Abstract
Background
Approximately 6% of all pregnancies in Denmark are affected by maternal pre-existing or gestational diabetes. Maternal diabetes is a well-known risk factor for congenital heart ...defects. Among the most common congenital heart defects is bicuspid aortic valve (BAV), which is present in 0.8% of newborns. Familial clustering of BAV is seen in 30-40%, but the heritability is not completely understood and since most cases are sporadic, a multifactorial aetiology has been proposed. The association between maternal diabetes and BAV in the offspring has been sparsely investigated previously.
Purpose
The purpose was to assess the prevalence of BAV in newborns born to mothers with pre-existing or gestational diabetes compared with children born to mothers without diabetes.
Method
Systematic, standardized transthoracic echocardiography was performed within 60 days of birth in over 25,000 newborns included in a population-based, multicentre, cohort study between 2016 and 2018. Maternal diabetes-status was collected from obstetrical records maintained by the obstetrical departments of the participating hospitals, supplemented by records from a nationwide registry covering patients contacts with private and public hospitals since 1976. Maternal diabetes was categorized as type 1, type 2, or gestational diabetes (GDM) using the ICD-10 codes DO240, DO241, and DO244, respectively.
The exposed newborns were compared with newborns not exposed to maternal diabetes.
Results
In total, the cohort consisted of 25,553 new-borns of whom 24,707 (96.7%) were not exposed to diabetes, 648 (2.5%) were exposed to GDM, and 198 were exposed to pre-existing diabetes; 136 (0.5%) to type 1 and 62 (0.2%) to type 2 diabetes. Median gestational age was 281 days (interquartile range (IQR) 273;287), median age at examination was 11 days (IQR 7;15), and 48% were female. None of the newborns exposed to pre-existing diabetes had a BAV. Nine (1.4%) new-borns exposed to GDM, and 179 (0.7%) newborns not exposed to diabetes were found to have a BAV, corresponding to a relative risk of 1.92 (95%CI 0.99-3.73), p= 0.056.
Conclusion
Exposure to maternal diabetes is associated with an increased risk of congenital heart disease. In our large cohort of unselected newborns, the association between diabetes and BAV did not reach statistical significance, but the numerically observed twice higher risk of BAV in children born to women with gestational diabetes is nevertheless intriguing and deserves future attention.
Abstract
Background
Primary cardiac tumours in children are rare. The most common cardiac tumour in newborns is rhabdomyomas, associated with tuberous sclerosis in >50% of cases. The estimated ...prevalence is 0.14‰ in fetuses, whereas in the paediatric population, a 20-fold difference in autopsy prevalence has been reported (0.017‰ to 0.27‰).
Purpose
To determine the pre- and postnatal prevalence of congenital cardiac tumours in a large, population-based cohort of prenatally enrolled newborns.
Methods
Systematic transthoracic echocardiography (TTE), including sub-xiphoid, apical, parasternal, and suprasternal views, was performed in unselected newborns included in a population study. Participants were included at time of the routine malformation scan (weeks 18-21), which included 4-chamber view, aortic and pulmonary outflow tracts, and three-vessel view.
Cardiac tumours were defined as solid, echogenic masses, and the echocardiographic description included location, size, and number (one/multiple) of the tumour. Information on subsequent diagnosis of tuberous sclerosis was collected from review of medical charts.
Results
A total of 25,588 newborns (age 12±8 days, 51.6% male) were enrolled and underwent TTE. Prenatally, no cardiac tumours were reported in any of the participants. Postnatally, cardiac tumours were detected in 7 newborns (4 males), corresponding to a prevalence of 0.3 0.1; 0.6 per 1,000 live-births. Through retrospective review of the prenatal scans, a possible tumour in the ventricle was suspected in 1 of the 7 cases; the remaining 6 cases showed no signs of tumours prenatally.
Sex, gestational age at birth, birth length and weight, APGAR 5-score, age and weight at TTE, and maternal age and pre-pregnancy BMI, did not significantly differ between newborns with (n=7) and without (n=25,581) cardiac tumours (all p>0.05). Smoking during pregnancy was significantly more frequent among mothers to newborns with cardiac tumours compared to the remaining cohort (29% vs 4%, p=0.023).
In all 7 newborns, the cardiac tumours were located in the ventricles (5 (71%) newborns with tumours in both ventricles, 2 (29%) with tumours in the right ventricle), with multiple tumours seen in 6 (86%), and with size ranging from 2.0x1.9 mm to 10.0x5.1 mm. All 7 newborns had otherwise structurally normal hearts and no flow obstruction. Three newborns with cardiac tumours in the ventricles (43%) were diagnosed with tuberous sclerosis within 4 months after birth.
Conclusions
Systematic TTE in unselected newborns revealed a prevalence of congenital cardiac tumours of 0.3‰. Prenatal screening in week 18-21 did not seem efficient for identification of cardiac tumours. Cardiac tumours were located in the ventricles and were most often multiple. Cardiac tumours in the ventricles were associated with tuberous sclerosis in almost half the cases. For newborns with cardiac tumours, maternal smoking during pregnancy was common (29%).Figure 1
Abstract
Background
Hypertensive disorders of pregnancy (HDP) - preeclampsia in particular - are important causes of pregnancy complications and death for both the mother and her offspring. ...Preeclampsia is also associated with both congenital heart defects (CHDs) in the offspring and subtle changes in left ventricular structure and function in the offspring. However, whether preeclampsia also affects the newborn’s cardiac conduction system is unknown.
Purpose
To assess whether newborns born after pregnancies complicated by HDP exhibit changes in their electrocardiogram (ECG) compared with newborns born after pregnancies without HDP.
Methods
This population-based cohort study included newborns, who had ECG data obtained within 30 days of birth. Information on maternal preeclampsia (ICD-10 codes DO14-14.2 and DO15-15.9) and maternal gestational hypertension (ICD-10 codes DO13-13.9) was retrieved from an obstetric database. ECG parameters of interest included heart rate, PR interval, QRS axis, QRS duration, uncorrected and corrected QT intervals, maximum R- and S-wave amplitudes in V1 and V6, respectively. ECG parameters of exposed and non-exposed newborns were compared using summary statistics and linear regression, adjusting for sex, gestational age at delivery and length, weight and age at examination. Sensitivity analyses were conducted with adjustments for maternal smoking, parity, age, and multiple pregnancies and the analyses were repeated after excluding neonates and mothers with CHD, newborns exposed to pre-gestational diabetes and children born preterm (<37 weeks’ gestation).
Results
Our study cohort included 11,826 newborns; 441 were exposed to maternal preeclampsia and 320 were exposed to maternal gestational hypertension (table). Newborns born to mothers with preeclampsia had significantly prolonged QRS duration compared to neonates born after pregnancies without HDP (adjusted mean difference of 0.6 ms, 95% CI 0.04 – 1.16, p=0.04). The maximum amplitude of the R-wave in the V1-recording was significantly lower in newborns born to mothers with preeclampsia by 5% (linear scale: 0.95, 95% CI 0.9 – 0.996, p=0.03). These associations persisted after adjustment for additional covariates and restrictions on the study population. Gestational hypertension was not associated with significant differences in any of the investigated ECG parameters.
Conclusion
The cardiac conduction was affected in children born to mothers with preeclampsia compared with newborns born after pregnancies without HDP, including prolonged QRS duration and lower amplitude of the R-wave in V1 in the ECG. These findings could be an indicator of thickening of the left ventricular myocardium in newborns of mothers with preeclampsia. The potential clinical implications of these changes – short or long-term – are unknown and require further investigation.Table
Abstract
Background/Introduction
Cardiovascular disease (CVD) is the leading cause of morbidity and mortality globally, and treatment of well-established lifestyle risk factors are cornerstones in ...CVD prevention. An atherogenic lipid profile with high concentrations of low-density lipoprotein (LDL) cholesterol and other apolipoprotein B containing lipoproteins is a driving force in the pathogenesis of atherosclerotic CVD (ASCVD). The lifelong atherosclerotic process is proportional to concentrations of apolipoprotein B-containing lipoproteins, hence risk of developing ASCVD is cumulative over time. The higher the baseline concentrations, the sooner the threshold for increased risk of ASCVD will be reached. It is therefore crucial to implement changes as early as possible and prevent risk factors in occurring – so-called primordial prevention. Childhood has been described as a "window of opportunity" for preventing risk factors in occurring and thus avoiding ASCVD. Whether concentrations of atherogenic lipoproteins at birth can predict future concentrations in early childhood and thus may indicate increased risk of dyslipidemia later in life remains unknown.
Purpose
The aim of the present study was to investigate atherogenic lipid traits during the first year of life, to identify influential factors for lipid concentrations, and to determine whether concentrations at birth can predict future lipid concentrations in early childhood.
Methods
For this purpose, we used the Copenhagen Baby Heart Study comprising more than 13,000 umbilical cord blood samples and parallel venous blood samples from children and parents at birth (n=444), at two months (n=363), and at 14-16 months (n=158). Lipid traits were determined in all samples.
Results
Concentrations of low-density lipoprotein (LDL) cholesterol, non-high-density lipoprotein (HDL) cholesterol, and apolipoprotein B increased during the first year of life. Girls had higher concentrations at birth and at two months compared with boys. Children born preterm had higher cord blood concentrations than children born at term. A linear mixed model showed that high concentrations of LDL cholesterol, non-HDL cholesterol and apolipoprotein B at birth predicted high concentrations at two months and at 14-16 months. Multivariable adjusted odds ratios (95% CI) for having high concentrations at two months when children had high concentrations at birth were 1.95 (1.01-3.79) for LDL cholesterol, 1.36 (0.69-2.67) for non-HDL cholesterol and 1.90 (1.02-3.53) for apolipoprotein B.
Conclusion
The lipid profile change during the first year of life and sex and gestational age influence concentrations. Children with high concentrations of LDL cholesterol, non-HDL cholesterol and apolipoprotein B at birth had higher levels at two and at 14-16 months. Concentrations at birth may thus be used to identify children at risk of dyslipidemia in later life.
Abstract
Background
Bicuspid aortic valve (BAV) is the most common congenital heart defect, affecting 0.8% of new-borns. BAV is associated with valve dysfunction, as well as an increased risk of ...aortopathy. The prevalence of BAV in first-degree relatives of symptomatic BAV patients, is reported to be 5–10%. First-degree relatives also have an increased risk of aortic dilatation, independently of aortic valve morphology.
Purpose
The purpose of the study was to determine the prevalence of BAV, associated valve dysfunction and aortopathy in first-degree relatives to children diagnosed with BAV neonatally in a population-based study.
Methods
Between April 2016 and October 2018 all expecting parents at three major maternity centres were offered inclusion in a large-scale population study with focus on congenital heart disease (N≥25,000). A total of 197 children, in 196 families, were diagnosed with BAV. All first-degree relatives, including half-siblings, were offered inclusion in the follow-up study with standardized transthoracic echocardiography. Adults were also examined with transoesophageal echocardiography. Aorta diameters were measured at the AV annulus, sinuses of Valsalva, sino-tubolare junction and in the proximal ascending aorta. Aortic dilatation in children were defined as any aortic root or ascending aorta diameter ≥2 standard deviations (SD) from the expected mean, calculated as z-score using formulas from the Paediatric Heart Network Echocardiogram Database. In adults, aortic dilatation was defined as aortic root and/or ascending aorta diameters indexed to body surface area (BSA) exceeding normal reference values established by the European Association of Cardiovascular Imaging.
Results
In total, 352 first-degree relatives (242 adults 35.3 years SD 5.5 and 110 children 4.5 years, SD 3.5 were included. BAV was diagnosed in 24 relatives (6.8%). BAV could not be conclusively ruled out in 52 relatives (14.8%), who are awaiting further examination with transoesophageal echocardiography. Dilatation of the aortic root was observed in 8 adult relatives and in 17 children (7.1%). Aortic valve regurgitation was observed in 23 relatives (6.5%). In total 58 relatives (16.2%) were diagnosed with either BAV, dilated aorta, or aortic regurgitation.
Conclusion
One in fifteen first-degree relatives to children diagnosed with BAV neonatally, also had BAV, corresponding to >8 fold increase in prevalence compared with the background population. One in six relatives had BAV, dilated aorta, or aortic regurgitation. These findings are of importance for family-screening programs of BAV.
Funding Acknowledgement
Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): Danish Children's Heart Association
Abstract
Introduction
Maternal factors such as smoking during pregnancy, advanced age, and obesity are associated with increased risk of complex congenital heart defects in the offspring. It is ...unknown whether maternal risk factors may also cause subtle abnormalities in cardiac structure and function.
Purpose
To investigate whether the following maternal factors: advanced age, high body mass index (BMI), and smoking during pregnancy are associated with changes in left ventricle (LV) dimensions and systolic function in the newborn child.
Methods
Data was obtained as part of a population-based cohort study with prenatal inclusion and postnatal transthoracic echocardiography (TTE) of newborns within 60 days of birth. The TTE protocol included measurements of: Interventricular septal thickness at end-diastole (IVSd), LV posterior wall thickness at end-diastole (LVPWd), LV internal diameter at end-diastole (LVIDd) and LV internal diameter at end-systole (LVIDs). Fractional shortening (FS) was calculated by use of Teicholz's formula.
Children of mothers with data available on age, BMI, and smoking status, respectively, were divided into the following groups depending on whether their mothers were: of young age <25 years, 25–29 years, 30–34 years (reference group), 35–39 years, and advanced age ≥40 years; underweight BMI <18.5, normal range BMI 18.5–24.9 (reference group), preobese BMI 25–29.9, and obese BMI ≥30; smoking or nonsmoking (reference group).
Associations between different groups with each maternal risk factor and newborn LV parameters were analysed using a multiple linear regression model.
Results
Children of mothers with advanced age at the time of childbirth (n=1,411) had significantly smaller LVIDd and LVIDs (Table 1) compared to children of mothers in their early thirties (n=10,045). Children of preobese (n=4,707) and obese mothers (n=2,138) had significantly smaller LVIDd and LVIDs than children of mothers in the normal BMI range (n=17,654). Children of mothers who smoked during pregnancy (n=808) had significantly larger LVPWd than children of non-smoking mothers (n=24,072). A significant difference in FS was only seen in children of obese mothers.
Subanalyses of the quantity of maternal smoking (available data in n=548 67.8% of mothers who smoked during pregnancy) showed that children of heavy smoking mothers (≥15 cigarettes/day, n=101), had significantly thicker IVSd and LVPWd compared with children of nonsmoking mothers, whereas no significant effect was identified in newborns of mothers smoking less than 15 cigarettes per day (Table 2).
Conclusions
Systematic population-based echocardiography of newborns showed that an increased maternal BMI and maternal age above 40 years were associated with smaller LV cavity dimensions in the offspring and that heavy smoking during pregnancy was associated with increased LV myocardial thickness. FS was only affected in children of obese mothers. The long-term effects of these novel findings are unknown.
Funding Acknowledgement
Type of funding sources: Foundation. Main funding source(s): Herlev-Gentofte Hospital Internal Funding for Cardiological Research andThe Novo Nordisk Foundation
Abstract
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
Abstract
Background
Cardiac dimensions and function are key parameters in the management of children with cardiopulmonary abnormalities and are important predictors of clinical outcome. In ...particular, left ventricular (LV) dimensions and function are important predictors of clinical outcome and prognosis. In pediatric echocardiography, nomograms are essential in the separation of normal variation from pathological conditions and ascertaining normal growth. However, data from cohorts of newborns are limited, and current nomograms remain an insufficient approximation of the range of values that should be considered normal.
Purpose
We developed nomograms and Z scores for two-dimensional echocardiographic measurements of LV structure and function in a large group of healthy newborns.
Methods
Our study population included newborns from a large population study of newborns (n >25,000) who were born at term to healthy mothers, had a systematic transthoracic echocardiogram (TTE) performed within 30 days of birth, and with no signs of any major congenital heart diseases. We developed nomograms for 10 LV parameters by modelling these parameters as a function of body surface area (BSA) through joint modelling of the mean, standard deviation, skewness, and kurtosis. We then evaluated the impact of infant sex and age at time of echocardiography on the model fit.
Results
The 13,454 infants in the study population (48.5% females), had a median age of 12 days at TTE for both boys and girls (interquartile range IQR 8–15 and 8–12 days, respectively), and a median BSA of 0.23 m2 (IQR 0.22 m2 - 0.24 m2). All nomograms had acceptable goodness-of-fit within strata of sex. In contrast, model fit was worse for infants examined <7 days of age, compared with those examined from 7 to 30 days of age, necessitating the creation of separate nomograms for the two age groups. Examples of the plotted Z scores of one of the 10 LV parameters is shown in the figure.
Conclusions
We provide a large normative dataset and Z scores for echocardiographic measures of LV structure and function in neonates. Normative data is crucial in the management of patients with heart disease and these results provide a needed tool for evaluation of LV size and function in the newborn population.Plotted Z scores of the IVSd
Abstract
Background
The prevalence of bicuspid aortic valve (BAV) in newborns is 0.8%. BAV is associated with an increased risk of aortic valve dysfunction and aortopathy. Aortopathy with increased ...aortic diameters has recently been reported in newborns with BAV. As most patients with BAV are diagnosed in adulthood the development of BAV and associated aortopathy during early years of life is not well described.
Purpose
The purpose of the study was to assess changes in aortic valve function and aortic dimensions at two to four years of age in children diagnosed with BAV neonatally.
Methods
Children with BAV were included from a population-based cohort study, in which newborns (n≈25,000) underwent standardized transthoracic echocardiography (TTE). Follow-up TTE was performed and analyzed according to established guidelines. Neonatal (baseline) and follow-up data were compared. Diameters were indexed to body surface area (BSA). Z-scores were calculated using formulas from the Pediatric Heart Network Echocardiogram Database.
Results
At follow-up 101 newborns with BAV (mean age 2 years 5 months, SD 11 months), 75% male) were examined from May 2019 to April 2021. From baseline to follow-up there was an increase in the BSA-adjusted diameter of the aortic valve annulus (z-score −0.19 at baseline vs 0.95 at follow up, p<0.001), and of the sino-tubular junction (z-score 0.16 at baseline vs 0.43 at follow up, p<0.05). Conversely, there was a decrease in the Z-score for the diameter measured 1 cm from the valve annulus (z-score 1.31 at baseline vs 0.68 at follow up, p<0.001) and at the widest point of the visualized ascending aorta (z-score 2.44 at baseline vs 1.45 at follow up, p<0.001). There was no significant change in the diameter of the sinus of Valsalva (z-score 0.83 at baseline vs 0.80 at follow up, p=0.92). The number of children with at least one aortic z-score >3 was 31 (30.6%) at baseline and 17 (17.8%) at follow up. At baseline mild aortic valve regurgitation was observed in 18 children (17.8%) and in 23 children at follow up (23%). Mean maximum systolic velocities across the aortic valve were 1.03 m/s at baseline (SD 0.24) and 1.11 m/s at follow up (SD 0.27), p<0.05. Aortic stenosis, defined as flow velocity >2.5 m/s was seen in one child both at baseline and at follow-up.
Conclusion
In children diagnosed with BAV neonatally, re-examination at the age of 2.5 years showed significant increases in the diameter of the aortic valve annulus and the sino-tubular junction, but a significant decrease in the diameter of the ascending aorta. The maximum blood flow velocity across the aortic valve increased and more children had developed mild aortic valve regurgitation. Thus, the bicuspid aortic valve and the associated aortopathy seem to undergo remodeling during early childhood.
Funding Acknowledgement
Type of funding sources: Foundation. Main funding source(s): The Danish Children's Heart Foundation, Boernehjertefonden.
Abstract
Introduction
Patency of the oval foramen (PFO) and atrial septal defects (ASDs), i.e. interatrial communications, have been reported to be present in 24–92% of newborns. For isolated ASDs, ...the reported prevalence varies from 0.3–2.4 per 1000 livebirths. This broad range partly reflects the absence of a clear and universal clinical classification of interatrial communications. On this basis we have recently proposed a clinically applicable echocardiographic algorithm for classification of interatrial communications (figure 1), which proved superior to standard assessment by experts in terms of inter- and intraobserver agreement.
Purpose
To determine the prevalence of interatrial communications in newborns.
Methods
Echocardiograms (TTEs) from newborns (0–30 days) included in a population study (N>25,000) were assessed/analyzed for interatrial communications according to the new algorithm and categorized into three PFO subtypes and three ASD subtypes.
Results
TTEs from 16,420 newborns were analyzed; 3,694 (22.5%) were excluded due to suboptimal image quality and 9 (<0.1%) were excluded due to concurrent severe congenital heart disease. Of the remaining 12,718 included newborns (median age 12 days 8; 15, 48.1% female), an interatrial communication was present in 10,033 (78.9%) cases; 9,274 (72.9%) cases were classified as PFO while 759 (6.0%) were classified as ASD. In the ASD group, 368 (48.5%) had a defect size ≥4 mm, 364 (48.0%) had multiple interatrial communications, and 27 (3.6%) had the defect located in the lower 1/3 part of the septum (figure 2).
Conclusion
An interatrial communication was present in almost 4 out of 5 newborns. ASD was diagnosed in 6% of the newborns and the prevalence of PFO was 12 times higher than the prevalence of ASD. Follow-up studies of these children are expected to provide clinically useful information on the long term structural and hemodynamic impact of these well categorized ASD and PFO subtypes.
Funding Acknowledgement
Type of funding sources: Foundation. Main funding source(s): Candy's Foundation, The Danish Children's Heart Foundation
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