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Dilated cardiomyopathy (DCM) is a leading cause of heart failure and cardiac transplantation. We report a genome-wide association study and multi-trait analysis of DCM (14,256 cases) and three left ventricular traits (36,203 UK Biobank participants). We identified 80 genomic risk loci and prioritized 62 putative effector genes, including several with rare variant DCM associations (MAP3K7, NEDD4L and SSPN). Using single-nucleus transcriptomics, we identify cellular states, biological pathways, and intracellular communications that drive pathogenesis. We demonstrate that polygenic scores predict DCM in the general population and modify penetrance in carriers of rare DCM variants. Our findings may inform the design of genetic testing strategies that incorporate polygenic background. They also provide insights into the molecular etiology of DCM that may facilitate the development of targeted therapeutics.

Introduction: Myocardial development is still transitioning by the time of birth making the cardiomyocyte vulnerable to maternal and perinatal factors. We aimed at investigating the impact of maternal and perinatal factors on the neonatal electrocardiogram. Methods: In a prospective cohort study, neonates underwent cardiac evaluation with electrocardiograms and echocardiograms (age 0–30 days). Associations between medical and demographic data, pregnancy, and birth-related factors, and electrocardiographic parameters were assessed. Results: A total of 15,928 singletons with normal echocardiograms were included (52% boys). Neonates were divided into groups by accumulated number of maternal/perinatal factors: 0, 1, 2, 3, 4, and ≥5, and between-group differences in electrocardiographic parameters were analysed. We observed an additive effect with a leftward shift of the QRS axis and QT prolongation (all p < 0.01). Comparing extreme groups (0 vs. ≥5 maternal/perinatal factors), we found a 4.3% more left-shifted QRS axis (117 vs. 112°, p < 0.001) and a 0.8% prolonged QTcFridericia (QTcF; 363 vs. 366 ms, p < 0.001); the effect on QTcF was most pronounced in neonates examined in the first week of life (360 vs. 368 ms, p < 0.0001). Conclusion: We observed a cumulative effect of maternal and perinatal factors on neonatal electrocardiographic parameters, including a more left-shifted QRS axis and increased QT duration, although the variation was within normal reference ranges. Our findings add to the knowledge on the neonatal cardiac transition and the cardiac effect of maternal/perinatal factors. Keywords:Cardiac conduction system, Electrocardiography, Neonates, Maternal factors, Perinatal factors, Introduction: Myocardial development is still transitioning by the time of birth making the cardiomyocyte vulnerable to maternal and perinatal factors. We aimed at investigating the impact of maternal and perinatal factors on the neonatal electrocardiogram. Methods: In a prospective cohort study, neonates underwent cardiac evaluation with electrocardiograms and echocardiograms (age 0-30 days). Associations between medical and demographic data, pregnancy, and birth-related factors, and electrocardiographic parameters were assessed. Results: A total of 15,928 singletons with normal echocardiograms were included (52% boys). Neonates were divided into groups by accumulated number of maternal/perinatal factors: 0, 1, 2, 3, 4, and ≥5, and between-group differences in electrocardiographic parameters were analysed. We observed an additive effect with a leftward shift of the QRS axis and QT prolongation (all p < 0.01). Comparing extreme groups (0 vs. ≥5 maternal/perinatal factors), we found a 4.3% more left-shifted QRS axis (117 vs. 112°, p < 0.001) and a 0.8% prolonged QTcFridericia (QTcF; 363 vs. 366 ms, p < 0.001); the effect on QTcF was most pronounced in neonates examined in the first week of life (360 vs. 368 ms, p < 0.0001). Conclusion: We observed a cumulative effect of maternal and perinatal factors on neonatal electrocardiographic parameters, including a more left-shifted QRS axis and increased QT duration, although the variation was within normal reference ranges. Our findings add to the knowledge on the neonatal cardiac transition and the cardiac effect of maternal/perinatal factors.

Importance: Recurrent pericarditis is a treatment challenge and often a debilitating condition. Drugs inhibiting interleukin 1 cytokines are a promising new treatment option, but their use is based on scarce biological evidence and clinical trials of modest sizes, and the contributions of innate and adaptive immune processes to the pathophysiology are incompletely understood. Objective: To use human genomics, transcriptomics, and proteomics to shed light on the pathogenesis of pericarditis. Design, Setting, and Participants: This was a meta-analysis of genome-wide association studies of pericarditis from 5 countries. Associations were examined between the pericarditis-associated variants and pericarditis subtypes (including recurrent pericarditis) and secondary phenotypes. To explore mechanisms, associations with messenger RNA expression (cis-eQTL), plasma protein levels (pQTL), and CpG methylation of DNA (ASM-QTL) were assessed. Data from Iceland (deCODE genetics, 1983-2020), Denmark (Copenhagen Hospital Biobank/Danish Blood Donor Study, 1977-2022), the UK (UK Biobank, 1953-2021), the US (Intermountain, 1996-2022), and Finland (FinnGen, 1970-2022) were included. Data were analyzed from September 2022 to August 2023. Exposure: Genotype. Main Outcomes and Measures: Pericarditis. Results: In this genome-wide association study of 4894 individuals with pericarditis (mean [SD] age at diagnosis, 51.4 [17.9] years, 2734 [67.6%] male, excluding the FinnGen cohort), associations were identified with 2 independent common intergenic variants at the interleukin 1 locus on chromosome 2q14. The lead variant was rs12992780 (T) (effect allele frequency [EAF], 31%-40%; odds ratio [OR], 0.83; 95% CI, 0.79-0.87; P = 6.67 × 10-16), downstream of IL1B and the secondary variant rs7575402 (A or T) (EAF, 45%-55%; adjusted OR, 0.89; 95% CI, 0.85-0.93; adjusted P = 9.6 × 10-8). The lead variant rs12992780 had a smaller odds ratio for recurrent pericarditis (0.76) tha

Objectives: Red blood cell parameters are frequently used biomarkers when assessing clinical status in newborns and in early childhood. Cell counts, amounts, and concentrations of these parameters change through gestation and after birth. Robust age-specific reference intervals are needed to optimize clinical decision making. Methods: The Copenhagen Baby Heart Study (CBHS) and the COMPARE study are prospective cohort studies including red blood cell parameters from 7,938 umbilical cord blood samples and 295 parallel venous blood samples from newborns with follow-up at two and at 14–16 months after birth. Results: For venous blood at birth, reference intervals for hemoglobin, erythrocytes, and hematocrit were 145–224 g/L, 4.1–6.4 × 1012/L, and 0.44–0.64, respectively. Hemoglobin, erythrocytes, and hematocrit were lower at birth in children delivered by prelabor cesarean section compared to vaginal delivery. Conversion algorithms based on term newborns were: venous hemoglobin=(umbilical cord hemoglobin-86.4)/0.39; venous erythrocytes=(umbilical cord erythrocytes-2.20)/0.44; and venous hematocrit=(umbilical cord hematocrit-0.24)/0.45. Conclusions: This study presents new reference intervals for red blood cell parameters in early childhood, describes the impact of delivery mode, and provide exact functions for converting umbilical cord to venous blood measurements for term newborns. These findings may improve clinical decision making within neonatology and infancy and enhance our clinical understanding of red blood cell parameters for health and diseases in early life.

IMPORTANCE Valsartan has shown promise in attenuating cardiac remodeling in patients with early-stage sarcomeric hypertrophic cardiomyopathy (HCM). Genetic testing can identify individuals at risk of HCM in a subclinical stage who could benefit from therapies that prevent disease progression. OBJECTIVE To explore the potential for valsartan to modify disease development, and to characterize short-term phenotypic progression in subclinical HCM. DESIGN, SETTING, AND PARTICIPANTS The multicenter, double-blind, placebo-controlled Valsartan for Attenuating Disease Evolution in Early Sarcomeric Hypertrophic Cardiomyopathy (VANISH) randomized clinical trial was conducted from April 2014 to July 2019 at 17 sites in 4 countries (Brazil, Canada, Denmark, and the US), with 2 years of follow-up. The prespecified exploratory VANISH cohort studied here included sarcomere variant carriers with subclinical HCM and early phenotypic manifestations (reduced E' velocity, electrocardiographic abnormalities, or an increased left ventricular [LV] wall thickness [LVWT] to cavity diameter ratio) but no LV hypertrophy (LVH). Data were analyzed between March and December 2022. INTERVENTIONS Treatment with placebo or valsartan (80mg/d for children weighing <35 kg, 160mg/d for children weighing ≥ 35kg, or 320mg/d for adults aged ≥18 years). MAIN OUTCOMES AND MEASURES The primary outcomewas a composite z score incorporating changes in 9 parameters of cardiac remodeling (LV cavity volume, LVWT, and LV mass; left atrial [LA] volume; E' velocity and S' velocity; and serum troponin and N-terminal prohormone of brain natriuretic peptide levels). RESULTS This study included 34 participants, with a mean (SD) age of 16 (5) years (all were White). A total of 18 participants (8 female [44%] and 10 male [56%]) were randomized to valsartan and 16 (9 female [56%] and 7 male [44%]) were randomized to placebo. No statistically significant effects of valsartan on cardiac remodeling were detected (mean cha

Ventricular septal defects (VSD) represent the most common congenital heart defect in newborns. We assessed the electrocardiographic characteristics of newborns with VSDs in a general population sample. The Copenhagen Baby Heart Study is a prospective population–based cohort study offering cardiac evaluation of newborns. Echocardiograms and electrocardiograms were obtained within 30 days after birth and systematically analysed. A VSD was identified in 530 newborns (mean age 11 ± 7 days, 42% boys). Newborns with VSDs had a more left-shifted QRS axis (116 ± 34 vs. 120 ± 3°, p = 0.02), and a higher S-wave amplitude in V1 (721 ± 584 vs. 636 ± 549 µV, p = 0.001) than controls. The largest differences were found in newborns with large or perimembraneous VSDs with a higher frequency of left axis deviation, higher S-wave amplitudes in V1, and higher R- and S-wave amplitudes in V6 compared with controls. R-waves in V1 and V6 were significantly associated to left ventricular mass, whereas S-waves in V1 and V6 were dependent on left ventricular end-diastolic diameter on echocardiography. Conclusion: Newborns with VSDs showed significant differences in QRS axis, and R- and S-wave precordial amplitudes compared to matched controls. Perimembranous and large VSDs had the greatest effect on the neonatal ECG., Ventricular septal defects (VSD) represent the most common congenital heart defect in newborns. We assessed the electrocardiographic characteristics of newborns with VSDs in a general population sample. The Copenhagen Baby Heart Study is a prospective population–based cohort study offering cardiac evaluation of newborns. Echocardiograms and electrocardiograms were obtained within 30 days after birth and systematically analysed. A VSD was identified in 530 newborns (mean age 11 ± 7 days, 42% boys). Newborns with VSDs had a more left-shifted QRS axis (116 ± 34 vs. 120 ± 3°, p = 0.02), and a higher S-wave amplitude in V1 (721 ± 584 vs. 636 ± 549 µV, p = 0.001) than controls. The largest differences were found in newborns with large or perimembraneous VSDs with a higher frequency of left axis deviation, higher S-wave amplitudes in V1, and higher R- and S-wave amplitudes in V6 compared with controls. R-waves in V1 and V6 were significantly associated to left ventricular mass, whereas S-waves in V1 and V6 were dependent on left ventricular end-diastolic diameter on echocardiography. Conclusion: Newborns with VSDs showed significant differences in QRS axis, and R- and S-wave precordial amplitudes compared to matched controls. Perimembranous and large VSDs had the greatest effect on the neonatal ECG. What is Known: • Ventricular septal defects in newborns are prevalent and may affect cardiac function and structure. What is New: • The Copenhagen Baby Heart Study is the largest study including a cohort of unselected newborns undergoing postnatal cardiac examination. • We found that newborns with VSD showed significant electrocardiographic differences depending on size and type of VSD compared with healthy newborns.

Atrial septal defect (ASD) is characterized by a left-to-right shunt causing dilatation of the right atrium and right ventricle as well as pulmonary hyperperfusion. The detection of ASDs often occurs late in childhood or adulthood. Little is known about cardiac structure and function in neonates with ASD. We analyzed neonatal echocardiograms from the Copenhagen Baby Heart Study, a multicenter, population-based cohort study of 27,595 neonates. We included 716 neonates with secundum-type ASDs and matched them 1:1 on sex and age at examination with neonates without ASD from the same birth cohort. Neonates with an ASD (median age 11 days, 52% female) had larger right ventricular (RV) dimensions than matched controls (RV longitudinal dimension end-diastole: 27.7 mm vs. 26.7 mm, p < 0.001; RV basal dimension end-diastole: 14.9 mm vs. 13.8 mm, p < 0.001; and RV outflow tract diameter 13.6 mm vs. 12.4 mm, p < 0.001). Atrial volumes were larger in neonates with ASD compared to controls (right atrial end-systolic volume: 2.9 ml vs. 2.1 ml, p < 0.001; and left atrial end-systolic volume 2.0 ml vs. 1.8 ml, p < 0.001). Tricuspid annular plane systolic excursion was larger in neonates with ASD than in controls (10.2 mm vs. 9.6 mm, p < 0.001). Left ventricular dimensions and function did not differ between neonates with ASD and controls. In conclusion, ASDs were associated with altered cardiac dimensions already in the neonatal period, with larger right ventricular dimensions and larger atrial volumes at echocardiography within the first 30 days after birth. ClinicalTrials.gov Identifier: NCT02753348 (April 27, 2016).

Background: Patients with hypertrophic cardiomyopathy (HCM) are generally regarded as having increased risk of arrhythmia, stroke, heart failure, and sudden cardiac death, but reported mortality rates vary considerably and originate from selected populations. Study objective: We aimed to investigate the long-term mortality rate in a nationwide cohort of patients with HCM compared to a matched cohort from the general Danish population. Methods: All patients with a first-time HCM diagnosis in Denmark between January 1, 2007 and December 31, 2018 were identified through nationwide registries. In the main analysis, two visits in an outpatient clinic were required in order to increase specificity. Patients were matched to controls from the background population in a 1:3 ratio based on age, sex, selected comorbidities and date of HCM. Mortalities were compared using Kaplan Meier estimator and multivariable Cox regression models. Results: We identified 3126 patients with a first-time diagnosis of HCM. 1197 patients had at least two visits in the outpatient clinic (43 % female, median age 63.1 [25th–75th percentile 52.1–72.1] years). All-cause mortality was significantly higher in HCM patients than in matched controls: 10-year probabilities of death were 36.4 % (95 % CI 30.2–43.5 %) for HCM patients and 19.4 % (95 % CI 16.8–22.5 %) for controls. After adjusting for additional comorbidities and medications, a diagnosis with HCM was associated with an increased mortality rate (HR 1.48 (95 % CI 1.18–1.84, p = 0.001)). Conclusion: Compared to matched controls from the background population, presence of HCM was associated with a significant increase in mortality rate.

Background: The ductus arteriosus is part of the fetal circulation. Normally, the vessel closes during the cardiac transition. Delayed closure is associated with complications. The aim of this study was to evaluate the age-related prevalence of open ductus arteriosus in full-term neonates. Methods: Echocardiograms were collected in the population study, the Copenhagen Baby Heart Study. The present study included full-term neonates with an echocardiogram performed within 28 days after birth. All echocardiograms were reviewed to assess ductus arteriosus patency. Results: A total of 21,649 neonates were included. In neonates examined at day zero and day seven, an open ductus arteriosus was found in 36% and 0.6%, respectively. Beyond day seven, the prevalence remained stable at 0.6%. Conclusion: More than one-third of full-term neonates had an open ductus arteriosus on the first day of life, declining rapidly within the first week and stabilizing below 1% after day seven. Keywords:Congenital heart defect, Patent ductus arteriosus, Ductus arteriosus, Echocardiography, Neonatology, Background: The ductus arteriosus is part of the fetal circulation. Normally, the vessel closes during the cardiac transition. Delayed closure is associated with complications. The aim of this study was to evaluate the age-related prevalence of open ductus arteriosus in full-term neonates. Methods: Echocardiograms were collected in the population study, the Copenhagen Baby Heart Study. The present study included full-term neonates with an echocardiogram performed within 28 days after birth. All echocardiograms were reviewed to assess ductus arteriosus patency. Results: A total of 21,649 neonates were included. In neonates examined at day zero and day seven, an open ductus arteriosus was found in 36% and 0.6%, respectively. Beyond day seven, the prevalence remained stable at 0.6%. Conclusion: More than one-third of full-term neonates had an open ductus arteriosus on the first day of life, declining rapidly within the first week and stabilizing below 1% after day seven.

Aims Wolff–Parkinson–White (WPW) syndrome is a conduction disorder characterized by an accessory electrical pathway between the atria and ventricles, which may predispose to supraventricular tachycardia (SVT) and sudden cardiac death. It can be seen as an isolated finding or associated with structural heart disease. Our aims were to determine the prevalence of a WPW pattern in a large and unselected cohort of neonates and to describe the electro- and echocardiographic characteristics as well as the natural history during early childhood. Methods and results Electrocardiograms and echocardiograms of neonates (aged 0–30 days) from a large, prospective, population-based cohort study were included. Neonates with a WPW pattern were identified and matched 1:4 to controls. Localization of the accessory pathway was assessed by different algorithms. Among 17 489 neonates, we identified 17 (76% boys) with a WPW pattern consistent with a prevalence of 0.1%. One neonate had moderate mitral regurgitation while other echocardiographic parameters were similar between cases and controls (all P > 0.05). The accessory pathways were primarily predicted to be left-sided. At follow-up (available in 14/17 children; mean age 3.2 years) the pre-excitation pattern persisted in only four of the children and none of the children had experienced any episodes of SVT. Conclusion The prevalence of a WPW pattern in our cohort of unselected neonates was 0.1%. The WPW pattern was more frequent in boys and generally not associated with structural heart disease, and the accessory pathways were primarily left-sided. At follow-up, the WPW pattern had disappeared in most of the children suggesting either an intermittent nature or that normalization occurs. Clinical Trial Registration Copenhagen Baby Heart, NCT02753348., AIMS: Wolff-Parkinson-White (WPW) syndrome is a conduction disorder characterized by an accessory electrical pathway between the atria and ventricles, which may predispose to supraventricular tachycardia (SVT) and sudden cardiac death. It can be seen as an isolated finding or associated with structural heart disease. Our aims were to determine the prevalence of a WPW pattern in a large and unselected cohort of neonates and to describe the electro- and echocardiographic characteristics as well as the natural history during early childhood.METHODS AND RESULTS: Electrocardiograms and echocardiograms of neonates (aged 0-30 days) from a large, prospective, population-based cohort study were included. Neonates with a WPW pattern were identified and matched 1:4 to controls. Localization of the accessory pathway was assessed by different algorithms. Among 17 489 neonates, we identified 17 (76% boys) with a WPW pattern consistent with a prevalence of 0.1%. One neonate had moderate mitral regurgitation while other echocardiographic parameters were similar between cases and controls (all P > 0.05). The accessory pathways were primarily predicted to be left-sided. At follow-up (available in 14/17 children; mean age 3.2 years) the pre-excitation pattern persisted in only four of the children and none of the children had experienced any episodes of SVT.CONCLUSION: The prevalence of a WPW pattern in our cohort of unselected neonates was 0.1%. The WPW pattern was more frequent in boys and generally not associated with structural heart disease, and the accessory pathways were primarily left-sided. At follow-up, the WPW pattern had disappeared in most of the children suggesting either an intermittent nature or that normalization occurs.CLINICAL TRIAL REGISTRATION: Copenhagen Baby Heart, NCT02753348.

BACKGROUND: The mineralocorticoid receptor antagonists (MRAs) eplerenone and spironolactone are beneficial in heart failure with reduced ejection fraction (HFrEF), but have not been prospectively compared. We compared clinical outcomes, daily dosages, and discontinuation rates for the two drugs in a nationwide cohort.METHODS: We identified all patients with HFrEF in the period 2016-2020, who were alive and had initiated MRA treatment at study start, 180 days after HF diagnosis. We estimated the 2-year risk of a composite of death and HF hospitalization, as well as each component separately, using Kaplan-Meier, cumulative incidence functions, and Cox proportional hazards models adjusted for age, sex, and comorbidities. Secondly, we assessed treatment withdrawal, cross-over, and daily drug dosage.RESULTS: We included 7479 patients; 653 (9%) on eplerenone and 6840 (91%) on spironolactone. Patients in the eplerenone group were younger (median age 65 vs. 69 years), and more often men (91% vs. 68%), both P < 0.001. In adjusted analyses, with spironolactone as reference, there were no differences in the risk of the composite of all-cause death and HF hospitalization (HR 1.02, 95% CI 0.82-1.27), all-cause death (HR 0.93, 95% CI 0.67-1.30), or HF hospitalization (HR 1.10, 95% CI 0.84-1.42). Treatment withdrawal occurred in 34% in the eplerenone group and 53% in the spironolactone group (P < 0.001), treatment cross-over in 3%, and 10%, respectively. Daily dose >25 mg at 12 months, was observed in 230 patients (37%) in the eplerenone group and 771 patients (12%) in the spironolactone (P < 0.001).CONCLUSIONS: In a contemporary nationwide cohort of patients with new-onset HFrEF who initiated MRA, we found no differences in clinical outcomes associated with initiation of eplerenone vs. spironolactone. Treatment was more frequently withdrawn, and daily drug dosage was lower among patients treated with spironolactone.

Background Maternal obesity and advanced age have been associated with an increased risk of structural congenital heart defects in the offspring. Whether these factors may also cause abnormalities in infant cardiac dimension and function is unknown. This study investigates whether maternal body mass index (BMI) and maternal age are associated with changes in left ventricular (LV) dimensions and function in the newborn. Methods Infants enrolled in the Copenhagen Baby Heart Study (CBHS), who were born at term, and contributed with a transthoracic echocardiography (TTE) within 60 days of birth were included. The exposure variables were prepregnancy maternal BMI (kg/m2) < 18.5; 18.5–24.9 (reference); 25–29.9; 30–34.9 and ≥ 35 and maternal age (years) < 25; 25–29; 30–34 (reference); 35–39 and ≥ 40. Outcomes were LV parameters ascertained by 2D-echocardiography. Associations between each maternal factor and infant LV parameters were analysed with either a linear model adjusted for the child’s weight and length at birth, gestational age, sex, age at TTE, and maternal smoking, or a linear mixed model, further adjusted for random effects of analyst and month of analysis. Analyses investigating impact of maternal BMI were adjusted for maternal age, and vice versa. Results The study cohort included 24,294 infants. Compared with infants in the BMI reference group, infants born to women with a BMI ≥ 25 kg/m2 generally had smaller measures of LV internal diameters in end-diastole, reaching statistical significance for BMI 30–34.9 kg/m2 [-0.11 ± 0.04 mm, p = 0.01]. All groups of infants born to women with a BMI ≥ 25 kg/m2 had significantly smaller LV internal diameters in end-systole: BMI 25–29.9 kg/m2 [-0.04 ± 0.02 mm, p = 0.04], BMI 30–34.9 kg/m2 [-0.12 ± 0.03 mm, p = 0.001] and BMI ≥ 35 kg/m2 [-0.11 ± 0.05 mm, p = 0.03]. Compared with infants in the age reference group, infants born to women ≥ 40 years had significantly smaller LV in, Background: Maternal obesity and advanced age have been associated with an increased risk of structural congenital heart defects in the offspring. Whether these factors may also cause abnormalities in infant cardiac dimension and function is unknown. This study investigates whether maternal body mass index (BMI) and maternal age are associated with changes in left ventricular (LV) dimensions and function in the newborn. Methods: Infants enrolled in the Copenhagen Baby Heart Study (CBHS), who were born at term, and contributed with a transthoracic echocardiography (TTE) within 60 days of birth were included. The exposure variables were prepregnancy maternal BMI (kg/m2) < 18.5; 18.5–24.9 (reference); 25–29.9; 30–34.9 and ≥ 35 and maternal age (years) < 25; 25–29; 30–34 (reference); 35–39 and ≥ 40. Outcomes were LV parameters ascertained by 2D-echocardiography. Associations between each maternal factor and infant LV parameters were analysed with either a linear model adjusted for the child’s weight and length at birth, gestational age, sex, age at TTE, and maternal smoking, or a linear mixed model, further adjusted for random effects of analyst and month of analysis. Analyses investigating impact of maternal BMI were adjusted for maternal age, and vice versa. Results: The study cohort included 24,294 infants. Compared with infants in the BMI reference group, infants born to women with a BMI ≥ 25 kg/m2 generally had smaller measures of LV internal diameters in end-diastole, reaching statistical significance for BMI 30–34.9 kg/m2 [-0.11 ± 0.04 mm, p = 0.01]. All groups of infants born to women with a BMI ≥ 25 kg/m2 had significantly smaller LV internal diameters in end-systole: BMI 25–29.9 kg/m2 [-0.04 ± 0.02 mm, p = 0.04], BMI 30–34.9 kg/m2 [-0.12 ± 0.03 mm, p = 0.001] and BMI ≥ 35 kg/m2 [-0.11 ± 0.05 mm, p = 0.03]. Compared with infants in the age reference group, infants born to wome

Background and Aims The aims of this study were to investigate lipid parameters during the first 14–16 months of life, to identify influential factors, and to test whether high concentrations at birth predict high concentrations at 2- and 14–16 months. Methods The Copenhagen Baby Heart Study, including 13,354 umbilical cord blood samples and parallel venous blood samples from children and parents at birth (n = 444), 2 months (n = 364), and 14–16 months (n = 168), was used. Results Concentrations of lipids, lipoproteins, and apolipoproteins in umbilical cord blood samples correlated highly with venous blood samples from newborns. Concentrations of low-density lipoprotein (LDL) cholesterol, non-high-density lipoprotein (HDL) cholesterol, apolipoprotein B, and lipoprotein(a) increased stepwise from birth to 2 months to 14–16 months. Linear mixed models showed that concentrations of LDL cholesterol, non-HDL cholesterol, and lipoprotein(a) above the 80th percentile at birth were associated with significantly higher concentrations at 2 and 14–16 months. Finally, lipid concentrations differed according to sex, gestational age, birth weight, breastfeeding, and parental lipid concentrations. Conclusions Lipid parameters changed during the first 14–16 months of life, and sex, gestational age, birth weight, breastfeeding, and high parental concentrations influenced concentrations. Children with high concentrations of atherogenic lipid traits at birth had higher concentrations at 2 and 14–16 months. These findings increase our knowledge of how lipid traits develop over the first 14–16 months of life and may help in deciding the optimal child age for universal familial hypercholesterolaemia screening., Background and The aims of this study were to investigate lipid parameters during the first 14–16 months of life, to identify influential factors, Aims and to test whether high concentrations at birth predict high concentrations at 2- and 14–16 months. Methods The Copenhagen Baby Heart Study, including 13,354 umbilical cord blood samples and parallel venous blood samples from children and parents at birth (n = 444), 2 months (n = 364), and 14–16 months (n = 168), was used. Results Concentrations of lipids, lipoproteins, and apolipoproteins in umbilical cord blood samples correlated highly with venous blood samples from newborns. Concentrations of low-density lipoprotein (LDL) cholesterol, non-high-density lipoprotein (HDL) cholesterol, apolipoprotein B, and lipoprotein(a) increased stepwise from birth to 2 months to 14–16 months. Linear mixed models showed that concentrations of LDL cholesterol, non-HDL cholesterol, and lipoprotein(a) above the 80th percentile at birth were associated with significantly higher concentrations at 2 and 14–16 months. Finally, lipid concentrations differed according to sex, gestational age, birth weight, breastfeeding, and parental lipid concentrations. Conclusions Lipid parameters changed during the first 14–16 months of life, and sex, gestational age, birth weight, breastfeeding, and high parental concentrations influenced concentrations. Children with high concentrations of atherogenic lipid traits at birth had higher concentrations at 2 and 14–16 months. These findings increase our knowledge of how lipid traits develop over the first 14–16 months of life and may help in deciding the optimal child age for universal familial hypercholesterolaemia screening.

Background: In pediatric echocardiography, reference intervals are required to distinguish normal variation from pathology. Left ventricular (LV) parameters are particularly important predictors of clinical outcome. However, data from healthy newborns are limited, and current reference intervals provide an inadequate approximation of normal reference ranges. Objectives: Normative reference intervals and z-scores for 2-dimensional echocardiographic measurements of LV structure and function based on a large group of healthy newborns were developed. Methods: The study population included 13,454 healthy newborns from the Copenhagen Baby Heart Study who were born at term to healthy mothers, had an echocardiogram performed within 30 days of birth, and did not have congenital heart disease. To develop normative reference intervals, this study modeled 10 LV parameters as a function of body surface area through joint modeling of 4 statistical components. Results: Infants in the study population (48.5% were female) had a median body surface area of 0.23 m2 (IQR: 0.22-0.25 m2) and median age of 12.0 days (IQR: 8.0-15.0 days) at examination. All normative reference intervals performed well in both sexes without stratification on infant sex. In contrast, creation of separate reference models for infants examined at <7 days of age and those examined at 7-30 days of age was necessary to optimize the performance of the reference intervals. Conclusions: This study provides normative reference intervals and z-scores for 10 clinical, widely used echocardiographic measures of LV structure and function based on a large cohort of newborns. These results provide highly needed reference material for clinical application by pediatric cardiologists.

Background: Left ventricular noncompaction (LVNC) is characterized by excessive trabeculations of the LV and may be associated with reduced systolic function or severe adverse outcomes. Several aspects remain to be elucidated; there is controversy to whether LVNC cardiomyopathy is a distinct cardiomyopathy caused by failure of the spongy fetal myocardium to condense during fetal development or acquired later in life as a morphological trait associated with other types of cardiomyopathy; the prevalence in unselected populations is unknown and the distinction between normal variation and pathology remains to be defined. In this study, we aimed to determine the prevalence of LVNC and the association to LV systolic function in a large, population-based cohort of neonates. In addition, we assessed the normal ratio of noncompact to compact (NC:C) myocardium in 150 healthy neonates. Methods: Echocardiographic data were prospectively collected in the population study Copenhagen Baby Heart Study. The ratio of NC:C was measured in 12 ventricular segments. LVNC was defined as NC:C ≥2 in at least one segment. Neonates with LVNC were matched 1:10 to controls on sex, gestational age, and weight and age at the examination day. Results: In total, 25 590 neonates (52% males, median age 11 [interquartile range, 7-15] days) underwent echocardiography. Among 21 133 with satisfactory visualization of ventricular segments, we identified a prevalence of LVNC of 0.076% (95% CI, 0.047-0.123). LV ejection fraction was lower in neonates with LVNC compared with matched controls (median 49.5 versus 59.0%; P<0.0001). In neonates with otherwise healthy hearts, the median NC:C ratio ranged from 0.0 to 0.7 and the 99th percentiles from 1.0 to 1.9 for each of the 12 segments. Conclusions: The prevalence of LVNC based on neonatal echocardiography was 0.076%. LVNC was associated with lower LV systolic function. The findings in normal newborns support the cutoff NC:C ≥2 as an appropriate diagnost

Importance: The prevalence and characteristics of bicuspid aortic valve (BAV) are mainly reported from selected cohorts. BAV is associated with aortopathy, but it is unclear if it represents a fetal developmental defect or is secondary to abnormal valve dynamics. Objective: To determine the prevalence of BAV and BAV subtypes and to describe the associated aortopathy in a large, population-based cohort of newborns. Design, Setting, and Participants: The Copenhagen Baby Heart Study was a cross-sectional, population-based study open to all newborns born in Copenhagen between April 1, 2016, and October 31, 2018. Newborns with BAV were matched 1:2 to newborns with a tricuspid aortic valve (non-BAV group) on sex, singleton/twin pregnancy, gestational age, weight, and age at time of examination. Exposures: Transthoracic echocardiography within 60 days after birth. Main Outcomes and Measures: Primary outcome was BAV prevalence and types, ie, number of raphes and spatial orientation of raphes or cusps (no raphes), according to the classification system of Sievers and Schmidtke (classified as type 0, 1, or 2, with numbers indicating the number of raphes). Secondary outcome was valve function and BAV-associated aortopathy, defined as aortic diameter z score of 3 or greater or coarctation. Results: In total, 25556 newborns (51.7% male; mean age, 12 [SD, 8] days) underwent echocardiography. BAV was diagnosed in 196 newborns (prevalence, 0.77% [95% CI, 0.67%-0.88%]), with male-female ratio 2.1:1. BAV was classified as type 0 in 17 newborns (8.7% [95% CI, 5.5%-13.5%]), type 1 in 178 (90.8% [95% CI, 86.0%-94.1%]) (147 [75.0% {95% CI, 68.5%-80.5%}] right-left coronary raphe, 27 [13.8% {95% CI, 9.6%-19.3%}] right coronary-noncoronary raphe, 4 [2.0% {95% CI, 0.8%-5.1%}] left coronary-noncoronary raphe), and type 2 in 1 (0.5% [95% CI, 0.1%-2.8%]). Aortic regurgitation was more prevalent in newborns with BAV (n = 29 [14.7%]) than in those without BAV (1.3%) (absolute % difference, 13