Michael Christiansen

Statens Serum Institut | ssi · Department for Congenital Disorders

Purpose Omphalocele is a congenital abdominal wall defect associated with a high risk of morbidity and mortality, with co-occurring congenital malformations often being the most important prognostic factor. High rates of spontaneous and medical terminations have been reported among pregnancies with omphalocele and co-occurring malformations. Few st...

APOE-ɛ4 is a genetic risk factor for Alzheimer's disease (AD). AD is associated with reduced cerebral blood flow (CBF) and with microvascular changes that limit the transport of oxygen from blood into brain tissue: reduced microvascular cerebral blood volume and high relative transit time heterogeneity (RTH). Healthy APOE-ɛ4 carriers reveal brain r...

Background Birth weight (BW) is associated with risk of cardiometabolic disease (CMD) in adulthood, which may depend on the state of obesity, in particular if developed at a young age. We hypothesised that BW and a polygenic score (PGS) for BW were associated with cardiometabolic risk and related plasma protein levels in children and adolescents. W...

Objective To evaluate the association between maternal BMI and congenital heart defects (CHDs) in the offspring when including live births, stillbirths, aborted and terminated pregnancies and to investigate if maternal interpregnancy weight changes between the first and second pregnancy influences the risk of foetal CHDs. Methods A nationwide coho...

Context Pediatric obesity is characterized by insulin resistance, yet it remains unclear whether insulin resistance contributes to abnormalities in glucagon and incretin secretion. Objective To examine whether fasting and stimulated glucagon, GLP-1, and GIP concentrations differ between children and adolescents with obesity and insulin resistance...

Background: Childhood obesity is a multifactorial disease with complex etiology. Obstetrical factors are seldom taken into considerations. Objectives: To investigate the association between parental, obstetric and lifestyle characteristics, and childhood overweight and obesity. Methods: This retrospective cohort study evaluated associations between...

Objective To evaluate the association between maternal BMI and congenital heart defects (CHDs) in the offspring when including live births, stillbirths, aborted and terminated pregnancies and to investigate if maternal interpregnancy weight changes between the first and second pregnancy influences risk of foetal CHDs. Methods A nationwide cohort st...

Objective: To determine whether mitochondrial haplogroups function as disease-modifiers or as susceptibility factors in preeclampsia using a traditional haplogroup association model. Methods: This retrospective study haplotyped 235 control and 78 preeclamptic pregnancies from Denmark using either real-time PCR or Sanger sequencing depending on the...

Background & aims: Genome-wide association studies have identified steatogenic variants that also showed pleiotropic effects on cardiometabolic traits in adults. We investigated the effect of eight previously reported genome-wide significant steatogenic variants, individually and combined in a weighted genetic risk score (GRS), on liver and cardio...

Background and purpose: Congenital clubfoot is a common musculoskeletal anomaly, with a suspected multifactorial etiopathogenesis. To begin examining its etiopathogenesis in a nationwide Danish population, liveborn infants with clubfoot were ascertained to classify co-occurring congenital anomalies, estimate annual prevalence, and compare occurrenc...

Numerous circulating microRNAs (miRNAs) have been detected in maternal blood. Initial studies in third trimester demonstrated differential miRNA expression profiles between uncomplicated pregnancies and pregnancies complicated by pre-eclampsia (PE). Recently, studies in first trimester have shown similar differential profiles, however, these studie...

Introduction Pre-eclampsia (PE) is a leading cause of perinatal morbidity and mortality worldwide. Low-dose aspirin can prevent PE in high risk pregnancies if started early. However, despite intense research into the area, early pregnancy screening for PE risk is still not a routine part of pregnancy care. Several studies have described the applica...

In Denmark, a nationwide COVID-19 lockdown was implemented on March 12, 2020 and eased on April 14, 2020. The COVID-19 lockdown featured reduced prevalence of extremely preterm or extremely low birthweight births. This study aims to explore the impact of this COVID-19 lockdown on term birthweights in Denmark. We conducted a nationwide register-base...

Objective: To evaluate the association between maternal obesity and congenital heart defects (CHDs) in the offspring when including live births, stillbirths and terminated pregnancies and to investigate if interpregnancy weight change between the first and second pregnancy influences risk of fetal CHDs. Methods: A nationwide cohort study of all sin...

Background Lectin‐like oxidized low‐density lipoprotein (ox‐LDL) receptor‐1 is a scavenger receptor for oxidized low‐density lipoprotein. In adults, higher soluble lectin‐like ox‐LDL receptor‐1 (sLOX‐1) levels are associated with cardiovascular disease, type 2 diabetes, and obesity, but a similar link in pediatric overweight/obesity remains uncerta...

Hydrocephalus is one of the most common congenital disorders of the central nervous system and often displays psychiatric co-morbidities, in particular autism spectrum disorder. The disease mechanisms behind hydrocephalus are complex and not well understood, but some association with dysfunctional cilia in the brain ventricles and subarachnoid spac...

The world has seen numerous infectious disease outbreaks in the past decade. In many cases these outbreaks have had considerable perinatal health consequences including increased risk of preterm delivery (e.g., influenza, measles, and COVID-19), and the delivery of low birth weight or small for gestational age babies (e.g., influenza, COVID-19). Fu...

The serum adiponectin/leptin ratio (A/L ratio) is a surrogate marker of insulin sensitivity. Pre-eclampsia (PE) is associated with maternal metabolic syndrome and occasionally impaired fetal growth. We assessed whether the A/L ratio in first-trimester maternal serum was associated with PE and/or birth weight. Adiponectin and leptin were quantitated...

The serum adiponectin-leptin ratio (A/L ratio) is a surrogate marker of insulin sensitivity. Pre-eclampsia (PE) is associated with maternal metabolic syndrome and occasionally impaired fetal growth. We assessed whether the A/L ratio in first-trimester maternal serum was associated with PE and/or birth weight. Adiponectin and leptin were quantitated...

In Denmark, a nationwide COVID–19 lockdown was implemented on March 12, 2020 and eased on April 14, 2020. The COVID–19 lockdown featured reduced prevalence of extremely preterm or extremely low birth weight births. Here we explore the impact of this COVID–19 lockdown on term birth weights in Denmark. We conducted a nationwide register–based cohort...

Denmark's response to the COVID-19 pandemic was to issue guidelines on containment, isolation, and surveillance. Subsequently, Denmark entered a period with variable mitigation measures including closures of schools and workplaces, travel restrictions, and restrictions on public gatherings. A Danish study covering the lockdown period (March 12 – Ap...

Hydrocephalus is a genetically and phenotypically heterogenous condition with complex etiology. Ciliary dysfunction has been shown to play a role, either through interference with signaling functions in primary cilia, cerebrospinal fluid flow by motile cilia, or both. Ciliary function is highly energy-dependent, consequently, variation in mitochond...

Introduction Pre-eclampsia (PE) is a leading cause of perinatal morbidity and mortality worldwide. Low-dose aspirin can prevent PE in high risk pregnancies if started early. However, despite intense research into the area, first-trimester screening for PE risk is still not a routine part of pregnancy care. Several studies have described the applica...

Objectives Pre-eclampsia (PE) is an important cause of perinatal morbidity and mortality. Despite an elusive pathophysiology, PE has been associated with changes in maternal serum concentrations of adipokines in early pregnancy. We hypothesized, that symbolic regression might identify interactions between adipokines and PE, which may have eluded re...

Background Hydrocephalus is one of the most common congenital disorders of the central nervous system and often displays psychiatric co-morbidities, in particular autism spectrum disorder. The disease mechanisms behind hydrocephalus are complex and not well understood, but some association with dysfunctional cilia in the brain ventricles and subara...

The aim of this study was to determine whether COVID-19 restrictions had an impact on Chlamydia trachomatis infections compared with 2018 and 2019. A retrospective nationwide observational study was performed using monthly incidences of laboratory-confirmed chlamydia cases and number of tests, obtained from Danish national surveillance data. Testin...

Using provisional or opportunistic data, three nationwide studies (The Netherlands, the USA and Denmark) have identified a reduction in preterm or extremely preterm births during periods of COVID-19 restrictions. However, none of the studies accounted for perinatal deaths. To determine whether the reduction in extremely preterm births, observed in...

Context In adults, hyperglucagonemia is associated with type 2 diabetes, impaired glucose tolerance, and obesity. The role of glucagon in pediatric overweight/obesity remains unclear. Objective We examined whether fasting concentrations of glucagon are elevated in youth with overweight/obesity and whether this associates with cardiometabolic risk...

Importance: Preterm birth, particularly extremely preterm birth, has been associated with substantial morbidity and mortality. Research during SARS-CoV-2-related lockdowns revealed reductions in the more severe subtypes of preterm birth in some countries, suggesting the presence of preventable risk factors, such as infectious diseases or social be...

Background The association between autism spectrum disorder and hydrocephalus is not well understood, despite demonstrated links between autism spectrum disorder and cerebrospinal fluid abnormalities. Based on the hypothesis that autism spectrum disorder and hydrocephalus may, at least in some cases, be two manifestations of a shared congenital bra...

Objective To investigate the relationship between in utero growth conditions, as indicated by neonatal anthropometrics, and childhood obesity treatment response in order to examine the potential usefulness of neonatal anthropometrics as a potential childhood obesity treatment stratification tool. Study design The study included 2,474 children and...

Aims We examined if a congenital long QT syndrome (cLQTS) diagnosis and severity of cLQTS disease manifestation was associated with increased risk of depression, anxiety, and all-cause mortality. Methods and results All patients with known cLQTS in Denmark were identified using nationwide registries and specialized inherited cardiac disease clinic...

Objectives: COVID-19 policies have been employed in Denmark since March 2020. We examined whether COVID-19 restrictions had an impact on Chlamydia trachomatis infections compared with 2018 and 2019. Methods: This retrospective nation-wide Danish observational study was performed using monthly incidences of laboratory confirmed chlamydia cases and n...

Objectives: Human milk oligosaccharides (HMOs) impact the intestinal microbiota by increasing beneficial bacteria in infants and adults, and are safe and well tolerated in these age groups. Effects on intestinal microbiota, safety, and digestive tolerance in children have not been, however, assessed. The aims of this trial were to evaluate if HMOs...

Importance: Using provisional or opportunistic data, three nationwide studies (The Netherlands, USA, and Denmark) have identified a reduction in preterm or extremely preterm births during periods of COVID-19 restrictions. However, these findings have been challenged as none of the studies accounted for perinatal deaths. Objective: To determine whet...

Background Congenital heart defects (CHDs) are the most common congenital malformations. The aetiology of CHDs is complex. Large cohort studies and systematic reviews and meta-analyses based on these have reported an association between higher risk of CHDs in the offspring and individual maternal metabolic disorders such as obesity, diabetes, hyper...

Leptin is secreted by the placenta and has a multi-facetted role in the regulation of functions related to pregnancy. Metabolic disorders and insufficient homeostatic compensatory mechanisms involving leptin during pregnancy play a decisive role in the development of pre-eclampsia (PE) and give rise to compromised intrauterine growth conditions and...

Introduction Central nervous system (CNS) tumors constitute the most common form of solid neoplasms in children, but knowledge on genetic predisposition is sparse. In particular, whether susceptibility attributable to common variants is shared across CNS tumor types in children has not been investigated. The purpose of this study was to explore pot...

Context: The importance of fasting GLP-1 in altered metabolic outcomes has been questioned. Objective: To assess if fasting GLP-1 differs in children and adolescents with overweight/obesity compared to a population-based reference, and whether concentrations predict cardiometabolic risk (CMR) factors. Methods: Analyses were based on The Danish...

Introduction The congenital Long QT Syndrome (cLQTS) is associated with an increased risk of sudden cardiac death (SCD). Thus, cLQTS patients are susceptible to develop depression or anxiety, both of which have been associated with poor outcomes including risk of mortality. Aim We examined if a cLQTS diagnosis and the severity of cLQTS disease ons...

To explore the impact of COVID-19 lockdown on premature birth rates in Denmark, a nationwide register-based prevalence proportion study was conducted on all 31 180 live singleton infants born in Denmark between 12 March and 14 April during 2015–2020. The distribution of gestational ages (GAs) was significantly different (p=0.004) during the lockdow...

B-type natriuretic peptide (BNP) is a cardiac hormone secreted predominantly from the ventricles in response to increased ventricular pressure. Along this line, hypertensive patients with left ventricular hypertrophy typically have high circulating BNP concentrations. BNP has natriuretic and vasodilatory actions. Obese persons have low circulating...

Background: Foetal development indicates the risk of later disease, but has only been associated with few psychiatric disorders. An aggregated molecular marker of development - DNA methylation based estimates of gestational age (DNAmGA) adjusted for GA, can be indicative of foetal health and development. Twins have the same chronological GA and mon...

Background The association between autism spectrum disorder and hydrocephalus is not well understood, despite demonstrated links between autism spectrum disorder and cerebrospinal fluid abnormalities. Based on the hypothesis that autism spectrum disorder and hydrocephalus may, at least in some cases, be two manifestations of a shared congenital bra...

Background The association between autism spectrum disorder and hydrocephalus is not well understood, despite demonstrated links between autism spectrum disorder and cerebrospinal fluid abnormalities. Based on the hypothesis that autism spectrum disorder and hydrocephalus may, at least in some cases, be two manifestations of a shared congenital bra...

Mitochondrial DNA (mtDNA) haplogroup (hg) H has been reported as a susceptibility factor for hypertrophic cardiomyopathy (HCM). This was established in genetic association studies, however, the SNP or SNP’s that are associated with the increased risk have not been identified. Hg H is the most frequent European mtDNA hg with greater than 80 subhaplo...

Congenital heart defects (CHDs) are the most common congenital malformation and will, in severe cases, have a serious impact on neonatal mortality and morbidity. The aetiology of CHDs is complex. Large cohort studies have reported an association between increased risk of CHDs in the offspring and individual maternal metabolic disorders such as diab...

Objectives To explore the impact of COVID-19 lockdown on premature birth rates in Denmark Design Nationwide register-based prevalence proportion study. Participants 31,180 live singleton infants born in Denmark between March 12, and April 14, from 2015 to 2020 Main outcome measures The Main outcome measure was the odds ratio of premature birth, per...

Background: Long QT syndrome (LQTS) is a rare genetic disorder and a major preventable cause of sudden cardiac death in the young. A causal rare genetic variant with large effect size is identified in up to 80% of probands (genotype positive) and cascade family screening shows incomplete penetrance of genetic variants. Furthermore, a proportion of...

Background and aims Pediatric obesity associates with both low-grade inflammation and cardiometabolic risk on the population level. Yet on an individual patient level, overweight/obesity does not always equal increased cardiometabolic risk. In this study, we examine whether low-grade inflammation associates with cardiometabolic risk in Danish child...

Monkeypox (MP) is a rare zoonotic disease that most commonly transmits from bush animals to humans in the Congo Basin of Africa. However, an increase in cases of MP has been observed over the past decades with frequent outbreaks as well as export of the disease out of the African continent. MP belongs to the same genus of viruses as smallpox, the O...

Background: It is imperative to develop markers for risk stratification and detection of cardiometabolic comorbidities in children with obesity. The adipokines leptin and adiponectin are both involved in fat mass regulation and the development of obesity-related disorders, furthermore, their ratio (L/A ratio) is suggested to be associated with ins...

Background The association between thyroid-stimulating hormone (TSH) concentrations and blood pressure is well described in adults, but only studied to a limited extent in children and adolescents and almost entirely in population-based cohorts. The present study investigates the association between TSH and blood pressure, and the influence of lept...

Mental disorders have for the majority of cases an unknown etiology, but several studies indicate that neurodevelopmental changes happen in utero or early after birth. We performed a nested case–control study of the relation between blood levels of neuro-developmental (S100B, BDNF, and VEGF-A) and inflammatory (MCP-1, TARC, IL-8, IL-18, CRP, and Ig...

Background Syncope is a common condition in the general population causing frequent hospitalisation and visits to the emergency department. Family aggregation and twin studies have previously indicated that syncope and collapse has a heritable component. Purpose We investigated whether common genetic variants predispose to syncope and collapse. M...

Background: We aimed to determine the mutation yield and clinical applicability of "molecular autopsy" following sudden arrhythmic death syndrome (SADS) by validating and utilizing low-cost high-throughput technologies: Fluidigm Access Array PCR-enrichment with Illumina HiSeq 2000 next generation sequencing (NGS). Methods: We validated and optim...

Age and apolipoprotein E (APOE) e4 genotype are two of the strongest known risk factors for sporadic Alzheimer's disease (AD). Neuroimaging has shown hemodynamic response changes with age, in asymptomatic carriers of the APOE e4 allele, and in AD. In this study, we aimed to characterize and differentiate age- and APOE gene-specific hemodynamic chan...

Aims Syncope is a common condition associated with frequent hospitalization or visits to the emergency department. Family aggregation and twin studies have shown that syncope has a heritable component. We investigated whether common genetic variants predispose to syncope and collapse. Methods and results We used genome-wide association data on syn...

Aims: It is Class I recommendation that congenital long QT syndrome (cLQTS) patients should avoid drugs that can cause torsades de pointes (TdP). We determined use of TdP risk drugs after cLQTS diagnosis and associated risk of ventricular arrhythmia and all-cause mortality. Methods and results: Congenital long QT syndrome patients (1995-2015) we...

Background Alterations in glucose metabolism that lead to the development of metabolic and cardiovascular disease may begin already in childhood. Objective This study aims to generate pediatric age and sex‐specific reference values for fasting concentrations of glucose, hemoglobin A1c (HbA1c), insulin, C‐peptide, and homeostasis model assessment:...

Thyroid-stimulating hormone (TSH) and thyroid hormones influence the functions of many organ systems, as well as child development and growth. Several studies have reported an association between ethnicity and thyroid hormones. This study aims to explore pediatric serum concentrations of TSH, free triiodothyronine (fT3), and free thyroxine (fT4) an...

Background Leptin and adiponectin are two key adipocyte secreted hormones and both are involved in several essential physiological mechanisms. Due to their central role in energy homeostasis their ratio, the leptin/adiponectin ratio, is believed to be a marker of metabolic derangement. Pediatric reference values are needed for the risk stratificati...

Mitochondrial dysfunction has been associated with schizophrenia (SZ) and bipolar disorder (BD). This review examines recent publications and novel associations between mitochondrial genes and SZ and BD. Associations of nuclear-encoded mitochondrial variants with SZ were found using gene- and pathway-based approaches. Two control region mitochondri...

Background Mitochondria play a significant role in human diseases. Genetic variants in mitochondrial DNA (mtDNA) – and in nuclear genes coding for mitochondrial function - have been associated with disease. Mitochondrial disease is clinically characterised by complex metabolic, neurological, muscular and psychiatric symptoms. SNPs in mtDNA have bee...

Background Disturbed mitochondrial function has been implicated in psychiatric disease. All mitochondria contain a small maternally inherited DNA (mtDNA) of 16.6 kb. Through evolution and genetic drift, the mtDNA sequence has become fixed into haplogroups (hgs) with a characteristic population and geographical distribution. Different hgs exhibit va...

Background Schizophrenia (SCZ) is a severe psychiatric disorder wherein the genetic risk factors are far from being fully understood. Multiple lines of evidence have suggested mitochondrial dysfunction in SCZ, but association of mitochondrial variants with SCZ has not been extensively investigated. Methods We conducted gene-based and gene-set anal...

Background Mitochondrial DNA (mtDNA) haplogroups (hgs) are evolutionarily conserved sets of mtDNA SNPs. Associations of hgs with geographical origin, disease and physiological characteristics have been reported, but have frequently not been reproducible. We assessed, using 418 mtDNA SNPs on the PsychChip (Illumina), the spatio-temporal distribution...

Mitochondrial DNA (mtDNA) haplogroups (hgs) are evolutionarily conserved sets of mtDNA SNP-haplotypes with characteristic geographical distribution. Associations of hgs with disease and physiological characteristics have been reported, but have frequently not been reproducible. Using 418 mtDNA SNPs on the PsychChip (Illumina), we assessed the spati...