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Objective Maternal smoking is associated with as much as a 50% reduced risk of preeclampsia, despite increasing risk of other poor pregnancy outcomes that often co-occur with preeclampsia, such as preterm birth and fetal growth restriction. Researchers have long sought to understand whether this perplexing association is biologically based, or a result of noncausal mechanisms. We examined whether smoking-response genes modify the smoking-preeclampsia association to investigate potential biological explanations. Study Design We conducted a nested case–control study within the Norwegian Mother, Father and Child Birth Cohort (1999–2008) of 2,596 mother–child dyads. We used family-based log-linear Poisson regression to examine modification of the maternal smoking-preeclampsia relationship by maternal and fetal single nucleotide polymorphisms involved in cellular processes related to components of cigarette smoke (n = 1,915 with minor allele frequency ≥10%). We further investigated the influence of smoking cessation during pregnancy. Results Three polymorphisms showed overall (p < 0.001) multiplicative interaction between smoking and maternal genotype. For rs3765692 (TP73) and rs10770343 (PIK3C2G), protection associated with smoking was reduced with two maternal copies of the risk allele and was stronger in continuers than quitters (interaction p = 0.02 for both loci, based on testing 3-level smoking by 3-level genotype). For rs2278361 (APAF1) the inverse smoking-preeclampsia association was eliminated by the presence of a single risk allele, and again the trend was stronger in continuers than in quitters (interaction p = 0.01). Conclusion Evidence for gene–smoking interaction was limited, but differences by smoking cessation warrant further investigation. We demonstrate the potential utility of expanded dyad methods and gene–environment interaction analyses for outcomes with complex relationships between maternal and fetal genotypes and exposures. Key Points Maternal and fetal genotype may differentially influence preeclampsia. Smoking-related genes did not strongly modify smoking–preeclampsia association. Smoking cessation reduced strength of gene by smoking interactions. [ABSTRACT FROM AUTHOR]

Background: Understanding how booster vaccination can prevent moderate and severe illness without hospitalization is crucial to evaluate the full advantage of mRNA boosters.Methods: We followed 85 801 participants (aged 31-81 years) in 2 large population-based cohorts during the Omicron BA.1/2 wave. Information on home testing, PCR testing, and symptoms of coronavirus disease 2019 (COVID-19) was extracted from biweekly questionnaires covering the period 12 January 2022 to 7 April 2022. Vaccination status and data on previous SARS-CoV-2 infection were obtained from national registries. Cox regression was used to estimate the effectiveness of booster vaccination compared to receipt of 2-dose primary series >130 days previously.Results: The effectiveness of booster vaccination increased with increasing severity of COVID-19 and decreased with time since booster vaccination. The effectiveness against severe COVID-19 was reduced from 80.9% shortly after booster vaccination to 63.4% in the period >90 days after vaccination. There was hardly any effect against mild COVID-19. The effectiveness tended to be lower among subjects aged ≥60 years than those aged <50 years.Conclusions: This is the first population-based study to evaluate booster effectiveness against self-reported mild, moderate, and severe COVID-19. Our findings contribute valuable information on duration of protection and thus timing of additional booster vaccinations. [ABSTRACT FROM AUTHOR]

Introduction: Maternal cytomegalovirus (CMV) infection in pregnancy may result in vertical transmission of CMV to the child. Long-term effects of congenital CMV infection include visual, cognitive as well as neurological impairment. The aim of this study was to estimate the odds ratios for CMV seropositivity and seroconversion in mothers, with and without delayed language development in 3 year old children, nested within a large cohort. Material and methods: The Norwegian Mother, Father and Child Cohort Study (MoBa) is a prospective population-based pregnancy cohort that includes 95 200 mothers and 114 500 children. Blood samples were obtained from mothers during pregnancy weeks 17 or 18 in pregnancy and after birth. We included 300 women from MoBa with children suffering from delayed language development at three years of age, based on validated questionnaires. Within the cohort, 1350 randomly selected women were included as controls to perform a nested case-control study. The cases and controls were tested for CMV IgG antibodies by an enzyme-linked immunosorbent assay. Results: Among mothers of cases, 63.2% were CMV-IgG positive in the sample at birth, as compared to 55.9% among controls; OR 1.36, (95% CI; 1.05 to 1.76). Also, among case mothers, 8/118 (6.8%) initially seronegative cases, seroconverted. Among initially seronegative controls, seroconversion occurred in 23/618 (3.7%) mothers. The OR for seroconversion in cases as compared to control mothers was 1.88 (CI; 0.82 to 4.31), thus not statistically significant different. Conclusion: This study shows a higher risk of delayed language development at three years of age in children born by mothers seropositive for CMV, compared to children born from seronegative mothers. [ABSTRACT FROM AUTHOR]

Background: Whether type-specific human papillomavirus (HPV) infection influences the risk of acquiring infections with other HPV types is unclear. We studied concurrent HPV infections in 17-year-old girls from 2 birth cohorts; the first vaccine-eligible cohort in Norway and a prevaccination cohort.Methods: Urine samples were collected and tested for 37 HPV genotypes. This study was restricted to unvaccinated girls from the prevaccination cohort (n = 5245) and vaccinated girls from the vaccine-eligible cohort (n = 4904). Risk of HPV infection was modelled using mixed-effect logistic regression. Expected frequencies of concurrent infection with each pairwise combination of the vaccine types and high-risk types (6/11/16/18/31/33/35/39/45/51/52/56/58/59) were compared to observed frequencies.Results: Infection with multiple HPV types was more common among unvaccinated girls than vaccinated girls (9.2% vs 3.7%). HPV33 and HPV51 was the only HPV pair that was detected together more often than expected among both unvaccinated (P = .002) and vaccinated girls (P < .001). No HPV pairs were observed significantly less often than expected.Conclusions: HPV33 and HPV51 tended to be involved in coinfection among both unvaccinated and vaccinated girls. The introduction of HPV vaccination does not seem to have had an effect on the tendency of specific HPV types to cluster together. [ABSTRACT FROM AUTHOR]

Background: Interventions targeting the same disease but at different points along the disease continuum (e.g., screening and vaccination to prevent cervical cancer [CC]) are often evaluated in isolation, which can affect cost-effectiveness profiles and policy conclusions. We evaluated nonavalent human papillomavirus (HPV) vaccine (9vHPV) compared with bivalent HPV vaccine (2vHPV) alongside deintensified screening intervals for a vaccinated birth cohort to inform a single optimal integrated CC prevention policy. Methods: Using a multimodeling approach, we evaluated the health and economic impacts of alternative CC screening strategies for a Norwegian birth cohort eligible for HPV vaccination in 2021 assuming they received 1) 2vHPV or 2) 9vHPV. We conducted 1) a restricted analysis that evaluated the optimal HPV vaccine under current screening guidelines; and 2) a comprehensive analysis including alternative screening and vaccination strategy combinations. We calculated incremental cost-effectiveness ratios (ICERs) and evaluated them according to different cost-effectiveness thresholds. Results: Assuming a cost-effectiveness threshold of $40,000 per quality-adjusted life year (QALY) gained, we found that, while holding screening intensity fixed, switching the routine vaccination program in Norway from 2vHPV to 9vHPV would not be considered cost-effective (ICER of $132,700 per QALY gained). However, when allowing for varying intensities of CC screening, we found that switching to 9vHPV would be cost-effective compared with 2vHPV under an alternative threshold of $55,000 per QALY gained, if coupled with reductions in the number of lifetime screens. Conclusions: Our analysis highlights the importance of evaluating the full potential policy landscape for country-level decision makers considering policy adoption, including nonindependent primary and secondary prevention efforts, to draw appropriate conclusions and avoid sub-optimal outcomes. Highlights: Without evaluating the full potential policy landscape, including primary and secondary prevention efforts, country-level decision makers may not be able to draw appropriate policy conclusions, resulting in suboptimal outcomes. An applied example from cervical cancer prevention in Norway compared a restricted analysis of current screening guidelines to a comprehensive analysis including alternative screening and vaccination strategy combinations. We found that a switch from bivalent to nonavalent human papillomavirus vaccine would be considered cost-effective in Norway if coupled with reductions in the number of lifetime screens compared with the current screening strategy. A comprehensive analysis that considers how different types of interventions along the disease continuum affect each other will be critical for decision makers interpreting cost-effectiveness analysis results. [ABSTRACT FROM AUTHOR]

Keywords: antibiotic use; pediatric; multi-national comparison; antimicrobial consumption; prescription patterns EN antibiotic use pediatric multi-national comparison antimicrobial consumption prescription patterns 937 947 11 10/03/22 20220801 NES 220801 Introduction In 2015, the World Health Organization launched a Global Action Plan on Antimicrobial Resistance with the objective to increase awareness of antibiotic resistance, prevent infections, optimize the use of antibiotics, increase knowledge through research and surveillance, and foster the development of new antimicrobial drugs.[1] Children are common recipients of antibiotics.[2] Using between-country comparisons of antibiotic prescription rates may reveal areas for promoting rational antibiotic prescribing. Antibiotic prescriptions redeemed within 14 days of the previous antibiotic prescription were regarded as one treatment episode. Results Throughout the study period, the rates of antibiotic treatment episodes for all children aged 0-14 years were highest in Finland, followed by Denmark, Sweden, and Norway (Figure 1, Table S3). Penicillins with extended spectrum were the most frequently used antibiotics in Finland at all ages and among the youngest children in Denmark, while beta-lactamase sensitive penicillins were most frequently used in Norway and Sweden. [Extracted from the article]

Several dietary substances have been hypothesized to influence the risk of preeclampsia. Our aim in this study was to estimate the association between dietary patterns during pregnancy and the risk of preeclampsia in 23,423 nulliparous pregnant women taking part in the Norwegian Mother and Child Cohort Study (MoBa). Women participating in MoBa answered questionnaires at gestational wk 15 (a general health questionnaire) and 17-22 (a FFQ). The pregnancy outcomes were obtained from the Medical Birth Registry of Norway. Exploratory factor analysis was used to assess the associations among food variables. Principal component factor analysis identified 4 primary dietary patterns that were labeled: vegetable, processed food, potato and fish, and cakes and sweets. Relative risks of preeclampsia were estimated as odds ratios (OR) and confounder control was performed with multiple logistic regression. Women with high scores on a pattern characterized by vegetables, plant foods, and vegetable oils were at decreased risk [relative risk (OR) for tertile 3 vs. tertile 1: 0.72; 95% CI: 0.62, 0.85]. Women with high scores on a pattern characterized by processed meat, salty snacks, and sweet drinks were at increased risk [OR for tertile 3 vs. tertile 1: 1.21; 95% CI: 1.03, 1.42]. These findings suggest that a dietary pattern characterized by high intake of vegetables, plant foods, and vegetable oils decreases the risk of preeclampsia, whereas a dietary pattern characterized by high consumption of processed meat, sweet drinks, and salty snacks increases the risk.

Purpose: Comparing rates of childhood infectious disease hospitalisations across countries may uncover areas for improvement in the prevention of severe childhood infections. We compared rates of childhood infectious disease hospital contacts across Denmark, Finland, Norway, and Sweden with the overall objective to elucidate potential differences in burden of disease and in organisational and registration practices. Methods: Using national registries, we estimated incidence rates for infectious disease hospital contacts between 2008 and 2017 among children aged 0– 14 years. We investigated the rates for different types of contacts (inpatient or outpatient including emergency room), duration of admission, and by sex. Results: During the study period, the rate of all hospital contacts per 1000 person-years was highest in Sweden (125.2) followed by Finland (87.1), Denmark (79.0), and Norway (62.1). The rates aligned for inpatient contacts with overnight stays; 19.3 (Denmark), 16.6 (Finland), 16.3 (Norway), and 13.0 (Sweden); these were highest in early infancy in all countries. A peak around 1 year of age was seen in all countries except in Sweden. The rates were higher among boys compared with girls in early childhood, after 13 years of age the rates among girls surpassed the boys. Conclusion: Large cross-country differences were observed for outpatient and short-term hospital contacts for infectious diseases, affected by differences in organisational structures and coding practices across and within countries over time. Inpatient contacts requiring overnight stays reflected more comparable levels of severe infections across countries. Childhood infectious disease morbidity was greatest among boys and before 2 years of age. [ABSTRACT FROM AUTHOR]

Background: In 2009, a new influenza A H1N1 virus emerged causing a global pandemic. A range of monovalent influenza A H1N1pdm09 vaccines with or without adjuvants were developed. After the mass vaccination campaigns safety concerns related to H1N1pdm09 vaccines were reported. More than a decade later, reported AEFIs are still under scrutiny. We performed a systematic review aiming to synthesize the evidence on the safety of the H1N1pdm09 vaccines on reported outcomes from existing systematic reviews. Methods: Four electronic databases, PubMed, EMBASE, Epistimonikos and the Cochrane Database of Systematic Reviews were searched for articles on H1N1pdm09 vaccination published from 2009 to January 2021. Systematic reviews assessing short- or long-term adverse events after H1N1pdm09 vaccination were considered for inclusion. Data was extracted from all selected reviews. Outcomes were grouped and results from each included review were presented narratively and in tables. Results: 16 systematic reviews met the inclusion criteria. Reported outcomes were short-term events (3 reviews), fetal/pregnancy outcomes (8 reviews), Guillain-Barré syndrome (GBS) (4 reviews), narcolepsy (2 reviews) demyelinating diseases (1 review based on one study only) and inflammatory bowel disease (IBD) (1 review). Short-term serious adverse events were rare, 3 cases amongst 16725 subjects in 18 randomized controlled trials (0.018%). No deaths were reported. The risks of local events were generally higher for adjuvanted vaccines as compared to unadjuvanted vaccines. Maternal H1N1pdm09 vaccination in any trimester was not associated with an increase in preterm birth, small for gestational age, congenital malformations or fetal death. For GBS, results were conflicting. The main systematic review on narcolepsy found a 5-14-fold increased risk in children, and a 2-7- fold increased risk in adults after vaccination with Pandemrix. The attributable risk of narcolepsy one year after vaccination was 1 case per 18 400 vaccine doses in children/adolescents, and 1 case per 181 000 vaccine doses in adults. Conclusion: Adjuvanted vaccines had more local but not serious adverse events compared to unadjuvanted vaccines. Vaccination with Pandemrix was strongly associated with narcolepsy, particularly in children. No increased risks of pregnancy outcomes were seen after pandemic vaccination. The findings on GBS were inconclusive. [ABSTRACT FROM AUTHOR]

Introduction: Parvovirus B19 (B19V) is the infectious cause of exanthema infectiosum. In Europe around 40% of pregnant women are susceptible to infection. Having small children at home is the main risk factor for contracting an infection during pregnancy. The association between B19V-infection and perinatal death is not yet settled. The aims of the study were to estimate the association between maternal parvovirus B19 infection in pregnancy and perinatal death, and to assess the significance of a positive B19V PCR in pregnancy.Material and Methods: The study population consists of women included in the Norwegian Mother and Child Cohort Study, a prospective population-based pregnancy cohort of nearly 100 000 women. Blood samples were obtained during weeks 17-18 in pregnancy (M1), at birth, and in umbilical cord blood. Within participants in the pregnancy cohort, 138 cases of perinatal death and 1350 controls with live-born children were included in a nested case-control study. Samples were analyzed with B19V serology and B19V PCR according to a predefined test algorithm. For cases, medical records and laboratory results from hospitals were combined with the results of B19V serology and PCR. The reported causes of perinatal death were categorized using the classification system: Causes Of Death and Associated Conditions (CODAC).Results: The B19V seroconversion rates were 9.8% for cases and 6.8% for control mothers. The odds ratio for maternal B19V infection in cases compared with controls was 1.28 (95% CI 0.35-4.70), adjusted for age, parity, body mass index and tobacco use. B19V-PCR-positive samples were detected at weeks 17-18 of gestation in both cases and controls. The proportion of positive samples was similar in cases and controls, 24% and 28.2%, respectively. Mothers with PCR-positive M1 samples transmitted B19V vertically in 9.1% of cases and in 11.9% of the controls. Of all perinatal deaths, 53% were attributed to placental pathology or unknown causes.Conclusions: B19V PCR positivity was high and similar in both cases and controls. In our study B19V DNAemia was not seen to be associated with fatal outcome of pregnancy. The clinical significance of B19V DNA detection during pregnancy is uncertain. Caution is needed when diagnosing a B19V infection based only on B19V DNAemia. [ABSTRACT FROM AUTHOR]

Background: Reliable exposure information is crucial for assessing health outcomes of influenza infection and vaccination. Current serological methods are unable to distinguish between anti‐hemagglutinin (HA) antibodies induced by infection or vaccination. Objectives: We aimed to explore an alternative method for differentiating influenza infection and vaccination. Methods: Sera from animals inoculated with influenza viruses or purified H1N1pdm09 HA were obtained. Human samples were selected from a pregnancy cohort established during the 2009 H1N1 pandemic. Unvaccinated, laboratory‐confirmed cases (N = 18), vaccinated cases without influenza‐like‐illness (N = 18) and uninfected, unvaccinated controls (N = 18) were identified based on exposure data from questionnaires, national registries and maternal hemagglutination inhibition (HI) titres at delivery. Animal and human samples were tested for antibodies against the non‐structural protein 1 (NS1) and HA from H1N1pdm09, using a Luciferase Immunoprecipitation System (LIPS). Results: Anti‐NS1 H1N1pdm09 antibodies were detected in sera from experimentally infected, but not from vaccinated, animals. Anti‐HA H1N1pdm09 antibodies were detectable after either of these exposures. In human samples, 28% of individuals with laboratory‐confirmed influenza were seropositive for H1N1pdm09 NS1, whereas vaccinated cases and controls were seronegative. There was a trend for H1N1pdm09 NS1 seropositive cases reporting more severe and longer duration of symptomatic illness than seronegative cases. Anti‐HA H1N1pdm09 antibodies were detected in all cases and in 61% of controls. Conclusions: The LIPS method could differentiate between sera from experimentally infected and vaccinated animals. However, in human samples obtained more than 6 months after the pandemic, LIPS was specific, but not sufficiently sensitive for ascertaining cases by exposure. [ABSTRACT FROM AUTHOR]

Background: A population‐based pregnancy cohort was established in Norway to study potential effects of exposure to the 2009 influenza pandemic or pandemic vaccination during pregnancy. Objectives: We studied maternal A(H1N1)pdm09‐specific hemagglutination inhibition (HI)‐titer levels and waning in women with influenza‐like illness (ILI) in pregnancy compared to vaccinated women. Moreover, we studied the association between HI‐titers and self‐reported severity and duration of ILI. Methods: HI‐titers against the pandemic virus were measured in maternal blood samples obtained at birth, 3‐9 months after exposure, and linked with information about pregnancy, influenza and vaccination from national registries and a cohort questionnaire. Results: Among 1821 pregnant women included, 43.7% were unvaccinated and 19.3% of these had ILI. HI‐titers were low (geometric mean titer (GMT) 11.3) in the unvaccinated women with ILI. Higher HI‐titers (GMT 37.8) were measured in the vaccinated women. Estimated HI‐titer waning was similar for vaccinated women and women with ILI. Most ILI episodes were moderate and lasted 3‐5 days. Women with ILI reporting specific influenza symptoms such as fever or cough had higher HI‐titers than women without these symptoms. Women who reported being "very ill" or illness duration of >5 days had higher HI‐titers than women reporting less severe illness or illness of shorter duration, respectively. Conclusions: Antibody waning was similar in vaccinated women and women with ILI. More severe ILI or longer duration of illness was associated with higher HI‐titers. Most unvaccinated pregnant women with ILI had low HI‐titers, probably due to moderate illness and HI‐titer waning between exposure and sampling. [ABSTRACT FROM AUTHOR]

CMV is the most common cause of congenital infection. During the past few decades, there has been a change in behaviour that possibly has affected the CMV infection rate of mother and child. We investigated 1350 randomly selected pregnant women from the Norwegian Mother and Child Cohort Study using an algorithm for detection of maternal and congenital CMV (cCMV) infection including both serology and nucleic acid amplification assay. The CMV IgG seroprevalence was 54% and 23 (3.7%) mothers seroconverted. Three (0.22%) children had a positive CMV PCR in the umbilical cord blood. The transmission rate was lower than reported in previous studies, probably due to lower sensitivity in plasma compared to saliva and urine. The prevalence of cCMV in the present study was compared with the number registered with the ICD‐10 code P.35.1‐congenital CMV infection in the Norwegian Patient Register. The number registered was lower than the number of estimated infections. Factors like lower level of education and parity were associated with higher CMV IgG seroprevalence, but no significant difference could be linked to age. In conclusion, in this cohort of pregnant women, a high CMV IgG seroconversion rate was found, while the vertical transmission rate was low. [ABSTRACT FROM AUTHOR]