Publications by authors named "Engelbrechtsen L"

This review summarises the present knowledge of prophylactic progesterone and preterm birth. Preterm birth (less-than 37 weeks) is a leading cause of neonatal mortality and morbidity worldwide. The incidence varies globally but remains low in the Nordic countries (5-6%).

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The fetal insulin hypothesis proposes that low birthweight and type 2 diabetes (T2D) in adulthood may be two phenotypes of the same genotype. In this study we aimed to explore this theory further by testing the effects of GWAS-identified genetic variants related to insulin release and sensitivity on fetal growth and blood flow from week 20 of gestation to birth and on placental weight at birth. We calculated genetic risk scores (GRS) of first phase insulin release (FPIR), fasting insulin (FI), combined insulin resistance and dyslipidaemia (IR + DLD) and insulin sensitivity (IS) in a study population of 665 genotyped newborns.

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Article Synopsis
  • A healthy placenta is crucial for both the mother and fetus during pregnancy, and this study uses placental weight as a measure of its growth.
  • Genome-wide analyses across the genomes of mothers, fathers, and fetuses identified 40 genetic signals related to placental weight, revealing a mix of influences from both parents and the fetus.
  • The findings suggest that higher placental weight, driven by fetal genetics, is linked to an increased risk of preeclampsia and shorter pregnancy duration, highlighting the role of fetal insulin in regulating placental growth.
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  • Bilirubin is the product of red blood cell breakdown and has protective health benefits, being linked to lower risks of cardiovascular disease and type 2 diabetes in adults.
  • The study explored the connections between bilirubin levels, cardiometabolic risk factors, and inflammation in Danish children and adolescents, examining over 3,300 participants.
  • Results indicated that higher bilirubin levels were significantly associated with healthier cardiometabolic profiles while also showing positive associations with certain inflammatory markers.
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Aims: Rare variants in the glucokinase gene (GCK) cause Maturity-Onset Diabetes of the Young (MODY2/GCK-MODY). We investigated the prevalence of GCK variants, phenotypic characteristics, micro- and macrovascular disease at baseline and follow-up, and treatment among individuals with and without pathogenic GCK variants.

Methods: This is a cross-sectional study in a population-based cohort of 5,433 individuals without diabetes (Inter99 cohort) and in 2,855 patients with a new clinical diagnosis of type 2 diabetes (DD2 cohort) with sequencing of GCK.

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Maternal morbidity and mortality continue to rise, and pre-eclampsia is a major driver of this burden. Yet the ability to assess underlying pathophysiology before clinical presentation to enable identification of pregnancies at risk remains elusive. Here we demonstrate the ability of plasma cell-free RNA (cfRNA) to reveal patterns of normal pregnancy progression and determine the risk of developing pre-eclampsia months before clinical presentation.

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Body mass index (BMI) is a highly heritable polygenic trait. It is also affected by various environmental and behavioral risk factors. We used a BMI polygenic risk score (PRS) to study the interplay between the genetic and environmental factors defining BMI.

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Overweight in children is strongly associated with parental body mass index (BMI) and overweight. We assessed parental transmitted and non-transmitted genetic contributions to overweight in children from the Danish National Birth Cohort by constructing genetic risk scores (GRSs) from 941 common genetic variants associated with adult BMI and estimating associations of transmitted maternal/paternal and non-transmitted maternal GRS with child overweight. Maternal and paternal BMI (standard deviation (SD) units) had a strong association with childhood overweight [Odds ratio (OR): 2.

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Objectives: The aim of this study is to explore the contribution of genetically driven cardiometabolic risk factors for development of carotid arterial thickening in patients with type 2 diabetes.

Methods: In total, 12 genetic risk scores for blood pressure, blood lipids and glycaemic traits were constructed. The genetic risk scores were tested for association with carotid intima-media thickness and plaques in patients with type 2 diabetes ( n = 401) and in non-diabetic individuals ( n = 648) and for association with glucose levels in two population-based cohorts ( n = 1328 and n = 6161).

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Background: Recent GWAS studies have identified more than 300 SNPs associated with variation in blood pressure. We investigated whether a genetic risk score constructed from these variants is associated with burden of coronary heart disease.

Methods: From 2010-2014, 4,809 individuals admitted to coronary angiography in Capital Region of Copenhagen were genotyped.

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Fetal intrauterine growth is influenced by complex interactions between the maternal genes, environment and fetal genes. The aim of this study was to assess the effect of GWAS-identified genetic variants associated with birth weight on intrauterine fetal growth in 665 children. Fetal growth was estimated by two-dimensional ultrasound scans at 20, 25 and 32 weeks of gestation and growth trajectories were modeled using mixed linear regression.

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Background: Patients with long QT syndrome due to rare loss-of-function mutations in the human ether-á-go-go-related gene (hERG) have prolonged QT interval, risk of arrhythmias, increased secretion of insulin and incretins and impaired glucagon response to hypoglycemia. This is caused by a dysfunctional Kv11.1 voltage-gated potassium channel.

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Background: Dislipidaemia and increased levels of apolipoprotein B (apoB) in individuals with obesity are risk factors for development of cardiovascular disease (CVD). The aim of this study was to investigate the effect of weight loss and weight maintenance with and without liraglutide treatment on plasma lipid profiles and apoB.

Methods: Fifty-eight individuals with obesity (body mass index 34.

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Key Points: Obesity during pregnancy and childbirth is associated with labour dystocia leading to instrumental or operative delivery, but the underlying pathophysiological mechanisms remain unclear and insufficient uterine contractility has been suggested. This study examined whether reduced myometrial mitochondrial capacity or quantity could contribute as a pathophysiological mechanism to labour dystocia. Data did not support reduced myometrial mitochondrial capacity or quantity in the myometrium at term in obese women, but a reduced myocyte density with increased triglyceride content was demonstrated, which could lead to poorer uterine contractility.

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The TCF7L2 rs7903146 T-allele shows the strongest association with type 2 diabetes (T2D) among common gene variants. The aim of this study was to assess circulating levels of metabolites following a meal test in individuals carrying the high risk rs790346 TT genotype (cases) and low-risk CC genotype (controls). Sixty-two men were recruited based on TCF7L2 genotype, 31 were TT carriers and 31 were age- and BMI-matched CC carriers.

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Statins are a widely used group of drugs which can lower cholesterol levels. Recently, there has been emerging evidence that statins may decrease the formation of cholesterol gallstones and several studies have reported invert association between symptomatic cholesterol gallstones and statin use. Subsequent evidence for decrease in gallstone-associated complications among statin users have not been clearly described.

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The aim of this study was to summarize current knowledge and provide perspectives on the relationships between human genetic variants, type 2 diabetes, antidiabetic treatment, and disease progression. Type 2 diabetes is a complex disease with clear-cut diagnostic criteria and treatment guidelines. Yet, the interindividual response to therapy and slope of disease progression varies markedly among patients with type 2 diabetes.

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It is important to be aware of the risk of abnormally invasive placenta in patients with a history of Asherman syndrome and uterine scarring. A prenatal diagnosis by ultrasonography is useful when planning of mode of delivery.

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Background: Although management of twin deliveries has been a topic of discussion for decades, a consensus on how to deliver twins is lacking. The objective of this study was to examine short-term neonatal outcome of the second twin delivered by cesarean section after vaginal delivery of the first-born twin (combined delivery) and to identify predictors of combined delivery.

Methods: This study was a 3-year, population-based, retrospective cohort investigation of 1,254 twin births in Denmark.

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Objectives: To assess the detection rate of triploidy at first-trimester screening for trisomy 21 and evaluate outcome in triploid pregnancies.

Methods: From 2008 to 2011, 198 427 women with singleton pregnancies underwent first-trimester screening between 11 + 2 and 14 + 0 weeks' gestation. Screening parameters included nuchal translucency, maternal serum free β-human chorionic gonadotropin (β-hCG) and pregnancy-associated plasma protein-A (PAPP-A).

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