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.

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.

Determinants of vascular structure and function in at-risk children born to mothers managed for pre-eclampsia (FINNCARE study).

Background and aim: Pre-eclampsia (PE) is related to elevated blood pressure (BP) in children. The study aims to investigate if elevated BP is reflected in child arterial health and how anthropometrics, body composition, and gestational and perinatal factors influenced this. Methods: In this prospective cohort study, we assessed the arteries of 182 children exposed (46 had an early onset, with a diagnosis before 34 gestational weeks, and 136 had a late onset) and 85 children unexposed (non-PE) to PE at 8-12 years from delivery using ultra-high-frequency ultrasound in addition to ambulatory and central BPs, body composition and anthropometrics, and tonometry-derived pulse wave velocity (PWV). Results: No differences were found in intima-media thickness (IMT), adventitia thickness (AT), lumen diameter (LD), local carotid artery stiffness, distensibility, or wall stress between PE-exposed and non-PE-exposed children. All children's brachial, radial, and femoral artery IMTs were associated with 24-h systolic BP (SBP) and pulse pressure, carotid-femoral PWV, and anthropometric measures. The 24-h SBP and anthropometrics, notably lean body mass, were independent predictors of peripheral artery IMTs (brachial R2 = 0.217, radial R2 = 0.208, femoral R2 = 0.214; p < 0.001). Head circumference predicted carotid artery IMT and LD (ß = 0.163, p = 0.009; ß = 0.417, p < 0.001, respectively), but carotid artery IMT was not associated with BP. No independent associations were found for peripheral artery ATs. Local carotid artery stiffness, distensibility, and wall stress were independently associated with adiposity. No significant associations were found between gestational or perinatal factors and child vascular health parameters. Conclusions: The peripheral artery IMT of PE-exposed children is identical to that of non-PE-exposed children, but associated with BP. Adiposity is related to local carotid artery stiffness. These adverse associations in arterial health may reflect the early progression of cardiovascular disease in PE-exposed children.

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.

Blood pressure, arterial stiffness, and cardiovascular risk profiles in 8-12-year-old children following preeclampsia (FINNCARE-study).

OBJECTIVES: The aim was to study if children following preeclampsia (PE) develop alterations in blood pressure (BP) and arterial stiffness already early in life, and how this is associated with gestational, perinatal and child cardiovascular risk profiles. METHODS: One hundred eighty-two PE (46 early-onset with diagnosis before 34 gestational weeks, and 136 late-onset) and 85 non-PE children were assessed 8-12 years from delivery. Office and 24-h ambulatory BP, body composition, anthropometrics, lipids, glucose, inflammatory markers, and tonometry-derived pulse wave velocity (PWV) and central BPs were assessed. RESULTS: Office BP, central BPs, 24-h systolic BP (SBP) and pulse pressure (PP) were higher in PE compared with non-PE. Early-onset PE children had the highest SBP, SBP-loads, and PP. SBP nondipping during night-time was common among PE. The higher child 24-h mean SBP among PE was explained by maternal SBP at first antenatal visit and prematurity (birth weight or gestational weeks), but child 24-h mean PP remained related with PE and child adiposity after adjustments. Central and peripheral PWVs were elevated in late-onset PE subgroup only and attributed to child age and anthropometrics, child and maternal office SBP at follow-up, but relations with maternal antenatal SBPs and prematurity were not found. There were no differences in body anthropometrics, composition, or blood parameters. CONCLUSIONS: PE children develop an adverse BP profile and arterial stiffness early in life. PE-related BP is related with maternal gestational BP and prematurity, whereas arterial stiffness is determined by child characteristics at follow-up. The alterations in BP are pronounced in early-onset PE.Clinical Trial Registration information: https://clinicaltrials.gov/ct2/show/NCT04676295ClinicalTrials.gov Identifier: NCT04676295.

Adverse childhood experiences and neurodevelopmental disorders among youth with and without prenatal substance exposure: A longitudinal matched register-based cohort study.

Background: Previous research has shown an association between adverse childhood experiences (ACEs) and secondary mental health problems in youth with prenatal substance exposure (PSE), but the association between ACEs and neurodevelopmental disorders is less clear. Methods: This longitudinal register-based cohort study investigated relationships between health at birth, ACEs (out-of-home care (OHC) and maternal adversities), and neurodevelopmental disorders among youth with PSE (alcohol/drugs, n = 615) and matched unexposed controls (n = 1787). Hospital medical records and register data were merged and analysed using Cox regression models. Results: Conduct and emotional disorders (International Statistical Classification of Diseases and Related Health Problems ICD-10, F90-F94) were more common among the exposed than the controls but only when the exposed and controls with no OHC were compared. The difference appeared in hyperkinetic disorders (ADHD, F90), mixed disorders of conduct and emotions (F92) and emotional disorders with onset specific to childhood (F93). Among the exposed and controls with OHC, over 40% had received an F90-F94 diagnosis. Regarding specific developmental disorders (F80-F83, e.g., impairments in speech and language and scholastic skills) the moderate difference between the exposed and controls attenuated after adjustment for OHC. Again, the rates were highest among the exposed with OHC and the controls with OHC. OHC and maternal risks were interrelated and, together with male sex and low birth weight, were associated with neurodevelopmental disorders both among the exposed and controls and decreased the difference between them. Conclusions: A strong association between ACEs and neurodevelopmental disorders was found. Brain research is needed to examine whether ACEs worsen neurodevelopmental outcomes caused by PSE.

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.

Predictors of blood pressure and hypertension long-term after treatment of isolated coarctation of the aorta in children-a population-based study.

OBJECTIVES: The aim of this study was to assess predictors of BP and hypertension and relations between BP and LV mass in a population-based retrospective study of repaired isolated coarctation of aorta. METHODS: We collected follow-up data until 2018 of 284/304 (93%) patients with coarctation treated by surgery (n = 235) or balloon angioplasty/stent (n = 37/12) in our unit 2000-2012. Systolic hypertension was defined as systolic BP (SBP) z-score ≥+2 standard deviation (SD) or regular use of BP medication. LV hypertrophy was defined as LV mass z-score ≥+2 SD or LV mass index g/m2.7 ≥95th percentile. RESULTS: The median (25-75th percentiles) follow-up time and age at follow-up were 9.7 years (6.9-13.2) and 11.8 years (7.9-16.0), respectively. Age at first procedure (P = 0.011) and systolic arm-leg-gradient (P = 0.007) were positively and transverse arch (P = 0.007) and isthmus diameter (P = 0.001) z-scores at follow-up were negatively associated with SBP z-score adjusted for age at follow-up and need for reintervention for coarctation. Systolic hypertension was present in 53/284 (18.7%) and related with increasing age at first procedure (median 33.2 vs 0.6 months; P < 0.001) and arm-leg-gradient at follow-up (mean ± SD, -0.3 ± 14.6 vs -6.4 ± 11.6 mmHg; P = 0.047) adjusted for reintervention for coarctation and age at follow-up. LV hypertrophy was present in 20/227 (9.3%) and related with SBP z-score. CONCLUSIONS: Higher SBP and hypertension in repaired coarctation of aorta are related with increasing age at first procedure and arm-leg-gradient at follow-up. Transverse arch and isthmus diameters at follow-up are inversely related with SBP.

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.

Parental perceptions and experiences of an oral health care promotion intervention for children with congenital heart defects.

PURPOSE: Congenital heart disease (CHD) is one of the most common congenital anomalies in children. Children with major CHD are at risk for developing endocarditis. Acute endocarditis may be life threatening and lead to heart failure. The purpose of this study was to explore parental perceptions and experiences of an early oral health promotion intervention (OHPI) targeting children with major CHD at risk for developing endocarditis later in life, and use this information to examine intervention feasibility. METHODS: Nine parents (three fathers and six mothers) participating in a one and a half year OHPI were purposefully selected for qualitative evaluation of intervention feasibility using semi-structured interviews. The interviews were analysed with an inductive content analysis method. RESULTS: The analysis resulted in four main categories and 14 subcategories that describe parental perceptions and experiences of the OHPI. The four main categories were timing of first intervention contact, effortlessness of intervention process, individuality of support, and relevancy of support. CONCLUSION: Parents of children with CHD perceived the OHPI as important and feasible to be implemented in daily life in children with systemic diseases overall. Further studies on timing of first contact and use of additional Web-based support are needed.

Ultra-high frequency ultrasound delineated changes in carotid and muscular artery intima-media and adventitia thickness in obese early middle-aged women.

Obesity is linked to increased arterial size, carotid intima-media thickness and arterial stiffness. The effects of obesity and body composition on muscular artery intima-media and adventitia thickness has previously not been established. The aim of this study was to explore associations between carotid and muscular artery wall layer thickness with body composition and cardiovascular risk factors in early middle-aged women. This is a cross-sectional study including 199 women aged 40±4 years. Arterial lumen (LD), intima-media (IMT) and adventitia thickness (AT) were measured from carotid, brachial and radial arteries using ultra-high frequency ultrasound (22-71 MHz). Women with obesity had increased IMT in carotid (0.47 vs 0.45 mm), brachial (0.19 vs 0.17 mm) and radial arteries (0.16 vs 0.15 mm) and increased brachial AT (0.14 vs 0.13 mm). In multiple regression models all arterial LD (ß-range 0.02-0.03 mm/kg/m2), IMT (ß-range 0.91-3.37 µm/kg/m2), AT (ß-range 0.73-1.38 µm/kg/m2) were significantly associated with BMI. The IMT of all arteries were significantly associated with systolic blood pressure (ß-range 0.36-0.85 µm/mmHg), attenuating the association between IMT and BMI (ß-range 0.18-2.24 µm/kg/m2). Obese early middle-aged women have increased arterial intima media thickness and brachial artery adventitia thickness compared to non-obese counterparts. The association between BMI and intima-media thickness is partly mediated through blood pressure levels.

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.

Mood and neurotic disorders among youth with prenatal substance exposure: A longitudinal register-based cohort study.

BACKGROUND: Prenatal substance exposure is associated with mood and neurotic disorders but this association is complex and understudied. This study investigated the recorded use of specialised healthcare services for mood and neurotic disorders among youth with prenatal substance exposure in comparison with an unexposed matched cohort. Furthermore, the influence of adverse maternal characteristics and out-of-home care (OHC) is investigated. METHODS: This longitudinal register-based matched cohort study included 594 exposed and 1735 unexposed youth. Cox proportional hazard regression models were applied to study the first episode of mood and neurotic disorders in specialised healthcare from 13 years of age, and the influence of adverse maternal characteristics and OHC. Mediation analysis was applied to study the mediating effect of OHC on the association between prenatal substance exposure and the disorders. RESULTS: The exposed cohort had a two-fold higher likelihood of being treated at specialised healthcare for mood and neurotic disorders compared with the unexposed cohort (HR 2.34, 95% CI 1.86-2.95), but this difference was attenuated to non-significant levels (AHR 1.29, 95% CI 0.92-1.81) following adjustments with adverse maternal characteristics and OHC. OHC mediated 61% (95% CI 0.41-0.94) of the association between prenatal substance exposure and youth's mood and neurotic disorders. LIMITATIONS: Register data likely include more severe cases of disorders, and as an observational study, causality cannot be assessed. CONCLUSION: Mood and neurotic disorders are more common following prenatal exposure to substances and interlinked with significant adversities in the postnatal caregiving environment and OHC.

Protocol: A randomized controlled trial to assess effectiveness of a 12-month lifestyle intervention to reduce cardiovascular disease risk in families ten years after pre-eclampsia (FINNCARE).

Pre-eclampsia (PE) is a multisystem progressive disorder affecting 3-5% of pregnancies. PE independently increases the risk for premature cardiovascular disease (CVD) in mothers and their children long-term. The effectiveness of a family-centered lifestyle intervention to lower CVD risk in PE families has not previously been evaluated. In the current FINNCARE study, we prospectively compare CVD risk and CVD progression in PE families (mother, father and child) in a cross-sectional study setting 8-12 years from delivery with non-PE control families of comparable age. Furthermore, we evaluate the effectiveness and feasibility of an interactive web-based behavioral 12-month lifestyle intervention to reduce blood pressure and the CVD risk profile overall in a randomized controlled trial. In total, 300 PE families will be randomized 1:1 to a PE-intervention or a PE-control group, and the 100 non-PE control families similarly followed-up at 12 months. Primary outcome is 24-hour mean systolic BP change from baseline in mother and child. Study aims to provide information on CVD progression and CVD risk management in the family following PE.

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.

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.

Pericardial Constriction and Myocardial Restriction in Pediatric Mulibrey Nanism: A Complex Disease With Diastolic Dysfunction.

BACKGROUND: Mulibrey nanism (MUL) is a rare condition with profound growth delay. Congestive heart failure is a major determinant of prognosis. The aim was to delineate pericardial constriction and myocardial functional abnormalities in a pediatric MUL sample. METHODS: A total of 23 MUL patients and 23 individually sex- and age-matched healthy control subjects were prospectively assessed in a cross-sectional study with echocardiography. RESULTS: Clinical signs of heart failure were present in 7 MUL patients, with severe congestive heart failure in 2. Significant diastolic dysfunction, mainly related to constriction, was found in MUL patients without pericardiectomy (N = 18)-septal bounce, pronounced hepatic vein atrial reversal and right heart inflow-outflow variations, and decreased inferior vena cava collapse during respiration. The appearance of the pericardium was not different from that of control subjects. Longitudinal diastolic myocardial velocities were similar to those in control subjects, suggesting an absence of significant myocardial restriction. Right ventricular free wall longitudinal systolic strain and bilateral longitudinal myocardial systolic velocities were decreased in MUL patients, indicating mild biventricular systolic dysfunction. Myocardial motion abnormalities and persistent congestive heart failure were common (in 3 of 6) in MUL patients with a history of pericardiectomy. Cardiac dimensions were similar between MUL patients and control subjects when adjusting for body size, except for smaller biventricular volumes. CONCLUSIONS: MUL disease presents with significant constriction-related diastolic dysfunction and mild bilateral systolic dysfunction. Constriction-restriction assessments during follow-up could be of benefit in decision-making regarding pericardiectomy in MUL disease. Myocardial abnormalities were prevalent among MUL patients who had undergone pericardiectomy and are consistent with progression of myocardial disease in a significant proportion of patients.

CONTEXTE: Le nanisme Mulibrey (MUL) est une maladie rare qui donne lieu à un retard de croissance marqué. L'insuffisance cardiaque congestive est un déterminant majeur du pronostic. L'objectif de cette étude était de caractériser la constriction péricardique et les anomalies fonctionnelles myocardiques dans un échantillon de cas de MUL pédiatrique. MÉTHODOLOGIE: Au total, 23 patients atteints de MUL et 23 sujets témoins en bonne santé ont été appariés individuellement selon le sexe et l'âge et soumis à une évaluation prospective dans le cadre d'une étude transversale avec échocardiographie. RÉSULTATS: Sept patients atteints de MUL présentaient des signes cliniques d'insuffisance cardiaque, et deux, une insuffisance cardiaque congestive sévère. Une dysfonction diastolique significative, principalement liée à la constriction, a été observée chez les patients atteints de MUL n'ayant pas subi de péricardiectomie (N = 18) ­ rebond septal, inversion auriculaire marquée du flux de la veine hépatique, variations prononcées du flux entrant et sortant du cœur droit, diminution du collapsus de la veine cave inférieure pendant la respiration. L'apparence du péricarde n'était pas différente de celle notée chez les sujets témoins. Les vélocités myocardiques longitudinales pendant la diastole étaient similaires à celles relevées chez les sujets témoins, ce qui suggère l'absence de restriction myocardique significative. La déformation longitudinale de la paroi libre du ventricule droit et les vélocités myocardiques longitudinales bilatérales étaient diminuées pendant la systole chez les patients atteints de MUL, ce qui indique une dysfonction systolique biventriculaire légère. Les anomalies de la cinétique myocardique et la persistance de l'insuffisance cardiaque congestive étaient fréquentes (dans trois cas sur six) chez les patients atteints de MUL ayant des antécédents de péricardiectomie. Les dimensions cardiaques chez les patients atteints de MUL étaient similaires à celles observées chez les sujets témoins après les ajustements en fonction de la taille corporelle, à l'exception des volumes biventriculaires, qui étaient plus petits. CONCLUSIONS: Le MUL entraîne une dysfonction diastolique significative liée à la constriction et une légère dysfonction systolique bilatérale. Les évaluations axées sur la constriction et la restriction effectuées au cours du suivi pourraient être utiles pour la prise de décisions concernant le recours à la péricardiectomie dans les cas de MUL. Les anomalies myocardiques étaient fréquentes chez les patients atteints de MUL qui avaient subi une péricardiectomie et concordent avec la progression de la myocardiopathie dans une proportion significative de cas.

Cardiac Function After Cardiotoxic Treatments for Childhood Cancer-Left Ventricular Longitudinal Strain in Screening.

Background: The majority of childhood cancer survivors (CCSs) have been exposed to cardiotoxic treatments and often present with modifiable cardiovascular risk factors. Our aim was to evaluate the value of left ventricular (LV) longitudinal strain for increasing the sensitivity of cardiac dysfunction detection among CCSs. Methods: We combined two national cohorts: neuroblastoma and other childhood cancer survivors treated with anthracyclines. The final data consisted of 90 long-term CCSs exposed to anthracyclines and/or high-dose chemotherapy with autologous stem cell rescue and followed up for > 5 years and their controls (n = 86). LV longitudinal strain was assessed with speckle tracking (Qlab) and LV ejection fraction (EF) by three-dimensional echocardiography (3DE). Results: Of the CCSs, 11% (10/90) had abnormal LV longitudinal strain (i.e., < -17.5%); of those, 70% (7/10) had normal 3DE LV EF. Multivariable linear model analysis demonstrated that follow-up time (p = 0.027), sex (p = 0.020), and BMI (p = 0.002) were significantly associated with LV longitudinal strain. Conversely, cardiac risk group, hypertension, age, cumulative anthracycline dose or exposure to chest radiation were not. Conclusion: LV longitudinal strain is a more sensitive method than LV EF for the detection of cardiac dysfunction among CCSs. Therefore, LV longitudinal strain should be added to the screening panel, especially for those with modifiable cardiovascular risk factors.

Ideal Cardiovascular Health and Vascular Phenotype Associations in Mothers with Obesity and Their Six-Year-Old Children.

BACKGROUND: Heredity and family-shared lifestyle contribute to cardiovascular risk, but the magnitude of their influence on arterial structure and function in early childhood is unknown. We aimed to assess associations between child and maternal ideal cardiovascular health, maternal subclinical atherosclerosis, and child arterial phenotype. METHODS: Cross-sectional analysis of 201 mother-child pairs originating from the Finnish Gestational Diabetes Prevention Study (RADIEL) longitudinal cohort was done at child age 6.1 ± 0.5 years with assessments of ideal cardiovascular health (BMI, blood pressure, fasting glucose, total cholesterol, diet quality, physical activity, smoking), body composition, very-high frequency ultrasound of carotid arteries (25 and 35 MHz), and pulse wave velocity. RESULTS: We found no association between child and maternal ideal cardiovascular health but report evidence of particular metrics correlations: total cholesterol (r=0.24, P=0.003), BMI (r=0.17, P=0.02), diastolic blood pressure (r=0.15, P=0.03), and diet quality (r=0.22, P=0.002). Child arterial phenotype was not associated with child or maternal ideal cardiovascular health. In the multivariable regression explanatory model adjusted for child sex, age, systolic blood pressure, lean body mass, and body fat percentage, child carotid intima-media thickness was independently associated only with maternal carotid intima-media thickness (0.1 mm increase [95% CI 0.05, 0.21, P=0.001] for each 1 mm increase in maternal carotid intima-media thickness). Children of mothers with subclinical atherosclerosis had decreased carotid artery distensibility (1.1 ± 0.2 vs 1.2 ± 0.2%/10 mmHg, P=0.01) and trend toward increased carotid intima-media thickness (0.37 ± 0.04 vs 0.35 ± 0.04 mm, P=0.06). CONCLUSION: Ideal Cardiovascular Health metrics are heterogeneously associated in mother-child pairs in early childhood. We found no evidence of child or maternal Ideal Cardiovascular Health effect on child arterial phenotype. Maternal carotid intima-media thickness predicts child carotid intima-media thickness, but the underlying mechanisms remain unclear. Maternal subclinical atherosclerosis is associated with local carotid arterial stiffness in early childhood.