Scandinavian Cohort Research Articles

Comparative cardiovascular and renal effectiveness of empagliflozin and dapagliflozin: Scandinavian cohort study.

To assess the comparative cardiovascular and renal effectiveness and safety of empagliflozin vs. dapagliflozin among patients with type 2 diabetes in routine clinical practice. Cohort study using data from nationwide registers in Sweden, Denmark, and Norway, from June 2014 to June 2021 included 141065 new users of empagliflozin and 58306 new users of dapagliflozin. Coprimary outcomes were major cardiovascular events (myocardial infarction, stroke, and cardiovascular death), heart failure (hospitalization or death because of heart failure) and serious renal events (renal replacement therapy, hospitalization for renal events, and death from renal causes). Secondary outcomes were the individual components of the primary outcomes, any cause death, and diabetic ketoacidosis. Use of empagliflozin vs. dapagliflozin was associated with similar risk of major cardiovascular events [adjusted incidence rate: 15.9 vs. 15.8 events per 1000 person-years; HR 1.02, (95% confidence interval 0.97-1.08)], heart failure [6.5 vs. 6.3 events per 1000 person-years; HR 1.05 (0.97-1.14)] and serious renal events [3.7 vs. 4.1 events per 1000 person-years; HR 0.97 (0.87-1.07)]. In secondary outcome analyses, the HRs for use of empagliflozin vs. dapagliflozin were 1.00 (0.93-1.07) for myocardial infarction, 1.03 (0.95-1.12) for stroke, 1.01 (0.92-1.13) for cardiovascular death, 1.06 (1.00-1.11) for any cause death, 0.77 (0.60-0.99) for renal replacement therapy, 1.20 (0.75-1.93) for renal death, 1.01 (0.90-1.12) for hospitalization for renal events and 1.12 (0.94-1.33) for diabetic ketoacidosis. Use of empagliflozin and dapagliflozin was associated with similar risk of cardiovascular and renal outcomes, mortality, and diabetic ketoacidosis.

Glucagon-like peptide 1 receptor agonist use and risk of thyroid cancer: Scandinavian cohort study

ObjectiveTo investigate whether use of glucagon-like peptide 1 (GLP1) receptor agonists is associated with increased risk of thyroid cancer.DesignScandinavian cohort study.SettingDenmark, Norway, and Sweden, 2007-21.ParticipantsPatients who started GLP1 receptor agonist...

Association of glucagon-like peptide-1 receptor agonists with serious liver events among patients with type 2 diabetes: A Scandinavian cohort study.

Association of glucagon-like peptide-1 receptor agonists with serious liver events among patients with type 2 diabetes: A Scandinavian cohort study.

Tobacco Smoke Exposure in Early Childhood and Later Risk of Inflammatory Bowel Disease: A Scandinavian Birth Cohort Study.

To examine the association between early-life smoking exposure and later risk of inflammatory bowel disease [IBD]. We followed 115663 participants from the Norwegian Mother, Father and Child [MoBa] and All Babies in Southeast Sweden [ABIS] cohorts from birth [1997-2009] through 2021. IBD was identified through national patient registers. Validated questionnaire data defined maternal smoking during pregnancy, maternal environmental tobacco smoke [ETS] exposure during pregnancy, and child ETS exposure by ages 12 and 36 months. Cox regression was used to estimate adjusted hazard ratios [aHRs] for sex, maternal age, education level, parental IBD, and origin. Cohort-specific estimates were pooled using a random-effects model. During 1 987 430 person-years of follow-up, 444 participants developed IBD [ABIS, 112; MoBa, 332]. Any vs no maternal smoking during pregnancy yielded a pooled aHR of 1.30 [95% CI = 0.97-1.74] for offspring IBD. Higher level of maternal smoking during pregnancy (compared with no smoking, average ≥6 cigarettes/day: pooled aHR = 1.60 [95% CI = 1.08-2.38]) was associated with offspring IBD, whereas a lower smoking level was not (average 1-5 cigarettes/day: pooled aHR = 1.09 [95% CI = 0.73-1.64]). Child ETS exposure in the first year of life was associated with later IBD (any vs no ETS, pooled aHR = 1.32 [95% CI = 1.03-1.69]). Estimates observed for child ETS exposure by 36 months were similar but not statistically significant. In this prospective Scandinavian cohort study, children exposed to higher levels of maternal smoking during pregnancy or ETS during the first year of life were at increased risk of later IBD.

Identification of biomarker candidates for exfoliative glaucoma from autoimmunity profiling

BackgroundExfoliative glaucoma (XFG) is a subtype of open-angle glaucoma characterized by distinctive extracellular fibrils and a yet unknown pathogenesis potentially involving immune-related factors. The aim of this exploratory study was to identify biomarkers for XFG using data from autoimmunity profiling performed on blood samples from a Scandinavian cohort of patients.MethodsAutoantibody screening was analyzed against 258 different protein fragments in blood samples taken from 30 patients diagnosed with XFG and 30 healthy donors. The 258 protein fragments were selected based on a preliminary study performed on 3072 randomly selected antigens and antigens associated with the eye. The “limma” package was used to perform moderated t-tests on the proteomic data to identify differentially expressed reactivity between the groups.ResultsMultiple associated genes were highlighted as possible biomarker candidates including FUT2, CDH5, and the LOX family genes. Using seven variables, our binary logistic regression model was able to classify the cases from the controls with an AUC of 0.85, and our reduced model using only one variable corresponding to the FUT2 gene provided an AUC of 0.75, based on LOOCV. Furthermore, over-representation gene analysis was performed to identify pathways that were associated with antigens differentially bound to self-antibodies. This highlighted the enrichment of pathways related to collagen fibril formation and the regulatory molecules mir-3176 and mir-876-5p.ConclusionsThis study suggests several potential biomarkers that may be useful in developing further models of the pathology of XFG. In particular, CDH5, FUT2, and the LOX family seem to have a relationship which merits additional exploration.

Early-life diet and risk of inflammatory bowel disease: a pooled study in two Scandinavian birth cohorts

ObjectiveWe assessed whether early-life diet quality and food intake frequencies were associated with subsequent IBD.DesignProspectively recorded 1-year and 3-year questionnaires in children from the All Babies in Southeast Sweden and...

Association of glucagon-like peptide-1 receptor agonists with serious liver events among patients with type 2 diabetes: A Scandinavian cohort study.

Clinical trials suggest that glucagon-like peptide-1 (GLP-1) receptor agonists may have beneficial effects on NAFLD, but the impact on hard hepatic end points is unknown. We assessed the association between the use of GLP-1 receptor agonists and the risk of serious liver events in routine clinical practice. Cohort study using data from nationwide registers in Sweden, Denmark, and Norway, 2007-2020, including 91,479 initiators of GLP-1 receptor agonists and 244,004 initiators of the active comparator, dipeptidyl peptidase-4 inhibitors, without a history of chronic liver disease other than NAFLD/NASH. The primary outcome was serious liver events: a composite of incident compensated and decompensated cirrhosis and HCC. Secondary outcomes were the individual components of the primary outcome. Cox regression was used to estimate HRs, using propensity score weighting to control for confounding. Users of GLP-1 receptor agonists had 608 serious liver events (adjusted incidence rate: 16.9 events per 10,000 person-years), compared with 1770 events among users of dipeptidyl peptidase-4 inhibitors (19.2 events per 10,000 person-years). The adjusted HR was 0.85 (95% CI: 0.75 to 0.97), and the rate difference was -2.1 (-4.4 to 0.1) events per 10,000 person-years. In secondary outcome analyses, the adjusted HR was 0.85 (0.75 to 0.97) for compensated and decompensated cirrhosis and 1.05 (0.80 to 1.39) for HCC. The use of GLP-1 receptor agonists was associated with a significantly reduced risk of serious liver events, driven by a reduction of compensated and decompensated cirrhosis.

Physical activity in childhood and later risk of inflammatory bowel disease: A Scandinavian birth cohort study.

Retrospective data have linked adult physical activity (PA) to reduced risk of inflammatory bowel disease (IBD). We aimed to prospectively examine the association of PA and screen time (ST) in childhood with later risk of IBD, for which data are scarce. Using two population-based birth cohorts (All Babies in Southeast Sweden [ABIS] and Norwegian Mother, Father, and Child Cohort Study [MoBa]), we retrieved parent-reported data on PA and ST degree at ages 3 and 8years. Data were modelled as binary (high vs. low) and numerical (hours/day) exposures. Inflammatory bowel disease was defined as ≥2 diagnostic records in national health registers. Cox regression estimated hazard ratios adjusted for potential confounding from parental IBD, country of origin, education, and smoking habits (Adjusted hazard ratio (aHR)). Our 8-year analyses included a 2-year lag period to reduce the risk of reverse causation. Cohort-specific estimates were pooled using random-effects model. Among 65,978 participants from ABIS (n=8810) and MoBa (n=57,168) with available data, 266 developed IBD. At 3years, children with high versus low PA had an aHR of 1.12 for IBD (95%CI=0.87-1.43); high versus low ST showed an aHR of 0.91 (95%CI=0.71-1.17). Conversely, at 8years, high versus low ST was associated with increased risk of later IBD (aHR=1.51; 95%CI=1.02-2.25), but PA at 8years, was not linked to IBD (aHR=1.19; 95%CI=0.80-1.76). Subtype-specific analyses for Crohn's disease and ulcerative colitis did not differ appreciably. Acknowledging possible confounding variables, children with high versus low ST at 8years were at increased risk of IBD. In contrast, PA degree was not linked to IBD at any age category.

Childhood Socioeconomic Characteristics and Risk of Inflammatory Bowel Disease: A Scandinavian Birth Cohort Study.

Ecological observations suggest a negative relationship between childhood socioeconomic status (SES) and inflammatory bowel disease (IBD) risk. Individual-level analyses have been inconsistent and mostly lacked refined assessments of SES. We aimed to comprehensively study the association between early-life SES and later IBD. This study included 117 493 participants from the Norwegian Mother, Father and Child cohort and Swedish All Babies in Southeast Sweden cohorts. Participants were followed from birth (1997-2009) through 2021. IBD was identified through national patient registers. Questionnaire and register data were used to define parental educational level, employment, and household income level. Cox regression estimated adjusted hazard ratios (aHRs), accounting for other SES exposures and covariates (eg, parental IBD). Cohort-specific estimates were pooled using a random-effects model. During 2 024 299 person-years of follow-up, 451 participants were diagnosed with IBD (All Babies in Southeast Sweden cohort, n = 113 and Norwegian Mother, Father and Child cohort, n = 338). Early-life maternal, but not paternal, educational level was associated with later IBD (low vs high educational level; pooled aHR, 1.81; 95% confidence interval [CI], 1.16-2.82; and pooled aHR, 1.20; 95% CI, 0.80-1.80; respectively). Having a nonworking mother or father was not significantly associated with IBD (pooled aHR, 0.69; 95% CI, 0.47-1.02; pooled aHR, 0.79; 95% CI, 0.45-1.37). High vs low household income level yielded a pooled aHR of 1.33 (95% CI, 0.94-1.89). Overall, results were largely consistent across cohorts. In this prospective Scandinavian cohort study, low maternal educational level was, independent of other SES and covariates, significantly associated with later IBD in her child. Further research is needed to elucidate factors that may mediate this relationship.

Use of DPP4 Inhibitors and GLP-1 Receptor Agonists and Risk of Intestinal Obstruction: Scandinavian Cohort Study

Concerns have been raised that the incretin-based diabetes drugs dipeptidyl peptidase 4 (DPP4) inhibitors and glucagon-like peptide 1 (GLP-1) receptor agonists may increase the risk of intestinal obstruction. We aimed to assess the association between use of DPP4 inhibitors and GLP-1 receptor agonists and the risk of intestinal obstruction. Using data from nationwide registers in Sweden, Denmark, and Norway, 2013-2021, we conducted 2 cohort studies, one for DPP4 inhibitors and one for GLP-1 receptor agonists, to investigate the risk of intestinal obstruction as compared with an active comparator drug class (sodium-glucose co-transporter 2 [SGLT2] inhibitors). Among 19,0321 new users of DPP4 inhibitors (median (interquartile range [IQR]) follow-up time, 1.3 [0.6-2.6] years) and 139,315 new users of SGLT2 inhibitors (median [IQR] follow-up time, 0.8 [0.4-1.7] years), 919 intestinal obstruction events occurred. Use of DPP4 inhibitors, as compared with SGLT2 inhibitors, was not associated with a statistically significant increase in risk of intestinal obstruction (adjusted incidence rate, 2.0 vs 1.8 per 1000 person-years; hazard ratio, 1.13; 95% confidence interval, 0.96-1.34). Among 121,254 new users of GLP-1 receptor agonists (median [standard deviation] follow-up time, 0.9 [0.4-1.9] years) and 185,027 new users of SGLT2 inhibitors (median [IQR] follow-up time, 0.8 [0.4-1.8] years), 557 intestinal obstruction events occurred. Use of GLP-1 receptor agonists was not associated with a statistically significant increase in risk of intestinal obstruction (adjusted incidence rate, 1.3 vs 1.6 per 1000 person-years; hazard ratio, 0.83; 95% confidence interval, 0.69-1.01). In this analysis of nationwide data from 3 countries, previous safety signals indicating an increased risk of intestinal obstruction with use of DPP4 inhibitors and GLP-1 receptor agonists were not confirmed.

α-Synuclein seed amplification assay as a diagnostic tool for parkinsonian disorders

IntroductionSynucleinopathies such as Parkinson's disease (PD) and multiple system atrophy (MSA) can be challenging to diagnose due to the symptom overlap with, for example, atypical parkinsonisms like progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD). Seed amplification assays (SAA), developed for the detection of α-synuclein (αSyn) aggregates in CSF, have been successful when used as a biomarker evaluation for synucleinopathies. In this study, we investigated the potential of this assay to not only detect αSyn seeds in CSF, but also discriminate between movement disorders. MethodsThe αSyn-SAA was tested in a Scandinavian cohort composed of 129 CSF samples from patients with PD (n = 55), MSA (n = 27), CBD (n = 7), and PSP (n = 16), as well as healthy controls (HC, n = 24). ResultsThe αSyn seed amplification assay (αSyn-SAA) was able to correctly identify all PD samples as positive (sensitivity of 100%) while also discriminating the PD group from HC (70.8% specificity, p < 0.0001) and tauopathies [CBD (71% specificity) and PSP (75% specificity), p < 0.0001)]. The αSyn-SAA was also able to identify almost all MSA samples as positive for αSyn aggregation (sensitivity of 92.6%). In general, this assay is able to discriminate between the synucleinopathies and tauopathies analyzed herein (p < 0.0001) despite the overlapping symptoms in these diseases. ConclusionThese findings suggest the αSyn-SAA is a useful diagnostic tool for differentiating between different parkinsonian disorders, although further optimization may be needed.

Birth mode is associated with development of atopic dermatitis in infancy and early childhood.

Birth by caesarean section (CS) is associated with development of allergic diseases, but its role in the development of atopic dermatitis (AD) is less convincing. Our primary aim was to determine if birth mode was associated with AD in 3-year-olds and secondarily to determine if birth mode was associated with early onset and/or persistent AD in the first 3 years of life. We included 2129 mother-child pairs from the Scandinavian population-based prospective PreventADALL cohort with information on birth mode including vaginal birth, either traditional (81.3%) or in water (4.0%), and CS before (6.3%) and after (8.5%) onset of labor. We defined early onset AD as eczema at 3 months and AD diagnosis by 3 years of age. Persistent AD was defined as eczema both in the first year and at 3 years of age, together with an AD diagnosis by 3 years of age. AD was diagnosed at 3, 6, 12, 24, and/or 36 months in 531 children (25%). Compared to vaginal delivery, CS was overall associated with increased odds of AD by 3 years of age, with adjusted odds ratio (95% confidence interval) of 1.33 (1.02-1.74), and higher odds of early onset AD (1.63, 1.06-2.48). The highest odds for early onset AD were observed in infants born by CS after onset of labor (1.83, 1.09-3.07). Birth mode was not associated with persistent AD. CS was associated with increased odds of AD by 3 years of age, particularly in infants presenting with eczema at 3 months of age.

A Globally Distributed Bacteroides caccae Strain Is the Most Prevalent Mother-Child Shared Bacteroidaceae Strain in a Large Scandinavian Cohort.

Bacteroides and Phocaeicola, members of the family Bacteroidaceae, are among the first microbes to colonize the human infant gut. While it is known that these microbes can be transmitted from mother to child, our understanding of the specific strains that are shared and potentially transmitted is limited. In this study, we aimed to investigate the shared strains of Bacteroides and Phocaeicola in mothers and their infants. We analyzed fecal samples from pregnant woman recruited at 18 weeks of gestation from the PreventADALL study, as well as offspring samples from early infancy, including skin swab samples taken within 10 min after birth, the first available fecal sample (meconium), and fecal samples at 3 months of age. We screened 464 meconium samples for Bacteroidaceae, with subsequent selection of 144 mother-child pairs for longitudinal analysis, based on the presence of Bacteroidaceae, longitudinal sample availability, and delivery mode. Our results showed that Bacteroidaceae members were mainly detected in samples from vaginally delivered infants. We identified high prevalences of Phocaeicola vulgatus, Phocaeicola dorei, Bacteroides caccae, and Bacteroides thetaiotaomicron in mothers and vaginally born infants. However, at the strain level, we observed high prevalences of only two strains: a B. caccae strain and a P. vulgatus strain. Notably, the B. caccae strain was identified as a novel component of mother-child shared strains, and its high prevalence was also observed in publicly available metagenomes worldwide. Our findings suggest that mode of delivery may play a role in shaping the early colonization of the infant gut microbiota, in particular the colonization of Bacteroidaceae members. IMPORTANCE Our study provides evidence that Bacteroidaceae strains present on infants' skin within 10 min after birth, in meconium samples, and in fecal samples at 3 months of age in vaginally delivered infants are shared with their mothers. Using strain resolution analyses, we identified two strains, belonging to Bacteroides caccae and Phocaeicola vulgatus, as shared between mothers and their infants. Interestingly, the B. caccae strain showed a high prevalence worldwide, while the P. vulgatus strain was less common. Our findings also showed that vaginal delivery was associated with early colonization of Bacteroidaceae members, whereas cesarean section delivery was associated with delayed colonization. Given the potential for these microbes to influence the colonic environment, our results suggest that understanding the bacterial-host relationship at the strain level may have implications for infant health and development later in life.

#2948 β-2-MICROGLOBULIN AND β-TRACE-PROTEIN DO NOT IMPROVE ESTIMATION OF GFR IN KIDNEY TRANSPLANT RECIPIENTS COMPARED TO CREATININE AND CYSTATIN C

Abstract Background and Aims Precise estimates of glomerular filtration rate (eGFR) are important in kidney transplant recipients (KTRs). Current eGFR formulas based on plasma creatinine and/or cystatin C are associated with significant bias. We investigated whether race free formulas based on plasma values of β-trace-protein and β-2-microglobulin performed better than formulas based on creatinine and cystatin C in a Scandinavian cohort of KTRs. Method We included samples and data from the randomised, controlled trial CONTEXT. GFR was measured by plasma clearance of 51Cr-EDTA or iodothalamate. eGFR was calculated using the new race-free CKD-EPI eGFR-creatinine and/or cystatin C(2021) formulas as well as the CKD-EPI eGFR-β-trace-protein and/or eGFR-β-2-microglobulin formulas. GFR estimates were evaluated at 3 (n = 82) and 12 (n = 64) months post-transplant using mean bias, precision, and accuracy. Also, formulas were analysed for their ability to correctly classify changes in measured GFR from 3 to 12 months. Results At 12 months eGFR-creatinine-cystatin C performed best according to mean bias (−4.54 ml/min/1.73 m2), precision (SD = 8.18 ml/min/1.73 m2) and accuracy (P10 = 47%) among creatinine and cystatin C based formulas (Table 1). Among the β-trace-protein and β-2-microglobulin based formulas, eGFR-β-trace-protein-β-2-microglobulin performed best according to precision (SD = 7.64 ml/min/1.73 m2) and accuracy (P10 = 36%) (Table 1). eGFR-β-trace-protein-β-2-microglobulin and eGFR-creatinine-cystatin C performed similar when comparing residuals (p = 0.481). eGFR-β-trace-protein, eGFR-β-trace-protein-β-2-microglobulin and eGFR-creatinine-cystatin C performed best in correctly classifying changes in mGFR from 3 to 12 months. Conclusion β-trace-protein and β-2-microglobulin do not improve the measurement of GFR compared to creatinine and cystatin C based formulas in KTRs.

400. Clinical Characteristics of Patients With ANCA-associated Vasculitis in a Scandinavian Cohort

400. Clinical Characteristics of Patients With ANCA-associated Vasculitis in a Scandinavian Cohort

Genome-wide association study of osteonecrosis of the jaw in Danish patients receiving antiresorptive therapy for osteoporosis: A case-control study

BackgroundPrior studies of the pharmacogenomics of osteonecrosis of the jaw (ONJ) have had various methodological limitations, including using candidate gene selection as their sole strategy, a small number of ONJ cases, or a study population based on an oncology setting. ObjectivesThe aim of our case-control study was to evaluate previously reported associations between genetic factors and ONJ, which were based on either genome-wide association studies (GWAS) or candidate gene approaches. Furthermore, we aimed to identify genetic risk factors for ONJ by using GWAS to determine single-nucleotide polymorphisms (SNPs) with statistically significant differences in frequency between ONJ patients and osteoporosis controls. MethodsPatients with medically confirmed ONJ and who were registered in the Scandinavian Cohort of ONJ patients were included. Controls from the general population were matched on age (±5 years), sex, and cumulative antiresorptive drug exposure. The ONJ diagnosis date for cases corresponded to the index date for matched controls. DNA isolation, genotyping, and data analyses were performed by Q2/EA Genomics using standard protocols and best practices. Blood or tissue samples for 55 ONJ cases and 125 controls were collected. Due to the low quality of the tissue samples, final analyses were based on blood samples of 40 ONJ cases and 124 controls. ResultsWe detected no significant genome-wide associations. Of the 43 SNPs with ONJ association in prior studies, none were replicated in our study. ConclusionsEven though our study sample is the largest to date, we had limited statistical power for GWAS but adequate power for replication analyses. Our study provides no evidence for any genetic predisposition to ONJ. Future studies could increase their statistical power by combining ONJ GWAS datasets and by performing a meta-analysis or pursuing a sequencing strategy in order to identify rare variants.

Sodium-Glucose Cotransporter 2 Inhibitor Treatment and Risk of Atrial Fibrillation: Scandinavian Cohort Study.

To assess the association between use of sodium-glucose cotransporter 2 (SGLT2) inhibitors and the risk of new-onset atrial fibrillation (AF) in routine clinical practice. We used nationwide registers in Denmark, Norway, and Sweden from 2013 to 2018 in order to include patients without a history of AF who were newly prescribed an SGLT2 inhibitor or an active comparator (glucagon-like peptide 1 [GLP-1] receptor agonist). We performed a cohort study to assess new-onset AF in intention-to-treat analyses using Cox regression, adjusted for baseline covariates with propensity score weighting. We identified 79,343 new users of SGLT2 inhibitors (59.2% dapagliflozin, 40.0% empagliflozin, 0.8% canagliflozin, <0.1% ertugliflozin) and 57,613 new users of GLP-1 receptor agonists. Mean age of the study cohort was 61 years and 60% were men. The adjusted incidence rate of new-onset AF was 8.6 per 1,000 person-years for new users of SGLT2 inhibitors compared with 10.0 per 1,000 person-years for new users of GLP-1 receptor agonists. The adjusted hazard ratio (aHR) was 0.89 (95% CI 0.81-0.96), and the rate difference was 1.4 fewer events per 1,000 person-years (95% CI 0.6-2.1). Using an as-treated exposure definition, the aHR for new-onset AF was 0.87 (95% CI 0.76-0.99). No statistically significant heterogeneity of the aHRs was observed between subgroups of patients with and without a history of heart failure or major cardiovascular disease. In this cohort study using nationwide data from three countries, use of SGLT2 inhibitors, compared with GLP-1 receptor agonists, was associated with a modestly reduced risk of new-onset AF.

Time without PSA recurrence after radical prostatectomy as a predictor of future biochemical recurrence, metastatic disease and prostate cancer death: a prospective Scandinavian cohort study

ObjectiveAlthough surveillance after radical prostatectomy routinely includes repeated prostate specific antigen (PSA)-testing for many years, biochemical recurrence often occurs without further clinical progression. We therefore hypothesised that follow-up can be...

Fetal thoracic circumference in mid-pregnancy and infant lung function.

Impaired lung function in early infancy is associated with later wheeze and asthma, while fetal thoracic circumference (TC) predicts severity of neonatal lung hypoplasia. Exploring fetal origins of lung function in infancy, we aimed to determine if fetal TC in mid-pregnancy was associated with infant lung function. From the prospective Scandinavian general population-based PreventADALL mother-child birth cohort, all 851 3-month-old infants with tidal flow-volume measurements in the awake state and ultrasound fetal size measures at 18 (min-max 16-22) weeks gestational age were included. Associations between fetal TC and time to peak tidal expiratory flow to expiratory time (tPTEF /tE ) were analyzed in linear regression models. To account for gestational age variation, we adjusted TC for simultaneously measured general fetal size, by head circumference (TC/HC), abdominal circumference (TC/AC), and femur length (TC/FL). Multivariable models were adjusted for maternal age, maternal asthma, pre-pregnancy body mass index, parity, nicotine exposure in utero, and infant sex. The infants (47.8% girls) were born at mean (SD) gestational age of 40.2 (1.30) weeks. The mean (SD) tPTEF /tE was 0.39 (0.08). The mean (SD) TC/HC was 0.75 (0.04), TC/AC0.87 (0.04),and TC/FL 4.17 (0.26), respectively. Neither TC/HC nor TC/AC were associated with infant tPTEF /tE while a week inverse association was observed between TC/FL and tPTEF /tE ( = -0.03, 95% confidence interval [-0.05, -0.007], p = 0.01). Mid-pregnancy fetal TC adjusted for fetal head or abdominal size was not associated with tPTEF /tE in healthy, awake 3-month-old infants, while a weak association was observed adjusting for fetal femur length.

Reference intervals for platelet large cell ratio, platelet distribution width, plateletcrit and standard haematological parameters determined on the Sysmex XN-10 in a cohort of 30,917 Danish blood donors

With the introduction of the Sysmex XN-10, new platelet indices reflecting platelet maturity can be obtained alongside with a full blood count. Therefore, the need for verified reference intervals is present. The purpose of this study was to establish reference intervals for the platelet indices: platelet large cell ratio (P-LCR), platelet distribution width (PDW) and plateletcrit (PCT) in a large Scandinavian cohort. Furthermore, we aimed to verify previously established reference intervals of haematological parameters included in a full blood count. Blood samples were obtained from healthy Danish blood donors and analysed by use of the Sysmex XN-10 analyser (Sysmex, Kobe, Japan). Non-parametric 95% reference intervals were determined as the 2.5 and 97.5 percentile and presented with 90% confidence intervals (CI). In total, 30,917 blood donors were included and the following reference intervals were established: P-LCR, ratio: 17.3 (90% CI: 17.2 – 17.5) – 46.2 (90% CI:45.9 – 46.4); P DW, fL:9.5 (90% CI: 9.5 – 9.5) – 17.2 (90% CI: 17.2 – 17.3) and PCT, fraction: 0.18 (0.18 – 0.18) – 0.38 (0.38 – 0.39). The reference intervals were stable across age and sex. Furthermore, reference intervals for the remaining haematological parameters included in a full blood count were verified and found in line with the previously established reference intervals.