Persistent Aortic Stiffness and Left Ventricular Hypertrophy in Children of Diabetic Mothers

Publisher Copyright: © 2020 Canadian Cardiovascular SocietyBackground: Fetuses of diabetic mothers develop left ventricular (LV) hypertrophy and are at increased long-term risk of cardiovascular disease. In our previous longitudinal study from midgestation to late infancy we showed persistence of LV hypertrophy and increased aortic stiffness compared with infants of healthy mothers, the latter of which correlated with third trimester maternal hemoglobin A1c. In the present study, we reexamined the same cohort in early childhood to determine if these cardiovascular abnormalities persisted. Methods: Height, weight, and right arm blood pressure were recorded. A full functional and structural echocardiogram was performed with offline analysis of LV posterior wall and interventricular septal diastolic thickness (IVSd), systolic and diastolic function, and aortic pulse wave velocity. Vascular reactivity was assessed using digital thermal monitoring. Participants also completed a physical activity questionnaire. Results: Twenty-five children of diabetic mothers (CDMs) and 20 children from healthy pregnancies (mean age, 5.6 ± 1.7 and 5.3 ± 1.3 years, respectively; P = not significant) were assessed. Compared with controls, IVSd z score was increased in CDMs (1.2 ± 0.6 vs 0.5 ± 0.3, respectively; P = 0.006), with one-fifth having a z score of more than +2.0. Aortic pulse wave velocity was increased in CDMs (3.2 ± 0.6 m/s vs 2.2 ± 0.4 m/s; P = 0.001), and correlated with IVSd z score (R2 = 0.81; P = 0.001) and third trimester maternal A1c (R2 = 0.65; P < 0.0001). Body surface area, height, weight, blood pressure, vascular reactivity, and physical activity scores did not differ between groups. Our longitudinal analysis showed that individuals with greater IVSd, and aortic stiffness in utero, early and late infancy also tended to have greater measures in early childhood (P < 0.001 and P < 0.0001, respectively). Conclusions: CDMs show persistently increased interventricular septal thickness and aortic stiffness in early childhood.Peer reviewe

Intrauterine exposure to chronic hypoxia in the rat leads to progressive diastolic function and increased aortic stiffness from early postnatal developmental stages

Aim We sought to explore whether fetal hypoxia exposure, an insult of placental insufficiency, is associated with left ventricular dysfunction and increased aortic stiffness at early postnatal ages. Methods Pregnant Sprague Dawley rats were exposed to hypoxic conditions (11.5% FiO2) from embryonic day E15‐21 or normoxic conditions (controls). After delivery, left ventricular function and aortic pulse wave velocity (measure of aortic stiffness) were assessed longitudinally by echocardiography from day 1 through week 8. A mixed ANOVA with repeated measures was performed to compare findings between groups across time. Myocardial hematoxylin and eosin and picro‐sirius staining were performed to evaluate myocyte nuclear shape and collagen fiber characteristics, respectively. Results Systolic function parameters transiently increased following hypoxia exposure primarily at week 2 (p \u3c .008). In contrast, diastolic dysfunction progressed following fetal hypoxia exposure beginning weeks 1–2 with lower early inflow Doppler velocities, and less of an increase in early to late inflow velocity ratios and annular and septal E’/A’ tissue velocities compared to controls (p \u3c .008). As further evidence of altered diastolic function, isovolumetric relaxation time was significantly shorter relative to the cardiac cycle following hypoxia exposure from week 1 onward (p \u3c .008). Aortic stiffness was greater following hypoxia from day 1 through week 8 (p \u3c .008, except week 4). Hypoxia exposure was also associated with altered nuclear shape at week 2 and increased collagen fiber thickness at week 4. Conclusion Chronic fetal hypoxia is associated with progressive LV diastolic dysfunction, which corresponds with changes in nuclear shape and collagen fiber thickness, and increased aortic stiffness from early postnatal stages

Maternal and cord blood hemoglobin as determinants of placental weight: A cross-sectional study

Background: Both high and low placental weights are associated with adverse pregnancy outcomes. Maternal hemoglobin levels can influence placental weight, but the evidence is conflicting. Since maternal hemoglobin does not invariably correlate with fetal/neonatal blood hemoglobin levels, we sought to determine whether cord blood hemoglobin or maternal hemoglobin status more closely associates with placental weight in women undergoing elective cesarean section at term. Methods: This was a cross-sectional study conducted at the Royal Alexandra Hospital, Edmonton, Canada, involving 202 women with term singleton pregnancies undergoing elective cesarean section. Maternal blood and mixed cord blood hemoglobin levels were analyzed using a HemoCue Hb201+ system. Birth weight, placental weight, one-and five-minute APGAR scores, American Society of Anesthesiologists physical state classification, maternal age, and maternal height were also recorded. Relationships between maternal and cord blood hemoglobin levels with placental weight, birth weight, and birth weight to placental weight ratio were the main outcome measures. Results: A total of 182 subjects were included in the analysis. Regression analysis showed that cord blood hemoglobin, but not maternal hemoglobin, was inversely related with placental weight (β = −2.4, p = 0.001) and positively related with the birth weight to placental weight ratio (β = 0.015, p = 0.001 and p = 0.63, respectively). Conclusions: Our findings suggest that measuring cord blood hemoglobin levels, rather than maternal hemoglobin levels, may provide important diagnostic information about in utero fetal adaptation to suboptimal placental function and neonatal health

Early Childhood Respiratory Morbidity and Health Services Utilization in Children Born Preterm or Small and Large for Gestational Age

Introduction Alterations in duration of gestation and fetal growth such as preterm birth (PTB) or small and large for gestational age (SGA, LGA) have long-term consequences on respiratory health. The risk of health services use for respiratory conditions in infants born PTB, SGA or LGA in Canada needs to be evaluated. Objectives and Approach We evaluated the association between PTB, SGA and LGA and health services utilization for respiratory diseases in early childhood. We linked three administrative health databases to identify all singleton live births in Alberta between 2005-2010. We obtained data on the number of hospital admissions and emergency department (ED) visits in the first five years of life for acute upper respiratory infections, acute lower respiratory infections, wheezing disorders, bronchopulmonary dysplasia, and influenza and pneumonia. Odds ratios (OR) of health services use for PTB, SGA, LGA were calculated adjusting for important covariates (e.g., maternal age, sex, socioeconomic status, total antepartum risk score). Results The cohort contained 206,994 infants of whom 9.1% were PTB, 8.5% were SGA and 9.4% were LGA. Babies born prematurely (PTB) were more likely to have a respiratory disease in the first five years of life than babies experienced fetal growth alterations (SGA or LGA). PTB increased significantly the odds of acute lower respiratory infections by 30 to 90%, of wheezing disorders by 40 to 70%, of influenza and pneumonia by 30 to 60%, and of acute upper respiratory infections by 10 to 50%. By contrast, SGA increased the odds of bronchopulmonary dysplasia by 3 to 300%, and LGA increased the odds of acute upper respiratory infections by 11 to 18% and of acute lower respiratory infections by 8 to 11%. Conclusion/Implications Prematurity and alterations in fetal growth are associated with increased hospital and ED admissions in early childhood. The patterns differ for PTB, SGA, and LGA. Linkage of administrative health data provides useful epidemiological evidence to inform the burden of early childhood respiratory diseases resulting from adverse birth outcomes

Cardiovascular Health of Offspring of Diabetic Mothers From the Fetal Through Late-Infancy Stages

Non peer reviewe

Assessment of intellectual impairment, health-related quality of life, and behavioral phenotype in patients with neurotransmitter related disorders: Data from the iNTD registry

Inherited disorders of neurotransmitter metabolism are a group of rare diseases, which are caused by impaired synthesis, transport, or degradation of neurotransmitters or cofactors and result in various degrees of delayed or impaired psychomotor development. To assess the effect of neurotransmitter deficiencies on intelligence, quality of life, and behavior, the data of 148 patients in the registry of the International Working Group on Neurotransmitter Related Disorders (iNTD) was evaluated using results from standardized age-adjusted tests and questionnaires. Patients with a primary disorder of monoamine metabolism had lower IQ scores (mean IQ 58, range 40-100) within the range of cognitive impairment (<70) compared to patients with a BH4 deficiency (mean IQ 84, range 40-129). Short attention span and distractibility were most frequently mentioned by parents, while patients reported most frequently anxiety and distractibility when asked for behavioral traits. In individuals with succinic semialdehyde dehydrogenase deficiency, self-stimulatory behaviors were commonly reported by parents, whereas in patients with dopamine transporter deficiency, DNAJC12 deficiency, and monoamine oxidase A deficiency, self-injurious or mutilating behaviors have commonly been observed. Phobic fears were increased in patients with 6-pyruvoyltetrahydropterin synthase deficiency, while individuals with sepiapterin reductase deficiency frequently experienced communication and sleep difficulties. Patients with BH4 deficiencies achieved significantly higher quality of life as compared to other groups. This analysis of the iNTD registry data highlights: (a) difference in IQ and subdomains of quality of life between BH4 deficiencies and primary neurotransmitter-related disorders and (b) previously underreported behavioral traits.Dietmar Hopp Stiftung (DE); Medical Faculty of the University of Heidelberg

Interdisciplinary-driven hypotheses on spatial associations of mixtures of industrial air pollutants with adverse birth outcomes

Background: Adverse birth outcomes (ABO) such as prematurity and small for gestational age confer a high risk of mortality and morbidity. ABO have been linked to air pollution; however, relationships with mixtures of industrial emissions are poorly understood. The exploration of relationships between ABO and mixtures is complex when hundreds of chemicals are analyzed simultaneously, requiring the use of novel approaches. Objective: We aimed to generate robust hypotheses spatially linking mixtures and the occurrence of ABO using a spatial data mining algorithm and subsequent geographical and statistical analysis. The spatial data mining approach aimed to reduce data dimensionality and efficiently identify spatial associations between multiple chemicals and ABO. Methods: We discovered co-location patterns of mixtures and ABO in Alberta, Canada (2006–2012). An ad-hoc spatial data mining algorithm allowed the extraction of primary co-location patterns of 136 chemicals released into the air by 6279 industrial facilities (National Pollutant Release Inventory), wind-patterns from 182 stations, and 333,247 singleton live births at the maternal postal code at delivery (Alberta Perinatal Health Program), from which we identified cases of preterm birth, small for gestational age, and low birth weight at term. We selected secondary patterns using a lift ratio metric from ABO and non-ABO impacted by the same mixture. The relevance of the secondary patterns was estimated using logistic models (adjusted by socioeconomic status and ABO-related maternal factors) and a geographic-based assignment of maternal exposure to the mixtures as calculated by kernel density. Results: From 136 chemicals and three ABO, spatial data mining identified 1700 primary patterns from which five secondary patterns of three-chemical mixtures, including particulate matter, methyl-ethyl-ketone, xylene, carbon monoxide, 2-butoxyethanol, and n-butyl alcohol, were subsequently analyzed. The significance of the associations (odds ratio > 1) between the five mixtures and ABO provided statistical support for a new set of hypotheses. Conclusion: This study demonstrated that, in complex research settings, spatial data mining followed by pattern selection and geographic and statistical analyses can catalyze future research on associations between air pollutant mixtures and adverse birth outcomes

Geography as a Determinant of Health: Health Services Utilization of Pediatric Respiratory Illness in a Canadian Province

Respiratory diseases contribute to high healthcare utilization rates among children. Although social inequalities play a major role in these conditions, little is known about the impact of geography as a determinant of health, particularly with regard to the difference between rural and urban centers. A regional geographic analysis was conducted using health repository data on singleton births between 2005 and 2010 in Alberta, Canada. Data were aggregated according to regional health sub-zones in the province and standardized prevalence ratios (SPRs) were determined for eight respiratory diseases (asthma, influenza, bronchitis, bronchiolitis, croup, pneumonia, and other upper and other lower respiratory tract infections). The results indicate that there are higher rates of healthcare utilization in northern compared to southern regions and in rural and remote regions compared to urban ones, after accounting for both material and social deprivation. Geography plays a role in discrepancies of healthcare utilization for pediatric respiratory diseases, and this can be used to inform the provision of health services and resource allocation across various regions

Geographic Inequalities of Respiratory Health Services Utilization during Childhood in Edmonton and Calgary, Canada: A Tale of Two Cities

Young children are susceptible to respiratory diseases. Inequalities exist across socioeconomic groups for paediatric respiratory health services utilization in Alberta. However, the geographic distribution of those inequalities has not been fully explored. The aim of this study was to identify geographic inequalities in respiratory health services utilization in early childhood in Calgary and Edmonton, two major urban centres in Western Canada. We conducted a geographic analysis of data from a retrospective cohort of all singleton live births occurred between 2005 and 2010. We aggregated at area-level the total number of episodes of respiratory care (hospitalizations and emergency department visits) that occurred during the first five years of life for bronchiolitis, pneumonia, lower/upper respiratory tract infections, influenza, and asthma-wheezing. We used spatial filters to identify geographic inequalities in the prevalence of acute paediatric respiratory health services utilization in Calgary and Edmonton. The average health gap between areas with the highest and the lowest prevalence of respiratory health services utilization was 1.5-fold in Calgary and 1.4-fold in Edmonton. Geographic inequalities were not completely explained by the spatial distribution of socioeconomic status, suggesting that other unmeasured factors at the neighbourhood level may explain local variability in the use of acute respiratory health services in early childhood