Association of maternal snuff use and smoking with Sudden Infant Death Syndrome: a national register study.

BACKGROUND: The aim was to study whether non-combustible nicotine (Swedish snuff) use in pregnancy is associated with elevated risk of post neonatal mortality, Sudden Infant Death Syndrome (SIDS), and Sudden Unexpected Infant Death (SUID) and to study how cessation before the antenatal booking influenced these risks. METHODS: This was a population-based register study of all infants with information on tobacco exposure in early pregnancy born in Sweden 1999-2019, n = 2,061,514. Self-reported tobacco use in early pregnancy was categorized as nonuse, snuff use, and moderate and heavy smoking. Multiple logistic regression models were used to estimate crude and adjusted odds ratios (aORs) with 95% confidence intervals (CIs). RESULTS: Maternal snuff use was associated with increased risks of post neonatal mortality, SIDS, and SUID. The risks of snuff use and moderate smoking were of similar magnitude. Heavy smoking was associated with the highest risks. Cessation of smoking and snuff use before the antenatal booking was associated with lower risks of SIDS and SUID compared to that of continuous usage. CONCLUSIONS: Maternal snuff use was associated with increased risks of post neonatal mortality, SIDS, and SUID. Nicotine is the common substance in cigarette smoke and snuff. These findings support the hypothesis that nicotine contributes to an elevated risk of SIDS. IMPACT: Maternal snuff use and smoking in early pregnancy were associated with increased risks of post neonatal mortality, SIDS, and SUID. Cessation of smoking and snuff use before the first antenatal visit was associated with reduced risks of SIDS and SUID. The common substance in cigarette smoke and snuff is nicotine. Our findings suggest that nicotine contributes to an elevated risk of SIDS and SUID. The implication of our findings is that all forms of nicotine should be avoided in pregnancy.

In-utero antibiotic exposure and subsequent infections in infancy: a register-based cohort study with sibling analysis.

BACKGROUND: Prenatal antibiotic use, the ensuing maternal dysbiosis, and subsequent acquisition of altered microbiota in early life have been linked to the offspring's increased susceptibility to childhood infections. However, infection risks during the first year of life associated with in-utero antibiotic exposure have not been comprehensively explored. OBJECTIVE: To investigate the associations between exposure to antibiotics in utero and subsequent infections during infancy and whether such associations differ by antibiotic class. STUDY DESIGN: All data were retrieved from Swedish population-based registers. Singletons live-born between 2006 and 2018 were followed up from birth to their first birthday. Exposure was maternal filling of at least 1 antibiotic prescription between the last menstrual period and delivery. Outcomes were the infants' antimicrobial prescription fills, incident infections diagnosed in specialist care, and deaths with infections indicated as underlying or contributing causes ("infection-related deaths"). Birth year, birth season, maternal age, place of residence, parity, comorbidity indicator, body mass index, proxies for general health status, education level, and smoking status were considered covariates. Poisson regression was used to estimate crude and adjusted incidence rate ratios with 95% confidence intervals for the number of antimicrobial prescriptions filled to the infant. Cox regression was used to estimate crude and adjusted hazard ratios with 95% confidence intervals for incident infections diagnosed in specialist care and at death. Sibling analyses were used to account for shared familial factors. Sensitivity of the results to exposure definition and perinatal factors prognostic for the outcomes were assessed in supplementary analyses. RESULTS: Of 1,347,018 infants in the full cohort, 294,657 (21.9%) were exposed to antibiotics in utero. There were 677,430 antimicrobial prescriptions filled (1.380 per 1000 person-days), 423,705 incident infections diagnosed in specialist care (0.870 per 1000 person-days), and 2800 infection-related deaths (0.006 deaths per 1000 person-days) during follow-up. Compared to unexposed, infants exposed to antibiotics in utero had higher rates of antimicrobial prescription fills (adjusted incidence rate ratio, 1.34; 95% confidence interval, 1.33-1.34), incident infections diagnosed in specialist care (adjusted hazard ratio, 1.28; 95% confidence interval, 1.27-1.29), and infection-related mortality (adjusted hazard ratio, 1.15; 95% confidence interval, 1.05-1.25). For antimicrobial prescriptions and infections diagnosed in specialist care, associations were consistent across most antibiotic classes but were attenuated in the sibling analyses: adjusted incidence rate ratio of 1.05 (95% confidence interval, 1.04-1.06) and adjusted hazard ratio of 1.05 (95% confidence interval, 1.03-1.07), respectively. No association with infant mortality was found in the sibling cohort (adjusted hazard ratio, 0.93; 95% confidence interval, 0.81-1.08). CONCLUSION: The minor associations between exposure to antibiotics in utero and infections during infancy were partly explained by shared familial factors and did not differ across frequently used antibiotic classes.

Novel Biomarkers Differentiating Viral from Bacterial Infection in Febrile Children: Future Perspectives for Management in Clinical Praxis.

Differentiating viral from bacterial infections in febrile children is challenging and often leads to an unnecessary use of antibiotics. There is a great need for more accurate diagnostic tools. New molecular methods have improved the particular diagnostics of viral respiratory tract infections, but defining etiology can still be challenging, as certain viruses are frequently detected in asymptomatic children. For the detection of bacterial infections, time consuming cultures with limited sensitivity are still the gold standard. As a response to infection, the immune system elicits a cascade of events, which aims to eliminate the invading pathogen. Recent studies have focused on these host-pathogen interactions to identify pathogen-specific biomarkers (gene expression profiles), or "pathogen signatures", as potential future diagnostic tools. Other studies have assessed combinations of traditional bacterial and viral biomarkers (C-reactive protein, interleukins, myxovirus resistance protein A, procalcitonin, tumor necrosis factor-related apoptosis-inducing ligand) to establish etiology. In this review we discuss the performance of such novel diagnostics and their potential role in clinical praxis. In conclusion, there are several promising novel biomarkers in the pipeline, but well-designed randomized controlled trials are needed to evaluate the safety of using these novel biomarkers to guide clinical decisions.

Adenoviral detection by recombinase polymerase amplification and vertical flow paper microarray.

Respiratory viral infections often mimic the symptoms of infections caused by bacteria; however, restricted and targeted administration of antibiotics is needed to combat growing antimicrobial resistance. This is particularly relevant in low-income settings. In this work, we describe the use of isothermal amplification of viral DNA at 37 °C coupled to a paper-based vertical flow microarray (VFM) setup that utilizes a colorimetric detection of amplicons using functionalized gold nanoparticles. Two oligonucleotide probes, one in-house designed and one known adenoviral probe were tested and validated for microarray detection down to 50 nM using a synthetic target template. Furthermore, primers were shown to function in a recombinase polymerase amplification reaction using both synthetic template and viral DNA. As a proof-of-concept, we demonstrate adenoviral detection with four different adenoviral species associated with respiratory infections using the paper-based VFM format. The presented assay was validated with selected adenoviral species using the in-house probe, enabling detection at 1 ng of starting material with intra- and inter-assay %CV of ≤ 9% and ≤ 13%. Finally, we validate our overall method using clinical samples. Based on the results, the combination of recombinase polymerase amplification, paper microarray analysis, and nanoparticle-based colorimetric detection could thus be a useful strategy towards rapid and affordable multiplexed viral diagnostics.

Frequent Respiratory Viral Infections in Children with Febrile Neutropenia - A Prospective Follow-Up Study.

OBJECTIVE: Febrile neutropenia is common in children undergoing chemotherapy for the treatment of malignancies. In the majority of cases, the cause of the fever is unknown. Although respiratory viruses are commonly associated with this condition, the etiologic significance of this finding remains unclear and is therefore the subject of this study. STUDY DESIGN: Nasopharyngeal aspirates were collected during 87 episodes of febrile neutropenia in children age 0-18 years, being treated at a children's oncology unit between January 2013 and June 2014. Real-time polymerase chain reaction was used to determine the presence of 16 respiratory viruses. Follow-up samples were collected from children who tested positive for one or more respiratory viruses. Rhinoviruses were genotyped by VP4/VP2 sequencing. Fisher's exact test and Mann-Whitney U test were used for group comparisons. RESULTS: At least one respiratory virus was detected in samples from 39 of 87 episodes of febrile neutropenia (45%), with rhinoviruses the most frequently detected. Follow-up samples were collected after a median of 28 days (range, 9-74 days) in 32 of the 39 virus-positive episodes. The respiratory viral infection had resolved in 25 episodes (78%). The same virus was detected at follow-up in one coronavirus and six rhinovirus episodes. Genotyping revealed a different rhinovirus species in two of the six rhinovirus infections. CONCLUSION: The frequency of respiratory viral infections in this group of patients suggests an etiologic role in febrile neutropenia. However, these findings must be confirmed in larger patient cohorts.

HIV-neutralizing activity of cationic polypeptides in cervicovaginal secretions of women in HIV-serodiscordant relationships.

BACKGROUND: HIV exposed seronegative (HESN) women represent the population most in need of a prophylactic antiviral strategy. Mucosal cationic polypeptides can potentially be regulated for this purpose and we here aimed to determine their endogenous expression and HIV neutralizing activity in genital secretions of women at risk of HIV infection. METHODOLOGY/PRINCIPAL FINDINGS: Cervicovaginal secretions (CVS) of Kenyan women in HIV-serodiscordant relationships (HESN, n = 164; HIV seropositive, n = 60) and low-risk controls (n = 72) were assessed for the cationic polypeptides HNP1-3, LL-37 and SLPI by ELISA and for HIV neutralizing activity by a PBMC-based assay using an HIV primary isolate. Median levels of HNP1-3 and LL-37 in CVS were similar across study groups. Neither HSV-2 serostatus, nor presence of bacterial vaginosis, correlated with levels of HNP1-3 or LL-37 in the HESN women. However, an association with their partner's viral load was observed. High viral load (>10,000 HIV RNA copies/ml plasma) correlated with higher levels of HNP1-3 and LL-37 (p = 0.04 and 0.03, respectively). SLPI was most abundant in the low-risk group and did not correlate with male partner's viral load in the HESN women. HIV neutralizing activity was found in CVS of all study groups. In experimental studies, selective depletion of cationic polypeptides from CVS rendered the remaining CVS fraction non-neutralizing, whereas the cationic polypeptide fraction retained the activity. Furthermore, recombinant HNP1-3 and LL-37 could induce neutralizing activity when added to CVS lacking intrinsic activity. CONCLUSIONS/SIGNIFICANCE: These findings show that CVS from HESN, low-risk, and HIV seropositive women contain HIV neutralizing activity. Although several innate immune proteins, including HNP1-3 and LL-37, contribute to this activity these molecules can also have inflammatory properties. This balance is influenced by hormonal and environmental factors and in the present HIV serodiscordant couple cohort study we show that a partner's viral load is associated with levels of such molecules.