHP) concentrations in maternal prenatal urine and croup in 1062 infants during the first year of life, when adjusted for potential confounders. A dose-response relationship was found between prenatal phthalates exposure and maternal reported croup in the children, with a significant association in boys. There was no clear indication with regard to associations between prenatal phthalate exposure and wheezing or otitis media in the children during the first year of life. CONCLUSION: Our analysis suggests that exposure to BBzP and DEHP phthalates was associated with maternal reports of croup in infants up to 12 months of age.

Cortical burst dynamics predict clinical outcome early in extremely preterm infants.

Intermittent bursts of electrical activity are a ubiquitous signature of very early brain activity. Previous studies have largely focused on assessing the amplitudes of these transient cortical bursts or the intervals between them. Recent advances in basic neuroscience have identified the presence of scale-free 'avalanche' processes in bursting patterns of cortical activity in other clinical contexts. Here, we hypothesize that cortical bursts in human preterm infants also exhibit scale-free properties, providing new insights into the nature, temporal evolution, and prognostic value of spontaneous brain activity in the days immediately following preterm birth. We examined electroencephalographic recordings from 43 extremely preterm infants (gestational age 22-28 weeks) and demonstrated that their cortical bursts exhibit scale-free properties as early as 12 h after birth. The scaling relationships of cortical bursts correlate significantly with later mental development-particularly within the first 12 h of life. These findings show that early preterm brain activity is characterized by scale-free dynamics which carry developmental significance, hence offering novel means for rapid and early clinical prediction of neurodevelopmental outcomes.

Early Detection of Preterm Intraventricular Hemorrhage From Clinical Electroencephalography.

OBJECTIVES: Intraventricular hemorrhage is a common neurologic complication of extremely preterm birth and leads to lifelong neurodevelopmental disabilities. Early bedside detection of intraventricular hemorrhage is crucial to enabling timely interventions. We sought to detect early markers of brain activity that preempt the occurrence of intraventricular hemorrhage in extremely preterm infants during the first postnatal days. DESIGN: Cross-sectional study. SETTING: Level III neonatal ICU. PATIENTS: Twenty-five extremely preterm infants (22-28 wk gestational age). MEASUREMENTS AND MAIN RESULTS: We quantitatively assessed electroencephalography in the first 72 hours of postnatal life, focusing on the electrical burst activity of the preterm. Cranial ultrasound was performed on day 1 (0-24 hr) and day 3 (48-72 hr). Outcomes were categorized into three classes: 1) no intraventricular hemorrhage (grade 0); 2) mild-moderate intraventricular hemorrhage (grades 1-2, i.e., germinal matrix hemorrhages or intraventricular hemorrhage without ventricular dilatation, respectively); and 3) severe intraventricular hemorrhage (grades 3-4, i.e., intraventricular hemorrhage with ventricular dilatation or intraparenchymal involvement). Quantitative assessment of electroencephalography burst shapes was used to preempt the occurrence and severity of intraventricular hemorrhage as detected by ultrasound. The shapes of electroencephalography bursts found in the intraventricular hemorrhage infants were significantly sharper (F = 13.78; p < 0.0001) and less symmetric (F = 6.91; p < 0.015) than in preterm infants without intraventricular hemorrhage. Diagnostic discrimination of intraventricular hemorrhage infants using measures of burst symmetry and sharpness yielded high true-positive rates (82% and 88%, respectively) and low false-positive rates (19% and 8%). Conventional electroencephalography measures of interburst intervals and burst counts were not significantly associated with intraventricular hemorrhage. CONCLUSIONS: Detection of intraventricular hemorrhage during the first postnatal days is possible from bedside measures of brain activity prior to ultrasound confirmation of intraventricular hemorrhage. Significantly, our novel automated assessment of electroencephalography preempts the occurrence of intraventricular hemorrhage in the extremely preterm. Early bedside detection of intraventricular hemorrhage holds promise for advancing individual care, targeted therapeutic trials, and understanding mechanisms of brain injury in neonates.

Associations between Motor Competence, Physical Activity and Sedentary Behaviour among Early School-Aged Children in the SELMA Cohort Study.

Low motor competence (MC) has been associated with lower physical activity (PA) and long-term health risks in children. Less is known about sex-specific patterns and associations during early school age. The aim of this study was to explore how motor difficulties are associated with PA levels, screen time, and organised sports participation (OSP). Data from 479 children, seven years of age, participating in the Swedish Environmental, Longitudinal, Mother and child, Asthma, and allergy (SELMA) pregnancy cohort study were used. MC and activity-related outcomes were assessed with questionnaires answered by parents. Associations between MC and outcomes were evaluated using logistic regression models adjusted for sex, overweight, and parental education level. Sex differences were investigated with interaction analyses and in stratified models. Children with motor difficulties had the same level of PA as their peers, but more screen time and lower OSP. Compared with children with normal MC, boys with motor difficulties had lower rates of OSP, but girls did not. This indicates that the identification and compensatory support for motor difficulties for boys at an early age, as well as the development of inclusive leisure time activities, are of importance to facilitate health-promoting activities on equal terms.

Neonatal therapeutic hypothermia in a regional swedish cohort: Adherence to guidelines, transport and outcomes.

AIM: Swedish guidelines for therapeutic hypothermia (TH) after perinatal asphyxia were established in 2007, following several randomised studies that demonstrated improved outcomes. We assessed the implementation of hypothermia treatment in a mid-Swedish region with a sizeable proportion of outborn infants. METHOD: A population-based TH cohort from 2007 to 2015 was scrutinised for adherence to national guidelines, interhospital transport, including the use of a cooling mattress made of phase change material for thermal management, and outcomes. RESULTS: Of 136 admitted infants, 99 (73 %) were born outside the hospital. Ninety-eight percent fulfilled the criteria for postnatal depression/acidosis, and all patients had moderate-to-severe encephalopathy. Treatment was initiated within 6 h in 85 % of patients; amplitude-integrated electroencephalography/electroencephalography was recorded in 98 %, cranial ultrasound in 78 %, brain magnetic resonance imaging in 79 %, hearing tests in all, and follow-up was performed in 93 %. Although target body temperature was attained later (p < 0.01) in outborn than in inborn infants, at a mean (standard deviations) age of 6.2 (3.2) h vs 4.4 (2.6) h, 40 % of those transported using the cooling mattress were already within the therapeutic temperature range on arrival, and few were excessively cooled. The mortality rate was 23 %, and 38 % of the survivors had neurodevelopmental impairment at a median of 2.5 years. CONCLUSION: The regionalisation of TH, including interhospital transport, was feasible and resulted in outcomes comparable to those of randomised controlled studies.

Premedication for intubation with morphine causes prolonged depression of electrocortical background activity in preterm infants.

BACKGROUND: Sedative and analgesic medications are used in critically ill newborns, but little is known about their effects on electrocortical activity in preterm infants. We hypothesized that morphine might induce prolonged neurodepression, independent of blood pressure, as compared with rapid sequence induction/intubation(RSI). METHODS: Of 34 infants enrolled in a randomized controlled trial (RCT) comparing RSI (including thiopental 2-3 mg/kg and remifentantil 1 mcg/kg) with morphine (0.3 mg/kg) as premedication for intubation, 28 infants (n = 14 + 14; median gestational age 26.1 wk and postnatal age 138 h) had continuous two-channel amplitude-integrated electroencephalogram (aEEG/EEG) and blood pressure monitoring during 24 h after the intubation. Thirteen infants not receiving any additional medication constituted the primary study group. Visual and quantitative analyses of aEEG/EEG and blood pressure were performed in 3-h epochs. RESULTS: RSI was associated with aEEG/EEG depression lasting <3 h. Morphine premedication resulted in aEEG/EEG depression with more discontinuous background and less developed cyclicity for 24 h, and during the first 9 h, interburst intervals (IBI) were significantly increased as compared with those of RSI treatment. The difference was not related to blood pressure. CONCLUSION: Premedication with morphine is associated with prolonged aEEG/EEG depression independent of blood pressure changes and may not be optimal for short procedures.

Prenatal exposures to mixtures of endocrine disrupting chemicals and sex-specific associations with children's BMI and overweight at 5.5 years of age in the SELMA study.

BACKGROUND: Prenatal exposure to mixtures of endocrine disrupting chemicals (EDC) has the potential to disrupt human metabolism. Prenatal periods are especially sensitive as many developmental processes are regulated by hormones. Prenatal exposure to EDCs has inconsistently been associated with children's body mass index (BMI) and obesity. The objective of this study was to investigate if prenatal exposure to a mixture of EDCs was associated with children's BMI and overweight (ISO-BMI ≥ 25) at 5.5 years of age, and if there were sex-specific effects. METHODS: A total of 1,105 mother-child pairs with complete data on prenatal EDCs concentrations (e.g., phthalates, non-phthalate plasticizers, phenols, PAH, pesticides, PFAS, organochlorine pesticides, and PCBs), children's measured height and weight, and selected covariates in the Swedish Environmental Longitudinal, Mother and child, Asthma and allergy (SELMA) study were included in this analysis. The mixture effect of EDCs with children's BMI and overweight was assessed using WQS regression with 100 repeated holdouts. A positively associated WQS index with higher BMI and odds of overweight was derived. Models with interaction term and stratified weights by sex was applied in order to evaluate sex-specific associations. RESULTS: A significant WQS*sex interaction term was identified and associations for boys and girls were in opposite directions. Higher prenatal exposure to a mixture of EDCs was associated with lower BMI (Mean ß = -0.19, 95%CI: -0.40, 0.01) and lower odds of overweight (Mean OR = 0.72, 95%CI: 0.48, 1.04) among girls with borderline significance. However, the association among boys did not reach statistical significance. Among girls, the possible chemicals of concern were MEP, 2-OHPH, BPF, BPS, DPP and PFNA. CONCLUSION: Prenatal exposure to a mixture of EDCs was associated with lower BMI and overweight among girls, and non-significant associations among boys. Chemicals of concern for girls included phthalates, non-phthalate plasticizers, bisphenols, PAHs, and PFAS.

Early single-channel aEEG/EEG predicts outcome in very preterm infants.

AIM: To characterize early amplitude-integrated electroencephalogram (aEEG) and single-channel EEG (aEEG/EEG) in very preterm (VPT) infants for prediction of long-term outcome. PATIENTS: Forty-nine infants with median (range) gestational age of 25 (22-30) weeks. METHODS: Amplitude-integrated electroencephalogram/EEG recorded during the first 72 h and analysed over 0-12, 12-24, 24-48 and 48-72 h, for background pattern, sleep-wake cycling, seizures, interburst intervals (IBI) and interburst percentage (IB%). In total, 2614 h of single-channel EEG examined for seizures. Survivors were assessed at 2 years corrected age with a neurological examination and Bayley Scales of Infant Development-II. Poor outcome was defined as death or survival with neurodevelopmental impairment. Good outcome was defined as survival without impairment. RESULTS: Thirty infants had good outcome. Poor outcome (n = 19) was associated with depressed aEEG/EEG already during the first 12 h (p = 0.023), and with prolonged IBI and higher IB% at 24 h. Seizures were present in 43% of the infants and associated with intraventricular haemorrhages but not with outcome. Best predictors of poor outcome were burst-suppression pattern [76% correctly predicted; positive predictive value (PPV) 63%, negative predictive value (NPV) 91%], IBI > 6 sec (74% correctly predicted; PPV 67%, NPV 79%) and IB% > 55% at 24 h age (79% correctly predicted; PPV 72%, NPV 80%). In 35 infants with normal cerebral ultrasound during the first 3 days, outcome was correctly predicted in 82% by IB% (PPV 82%, NPV 83%). CONCLUSION: Long-term outcome can be predicted by aEEG/EEG with 75-80% accuracy already at 24 postnatal hours in VPT infants, also in infants with no early indication of brain injury.

Carpal Tunnel Syndrome and Hand-Arm Vibration: A Swedish National Registry Case-Control Study.

OBJECTIVE: To investigate the increased risk for carpal tunnel syndrome (CTS) in men and women with hand-arm vibration (HAV) exposure. DESIGN: Case-control study of CTS where 4396 cases was obtained from National Outpatient Register between 2005 through 2016. Cases were matched to controls and exposure was estimated using a job exposure matrix. RESULTS: Exposure to HAV increased the risk of CTS with an OR of 1.61 (95% CI 1.46-1.77). The risk was highest in men <30 years of age and among women <30 years no increased risk was observed. The risk increased with a mean year exposure above 2.5 m/s2 to OR 1.84 (95% CI 1.38-2.46). CONCLUSIONS: HAV exposure increase the risk of CTS in both genders, with highest risk increase in younger men. This emphasize identification of HAV exposure in patients with CTS.

Rapid sequence induction is superior to morphine for intubation of preterm infants: a randomized controlled trial.

OBJECTIVES: To compare rapid sequence intubation (RSI) premedication with morphine for intubation of preterm infants. STUDY DESIGN: Preterm infants needing semi-urgent intubation were enrolled to either RSI (glycopyrrolate, thiopental, suxamethonium, and remifentanil, n = 17) or atropine and morphine (n = 17) in a randomized trial. The main outcome was "good intubation conditions" (score ≤10 assessed with intubation scoring), and secondary outcomes were procedural duration, physiological and biochemical variables, amplitude-integrated electroencephalogram, and pain scores. RESULTS: Infants receiving RSI had superior intubation conditions (16/17 versus 1/17, P < .001), the median (IQR) intubation score was 5 (5-6) compared with 12 (10.0-13.5, P < .001), and a shorter procedure duration of 45 seconds (35-154) compared with 97 seconds (49-365, P = .031). The morphine group had prolonged heart rate decrease (area under the curve, P < .009) and mean arterial blood pressure increase (area under the curve, P < .005 and %change: mean ± SD 21% ± 23% versus -2% ± 22%, P < .007) during the intubation, and a subsequent lower mean arterial blood pressure 3 hours after the intubation compared with baseline (P = .033), concomitant with neurophysiologic depression (P < .001) for 6 hours after. Plasma cortisol and stress/pain scores were similar. CONCLUSION: RSI with the drugs used can be implemented as medication for semi-urgent intubation in preterm infants. Because of circulatory changes and neurophysiological depression found during and after the intubation in infants given morphine, premedication with morphine should be avoided.

Arterial abnormalities in the hands of workers with vibration white fingers - a magnetic resonance angiography case series.

Vibration white finger (VWF) is a complication from exposure to hand-arm vibrations. Poor knowledge of the pathophysiology of VWF means that making an accurate prognosis is difficult. Thus, a better understanding of VWF's pathophysiology is of importance.The purpose of this study was to investigate whether there were arterial abnormalities in the hands in patients with VWF and a positive Allen's test, using ultrasound and MRA imaging.This was a case series where arterial abnormalities in the hands were investigated in ten participants with VWF and using prolonged Allen's test (> 5 s). The participants had an average vibration exposure of 22 years and underwent Doppler ultrasound and Magnetic Resonance Angiography (MRA) to check for arterial abnormalities.The participants had VWF classified as 1-3 on the Stockholm workshop scale. Ultrasound and MRA identified vascular abnormalities in all participants, the predominant finding was missing or incomplete superficial arch. Also, stenosis was identified in four participants.This study reveals a high proportion of arterial stenosis and abnormalities in patients with VWF and a prolonged Allen's test.

Phthalate levels in indoor dust and associations to croup in the SELMA study.

Phthalates are ubiquitous indoor pollutants which have been associated with child airway disease although results are inconclusive. This study examined associations between phthalate levels in residential indoor dust and croup during infancy. Settled indoor dust was collected in 482 homes of 6-month-old infants in the Swedish Environmental Longitudinal, Mother and child, Asthma and allergy (SELMA) study and analysed for seven phthalates and one phthalate replacement using gas chromatography tandem mass spectrometry. The incidence of parental reported croup at 12 months was 6.4% for girls and 13.4% for boys. Associations between phthalate dust levels and croup were analysed by logistic regression adjusted for potential confounders. We found significant associations between di-ethyl phthalate (DEP) and di-ethyl-hexyl phthalate (DEHP) in residential dust and parental reported croup (adjusted odds ratio (aOR) = 1.71; 95% CI: 1.08-2.73 and 2.07; 1.00-4.30, respectively). Stratified results for boys showed significant associations between DEP and butyl-benzyl phthalate (BBzP) in dust and infant croup (aOR = 1.86; 95% CI: 1.04-3.34 and 2.02; 1.04-3.90, respectively). Results for girls had questionable statistical power due to few cases. Our results suggest that exposure to phthalates in dust is a risk factor for airway inflammatory responses in infant children.

Prenatal exposures to mixtures of endocrine disrupting chemicals and children's weight trajectory up to age 5.5 in the SELMA study.

Exposure to endocrine disrupting chemicals (EDCs) may impact early growth, although information is limited on exposure to combination of multiple EDCs. We aimed to evaluate the effect of prenatal exposure to EDC mixtures on birthweight z-scores and childhood weight trajectories. Twenty-six proven and suspected EDCs, were analyzed in prenatal urine and blood samples from 1118 mothers participating in the Swedish Environmental Longitudinal Mother and child Asthma and allergy (SELMA) study. Two growth parameters were estimated from each child's weight trajectory from birth to 5.5 years of age: infant growth spurt rate and age at infant peak growth velocity (PGV). Weighted quantile sum (WQS) regression was used to estimate the mixture effect and identify chemicals of concern. A one-unit increase in the EDC mixture WQS index, was associated with decreased birthweight z-scores of 0.11 (95% CI - 0.16, - 0.06), slower infant growth spurt rate of 0.01 (95% CI - 0.03, - 0.01, on the log10 scale), and delayed age at infant PGV of 0.15 months (95% CI 0.07, 0.24) after adjusting for potential confounders. Stratified analysis by sex, showed that delayed age at infant PGV was mostly observed in girls with 0.51 months (95% CI 0.26, 0.76). Identified chemicals of concern included perfluorinated alkyl substances (PFAS), Triclosan, phthalates, non-phthalate plasticizers, bisphenols, polycyclic aromatic hydrocarbons, pesticides and PCBs. Prenatal exposure to EDC mixtures was associated with lower birthweight and altered infant weight gain trajectories.

Exposure to perfluoroalkyl substances in early pregnancy and risk of sporadic first trimester miscarriage.

Many first trimester sporadic miscarriages are unexplained and the role of environmental exposures is unknown. The present aim was to study if levels of Perfluoroalkyl substances (PFASs) in early pregnancy are associated with unexplained, sporadic first trimester miscarriage. The study was performed within the Swedish SELMA pregnancy cohort. Seventy-eight women with non-recurrent first trimester miscarriage were included and 1449 women were available as live birth controls. Eight PFASs were measured in first trimester serum. A doubling of perfluorooctanoic acid (PFOA) exposure, corresponding to an inter-quartile increase, was associated with an odds ratio (95%CI) for miscarriage of 1.48 (1.09-2.01) when adjusting for parity, age and smoking. Analyses per quartiles of PFOA exposure indicated a monotonic dose response association with miscarriage. A similar, but not significant, pattern was observed for perfluorononanoic acid (PFNA). For other PFAS, there were no associations with miscarriage. We have previously shown associations between early pregnancy PFAS exposures and preeclampsia, as well as lower birth weight. Now we report an association between PFOA and miscarriage within the same cohort, which may suggest shared but unknown mechanisms. The study can only represent a period of early placentation and clinical pregnancy loss during the second half of the first trimester.