Preeclampsia-exposed children's heart rate variability 8-12 yr after index pregnancy: FINNCARE study.

Preeclampsia is related with elevated systolic blood pressure (SBP) in children. We studied if preeclampsia-exposed (PE) children develop alterations in heart rate variability (HRV) and if this is reflected in their blood pressure (BP), as well as overall associations with body size and composition, gestational and perinatal factors. We examined 182 PE (46 early-onset PE) and 85 unexposed (non-PE) children 8-12 yr after preeclampsia exposure. HRV monitoring was performed 5 min in supine followed by 5 min in standing position and compared with office, 24-h ambulatory, and central BPs in relation to body anthropometrics and composition, gestational, and perinatal data. There were no major differences in HRV between PE and non-PE children. HRV in supine position was strongly associated with office and ambulatory heart rates (HRs), and HR was independently associated with office BPs. However, HRV was not related with office or 24-h SBP and PP, nor with elevated SBP in PE compared with non-PE children [adjusted mean differences for office and 24-h SBP 4.8 (P < 0.001) and 2.5 mmHg (P = 0.049), respectively]. In supine position, high-frequency (HF) power [ß, -0.04 (95% CI -0.06 to -0.01)], root mean square of successive differences in R-R intervals (rMSSD) [-0.015 (-0.028 to -0.002)], and the ratio of low-frequency (LF) to HF power [0.03 (0.01-0.04)] were independently associated with child fat mass. LF and HF power and rMSSD displayed independent inverse associations with child age. There were no significant associations between child HRV and gestational and perinatal factors. During prepuberty, the HRV in children with PE is similar to that in non-PE children. Elevated SBP following preeclampsia exposure is not related with HRV. Child adiposity could be related to decreased cardiac vagal tone.NEW & NOTEWORTHY Heart rate variability in preadolescent children exposed to preeclampsia in utero is no different from age-matched controls. Preeclampsia-exposed children's elevated SBP is not related to alterations in heart rate variability, which is a noninvasive measure of the modulation of heart rate by autonomic tone. However, childhood adiposity might be coupled with diminished cardiac vagal tone.

Associations Between Sedentary Time, Physical Activity, and Cardiovascular Health in 6-Year-Old Children Born to Mothers With Increased Cardiometabolic Risk.

PURPOSE: To assess associations between sedentary time (ST), physical activity (PA), and cardiovascular health in early childhood. METHOD: Cross-sectional study including 160 children (age 6.1 y [SD 0.5], 86 boys, 93 maternal body mass index ≥ 30 kg/m2, and 73 gestational diabetes) assessed for pulse wave velocity, echocardiography, ultra-high frequency 48-70 MHz vascular ultrasound, and accelerometery. RESULTS: Boys had 385 (SD 53) minutes per day ST, 305 (SD 44) minutes per day light PA, and 81 (SD 22) minutes per day moderate to vigorous PA (MVPA). Girls had 415 (SD 50) minutes per day ST, 283 (SD 40) minutes per day light PA, and 66 (SD 19) minutes per day MVPA. In adjusted analyses, MVPA was inversely associated with resting heart rate (ß = -6.6; 95% confidence interval, -12.5 to -0.7) and positively associated with left ventricular mass (ß = 6.8; 1.4-12.3), radial intima-media thickness (ß = 11.4; 5.4-17.5), brachial intima-media thickness (ß = 8.0; 2.0-14.0), and femoral intima-media thickness (ß = 1.3; 0.2-2.3). MVPA was inversely associated with body fat percentage (ß = -3.4; -6.6 to -0.2), diastolic blood pressure (ß = -0.05; -0.8 to -0.1), and femoral (ß = -18.1; -32.4 to -0.8) and radial (ß = -13.4; -24.0 to -2.9) circumferential wall stress in boys only. ST and pulse wave velocity showed no significant associations. CONCLUSIONS: In young at-risk children, MVPA is associated with cardiovascular remodeling, partly in a sex-dependant way, likely representing physiological adaptation, but ST shows no association with cardiovascular health in early childhood.

Early Counseling to Improve Oral Health Behavior in Children with Major Congenital Heart Defects: A Randomized Controlled Trial.

Maintaining optimal oral health behavior in children with a congenital heart defect (CHD) is important in managing the risk for caries development and infective endocarditis. The aim of this study was to evaluate the impact of an early and repeat oral health promotion intervention (OHPI) among children with major CHD. Randomized controlled trial including 72 out of 91 children born in Finland April 1, 2017-October 31, 2020 with (a) major CHD potentially included in the criteria of endocarditis prophylaxis or (b) any CHD with surgical repair combined with a chromosomal syndrome. A parallel passive control (C) group of 87 healthy children were recruited at birth. CHD children were randomized 1:1 to intervention (CHD-I) and control (CHD-C) groups. The OHPI included counseling by motivational interviewing, home delivered toothpaste and toothbrushes, and written information, and was provided at baseline, 6, 12, and 18 months of age to CHD-I group. The primary outcome measure at 24 months was child's oral health behavior (toothbrushing, sugar intake, and dental care contact). The secondary outcome measures were parents' awareness of the importance of oral health behavior, and oral health behavior as a predictor for child behavior. At 24 months, toothbrushing was performed twice a day in 20/27 (74%) among CHD-I, in 13/30 (43%) among CHD-C (CHD-I vs. CHD-C p = 0.03), and in 37/50 (74%) among healthy comparisons (CHD-C vs. C p = 0.01). Electric toothbrush use was 12/27 (44%) in CHD-I, 5/30 (17%) in CHD-C (CHD-I vs. CHD-C p = 0.04), and 7/50 (14%) in healthy comparison (CHD-C vs. C p = 0.76) children. Among CHD-I, toothbrushing and use of electric toothbrush improved between 12 months and 24 months. Sugar drink intake was more common among CHD-C (CHD-C vs. C p = 0.02), but comparable to CHD-I children. Parental toothbrushing predicted child toothbrushing twice a day. There were no statistical group differences in dental care contact. Children with CHD are at risk for poor oral health behavior. This could be improved with early and repeat oral health promotion parental counseling.

Oral health behavior during early childhood in children with major congenital heart defects.

BACKGROUND: Good oral health in children with congenital heart defect (CHD) is important. AIM: To assess oral health behavior during early childhood in children with CHD in comparison with children with no known systemic conditions and to explore parental oral health behavior associated with children's behavior. DESIGN: Seventy of all 89 children born in Finland between April 1, 2017, and March 31, 2020, with (a) major CHD potentially included in the criteria of endocarditis prophylaxis or (b) any CHD with surgical repair combined with a chromosomal syndrome, and a comparison group of 87 children with no known systemic conditions were recruited. Thirty-five children with CHD were randomized to usual care (no intensified counseling) and were compared with 87 matched comparison children by a parental questionnaire assessing child and parental oral health behavior at child age at 24 months. RESULTS: Toothbrushing twice a day (p = .008) and the use of fluoride toothpaste twice a day (p = .059) were less common in children with CHD than in children in the comparison group. Nonwater drinks between meals was more common among children in the CHD group than in the comparison group (p = .015). CONCLUSION: Children with major CHD experience poorer oral health behavior in comparison with children with no known systemic conditions during early childhood.

Liver pathology and biochemistry in patients with mutations in TRIM37 gene (Mulibrey nanism).

BACKGROUND AND AIMS: Mulibrey nanism (MUL) is a multiorgan disease caused by recessive mutations in the TRIM37 gene. Chronic heart failure and hepatopathy are major determinants of prognosis in MUL patients, which prompted us to study liver biochemistry and pathology in a national cohort of MUL patients. METHODS: Clinical, laboratory and imaging data were collected in a cross-sectional survey and retrospectively from hospital records. Liver histology and immunohistochemistry for 10 biomarkers were assessed. RESULTS: Twenty-one MUL patients (age 1-51 years) with tumour suspicion showed moderate congestion, steatosis and fibrosis in liver biopsies and marginally elevated levels of serum GGT, AST, ALT and AST to platelet ratio index (APRI) in 20%-66%. Similarly, GGT, AST, ALT and APRI levels were moderately elevated in 12%-69% of 17 MUL patients prior to pericardiectomy. In a cross-sectional evaluation of 36 MUL outpatients, GGT, total bilirubin and galactose half-life (Gal½) correlated with age (r = 0.45, p = .017; r = 0.512, p = .007; r = 0.44, p = .03 respectively). The frequency of clearly abnormal serum values of 15 parameters analysed, however, was low even in patients with signs of restrictive cardiomyopathy. Transient elastography (TE) of the liver revealed elevated levels in 50% of patients with signs of heart failure and TE levels correlated with several biochemistry parameters. Biomarkers of fibrosis, sinusoidal capillarization and hepatocyte metaplasia showed increased expression in autopsy liver samples from 15 MUL patients. CONCLUSION: Liver disease in MUL patients was characterized by sinusoidal dilatation, steatosis and fibrosis with individual progression to cirrhosis and moderate association of histology with cardiac function, liver biochemistry and elastography.

Accuracy of fetal echocardiography diagnosis and anticipated perinatal and early postnatal care in congenital heart disease in mid-gestation.

INTRODUCTION: The aim of this study was to determine discrepancies in fetal congenital heart disease (CHD) diagnoses and anticipated early postnatal care and outcomes. MATERIAL AND METHODS: A retrospective review of 462 randomly selected cases (23% of all cases) referred to a fetal cardiac assessment during the second trimester (mean 26 weeks) at the Children's Hospital in Helsinki between October 2010 and December 2020. Discrepancy between prenatal and postnatal CHD case evaluations was assessed with independently provided cardiac severity and surgical complexity scores. RESULTS: In all, 250 cases, 181 CHD and 69 normal, with complete prenatal and postnatal live birth data as well as seven fetal autopsy reports available were included in the analysis. There were 12 false normal and seven false abnormal prenatal assessments. The prenatally anticipated level of early neonatal care was actualized in 62% and prostaglandin infusion in 95%. In total, 32.7% (84/257) cardiac severity scores were discrepant and in 12,4% (32/257) cases the discrepancies were considered significant (≥ +/- 2 scores). Among significant discrepancies, CHD severity score was overestimated in 13 and underestimated in 19 in fetal assessment. Progression of CHD severity after mid-gestation and during early neonatal phase explained eight of 19 underestimated fetal assessments. The most common discrepant diagnostic categories included ventricular septal defects (n = 7), borderline ventricles (n = 7; 5 left heart, 1 right heart and 1 double outlet right ventricle/transposition of the great arteries), arch anomalies including coarctations (n = 5) and tricuspid valve dysplasias (n = 4) with a significant change in postnatal diagnoses and treatment. CONCLUSIONS: Although fetal CHD diagnosis and counseling is accurate and reliable in general, the study elaborates specific areas of uncertainty in clinical fetal cardiology practice that may be important to consider in fetal CHD evaluation and counseling provided in mid-gestation.

Childhood cardiovascular morphology and function following abnormal fetal growth.

Studies examining the link between abnormal fetal growth and cardiac changes in childhood have presented conflicting results. We studied the effect of abnormal fetal growth on cardiac morphology and function during childhood, while controlling for body size, composition and postnatal factors. We report on the follow-up of 90 children (median age 5.81 years, IQR 5.67; 5.95) born appropriate for gestational age (AGA, N = 48), small for gestational age (SGA, N = 23), or large for gestational age (LGA, N = 19); SGA and LGA defined as birth weight Z-score < - 2 and > + 2, respectively. We examined the heart using echocardiography, including Doppler and strain imaging, in relation to anthropometrics, body composition, blood pressure, physical activity, and diet. Although groupwise differences in body size decreased during the first year after birth, LGA remained larger at follow-up, with higher lean body mass and BMI, while SGA were smaller. Slight changes in left ventricular diastolic function were present in SGA and LGA, with SGA showing increased mitral diastolic E- and A-wave peak flow velocities, and increased septal E/E' ratio, and LGA showing larger left atrial volume adjusted for sex and lean body mass. In univariate analyses, lean body mass at follow-up was the strongest predictor of cardiac morphology. We found no groupwise differences at follow-up for ventricular sphericity, cardiac morphology adjusted for lean body mass and sex, or blood pressure, diet, or physical activity. Cardiac morphology is predicted by lean body mass during childhood, even in the setting of abnormal fetal growth. Our results are consistent with a limited effect of fetal programming on cardiac dimensions during childhood. Minor changes in diastolic function are present in both SGA and LGA children, however, the clinical significance of these changes at this stage is likely small.

Arterial health during early childhood following abnormal fetal growth.

BACKGROUND: Abnormal fetal growth is associated with increased cardiovascular risk in adulthood. We investigated the effect of fetal programming on arterial health and morphology during early childhood. METHODS: We examined 90 children (median age 5.81 years, interquartile range: 5.67; 5.95), born small for gestational age with fetal growth restriction, large or appropriate for gestational age (SGA, N = 23, LGA, N = 19, AGA N = 48). We measured body composition, anthropometrics, blood pressure, pulse wave velocity (PWV), lipids, glucose and inflammatory markers, and assessed carotid, brachial, radial and femoral arterial morphology and stiffness using very-high resolution ultrasound (46-71 MHz). RESULTS: LGA showed increased anthropometry, lean body mass and body mass index. SGA displayed decreased anthropometry and lean body mass. Blood pressure, PWV, carotid artery stiffness and blood work did not differ groupwise. Differences in lumen diameters, intima-media thicknesses (IMT) and adventitia thicknesses disappeared when adjusted for lean body mass and sex. In multiple regression models arterial dimensions were mainly predicted by lean body mass, with birth weight remaining associated only with carotid and brachial lumen dimensions, and not with IMTs. Carotid-femoral PWV was predicted by height and blood pressure only. No independent effect of adiposity was observed. CONCLUSIONS: Arterial dimensions in childhood associate with current anthropometrics, especially lean body mass, and sex, explaining differences in arterial layer thickness. We found no signs of fetal programming of cardiovascular risk or arterial health in early childhood.

Completed secondary education among youth with prenatal substance exposure: A longitudinal register-based matched cohort study.

INTRODUCTION: The dual impact of prenatal substance exposure (i.e. alcohol/drugs) and adverse postnatal caregiving environment on offspring secondary education completion is an understudied research area. The aim was to investigate the influence of childhood adversities, out-of-home care, and offspring's mental and/or behavioural disorders on secondary education completion among prenatally exposed offspring in comparison to matched unexposed offspring. METHODS: This is a longitudinal register-based matched cohort study in Finland including offspring with a history of prenatal substance exposure and a matched unexposed cohort. The study sample included 283 exposed and 820 unexposed offspring aged 18-23 years. RESULTS: The results showed a time lag in secondary education completion and lower educational attainment overall among exposed compared with unexposed (37.8% vs. 51.0%, respectively). The results from the multivariate logistic regression models showed that the differences in the secondary education completion between exposed and unexposed were diminished in the presence of covariates. A cumulative childhood adversity score and out-of-home care were not associated with secondary education completion in the multivariate models, whereas the different domains of offspring's mental and/or behavioural disorders including psychiatric disorders (AOR 0.65, 95% CI 0.45-0.96), neuropsychological disorders (AOR 0.35, 95% CI 0.23-0.54) and dual psychiatric and neuropsychological disorder (AOR 0.29, 95% CI 0.18-0.48) showed an independent negative effect on secondary education completion. CONCLUSIONS: Inferior educational outcomes may not be directly linked with prenatal substance exposure but may rather reflect the extent of evolving offspring's mental and/or behavioural disorders over time influenced by childhood adversities.

Dental caries prevalence in children with congenital heart disease - a systematic review.

AIM: Poor oral health is related with bacteraemia that may lead to endocarditis in children with congenital heart disease (CHD). The aim of this study was to conduct a systematic literature review to compare caries prevalence in children (<18 years of age) with CHD with healthy children. MATERIAL AND METHODS: A literature search of studies from two online databases (Pubmed (MEDLINE) and Scopus) published from January 2000 to October 2019 using Medical subject heading terms Congenital Heart Disease, Congenital Heart Defect, and Caries was done, and manual search from the reference lists of selected publications. PICO (Patient/Population, Intervention, Comparison group, and Outcome) criteria was applied. Quality of the publications was assessed with the modified Newcastle-Ottawa scale. RESULTS: The search resulted in 151 articles of which nine fulfilled the inclusion criteria. Caries prevalence was significantly higher in children with CHD compared to healthy children in three out of nine studies. Information on predisposing background factors was limited but difference in caries prevalence was not attributed to SES. The quality of the studies varied. CONCLUSIONS: Although evidence is limited, the current literature indicates that children with CHD experience a higher caries prevalence compared to healthy children.

Long-term renal prognosis and risk for hypertension after myeloablative therapies in survivors of childhood high-risk neuroblastoma: A nationwide study.

BACKGROUND: Patients with high-risk neuroblastoma (HR NBL) treated with myeloablative regimens are reported to be at risk for cardiovascular morbidity, and this risk may be increased by impaired renal function. PROCEDURE: Long-term renal function was assessed in a national cohort of 18 (age 22.4 ± 4.9 years) HR NBL survivors by plasma creatinine (P-Cr), urea, and cystatin C (P-Cys C) concentrations, urine albumin/creatinine ratio (ACR), and estimated glomerular filtration rate (eGFR). Ambulatory blood pressure was monitored, and common carotid intima-media thickness (CIMT) and left ventricular mass index (LVMI) were evaluated. RESULTS: No significant difference in P-Cr, P-Cys C, or eGFR was found between the NBL survivors and the age- and sex-matched 20 controls. P-Cys C-based eGFR (eGFRcysc) was significantly lower than the P-Cr-based eGFRcr (97 ± 17 mL/min/1.73 m2 vs 111 ± 19 mL/min/1.73 m2 , P < 0.001) among the NBL survivors. The eGFRcysc was below normal in 28%, and ACR was above normal in 22% of the NBL survivors. Abnormal blood pressure was found in 56% of the survivors, and an additional 17% were normotensive at daytime but had significant nocturnal hypertension. Both ACR and P-Cys C were associated with nighttime diastolic hypertension. CONCLUSIONS: Long-term survivors of childhood HR NBL showed signs of only mild renal dysfunction associated with diastolic hypertension. Elevated ACR and P-Cys C were the most sensitive indicators of glomerular renal dysfunction and hypertension in this patient cohort.

Long-term effects of a preconception lifestyle intervention on cardiometabolic health of overweight and obese women.

BACKGROUND: The global prevalence of obesity in women keeps increasing. The preconception period may be a window of opportunity to improve lifestyle, reduce obesity and improve cardiometabolic health. This study assessed the effect of a preconception lifestyle intervention on long-term cardiometabolic health in two randomized controlled trials (RCTs). METHODS: Participants of the LIFEstyle and RADIEL preconception lifestyle intervention studies with a baseline body mass index (BMI) ≥29 kg/m2 were eligible for this follow-up study. Both studies randomized between a lifestyle intervention targeting physical activity, diet and behaviour modification or usual care. We assessed cardiometabolic health 6 years after randomization. RESULTS: In the LIFEstyle study (n = 111) and RADIEL study (n = 39), no statistically significant differences between the intervention and control groups were found for body composition, blood pressure, arterial stiffness, fasting glucose, homeostasis model assessment of insulin resistance, HbA1c, lipids and high sensitive C-reactive protein levels 6 years after randomization. Participants of the LIFEstyle study who successfully lost ≥5% bodyweight or reached a BMI <29 kg/m2 during the intervention (n = 22, [44%]) had lower weight (-8.1 kg; 99% CI [-16.6 to -0.9]), BMI (-3.3 kg/m2; [-6.5 to -0.8]), waist circumference (-8.2 cm; [-15.3 to -1.3]), fasting glucose (-0.5 mmol/L; [-1.1 to -0.0]), HbA1c (-4.1 mmol/mol; [-9.1 to -0.8]), and higher HDL-C (0.3 mmol/L; [0.1-0.5]) compared with controls. CONCLUSION: We found no evidence of improved cardiometabolic health 6 years after a preconception lifestyle intervention among overweight and obese women in two RCTs. Women who successfully lost weight during the intervention had better cardiometabolic health 6 years later, emphasizing the potential of successful preconception lifestyle improvement.

Growth of Cardiovascular Structures from the Fetus to the Young Adult.

The size, hemodynamics, and function of cardiovascular structures change dramatically from the early fetal life to late adolescence. The principal determinants of cardiovascular dimensions are related to the blood flow needed to meet metabolic demands. This demand is in turn tightly related to body size and body composition, keeping in mind that various tissues may have different metabolic rates. There is no simple model that links cardiac dimensions with a single body size measurement. Consequently, despite abundant scientific literature, few studies have proposed pediatric reference values that efficiently and completely account for the effect of body size. Other factors influence cardiovascular size and function in children, including sex. The influence of sex is multifactorial and not fully understood, but differences in body size and body composition play an important role. We will first review the determinants of cardiovascular size and function in children. We then explore the evaluation and normalization of cardiovascular size and function in pediatric cardiology in relation to the growth of cardiovascular structures during childhood, with a particular focus on sex differences.

Radiotherapy-related arterial intima thickening and plaque formation in childhood cancer survivors detected with very-high resolution ultrasound during young adulthood.

BACKGROUND: The aim of the study was to evaluate arterial morphology and function in a national cohort of long-term survivors of high-risk neuroblastoma (NBL) treated with high-dose chemotherapy and autologous hematopoietic stem cell transplantation with or without total body irradiation (TBI). METHODS AND RESULTS: Common carotid, femoral, brachial, and radial artery morphology were assessed with very-high-resolution vascular ultrasound (25-55 MHz), and carotid artery stiffness and brachial artery flow-mediated dilatation measured with conventional vascular ultrasound in 19 adult or pubertal (age 22.7 ± 4.9 years, range 16-30) NBL survivors transplanted during 1984-1999 at the mean age of 2.5 ± 1.0 years. Results were compared with 20 age- and sex-matched healthy controls. The cardiovascular risk assessment included history, body mass index, fasting plasma lipids, glucose, and 24-h ambulatory blood pressure (BP). The survivors had consistently smaller arterial lumens, increased carotid intima-media thickness (IMT), plaque formation (N = 3), and stiffness, as well as increased radial artery intima thickness (N = 5) compared with the control group. Survivors displayed higher plasma triglyceride and cholesterol levels, and increased heart rate, as well as increased systolic and diastolic BPs. TBI (N = 10) and a low body surface area were independent predictors for decreased arterial lumen size and increased IMT. Three out of five survivors with subclinical intima thickening had arterial plaques. Plaques occurred only among TBI-treated survivors. CONCLUSIONS: Long-term childhood cancer survivors treated with TBI during early childhood display significant signs of premature arterial aging during young adulthood.

Fetal left ventricular noncompaction cardiomyopathy and fatal outcome due to complete deficiency of mitochondrial trifunctional protein.

We report a fetal case with fatal outcome having a novel mutation in the HADHB gene, coding the beta-subunit of the mitochondrial trifunctional protein. Parents had a previous pregnancy loss due to fetal heart failure and hydrops. The next pregnancy led to left ventricular noncompaction and increasing pleural effusions after 29 gestational weeks. The fetus was small for gestational age, and long bones were abnormally short. The baby was born severely asphyxiated at 32 gestational weeks by cesarean section. Intensive care was withdrawn due to failure to thrive and suspicion of a severe mitochondrial disorder. Postmortem brain MRI suggested microcephaly with a simplified gyral pattern. The lateral cerebral ventricles were normal. Chromosome analysis was normal (46, XX). Fibroblasts cultured from a skin biopsy of the baby revealed the large homozygous deletion c.1109+243_1438-703del in the HADHB gene, and heterozygous mutations were detected in both parents. The deletion has not been reported earlier. CONCLUSION: It is important to differentiate systemic metabolic diseases from disorders that affect only the cardiac muscle. Trifunctional protein deficiency is a relatively rare disorder of the fatty acid ß-oxidation cycle. The mutation in the HADHB gene causes a systemic disease with early-onset cardiomyopathy. Understanding the molecular genetic defect of the patient allows appropriate genetic counseling of the family. WHAT IS KNOWN: • Mitochondrial disorders as a group are an important etiology for fetal cardiomyopathies including human trifunctional protein (TFP) disorders and several other mitochondrial diseases. WHAT IS NEW: • We report a fetal case with fatal outcome having a novel mitochondrial trifunctional protein mutation (c.1109+243_1438-703del in the HADHB gene).

Screening for congenital heart defects by transabdominal ultrasound - role of early gestational screening and importance of operator training.

The majority of congenital heart defects occur without identifiable risk factors. Detection rates are therefore highly dependent on the experience and expertise of the obstetrical screening operator. In the first trimester, the risk of congenital heart defects increases with increasing nuchal thickness (≥2.5 mm detects 44% of major congenital heart defects), but because of the number of false positives, the positive predictive value is only a few percent. The anatomy of major congenital heart defects may be delineated in less than half of the fetuses during early second trimester. The reported yield of congenital heart defects detection during the mid-gestational routine obstetrical screening has improved over time and detection rates up to 85% of major congenital heart defects have been reported when outflow tract and three-vessel views are included in conjunction with the four-chamber view. Improved detection rates have been achieved following screening operator training interventions combined with a low referral threshold to obtain a detailed fetal echocardiographic study.

Cumulative risk factors for injuries and poisoning requiring hospital care in youth with prenatal substance exposure: A longitudinal controlled cohort study.

Aim: To investigate whether the youth with prenatal substance exposure (PSE) (aged 15-24 years, n = 615) had been in hospital care more often due to injuries and poisoning in comparison with unexposed matched controls (n = 1787). Methods: Data from medical records (exposure) and national health and social welfare registers (outcome and confounders) were combined and youths were monitored from birth until either outpatient or inpatient hospital care for injury or poisoning, death or the end of the study period (December 2016). Cox regression models were used in the analyses accounting for associated child and maternal risk factors. Results: Half (50.4%) of the exposed group and 40.6% of controls had been in hospital care due to injury or poisoning during the follow-up (p < 0.001). The difference between groups was diminished after controlling for postnatal child and maternal risk factors (hazard ratio [HR] = 0.88, 95% confidence interval [CI] 0.72-1.07, p > 0.05). Cumulative adversity, especially out-of-home care in combination with a diagnosed attention or behavioural dysregulation problem, posed the highest risk in both groups (exposed: HR = 1.65, 95% CI 1.24-2.19, p < 0.001; controls: HR = 1.84, 95% CI 1.33-2.56, p < 0.001). Conclusion: Hospital care for injury and poisoning is more common in youth with PSE, but this is largely explained by the related postnatal child and maternal factors. Long-term support to families with maternal substance abuse problems could prevent injury and poisoning among youth with PSE.

Cardiac Structure and Function in 8- to 12-Year-Old Children Following In-Utero Exposure to Preeclampsia (FINNCARE Study).

BACKGROUND: We evaluated how elevated blood pressure in children exposed to preeclampsia (PE) impacted on their cardiac structure and function, as well as relations with maternal, gestational, and perinatal factors and child body size and composition. METHODS AND RESULTS: A total of 182 PE (46 early-onset preeclampsia) and 85 unexposed (non-PE) children were examined in the FINNCARE study 8 to 12 years after the index pregnancy with echocardiography; office, central, and 24-hour ambulatory blood pressures; and body anthropometrics and composition. PE children had lower right ventricular basal sphericity index (mean difference, -0.26 95% CI, -0.39 to -0.12) and lower mitral lateral E'-wave peak velocity (-1.4 cm/s [95% CI, -2.1 to -0.6]), as well as higher E to E' ratio (0.40 [95% CI, 0.15-0.65]) and indexed tricuspid annular plane systolic excursion (0.03 [95% CI, 0.01-0.05]) compared with non-PE children. These differences were accentuated in early-onset PE children. Left ventricular mass (LVM) or left atrial volume were not different between PE and non-PE children. Lean body mass, body fat percentage, and 24-hour systolic blood pressure were independent predictors of LVM. Lean body mass and body fat percentage were independent predictors of left atrial volume. No significant associations between LVM or left atrial volume and maternal, gestational, or perinatal parameters were found. CONCLUSIONS: Preadolescent PE children display a more globular-shaped right ventricle with higher longitudinal systolic displacement as well as mildly altered diastolic indices, with the alterations being pronounced in early-onset preeclampsia. Lean body mass and adiposity are independently related with LVM and left atrial volume, and systolic blood pressure with LVM in both PE and non-PE children. These unfavorable associations indicate remodeling of cardiac structure in young children also reflected in mild functional changes in PE children. REGISTRATION: URL: https://www.clinicaltrials.gov; unique identifier: NCT04676295.

Evolution of the arterial structure and function from infancy to adolescence is related to anthropometric and blood pressure changes.

OBJECTIVE: To develop a normative data set and to study the relationship among arterial structure, different anthropometric measures, blood pressure, and arterial function during healthy childhood using very-high-resolution ultrasound (25-55 MHz). METHODS AND RESULTS: In 135 healthy children between 0 and 18 years of age, we assessed the structure of the carotid arteries, larger peripheral arteries, aorta, and left ventricle with ultrasound. Arterial stiffness was assessed by pulse wave velocity and endothelial function by brachial flow-mediated dilation. Reference curves adjusted for age and body surface area of arterial lumen diameters, intima-media thickness, and adventitia thickness were developed. Arterial walls thicken during childhood predominantly as a result of a progressive increase in intima-media thickness. There were significant associations among lumen diameter (R(2) range, 0.20-0.88 for different arteries; P<0.001), intima-media thickness (R(2) range, 0.47-0.85; P<0.001), left ventricular mass (R(2)=0.90; P<0.001), and adventitia thickness (R(2) range, 0.15-0.22; P<0.001) with sex, age, body surface, and systolic blood pressure. Arterial wall stress was associated with lumen diameter (R(2) range, 0.52-0.83; P<0.001) and intima-media thickness (R(2) range, 0.53-0.88; P<0.001). Limited relationships were found among arterial wall layer thickness, stiffness, and endothelial function. CONCLUSIONS: In healthy children, the evolution of the arterial structure is mainly related to anthropometrics and blood pressure.

Assessment of vascular remodeling after the Fontan procedure using a novel very high resolution ultrasound method: arterial wall thinning and venous thickening in late follow-up.

The Fontan circulation is associated with an increased central venous pressure, decreased ventricular preload, and increased afterload. We postulated that these central hemodynamic abnormalities would have consequences for the structural and functional properties of the peripheral arteries and veins, and performed a cross-sectional study in a tertiary health-care setting. We prospectively examined venous and arterial wall morphology by very high resolution ultrasound (VHRU, 25-55 MHz), and function by conventional vascular ultrasound (flow-mediated dilatation, FMD) and applanation tonometry (pulse wave velocity, PWV) in 28 patients after the Fontan procedure (age 14.8 ± 1.3 years) and 54 age-matched controls. Pig venous samples were studied with VHRU and compared with histology for accuracy. The precision of the venous VHRU method was studied in healthy volunteers. The lumen dimension was reduced in Fontans compared with controls in the common carotid, brachial, radial, and femoral arteries (p < 0.05). The common carotid, brachial, radial, ulnar, femoral, and dorsal tibial artery intima-media thicknesses (IMTs) and the brachial, ulnar, and femoral artery adventitial thicknesses were decreased (p < 0.05 for all), while the cubital and dorsal tibial vein IMTs were increased in Fontans (p < 0.001). FMD, abdominal aortic stiffness, and carotid-femoral PWV were similar, while carotid-radial artery PWV was increased in Fontans (p < 0.01). Venous wall layer assessment with VHRU was accurate and precise. The Fontan circulation is associated with significant arterial and venous remodeling, presumably reflecting abnormalities of central hemodynamics. These novel data may be of clinical importance in the circulatory management as well as the understanding of the early pathogenesis of vasculopathy in patients after the Fontan procedure.