Paediatric Inflammatory Multisystem Syndrome: Temporally Associated with SARS-CoV-2 (PIMS-TS): Cardiac Features, Management and Short-Term Outcomes at a UK Tertiary Paediatric Hospital.

Children were relatively spared during COVID-19 pandemic. However, the recently reported hyperinflammatory syndrome with overlapping features of Kawasaki disease and toxic shock syndrome-"Paediatric Inflammatory Multisystem Syndrome-temporally associated with SARS-CoV-2" (PIMS-TS) has caused concern. We describe cardiac findings and short-term outcomes in children with PIMS-TS at a tertiary children's hospital. Single-center observational study of children with PIMS-TS from 10th April to 9th May 2020. Data on ECG and echocardiogram were retrospectively analyzed along with demographics, clinical features and blood parameters. Fifteen children with median age of 8.8 (IQR 6.4-11.2) years were included, all were from African/Afro-Caribbean, South Asian, Mixed or other minority ethnic groups. All showed raised inflammatory/cardiac markers (CRP, ferritin, Troponin I, CK and pro-BNP). Transient valve regurgitation was present in 10 patients (67%). Left Ventricular ejection fraction was reduced in 12 (80%), fractional shortening in 8 (53%) with resolution in all but 2. Fourteen (93%) had coronary artery abnormalities, with normalization in 6. ECG abnormalities were present in 9 (60%) which normalized in 6 by discharge. Ten (67%) needed inotropes and/or vasopressors. None needed extracorporeal life support. Improvement in cardiac biochemical markers was closely followed by improvement in ECG/echocardiogram. All patients were discharged alive and twelve (80%) have been reviewed since. Our entire cohort with PIMS-TS had cardiac involvement and this degree of involvement is significantly more than other published series and emphasizes the need for specialist cardiac review. We believe that our multi-disciplinary team approach was crucial for the good short-term outcomes.

Visualization of coronary arteries in paediatric patients using whole-heart coronary magnetic resonance angiography: comparison of image-navigation and the standard approach for respiratory motion compensation.

AIMS: To investigate the use of respiratory motion compensation using image-based navigation (iNAV) with constant respiratory efficiency using single end-expiratory thresholding (CRUISE) for coronary magnetic resonance angiography (CMRA), and compare it to the conventional diaphragmatic navigator (dNAV) in paediatric patients with congenital or suspected heart disease. METHODS: iNAV allowed direct tracking of the respiratory heart motion and was generated using balanced steady state free precession startup echoes. Respiratory gating was achieved using CRUISE with a fixed 50% efficiency. Whole-heart CMRA was acquired with 1.3 mm isotropic resolution. For comparison, CMRA with identical imaging parameters were acquired using dNAV. Scan time, visualization of coronary artery origins and mid-course, imaging quality and sharpness was compared between the two sequences. RESULTS: Forty patients (13 females; median weight: 44 kg; median age: 12.6, range: 3 months-17 years) were enrolled. 25 scans were performed in awake patients. A contrast agent was used in 22 patients. The scan time was significantly reduced using iNAV for awake patients (iNAV 7:48 ± 1:26 vs dNAV 9:48 ± 3:11, P = 0.01) but not for patients under general anaesthesia (iNAV = 6:55 ± 1:50 versus dNAV = 6:32 ± 2:16; P = 0.32). In 98% of the cases, iNAV image quality had an equal or higher score than dNAV. The visual score analysis showed a clear difference, favouring iNAV (P = 0.002). The right coronary artery and the left anterior descending vessel sharpness was significantly improved (iNAV: 56.8% ± 10.1% vs dNAV: 53.7% ± 9.9%, P < 0.002 and iNAV: 55.8% ± 8.6% vs dNAV: 53% ± 9.2%, P = 0.001, respectively). CONCLUSION: iNAV allows for a higher success-rate and clearer depiction of the mid-course of coronary arteries in paediatric patients. Its acquisition time is shorter in awake patients and image quality score is equal or superior to the conventional method in most cases.

Maternal vitamin D and E intakes during pregnancy are associated with asthma in children.

Are maternal vitamin D and E intakes during pregnancy associated with asthma in 10-year-old children? In a longitudinal study of 1924 children born to women recruited during pregnancy, maternal vitamin D intake during pregnancy was assessed by the Food Frequency Questionnaire (FFQ) and vitamin E by FFQ and plasma α-tocopherol; respiratory questionnaires were completed for the 10-year-old children. Their treatment for asthma was also ascertained using administrative data. Longitudinal analyses included data collected at 1, 2, 5 and 10 years. Symptom data were available for 934 (49%) children and use of asthma medication for 1748 (91%). In the children maternal vitamin D intake during pregnancy was negatively associated with doctor-diagnosed asthma at 10 years of age (OR per intake quintile 0.86, 95% CI 0.74-0.99) and over the first 10 years (hazard ratio 0.90, 95% CI 0.81-1.00). Maternal plasma α-tocopherol at 11 weeks gestation was negatively associated with children receiving asthma treatment (OR per standard deviation increase 0.52, 95% CI 0.31-0.87). Maternal vitamin E intake was negatively associated with doctor-diagnosed asthma (OR 0.89, 95% CI 0.81-0.99) in the first 10 years. Low maternal vitamin D and E intakes during pregnancy are associated with increased risk of children developing asthma in the first 10 years of life. These associations may have significant public health implications.

An exploratory study of the associations between maternal iron status in pregnancy and childhood wheeze and atopy.

Maternal nutritional status during pregnancy has been reported to be associated with childhood asthma and atopic disease. The Avon Longitudinal Study of Parents and Children has reported associations between reduced umbilical cord Fe status and childhood wheeze and eczema; however, follow-up was short and lung function was not measured. In the present study, the associations between maternal Fe status during pregnancy and childhood outcomes in the first 10 years of life were investigated in a subgroup of 157 mother-child pairs from a birth cohort with complete maternal, fetal ultrasound, blood and child follow-up data. Maternal Fe intake was assessed using FFQ at 32 weeks of gestation and Hb concentrations and serum Fe status (ferritin, soluble transferrin receptor and TfR-F (transferrin receptor:ferritin) index) were measured at 11 weeks of gestation and at delivery. Maternal Fe intake, Hb concentrations and serum Fe status were found to be not associated with fetal or birth measurements. Unit increases in first-trimester maternal serum TfR concentrations (OR 1.44, 95% CI 1.05, 1.99) and TfR-F index (OR 1.42, 95% CI 1.10, 1.82) (i.e. decreasing Fe status) were found to be associated with an increased risk of wheeze, while unit increases in serum ferritin concentrations (i.e., increasing Fe status) were found to be associated with increases in standardised mean peak expiratory flow (PEF) (ß 0.25, 95% CI 0.09, 0.42) and forced expiratory volume in the first second (FEV1) (ß 0.20, 95% CI 0.08, 0.32) up to 10 years of age. Increasing maternal serum TfR-F index at delivery was found to be associated with an increased risk of atopic sensitisation (OR 1.35, 95% CI 1.02, 1.79). The results of the present study suggest that reduced maternal Fe status during pregnancy is adversely associated with childhood wheeze, lung function and atopic sensitisation, justifying further studies on maternal Fe status and childhood asthma and atopic disease.

First- and second-trimester fetal size and asthma outcomes at age 10 years.

RATIONALE: Greater early fetal size is associated with reduced asthma risk and improved lung function in early childhood. OBJECTIVES: To test the hypothesis that associations between early fetal size, asthma symptoms, and lung function persist into later childhood. METHODS: In a longitudinal study, first- and second-trimester fetal measurements were recorded. At 10 years of age a respiratory questionnaire was completed. Spirometry, bronchial challenge, and skin-prick testing were undertaken in a subset. MEASUREMENTS AND MAIN RESULTS: Fetal measurements were available in the first trimester for 853 individuals and the second trimester for 1,453. Questionnaires were returned for 927 children and 449 underwent detailed phenotyping. For each millimeter increase in first trimester size, asthma risk reduced by 6% (95% confidence interval[CI], 1­11) and FEV1 was higher by an average of 6 ml (95% CI, 1­11).First-trimester size was reduced in those with asthma at both 5 and 10 years compared with early or late onset wheeze (P , 0.02). Compared with persistent high growth in first and second trimesters,persistent low growth was associated with increased asthma risk(odds ratio, 2.8; 95% CI, 1.2­6.9) and a mean reduction in FEV1 of 103 ml (95% CI, 13­194), whereas increasing fetal size was associated with increased eczema risk (odds ratio, 2.5; 95% CI, 1.2­5.3). CONCLUSIONS: Reduced fetal size from the first trimester is associated with increased risk for asthma and obstructed lung function in childhood. Relative change in size after the first trimester is associated with eczema.

First trimester maternal tobacco smoking habits and fetal growth.

RATIONALE: Maternal smoking in pregnancy is associated with reduced birth weight and childhood lung function. This study determined when maternal smoking first influences fetal growth and how this relates to childhood respiratory outcomes. METHODS: A longitudinal cohort of 1924 pregnant women was recruited. Fetal ultrasound measurements at 11 weeks (crown-rump length, CRL) and at 20 weeks gestation (femur length, FL, and biparietal diameter, BPD) and birth measurements were recorded. Childhood respiratory symptoms and spirometry were ascertained. RESULTS: Of the 1924 original study participants, fetal size was determined in 903 in the first trimester, 1544 in the second trimester and at term in 1737 infants. Maternal smoking when first pregnant was reported in 593 (31%) and was not associated with reduced CRL. There was an inverse exposure-response relationship between cigarette consumption and FL (mean reduction in lowest compared with highest tertile 0.91 cm, p=0.033). Birth weight and length of those born to mothers who did (n=331) and did not (n=56) reduce cigarette consumption were similar and reduced compared with 186 infants whose mothers quit during the first trimester (p < or = 0.020). Children of mothers who continued smoking had increased wheeze at age 2 years (OR 1.58, p=0.017) and GP visits with wheeze at age 5 years (OR 2.18, p=0.030) and mean reduction in forced expiratory volume in 1 s of 62 ml (p=0.014) compared with controls. CONCLUSIONS: Maternal smoking is associated with reduced fetal measurements in the second and third trimesters but not in the first trimester. Mothers who do not quit smoking during the first trimester deliver smaller infants who go on to have adverse respiratory outcomes in childhood.