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OBJECTIVE: Metabolic syndrome components may cumulatively increase the risk of diabetic polyneuropathy (DPN) in type 2 diabetes mellitus (T2DM) patients, driven by insulin resistance and hyperinsulinemia. We investigated the prevalence of DPN in three T2DM subgroups based on indices of β-cell function and insulin sensitivity.RESEARCH DESIGN AND METHODS: We estimated β-cell function (HOMA2-B) and insulin sensitivity (HOMA2-S) in 4,388 Danish patients with newly diagnosed T2DM. Patients were categorized into subgroups of hyperinsulinemic (high HOMA2-B, low HOMA2-S), classical (low HOMA2-B, low HOMA2-S), and insulinopenic (low HOMA2-B, high HOMA2-S) T2DM. After a median follow-up of 3 years, patients filled the Michigan Neuropathy Screening Instrument questionnaire (MNSIq) to identify DPN (score ≥ 4). We used Poisson regression to calculate adjusted prevalence ratios (PRs) for DPN, and spline models to examine the association with HOMA2-B and HOMA2-S.RESULTS: A total of 3,397 (77%) patients filled in the MNSIq. The prevalence of DPN was 23% among hyperinsulinemic, 16% among classical, and 14% among insulinopenic patients. After adjusting for demographics, diabetes duration and therapy, lifestyle behaviors, and metabolic syndrome components (waist circumference, triglycerides, HDL cholesterol, hypertension, and HbA1c), the PR of DPN was 1.35 (95% CI 1.15-1.57) for the hyperinsulinemic compared with the classical patients. In spline analyses, we observed a linear relation of higher DPN prevalence with increasing HOMA2-B, independent of both metabolic syndrome components and HOMA2-S.CONCLUSIONS: Hyperinsulinemia marked by high HOMA2-B is likely an important risk factor for DPN beyond metabolic syndrome components and insulin resistance. This should be considered when developing interventions to prevent DPN.

BACKGROUND: Migraine carries risk of myocardial infarction (MI) and stroke. The risk of premature MI (i.e., among young adults) and stroke differs between men and women; previous studies indicate that migraine is mainly associated with an increased risk of stroke among young women. The aim of this study was to examine impact of migraine on the risk of premature (age ≤60 years) MI and ischemic/hemorrhagic stroke among men and women.METHODS AND FINDINGS: Using Danish medical registries, we conducted a nationwide population-based cohort study (1996 to 2018). Redeemed prescriptions for migraine-specific medication were used to identify women with migraine (n = 179,680) and men with migraine (n = 40,757). These individuals were matched on sex, index year, and birth year 1:5 with a random sample of the general population who did not use migraine-specific medication. All individuals were required to be between 18 and 60 years old. Median age was 41.5 years for women and 40.3 years for men. The main outcome measures to assess impact of migraine were absolute risk differences (RDs) and hazard ratios (HRs) with 95% confidence intervals (CIs) of premature MI, ischemic, and hemorrhagic stroke, comparing individuals with migraine to migraine-free individuals of the same sex. HRs were adjusted for age, index year, and comorbidities. The RD of premature MI for those with migraine versus no migraine was 0.3% (95% CI [0.2%, 0.4%]; p < 0.001) for women and 0.3% (95% CI [-0.1%, 0.6%]; p = 0.061) for men. The adjusted HR was 1.22 (95% CI [1.14, 1.31]; p < 0.001) for women and 1.07 (95% CI [0.97, 1.17]; p = 0.164) for men. The RD of premature ischemic stroke for migraine versus no migraine was 0.3% (95% CI [0.2%, 0.4%]; p < 0.001) for women and 0.5% (95% CI [0.1%, 0.8%]; p < 0.001) for men. The adjusted HR was 1.21 (95% CI [1.13, 1.30]; p < 0.001) for women and 1.23 (95% CI [1.10, 1.38]; p < 0.001) for men. The RD of premature hemorrhagic stroke for migraine versus no migraine was 0.1% (95% CI [0.0%, 0.2%]; p = 0.011) for women and -0.1% (95% CI [-0.3%, 0.0%]; p = 0.176) for men. The adjusted HR was 1.13 (95% CI [1.02, 1.24]; p = 0.014) for women and 0.85 (95% CI [0.69, 1.05]; p = 0.131) for men. The main limitation of this study was the risk of misclassification of migraine, which could lead to underestimation of the impact of migraine on each outcome.CONCLUSIONS: In this study, we observed that migraine was associated with similarly increased risk of premature ischemic stroke among men and women. For premature MI and hemorrhagic stroke, there may be an increased risk associated with migraine only among women.

Objective To examine prevalence of novel newborn types among 165 million livebirths in 23 countries from 2000 to 2021. Design Population-based, multi-country analysis. Setting National data systems in 23 middle and high-income countries.Population Liveborn infants Methods Country teams with high-quality data were invited to be part of the Vulnerable Newborn Measurement Collaboration. We classified livebirths by six newborn types based on gestational age information (preterm, PT, 90th centile) for gestational age, according to INTERGROWTH-21st standards. We considered small newborn types of any combination of preterm or SGA and Term+LGA was considered large. Time trends were analysed using three-year moving averages for small and large types.Main Outcome Measures Prevalence of six newborn types.Results We analysed 165,017,419 livebirths and the median prevalence of small types was 11.7% (highest in Malaysia (26%) and Qatar (15.7%)). Overall, 18.1% of newborns were large (T+LGA), and was highest in Estonia 28.8% and Denmark 25.9%. Time trends of small and large infants were relatively stable in most countries. Conclusions The distribution of newborn types varies across the 23 middle and high-income countries. Small newborn types were highest in West-Asian countries and large types in Europe. To better understand the global patterns of these novel newborn types, more information is needed especially from low- and middle- income countries.

Objective: To compare neonatal mortality associated with six novel vulnerable newborn types in 125.5 million livebirths across 15 countries, 2000 to 2020.Design: Population-based, multi-country study. Setting: National data systems in 15 middle and high-income countries.Methods: We used individual-level datasets identified for the Vulnerable Newborn Measurement Collaboration. We examined the contribution to neonatal mortality of six newborn types combining gestational age (preterm, PT vs term, T) and size-for-gestational age (small (SGA, 90th centile)) according to INTERGROWTH-21st newborn standards. Newborn babies with PT or SGA were defined as small and T+LGA was considered as large. We calculated risk ratios (RRs) and population attributable risks (PAR%) for the six newborn types. Main Outcome Measures Mortality of six newborn types Results Of 125.5 million livebirths analysed, risk ratios were highest amongst PT+SGA (median: 67.2, Interquartile Range, IQR, 45.6, 73.9), PT+AGA (median: 34.3, IQR, 23.9, 37.5), and PT+LGA (median: 28.3, IQR, 18.4, 32.3). At the population level, PT+AGA was the greatest contributor to newborn mortality (median PAR%: 53.7, IQR, 44.5, 54.9). Mortality risk was highest among newborns Conclusion Preterm newborn types were the most vulnerable, and associated with highest mortality, particularly with co-existence of preterm and SGA. As PT+AGA is more prevalent, it is responsible for greatest burden of neonatal deaths at population level.

ObjectiveTo compare neonatal mortality associated with six novel vulnerable newborn types in 125.5 million live births across 15 countries, 2000–2020.DesignPopulation-based, multi-country study.SettingNational data systems in 15 middle- and high-income countries.MethodsWe used individual-level data sets identified for the Vulnerable Newborn Measurement Collaboration. We examined the contribution to neonatal mortality of six newborn types combining gestational age (preterm [PT] versus term [T]) and size-for-gestational age (small [SGA], 90th centile) according to INTERGROWTH-21st newborn standards. Newborn babies with PT or SGA were defined as small and T + LGA was considered as large. We calculated risk ratios (RRs) and population attributable risks (PAR%) for the six newborn types.Main outcome measuresMortality of six newborn types.ResultsOf 125.5 million live births analysed, risk ratios were highest among PT + SGA (median 67.2, interquartile range [IQR] 45.6–73.9), PT + AGA (median 34.3, IQR 23.9–37.5) and PT + LGA (median 28.3, IQR 18.4–32.3). At the population level, PT + AGA was the greatest contributor to newborn mortality (median PAR% 53.7, IQR 44.5–54.9). Mortality risk was highest among newborns born before 28 weeks (median RR 279.5, IQR 234.2–388.5) compared with babies born between 37 and 42 completed weeks or with a birthweight less than 1000 g (median RR 282.8, IQR 194.7–342.8) compared with those between 2500 g and 4000 g as a reference group.ConclusionPreterm newborn types were the most vulnerable, and associated with the highest mortality, particularly with co-existence of preterm and SGA. As PT + AGA is more prevalent, it is responsible for the greatest burden of neonatal deaths at population level.

Objective: To examine the prevalence of novel newborn types among 165 million live births in 23 countries from 2000 to 2021. Design: Population-based, multi-country analysis. Setting: National data systems in 23 middle- and high-income countries. Population: Liveborn infants. Methods: Country teams with high-quality data were invited to be part of the Vulnerable Newborn Measurement Collaboration. We classified live births by six newborn types based on gestational age information (preterm 90th centile) for gestational age, according to INTERGROWTH-21st standards. We considered small newborn types of any combination of preterm or SGA, and term + LGA was considered large. Time trends were analysed using 3-year moving averages for small and large types. Main outcome measures: Prevalence of six newborn types. Results: We analysed 165 017 419 live births and the median prevalence of small types was 11.7% – highest in Malaysia (26%) and Qatar (15.7%). Overall, 18.1% of newborns were large (term + LGA) and was highest in Estonia 28.8% and Denmark 25.9%. Time trends of small and large infants were relatively stable in most countries. Conclusions: The distribution of newborn types varies across the 23 middle- and high-income countries. Small newborn types were highest in west Asian countries and large types were highest in Europe. To better understand the global patterns of these novel newborn types, more information is needed, especially from low- and middle-income countries.

Health registries provide opportunities for conducting large-scale, population-based studies, but attention must be devoted to their specific limitations. Herein, we describe potential limitations that may affect the validity of registry-based research. Our review includes descriptions of 1) populations, 2) variables, 3) medical coding systems for medical information and 4) selected key methodological challenges. Knowledge of such factors and epidemiological study designs in general is likely to increase the quality of registry-based research and reduce potential biases.

Objective: To compare neonatal mortality associated with six novel vulnerable newborn types in 125.5 million live births across 15 countries, 2000–2020. Design: Population-based, multi-country study. Setting: National data systems in 15 middle- and high-income countries. Methods: We used individual-level data sets identified for the Vulnerable Newborn Measurement Collaboration. We examined the contribution to neonatal mortality of six newborn types combining gestational age (preterm [PT] versus term [T]) and size-for-gestational age (small [SGA], 90th centile) according to INTERGROWTH-21st newborn standards. Newborn babies with PT or SGA were defined as small and T + LGA was considered as large. We calculated risk ratios (RRs) and population attributable risks (PAR%) for the six newborn types. Main outcome measures: Mortality of six newborn types. Results: Of 125.5 million live births analysed, risk ratios were highest among PT + SGA (median 67.2, interquartile range [IQR] 45.6–73.9), PT + AGA (median 34.3, IQR 23.9–37.5) and PT + LGA (median 28.3, IQR 18.4–32.3). At the population level, PT + AGA was the greatest contributor to newborn mortality (median PAR% 53.7, IQR 44.5–54.9). Mortality risk was highest among newborns born before 28 weeks (median RR 279.5, IQR 234.2–388.5) compared with babies born between 37 and 42 completed weeks or with a birthweight less than 1000 g (median RR 282.8, IQR 194.7–342.8) compared with those between 2500 g and 4000 g as a reference group. Conclusion: Preterm newborn types were the most vulnerable, and associated with the highest mortality, particularly with co-existence of preterm and SGA. As PT + AGA is more prevalent, it is responsible for the greatest burden of neonatal deaths at population level.

Objective: Most research on safety of attention-deficit/hyperactivity disorder (ADHD) medications during pregnancy concerns central nervous system stimulants, while little is known about the safety of atomoxetine, a primary treatment alternative. We assessed the prevalence of major congenital malformations overall, and cardiac malformations and limb malformations specifically, after first-trimester exposure. Methods: In this cohort study, we included all approximately 2.4 million pregnancies ending in live births recorded in the population-based nationwide health registers of Denmark, Iceland, Norway, and Sweden (2003-2017) and approximately 1.8 million publicly insured pregnancies ending in live births recorded in the US Medicaid Analytic eXtract (MAX, 2001-2013) health care claims database. We compared the prevalence of major congenital malformations in the newborn among pregnancies exposed and unexposed to atomoxetine. For each country, we calculated prevalence ratios (PRs), crude and stratified by propensity scores (PSs). We pooled the country-specific PS strata to obtain a PR adjusted for potential confounding factors. Results: We identified 368 pregnancies exposed to atomoxetine during the first trimester in the 4 Nordic countries and 622 in the US. The pooled crude PR for any major congenital malformation was 1.18 (95% CI, 0.88-1.60), and the adjusted PR was 0.99 (95% CI, 0.74-1.34). For cardiac malformations, the adjusted PR was 1.34 (95% CI, 0.86-2.09). For limb malformations, the adjusted PR was 0.90 (95% CI, 0.38-2.16). Conclusions: After atomoxetine exposure in early pregnancy, we observed no increase in major congenital malformations overall and, although with some uncertainty due to sample size, no statistically increased risk estimates for cardiac malformations and limb malformations.

Supplemental material, sj-docx-1-sjp-10.1177_14034948221147096 for Towards more comprehensive nationwide familial aggregation studies in Denmark: The Danish Civil Registration System versus the lite Danish Multi-Generation Register by Jeppe Klok Due, Marianne Giørtz Pedersen, Sussie Antonsen, Joen Rommedahl, Esben Agerbo, Preben Bo Mortensen, Henrik Toft Sørensen, Jonas Færch Lotz, Laura Cabello Piqueras, Constanza Fierro, Antonia Karamolegkou, Christian Igel, Phillip Rust, Anders Søgaard and Carsten Bøcker Pedersen in Scandinavian Journal of Public Health

Additional file 1: Figure 1. Type (1a) and Discipline (1b) of Post Program Publications; Danish American Research Exchange (DARE) students, 2015-2020.

Additional file 2: Figure 2. Academic Degrees of Danish American Research Exchange (DARE) Students, 2015-2020.