Background Myocardial development is still incomplete by the time of birth making the cardiomyocyte vulnerable in the perinatal period. However, little is known on whether perinatal factors affect the neonatal electrocardiogram, and if so, to what degree these effects persist in the neonatal period. Purpose To investigate the impact of maternal and perinatal factors on the neonatal electrocardiogram in a large unselected cohort of neonates. Methods In a multicentre, prospective, population-based cohort study, neonates underwent cardiac evaluation during the first month of life. Electrocardiograms and echocardiograms were obtained and systematically analysed. Medical and demographic information on the parents, pregnancy, and birth-related factors were registered, and the following perinatal risk factors were evaluated: maternal comorbidities, maternal BMI ≥25, use of assisted reproduction technology, parity, (preterm) premature rupture of membranes, placental disorders, abnormal foetus presentation, induction of labour with synthetic hormone, instrumental induction, administration of nitrous oxide, epidural/spinal administration, labour ≥24h, pushing stage ≥1h, Caesarean section, and instrumental delivery. Results A total of 15,928 singletons with normal echocardiograms were included (52% boys; median age at examination 11 days). The neonates were divided into groups by accumulated number of perinatal risk factors: 0 (n=1,587), 1 (n=3,718), 2 (n=4,026), 3–4 (n=4,998), and ≥5 (n=1,197), and differences in ECG parameters between the groups were analysed. Heart rate, QRS axis, uncorrected QT interval, QTcBazett, QTcFridericia, and maximum amplitudes in R-V1 and R-V6 differed across the five subgroups (all p<0.05). We observed a cumulative effect of perinatal risk factors on ECG parameters with increasing left-shift in the QRS axis, prolongation of the QT interval, and increasing amplitudes in R-V1 and R-V6. The subgroup with ≥5 perinatal risk factors differed the most, and absolute differences between this subgroup and neonates without any perinatal risk factors were 7.6% in maximum amplitudes in R-V6 (940 vs. 874 μV, p<0.01), 4.3% in R-V1 (1,201 vs. 1,152 μV, p<0.05), 5.1% in the QRS axis (111 vs 117°, p<0.0001) and 0.8% in QTcFridericia (366 vs. 363 ms, p<0.01). Conclusion We observed a cumulative effect of perinatal risk factors including a significantly more left-shifted QRS axis, increased values of the QT interval, and higher amplitudes in R-V1 and R-V6 in the subgroup with ≥5 perinatal risk factors. These findings suggest a relatively lower right ventricular dominance pattern, discrete prolongation of the QT interval and increased myocardial mass of the right ventricle in neonates exposed to multiple perinatal risk factors. However, the absolute differences in ECG parameters were relatively small. These findings may be useful for identification of neonates with increased cardiovascular risk. Funding Acknowledgement Type of funding sources: Public Institution(s). Main funding source(s): Department of Cardiology, Herlev-Gentofte Hospital, Internal Funding

Introduction Left ventricular non-compaction (LVNC) is characterized by excessive trabeculations of the left ventricular wall. LVNC may be associated with reduced systolic function but is also found in individuals with normal ventricular function. It is debated whether LVNC is only congenital or may develop later in life. The clinical importance and heredity of LVNC with normal systolic function is unclear. Purpose We aimed to describe the echocardiographic development of the left ventricular function and LVNC pattern in children with LVNC, diagnosed at birth, at follow-up at the age of 2–4 years compared to matched controls. Additionally, we aimed to describe the prevalence of LVNC in first-degree relatives. Methods A follow-up transthoracic echocardiography was performed in children at 2–4 years of age, diagnosed with LVNC at birth (<30 days) as part of a large population study of newborns (n>25,000). Cases were matched 1:4 to controls on mother's age at delivery, parity, and age of the child at follow-up. First-degree relatives (parents, siblings and half-siblings) of cases and controls were also offered inclusion. LVNC was defined as a ratio of non-compact to compact myocardium of ≥2 in at least one left ventricular segment measured in end-diastole perpendicular to the left ventricular cavity. Results 13 of the 16 children diagnosed with LVNC at birth (median age 3 (interquartile range (IQR) 3–4) years, 77% male) and 52 children without LVNC at birth (age 4 (IQR 3–4) years, 88% male) was reevaluated as well as 36 first-degree relatives of children with LVNC (age 30 (IQR 4–37) years, 44% male) and 136 first-degree relatives of children without LVNC (age 32 (IQR 10–38) years, 50% male). In probands, the number of segments fulfilling criteria (8% vs. 13%, p=0.4) and systolic function, measured as fractional shortening (FS), were unchanged from birth to follow-up, and within normal range (29% vs. 30%, p=0.34). However, at follow-up, FS was significantly lower in probands compared with matched controls (30% vs. 33%, p<0.001). Criteria of LVNC was fulfilled in 11 out of 36 (31%) first-degree relatives to probands, whereas none of the first-degree relatives of children without LVNC fulfilled criteria of LVNC (p<0.001). FS was significantly lower in first-degree relatives of probands fulfilling criteria of LVNC compared to first-degree relatives of matched controls (30% vs. 32%, p=0.01). Conclusion Children with LVNC diagnosed neonatally as part of a population study still had a reduced systolic function when compared to controls but showed no further progression of left ventricular dysfunction or extent of trabeculation at the age of 2–4 years. One third of first-degree relatives to children diagnosed with LVNC with a preserved systolic function, fulfilled criteria for LVNC and had reduced systolic function compared to controls. These findings strongly support family-screening and clinical follow-up of children with LVNC. Funding Acknowledgement Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): Novo Nordisk FoundationHerlev-Gentofte Hospital Internal Funding

Introduction: Left ventricular non-compaction (LVNC) is characterized by excessive trabeculations of the left ventricular wall and may be associated with reduced systolic function. It is debated whether LVNC is congenital or may develop later as part of other cardiomyopathies. The clinical importance and heredity of LVNC with normal systolic function is unclear. We aimed to describe the cardiac development in children with LVNC from birth to 2-4 years of age, compared to matched controls. Additionally, we aimed to describe the prevalence of LVNC in first-degree relatives. Methods: A follow-up transthoracic echocardiography was performed in children at 2-4 years of age diagnosed with LVNC at birth (<30 days) in the Copenhagen Baby Heart Study. Cases were matched to controls on mothers age at delivery, parity, and age of child at follow-up. First-degree relatives (parents, siblings and half-siblings) were also included. LVNC was defined as a non-compact to compact ratio of myocardium of ≥2 in at least one left ventricular segment, measured in 24 segments in end-diastole perpendicular to the left ventricular cavity as previously suggested. Results: Of the 16 children diagnosed with LVNC at birth, 10 have been reevaluated (age 3.5 (interquartile range (IQR) 3, 4) years, 80% male) together with 20 matched controls (age 4 (IQR 3, 4) years, 70% male), 29 first-degree relatives in case group (age 29 (IQR 4, 35) years, 45% male) and 55 first-degree relatives in control group (age 32 (IQR 11, 36) years, 51% male). In probands, the extent of trabeculation (13% vs. 12%, p=0.97) and fractional shortening (FS) (29% vs. 31%, p=0.24) were unchanged from birth to follow-up. At follow-up, the median left ventricular FS was significantly lower in probands compared to matched controls (31% vs. 33%, p=0.03). Ten (35%) first-degree relatives to probands fulfilled criteria for LVNC compared to 0 (0%) of first-degree relatives to controls (p<0.001). Conclusions: Children with LVNC diagnosed neonatally as part of a population study had no further progression of left ventricular dysfunction or extent of trabeculation at the age of 2-4 years, but systolic function was reduced compared to matched controls. One third of first-degree relatives to children with LVNC fulfilled criteria for LVNC.