Exposure to perfluoroalkyl substances during fetal life and hospitalization for infectious disease in childhood: A study among 1,503 children from the Odense Child Cohort.

INTRODUCTION: The immunosuppressive properties of PFASs are widely recognized. Early-life exposure to PFAS has been linked to reduced immune response to childhood vaccinations and increased rates of common infectious diseases, but implications for hospitalizations are unclear. OBJECTIVES: To investigate the association between maternal serum concentrations of five PFASs during pregnancy and the child's rate of hospitalization due to common infectious diseases between birth and 4 years of age. METHODS: Serum samples from first trimester pregnant women from the Odense Child Cohort (OCC) collected in 2010-2012 were analyzed for concentrations of perfluorooctanesulfonic acid (PFOS), perfluorooctanoic acid (PFOA) and three other PFASs. Data on child hospitalizations with an ICD-10 code for infectious disease was obtained from the Danish National Patient Register. The following were identified: upper respiratory tract infections (URTI), lower respiratory tract infections (LRTI), gastrointestinal infections (GI), and other infections. The Andersen-Gill Cox proportional hazard model for recurrent events was used to investigate the association between PFAS exposure and hospitalizations. The resulting estimates were hazard ratios (HRs), which express the relative change in the instantaneous risk of hospitalization with a doubling in maternal PFAS concentration. RESULTS: A total of 1,503 mother-child pairs were included, and 26% of the children were hospitalized at least once for infectious disease. A doubling in maternal PFOS concentration was associated with a 23% increase in the risk of hospitalization due to any infection (HR: 1.23 (95% CI: 1.05, 1.44). There was indication of an interaction between child sex and PFOS (p = 0.07) and PFDA (p = 0.06), although in opposite directions. Further, every doubling of PFOA or PFOS increased the risk of LRTI by 27% (HR: 1.27 (1.01, 1.59)) and 54% (HR: 1.54 (1.11, 2.15)), respectively. Similar tendencies were seen for URTI and the group of other infections. For GIs, the opposite pattern of association was seen as HR's were consistently below 1 (PFOA, HR: 0.55 (0.32, 0.95)). DISCUSSION: We found an association between PFOS and the overall risk of infectious disease, and between PFOS and PFOA exposures and the risk of LRTI's. These results are in agreement with previous findings from the OCC, in which maternal PFOS and PFOA concentrations were positively associated with the number of days that the children experienced fever, thereby suggesting that PFOS and PFOA may affect the prevalence of both mild and more severe infectious diseases even in a rather low-exposed population.

Breastfeeding and Infections in Early Childhood: A Cohort Study.

BACKGROUND: Studies on the association between breastfeeding and infections in children beyond the first year of life reveal conflicting results. In a population-based birth cohort, we investigated whether the duration of breastfeeding was associated with the number of hospitalizations due to infection and symptoms of infection at home. METHODS: In the Odense Child Cohort, text message questionnaires were used to register information on breastfeeding (weekly until end of weaning) and symptoms of infection (biweekly; 12-36 months of age). Hospitalization data were obtained from the Danish National Patient Registry. RESULTS: Of the 1087 invited, 815 mother-infant pairs were included. The median duration of any breastfeeding was 7.6 (interquartile range: 3.5-10.4) months and of exclusive breastfeeding was 2.1 (interquartile range: 0.7-4.4) months. Hospitalization due to infection was seen in 207 (25.4%) infants during the first 3 years of life. The adjusted incidence rate ratio (IRR) for hospitalization due to any infection decreased with a longer duration of any breastfeeding (adjusted IRR: 0.96; 95% confidence interval 0.93-0.99; P < .001). The strongest associations between the duration of any breastfeeding and hospitalizations due to infection were found within the first year of life, for lower respiratory tract infections, and other infections (P ≤ .05). For infants exclusively breastfed, the adjusted IRR for hospitalization was 0.88 (95% confidence interval: 0.80-0.96; P = .006). No protective associations were present between breastfeeding and infection symptoms registered at home from ages 12 to 36 months. CONCLUSIONS: The results suggest that increased duration of breastfeeding, especially exclusive breastfeeding, protects against infections requiring hospitalization in the first year of life but not hospitalizations or symptoms of infection at home beyond the first year.

Birth Season and Infection Risk Among Children Under 5 Years Old: A Study of Hospital Admissions and Short Message Service-reported Symptoms at Home.

BACKGROUND: The season in which a child is born may affect the immune system development and thereby influence the risk of infections. In this study, we examined the associations between birth season and the risk of hospital admission or symptoms associated with a wide range of infections. METHODS: This study is a prospective cohort study of 2434 children with an average follow-up of 3.5 years. Admission data were obtained from the Danish National Patient Registry. Via short message service (SMS) questionnaires, 1279 families reported symptoms of infections in a 1-year period. RESULTS: Of the 2434 children, 639 (26.3%) were admitted to the hospital, and the children experienced on average 64.4 days with symptoms of infection within 1 year. There was no association between birth season and hospital admissions due to all infectious causes [incidence rate ratio (IRR) = 0.89; 95% confidence interval (CI), 0.65-1.22; P = 0.471]. However, children born in the fall had a higher IRR for admission due to all infectious causes when excluding admissions within the first year of life. Winter- and spring-born children had lower IRRs for admission due to gastrointestinal infections than summer-born children, but this association was alone present when admissions within the first year of life were included. The short message service-survey showed significantly lower IRRs for any symptom of infection among winter-born (IRR = 0.85; 95% CI, 0.75-0.96; P = 0.009) and fall-born children (IRR = 0.88; 95% CI, 0.78-0.99; P = 0.033) in comparison with summer-born children. CONCLUSIONS: Birth season was not associated with hospital admission due to all infectious causes within the first 5 years of age; however, fall-birth was associated with a higher IRR for admissions due to all infectious causes after the first year of life. The association between birth season and admissions due to gastrointestinal infections was only seen when including children admitted under the age of one. Being born in fall or winter was associated with a decreased IRR for number of days with any symptom of infection registered at home.

Association Between Mode of Delivery and Risk of Infection in Early Childhood: A Cohort Study.

BACKGROUND: Infections are the leading cause of morbidity and mortality in children. Caesarean section as a potential risk factor for infection has recently gained interest. Delivery by caesarean section has increased greatly, with nonmedical reasons playing an increasing role. We aimed to analyze the association between mode of delivery and hospitalizations because of infection and symptoms of infection at home in early childhood. METHODS: A cohort study, based on the Odense Child Cohort, following infants from gestation until a mean age of 3.5 years. Data on hospitalization because of infections were collected from the Danish National Patient Registry. Data on symptoms of infection at home were collected via a text message-based questionnaire. RESULTS: A total of 1921 children were born by vaginal delivery, 283 by elective caesarean section and 227 by acute caesarean section. An adjusted regression model showed an incidence rate ratio for hospitalizations because of infection in children born by elective caesarean section compared with children born by vaginal delivery of 1.45 (95% confidence interval: 1.16-1.80; P = 0.001). The analyses on symptoms of infection at home found no associations between any symptom of infection and mode of delivery. Symptom-specific subanalyses showed contrasting results. CONCLUSIONS: Mode of delivery showed a strong association to hospitalization because of infectious disease during early childhood. Overall, no association was present between rate of symptoms of infection at home and mode of delivery.

Cord serum 25-hydroxyvitamin D is not associated with cranial anthropometrics in infants up to 6 months of age. An Odense Child Cohort study.

Skull changes are poorly described in vitamin D insufficiency [serum 25-hydroxyvitamin D (s-25(OH)D) 25-50 nmol/L]. We aimed to investigate factors associated with cranial anthropometrics in infants, especially s-25(OH)D. In infants 2.5-6 months old from the Odense Child Cohort, associations between cord and pregnancy s-25(OH)D and anterior fontanel area (n = 765), head circumference (HC, n = 1776) and head shape (n = 1527) were investigated along with other factors. Age was corrected for preterm birth. The mean (SD) s-25(OH)D in early pregnancy was 65.97 (21.33) nmol/L; late pregnancy 78.61 (27.18) nmol/L; and cord 47.1 (21.7) nmol/L. At median (IQR) age 3.7 (2.5-5.9) months, the fontanel area was 225 (0-1690) mm2, and mean (SD) HC was 41.5 (1.5) cm. Asymmetric/flat head shape was present in 846 infants (55.3%). No associations were found between cord, early or late pregnancy s-25(OH)D and any cranial measure by univariate or adjusted analysis. Among significant, independent associations in multivariate analysis, fontanel area was associated inversely with gestational age (GA); HC was associated directly with GA, maternal pre-pregnancy overweight and caesarean section and inversely with smoking; and asymmetrical head shape showed a novel association with male sex: adjusted OR = 1.54 (95% CI 1.25; 1.89), p < 0.001. Other associations with asymmetrical head shape included parity 3+, gestational age and maternal age 30+ years (all protective). In conclusion, neither pregnancy nor cord s-25(OH)D was associated with fontanel size, HC or asymmetrical head shape despite a high prevalence of cord s-25(OH)D < 50 nmol/L. Lower GA was associated with larger fontanel size, lower HC and asymmetrical head shape, and boys more frequently had asymmetrical head shape, probably due to heavier heads.

Infant Respiratory Tract Infections or Wheeze and Maternal Vitamin D in Pregnancy: A Systematic Review.

BACKGROUNDS: Respiratory tract infections (RTIs) are a common cause of morbidity and mortality in young children and can be associated with wheeze. Vitamin D can have a protective role against RTI. MATERIALS AND METHODS: A systematic search of PubMed, Embase and the Cochrane library was performed. Titles and abstracts were evaluated, and selected articles were reviewed by 2 authors. We included randomized controlled trials (RCTs) investigating the effect of vitamin D supplementation during pregnancy on RTIs or wheeze in children of 5 years of age or younger. Observational studies on the association between serum 25-hydroxyvitamin D during pregnancy, or at birth, and RTIs and/or wheeze were included. The protocol was registered on PROSPERO (Registration number: CRD42015019183). RESULTS: Of 4 RCTs, 1 showed a protective effect of a high daily dose (2000 IU) of vitamin D during pregnancy on offspring RTI doctor visits (P = 0.004; the RCT also included 800 IU/d supplement to the infants until 6 months). Meta-analysis of 3 RCTs showed a reduced relative risk for offspring wheeze when mothers were supplemented with vitamin D during pregnancy [relative risk: 0.81 (95% confidence interval: 0.68-0.97), P = 0.025]. In 3 of 4 strong-quality, and 5 of 10 moderate-quality observational studies, an inverse association between pregnancy and cord 25-hydroxyvitamin D and subsequent wheeze and/or RTI was seen. CONCLUSION: Growing evidence supports a preventive role of vitamin D during pregnancy on offspring wheeze and/or RTI. Recommendations in future intervention studies may need to exceed current recommendations of vitamin D supplementation during pregnancy to show benefit against childhood wheeze or infections.

Association between prenatal exposure to perfluorinated compounds and symptoms of infections at age 1-4years among 359 children in the Odense Child Cohort.

INTRODUCTION: Perfluorinated alkylated substances (PFAS) are persistent industrial chemicals that have resulted in global environmental exposures. Previous epidemiological studies have reported possible effects on the immune system after developmental PFAS exposure, but the possible impact on childhood infectious disease is unclear. OBJECTIVES: To investigate the association between prenatal exposure to PFAS and symptoms of infections at age 1-4years. METHODS: The Odense Child Cohort is an on-going prospective study on children's health, where serum concentrations of perfluorooctane sulfonic acid (PFOS), perfluorooctanoic acid (PFOA), perfluorohexane sulfonic acid (PFHxS), perfluorodecanoic acid (PFDA) and perfluorononanoic acid (PFNA) were measured in 649 pregnant women before gestational week 16. Of these women, 359 reported on symptoms of infection in their child every two weeks for a one-year period. The association between prenatal exposure to PFAS and the symptoms was estimated using a logistic regression model and a negative binomial regression model. For the latter, the outcome was reported as an incidence rate-ratio (IRR), and all models were adjusted for maternal age, educational level, parity and child age. RESULTS: On average, the children experienced symptoms of infection 23% of the time during one year. PFOS exposure in the high tertile compared to the low tertile was associated with a statistically significant increased proportion of days with fever (IRR: 1.65 (95% CI: 1.24, 2.18), P-trend<0.001) and an increased odds of experiencing days with fever above the median (OR: 2.35 (95% CI: 1.31, 4.11). The latter tendency was also apparent for PFOA (OR: 1.97 (95% CI: 1.07, 3.62). Further, higher concentrations of PFOS and PFOA tended to increase the number of episodes of co-occurrence of fever and coughing and fever and nasal discharge during the one-year study period. CONCLUSION: We found a positive association between prenatal exposure to PFOS and PFOA and the prevalence of fever, which may be a sensitive marker of infection. This finding is in agreement with an immunotoxic effect of prenatal exposure to PFAS. The wider implications for childhood infectious disease deserve attention.

Outbreak of Pseudomonas aeruginosa bacteraemia in a haematology department.

INTRODUCTION: Infection by Pseudomonas aeruginosa represents a major cause of morbidity and mortality among immunocompromised patients. In Denmark, an increase in P. aeruginosa isolates from blood cultures from a haematology department prompted a hygienic audit in 2007. METHODS: Blood cultures that tested positive for P. aeruginosa were collected from the laboratory information system (MADS, Skejby Hospital, Aarhus, Denmark). Environmental samples were obtained from shower heads in the department. The genotype was established by pulse field gel electrophoresis (PFGE). An audit was conducted during the outbreak and 12 months later. The audits were conducted by the method of direct observation. RESULTS: Several PFGE types were involved with no clear association to isolates from environmental samples. The audit revealed poor hygiene related to the handling of central venous catheters. After optimising catheter hygiene, the number of P. aeruginosa bacteraemia cases fell significantly. CONCLUSION: Since no clear association between patient and environmental genotype was established, it was suspected that central venous catheters were the main portal of entry. This was further supported by a simultaneous decline in bacteraemia cases with coagulase-negative staphylococci. Though several hygienic precautions were taken, the increased focus on disinfection of hubs and injection ports was presumably the more important element. FUNDING: not relevant. TRIAL REGISTRATION: not relevant.

Atrioventricular septal defects among infants in Europe: a population-based study of prevalence, associated anomalies, and survival.

OBJECTIVE: To describe the epidemiology of chromosomal and non-chromosomal cases of atrioventricular septal defects in Europe. METHODS: Data were obtained from EUROCAT, a European network of population-based registries collecting data on congenital anomalies. Data from 13 registries for the period 2000-2008 were included. RESULTS: There was a total of 993 cases of atrioventricular septal defects, with a total prevalence of 5.3 per 10,000 births (95% confidence interval 4.1 to 6.5). Of the total cases, 250 were isolated cardiac lesions, 583 were chromosomal cases, 79 had multiple anomalies, 58 had heterotaxia sequence, and 23 had a monogenic syndrome. The total prevalence of chromosomal cases was 3.1 per 10,000 (95% confidence interval 1.9 to 4.3), with a large variation between registers. Of the 993 cases, 639 cases were live births, 45 were stillbirths, and 309 were terminations of pregnancy owing to foetal anomaly. Among the groups, additional associated cardiac anomalies were most frequent in heterotaxia cases (38%) and least frequent in chromosomal cases (8%). Coarctation of the aorta was the most common associated cardiac defect. The 1-week survival rate for live births was 94%. CONCLUSION: Of all cases, three-quarters were associated with other anomalies, both chromosomal and non-chromosomal. For infants with atrioventricular septal defects and no chromosomal anomalies, cardiac defects were often more complex compared with infants with atrioventricular septal defects and a chromosomal anomaly. Clinical outcomes for atrioventricular septal defects varied between regions. The proportion of termination of pregnancy for foetal anomaly was higher for cases with multiple anomalies, chromosomal anomalies, and heterotaxia sequence.

Seismic evidence for overpressured subducted oceanic crust and megathrust fault sealing.

Water and hydrous minerals play a key part in geodynamic processes at subduction zones by weakening the plate boundary, aiding slip and permitting subduction-and indeed plate tectonics-to occur. The seismological signature of water within the forearc mantle wedge is evident in anomalies with low seismic shear velocity marking serpentinization. However, seismological observations bearing on the presence of water within the subducting plate itself are less well documented. Here we use converted teleseismic waves to obtain observations of anomalously high Poisson's ratios within the subducted oceanic crust from the Cascadia continental margin to its intersection with forearc mantle. On the basis of pressure, temperature and compositional considerations, the elevated Poisson's ratios indicate that water is pervasively present in fluid form at pore pressures near lithostatic values. Combined with observations of a strong negative velocity contrast at the top of the oceanic crust, our results imply that the megathrust is a low-permeability boundary. The transition from a low- to high-permeability plate interface downdip into the mantle wedge is explained by hydrofracturing of the seal by volume changes across the interface caused by the onset of crustal eclogitization and mantle serpentinization. These results may have important implications for our understanding of seismogenesis, subduction zone structure and the mechanism of episodic tremor and slip.