95th Centile Research Articles

Timing of Neonatal Discharge and Unplanned Readmission to PICUs Among Infants Born Preterm.

Children born very preterm (<32 weeks) are at risk of ongoing morbidity and admission to pediatric intensive care units (PICUs) in childhood. However, the influence of the timing of neonatal discharge on unplanned PICU admission has not been established. To examine whether the timing of neonatal discharge (postmenstrual age and season) is associated with subsequent unplanned PICU admission. This retrospective cohort study used linked national data from the National Neonatal Research Database and Paediatric Intensive Care Audit Network (PICANet) for children born from January 2013 to December 2018 at 22 to 31 weeks' gestational age who were admitted to a neonatal unit in England and Wales and were discharged home at 34 weeks' postmenstrual age or later. All National Health Service (NHS) neonatal units and PICUs in England and Wales were included. Children were followed up until 2 years of chronological age. Data analysis was conducted from October 2023 to August 2024. Timing of discharge. The primary outcome was unplanned PICU admission between neonatal discharge and chronological age 2 years to any PICU within England and Wales. Survival analysis using a flexible parametric model was conducted with season of discharge (time-dependent factor), gestation, sex, birth weight less than the 10th centile, bronchopulmonary dysplasia, necrotizing enterocolitis, brain injury, and earlier neonatal discharge (lower quartile of postmenstrual age at discharge for gestation) as variables. Of 39 938 children discharged home (median [IQR] gestational age, 29 [27-31] weeks; 21 602 [54.1%] male), 1878 (4.7%) had unplanned PICU admission. More than half of admissions occurred within 50 days of neonatal discharge (1080 [57.5%]). Compared with summer, the risk of unplanned PICU admission following neonatal discharge was 2.58 times higher in winter and 2.35 times higher in autumn (winter: adjusted hazard ratio [aHR], 2.58; 95% CI, 1.68-3.95; autumn: aHR, 2.35; 95% CI, 1.84-2.99). Among children born at 28 to 31 weeks' gestational age, earlier neonatal discharge was associated with increased risk (aHR, 1.30; 95% CI, 1.13-1.49), but this was not true for children born younger than 28 weeks' gestational age. In this retrospective cohort study of preterm children, autumn and winter discharge were associated with the highest risk of unplanned PICU admission following neonatal discharge. For children born at 28 to 31 weeks' gestational age, discharge at lower postmenstrual age was also associated with increased risk. Further work is required to understand whether delaying neonatal discharge for some children born at 28 to 31 weeks' gestational age is beneficial and to consider the wider costs and implications of prolonging neonatal care.

Metabolomic biomarkers in amniotic fluid for early diagnosis of preterm birth and fetal growth restriction.

Preterm birth, affecting about 10% of pregnancies, significantly contributes to perinatal morbidity and mortality. Recent research indicates that metabolomics could enhance pregnancy outcomes and reduce costs by identifying biomarkers related to common pregnancy complications. Our team focused on analyzing amniotic fluid collected during the second trimester to identify potential biomarkers for preterm birth using 1H-NMR metabolomic analysis. We compared amniotic fluid samples from women who delivered prematurely with those who delivered at term. Multivariate principal component analysis revealed dimethylglycine, glucose, myo-inositol, and succinic acid as potential biomarkers for preterm birth prognosis and early diagnosis. Further analysis demonstrated distinct regulation patterns of these metabolites in relation to fetal growth centiles. For instance, dimethylglycine and glucose were upregulated in fetuses above the 20th centile, while citrate and succinate were upregulated in those below it. With Area Under the Curve (AUROC) values over 0.75 and p-values less than 0.05, these metabolites show promise as reliable biomarkers for predicting fetal growth restriction. This approach could significantly impact maternal-fetal medicine by facilitating early diagnosis and personalized interventions. Future research should focus on validating these findings in larger populations and exploring the underlying mechanisms of metabolite regulation.

Number of inflamed coronary vessels in prediction of cardiac death and MACE among patients undergoing routine CCTA: the Oxford Risk Factors And Non-Invasive Imaging (ORFAN) Study

Abstract Background Coronary inflammation can be assessed by the changes in perivascular adipose tissue on routine coronary CT angiograms (CCTA). Fat attenuation index score (FAI Score) quantifies the degree of inflammation in each epicardial coronary artery, and adjusts for age, sex, scan technical parameters, biological and anatomical factors. Coronary inflammation assessment in a single coronary artery was previously shown to be predictive of cardiac events in the CRISP-CT study. However, the impact of inflammation in multiple coronary arteries on clinical outcome remains unclear. Purpose To evaluate the prognostic value of the number of inflamed coronary arteries with high inflammation in the risk of cardiac death, and major adverse cardiac events (MACE). Methods In a nested cohort within the Oxford Risk Factors And Non-invasive imaging (ORFAN) study, consecutive patients (n=3,393) who underwent routine clinical CCTA were followed up over a median(IQR) 7.7(6.4-9.1) years for cardiac mortality, and MACE (including myocardial infarction, new onset heart failure, cardiac mortality). FAI Score was calculated for each of the 3 epicardial coronary arteries. Results The number of inflamed arteries (FAI Score &amp;gt;75th centile) showed an additive impact on cardiac mortality compared with no inflamed arteries (all vessels FAI Score &amp;lt;25th centile), with hazard ratio 29.8 (95% CI 13.9-63.9, p&amp;lt;0.001) for 3 inflamed arteries, HR 20.4 (95% CI 9.4-44.7, p&amp;lt;0.001) for 2 inflamed arteries, and HR 13.0 (95% CI 5.9-28.8, p&amp;lt;0.001) for 1 inflamed artery. (Panel A) Similarly, patients with multiple inflamed arteries showed progressively higher risk for MACE (HR 7.2, 8.3 and 12.6 for 1-, 2- and 3-inflamed arteries respectively compared to patients with no inflamed artery). (Panel B) Patients with no inflamed arteries showed very low event rates for cardiac mortality and MACE. In patients with no obstructive CAD (n=2,651), similar trends were observed whereby patients with 3-inflamed arteries showed highest risk for cardiac mortality (Panel C) and MACE (Panel D), with intermediate risk for those with 1 or 2 inflamed arteries. Conclusion The number of coronary arteries with high inflammation, measured by FAI Score from routine CCTA, is associated with adverse cardiovascular events and cardiac mortality in an additive dose-response manner.

Growth Status of Bangladeshi Children in Functional Constipation: Experience From A Tertiary Care Hospital

Background: Constipation is one of the common complaints of children with long-term hazardous consequences. It is a frequent cause of hospital visit in both primary and specialized care which needs proper evaluation and management. Recently in few studies, impairment of growth status has been reported as a result of functional constipation. But the relation is not well evaluated, especially in the pediatric population of our country. Aim: To assess the growth status of Bangladeshi children in functional constipation. Methods: This analytical study was conducted at the department of Pediatric Gastroenterology and Nutrition, BSMMU, Dhaka. A total 150 children aged 2-18 years were enrolled in this study. Children were divided into two groups, 75 having functional constipation (FC) and 75 healthy children with no constipation. Samples were collected randomly from pediatric out-patient department of BSMMU with consent of parents and child’s approval. Diagnosis of functional constipation was made by Rome IV criteria. Children with any red flag sign, chronic disease and on treatment of constipation were excluded from the study. Growth status (weight, height &amp; BMI) was evaluated by using growth charts. Data collected in semi-structured questionnaire and analyzed by SPSS 23.0. Results: We evaluated 75 constipated children with the mean age of 7.61±3.50 years and 75 healthy children with the mean age of 7.40±3.88 years. The mean weight of children with functional constipation was 22.8±10.01 kg, mean height 117.7 ±18.4 cm and BMI 15.6±2.3 kg/m2. The mean weight of children with no constipation was 28.6± 13.72 kg, mean height 124.49±23.3 cm and BMI 18.11±2.9 kg/m2,demonstrated significant difference between two sets. In functional constipation group, on weight for age and height for age chart, 28% and 24% children were below the 3rd centile respectively and 18.6% children had BMI below 5th centile. All these parameters (weight, height, BMI) were statistically significant in compare to children without constipation and p value is &lt;.05. Presenting features of functional constipation were anorexia (64%), abdominal pain (73.3%), hard stool (84%), blood mixed hard stool (13.3%) and nausea (34%). Conclusion: Growth impairment occurs in children with functional constipation in comparison to children without constipation. Children aged 2 to 18 years with functional constipation may have decelerated weight, height and BMI growth. And this observation needs further large-scale multicenter study for ensuring optimal growth of children with constipation. J Shaheed Suhrawardy Med Coll 2023; 15(1): 73-77

Acceptability, validity and responsiveness of inertial measurement units for assessing motor recovery after gene therapy in infants with early onset spinal muscular atrophy: a prospective cohort study

BackgroundOnasemnogene abeparvovec gene replacement therapy (GT) has changed the prognosis of patients with spinal muscular atrophy (SMA) with variable outcome regarding motor development in symptomatic patients. This pilot study evaluates acceptability, validity and clinical relevance of Inertial Measurement Units (IMU) to monitor spontaneous movement recovery in early onset SMA patients after GT.MethodsClinical assessments including CHOPINTEND score (the gold standard motor score for infants with SMA) and IMU measurements were performed before (M0) and repeatedly after GT. Inertial data was recorded during a 25-min spontaneous movement task, the child lying on the back, without (10 min) and with a playset (15 min) wearing IMUs. Two commonly used parameters, norm acceleration 95th centile (||A||_95) and counts per minute (||A||_CPM) were computed for each wrist, elbow and foot sensors.Results23 SMA-patients were included (mean age at diagnosis 8 months [min 2, max 20], 19 SMA type 1, three type 2 and one presymptomatic) and 104 IMU-measurements were performed, all well accepted by families and 84/104 with a good child participation (evaluated with Brazelton scale). ||A||_95 and ||A||_CPM showed high internal consistency (without versus with a playset) with interclass correlation coefficient for the wrist sensors of 0.88 and 0.85 respectively and for the foot sensors of 0.93 and 0.91 respectively. ||A||_95 and ||A||_CPM were strongly correlated with CHOPINTEND (r for wrist sensors 0.74 and 0.67 respectively and for foot sensors 0.61 and 0.68 respectively, p-values < 0.001). ||A||_95 for the foot, the wrist, the elbow sensors and ||A||_CPM for the foot, the wrist, the elbow sensors increased significantly between baseline and the 12 months follow-up visit (respective p-values: 0.004, < 0.001, < 0.001, 0.006, < 0.001, < 0.001).ConclusionIMUs were well accepted, consistent, concurrently valid, responsive and associated with unaided sitting acquisition especially for the elbow sensors. This study is the first reporting a large set of inertial sensor derived data after GT in SMA patients and paves the way for IMU-based follow-up of SMA patients after treatment.

AAV gene therapy for Duchenne muscular dystrophy: the EMBARK phase 3 randomized trial.

Duchenne muscular dystrophy (DMD) is a rare, X-linked neuromuscular disease caused by pathogenic variants in the DMD gene that result in the absence of functional dystrophin, beginning at birth and leading to progressive impaired motor function, loss of ambulation and life-threatening cardiorespiratory complications. Delandistrogene moxeparvovec, an adeno-associated rh74-viral vector-based gene therapy, addresses absent functional dystrophin in DMD. Here the phase 3 EMBARK study aimed to assess the efficacy and safety of delandistrogene moxeparvovec in patients with DMD. Ambulatory males with DMD, ≥4 years to <8 years of age, were randomized and stratified by age group and North Star Ambulatory Assessment (NSAA) score to single-administration intravenous delandistrogene moxeparvovec (1.33 × 1014 vector genomes per kilogram; n = 63) or placebo (n = 62). At week 52, the primary endpoint, change from baseline in NSAA score, was not met (least squares mean 2.57 (delandistrogene moxeparvovec) versus 1.92 (placebo) points; between-group difference, 0.65; 95% confidence interval (CI), -0.45, 1.74; P = 0.2441). Secondary efficacy endpoints included mean micro-dystrophin expression at week 12: 34.29% (treated) versus 0.00% (placebo). Other secondary efficacy endpoints at week 52 (between-group differences (95% CI)) included: Time to Rise (-0.64 (-1.06, -0.23)), 10-meter Walk/Run (-0.42 (-0.71, -0.13)), stride velocity 95th centile (0.10 (0.00, 0.19)), 100-meter Walk/Run (-3.29 (-8.28, 1.70)), time to ascend 4 steps (-0.36 (-0.71, -0.01)), PROMIS Mobility and Upper Extremity (0.05 (-0.08, 0.19); -0.04 (-0.24, 0.17)) and number of NSAA skills gained/improved (0.19 (-0.67, 1.06)). In total, 674 adverse events were recorded with delandistrogene moxeparvovec and 514 with placebo. There were no deaths, discontinuations or clinically significant complement-mediated adverse events; 7 patients (11.1%) experienced 10 treatment-related serious adverse events. Delandistrogene moxeparvovec did not lead to a significant improvement in NSAA score at week 52. Some of the secondary endpoints numerically favored treatment, although no statistical significance can be claimed. Safety was manageable and consistent with previous delandistrogene moxeparvovec trials. ClinicalTrials.gov: NCT05096221.

Quantifying the effect of interpregnancy maternal weight and smoking status changes on childhood overweight and obesity in a UK population-based cohort.

Maternal preconception and pregnancy exposures have been linked to offspring adiposity. We aimed to quantify the effect of changes in maternal weight and smoking status between pregnancies on childhood overweight/obesity (≥ 85th centile) and obesity (≥ 95th centile) rates in second children. Records for 5612 women were drawn from a population-based cohort of routinely collected antenatal healthcare records (2003-2014) linked to measured child body mass index (BMI) age 4-5 years. We applied the parametric G-formula to estimate the effect of hypothetical changes between pregnancy-1 and pregnancy-2 compared to the natural course scenario (without change) on child-2 BMI. Observed overweight/obesity and obesity in child-2 at age 4-5 years were 22.2% and 8·5%, respectively. We estimated that if all mothers started pregnancy-2 with BMI 18·5-24·9 kg/m² and all smokers stopped smoking, then child-2 overweight/obesity and obesity natural course estimates of 22.3% (95% CI 21.2-23.5) and 8·3% (7·6-9·1), would be reduced to 18.5% (17.4-19.9) and 6.2% (5.5-7.0), respectively. For mothers who started pregnancy-1 with BMI 18·5-24·9 kg/m², if all smokers stopped smoking, child-2 overweight/obesity and obesity natural course estimates of 17.3% (16.0-18.6) and 5·9% (5·0-6·7) would be reduced to 16.0% (14.6-17.3) and 4·9% (4·1-5·7), respectively. For mothers who started pregnancy-1 with BMI ≥30 kg/m², if BMI was 18·5-24·9 kg/m² prior to pregnancy-2, child-2 overweight/obesity and obesity natural course estimates of 38.6% (34.7-42.3) and 17·7% (15·1-20·9) would be reduced to 31.3% (23.8-40.0) and 12.5 (8.3-17.4), respectively. If BMI was 25.0-29.9 kg/m² prior to pregnancy-2, these estimates would be 34.5% (29.4-40.4) and 14.6% (11.2-17.8), respectively. Interventions supporting women to lose/maintain weight and quit smoking between pregnancies could help reduce rates of overweight/obesity and obesity in second children. The most effective interventions may vary by maternal BMI prior to the first pregnancy.

8568 Prevalence of Raised Blood Pressure in Individuals With 46,XY DSD: an I-DSD Registry study

Abstract Disclosure: A.K. Lucas-Herald: None. J. Bryce: None. M. Chen: None. C. Naotunna: None. M. Sepich: None. L. Tack: None. M. Cools: None. S. Poyrazoglu: None. E. Globa: None. M. Stancampiano: None. H.L. Claahsen-van der Grinten: None. T. Guran: None. Z. Yavas Abali: None. L. de Vries: None. S.E. Hannema: None. A. Guven: None. D. Janus: None. H.A. AlShaikh: None. L. Guazzarotti: None. G. Herrmann: None. U. Probst: None. N. Lenherr-Taube: None. D. Konrad: None. M.W. O’Reilly: None. M. Steigert: None. A. Ucar: None. M. Wasniewska: None. R. Coco: None. P. Holterhus: None. V.M. Schwitzgebel: None. S.F. Ahmed: None. Introduction: Males with XY Differences of Sex Development (DSD) may have an increased risk of high blood pressure and accelerated vascular ageing. It is not clear which individuals are most at risk of this. Methods: Data were obtained from centres using the International Disorders of Sex Development (I-DSD) Registry on boys and men with 46,XY DSD. Blood pressure (BP) readings were requested as well as information on risk factors for hypertension (birthweight, obesity, family history, associated malformations) as well as ongoing management of any high BP readings. Results: In total BP readings from 208 individuals with 46,XY DSD were available from 22 centres worldwide. Of these, the median (range) age at the time of the BP reading was 13 years (1, 54). In total 97 (47%) had a non-specific XY DSD; 37 (18%) had a disorder of gonadal development; 34 (16%) had a disorder of androgen synthesis; 23 (11%) had a disorder of androgen action; 14 (7%) had hypogonadotrophic hypogonadism; and 3 (1%) had a disorder of Müllerian development. There were 77 (37%) cases ≥16 years of age, of whom 7 (10%) were classified as hypertensive. The median systolic BP of those adults with an underlying DSD was 120 mmHg (90, 153). Of the 131 (63%) individuals &amp;lt;16 years of age, 25 (19%) had a BP &amp;gt; 95th centile for age and height. The median BP standard deviation score (SDS) of those children with an underlying DSD was 0.3 (-2, 3). Of the 25 children with a raised BP, 6 (24%) had a BP &amp;gt;99.8th centile and 19 (76%) had a BP &amp;gt;98th centile. Boys with disorders of gonadal development had the highest median BP SDS at 0.9, although this was not significantly different to any other condition. There were no differences in BP SDS at the time of the study according to gestation at birth, birthweight, type of underlying of condition or presence of obesity or a co-existing anomaly however BP SDS was significantly associated with age. Of the 32 with hypertension, 3 (9%) were treated with antihypertensives; 2 (6%) had an echocardiogram and none (0%) are reported to have had ambulatory blood pressure monitoring. Conclusions: Up to 20% of young people with XY DSD have a BP in the hypertensive range during childhood at clinic compared to approximately 5% reported global prevalence in children. Our findings suggest that routine BP measurements should be recommended in this group as well as investigation to determine whether this is true hypertension or secondary to clinic anxiety. Management of these individuals requires adherence to international guidelines to prevent future cardiovascular damage. More research into the underlying cause of this phenomenon is required. Presentation: 6/1/2024

8568 Prevalence of Raised Blood Pressure in Individuals With 46,XY DSD: an I-DSD Registry study

Abstract Disclosure: A.K. Lucas-Herald: None. J. Bryce: None. M. Chen: None. C. Naotunna: None. M. Sepich: None. L. Tack: None. M. Cools: None. S. Poyrazoglu: None. E. Globa: None. M. Stancampiano: None. H.L. Claahsen-van der Grinten: None. T. Guran: None. Z. Yavas Abali: None. L. de Vries: None. S.E. Hannema: None. A. Guven: None. D. Janus: None. H.A. AlShaikh: None. L. Guazzarotti: None. G. Herrmann: None. U. Probst: None. N. Lenherr-Taube: None. D. Konrad: None. M.W. O’Reilly: None. M. Steigert: None. A. Ucar: None. M. Wasniewska: None. R. Coco: None. P. Holterhus: None. V.M. Schwitzgebel: None. S.F. Ahmed: None. Introduction: Males with XY Differences of Sex Development (DSD) may have an increased risk of high blood pressure and accelerated vascular ageing. It is not clear which individuals are most at risk of this. Methods: Data were obtained from centres using the International Disorders of Sex Development (I-DSD) Registry on boys and men with 46,XY DSD. Blood pressure (BP) readings were requested as well as information on risk factors for hypertension (birthweight, obesity, family history, associated malformations) as well as ongoing management of any high BP readings. Results: In total BP readings from 208 individuals with 46,XY DSD were available from 22 centres worldwide. Of these, the median (range) age at the time of the BP reading was 13 years (1, 54). In total 97 (47%) had a non-specific XY DSD; 37 (18%) had a disorder of gonadal development; 34 (16%) had a disorder of androgen synthesis; 23 (11%) had a disorder of androgen action; 14 (7%) had hypogonadotrophic hypogonadism; and 3 (1%) had a disorder of Müllerian development. There were 77 (37%) cases ≥16 years of age, of whom 7 (10%) were classified as hypertensive. The median systolic BP of those adults with an underlying DSD was 120 mmHg (90, 153). Of the 131 (63%) individuals &amp;lt;16 years of age, 25 (19%) had a BP &amp;gt; 95th centile for age and height. The median BP standard deviation score (SDS) of those children with an underlying DSD was 0.3 (-2, 3). Of the 25 children with a raised BP, 6 (24%) had a BP &amp;gt;99.8th centile and 19 (76%) had a BP &amp;gt;98th centile. Boys with disorders of gonadal development had the highest median BP SDS at 0.9, although this was not significantly different to any other condition. There were no differences in BP SDS at the time of the study according to gestation at birth, birthweight, type of underlying of condition or presence of obesity or a co-existing anomaly however BP SDS was significantly associated with age. Of the 32 with hypertension, 3 (9%) were treated with antihypertensives; 2 (6%) had an echocardiogram and none (0%) are reported to have had ambulatory blood pressure monitoring. Conclusions: Up to 20% of young people with XY DSD have a BP in the hypertensive range during childhood at clinic compared to approximately 5% reported global prevalence in children. Our findings suggest that routine BP measurements should be recommended in this group as well as investigation to determine whether this is true hypertension or secondary to clinic anxiety. Management of these individuals requires adherence to international guidelines to prevent future cardiovascular damage. More research into the underlying cause of this phenomenon is required. Presentation: 6/1/2024

Callosal injuries in cytomegalovirus fetopathy: a neurosonographic study.

Introduction - This study aimed to describe the rate and pattern of callosal injury in CMV fetopathy. Methods - This retrospective study included fetuses with confirmed CMV-PCR. Dedicated US including neurosonography was performed. Callosal Length below the 5th centile or morphological abnormalities were considered abnormal. Any additional abnormal findings were reported. Results - Seventy-two patients were included. In 76% infection occurred in the 1stT or periconceptional. In 34.7% a callosal anomaly was observed and it was never isolated. CNS abnormalities included: periventricular hyperechogenicity (PVHE) 55.5%, calcifications 52%, ventriculomegaly 33%, periventricular pseudocysts 31.4%, occipital cysts 22.2%, echogenic precaudate germinal matrix 30.5%, LSV 26.4%, sulcation abnormalities 22.2%, cerebellar findings 18% and HC below -2SD 18%. The most common association with CC insult was PVHE (56%) and calcifications (52%). Conclusion - Although not referred to as a classic brain structure affected by CMV infection, the CC was injured in one-third of our patients, including cases of late infection. The mechanism of disease and the prenatal patterns of callosal involvement in these cases appear to be different from the postnatal patterns and are not reversible. The presence of a callosal injury would imply a worse prognosis and a significant increment in the risk of neurodevelopmental impairment.

Evaluation of sonographic and clinical measures in early versus late third trimester for birth weight prediction.

To evaluate the optimal timing for fetal weight estimation during the third trimester. This retrospective cohort study involved fetal weight estimations from both early (28+0-36+6 weeks) and late (37+0 weeks and beyond) third trimester. These estimations were converted to predicted birth weights using the gestation-adjusted projection formula. Birth weight predictions were compared with actual birth weights, to identify the most effective timing for weight prediction. The study included 3549 cases, revealing mean percentage errors (MPE) of -3.69% for early sonographic assessments, -2.5% for late sonographic assessments, and -1.9% for late clinical assessments. A significant difference was found between early and late sonographic estimations (P < 0.001), whereas late sonographic and clinical assessments did not differ significantly (P = 0.771). Weight predictions for fetuses below the 10th and above the 90th centiles were less accurate than for those within the 10th-90th centiles (P < 0.001). In women with obesity, late clinical estimations were less precise (MPE of -5.85) compared with non-obese women (MPE of -1.66, P < 0.001). For women with diabetes, early sonographic estimations were more accurate (MPE of -1.31) compared with non-diabetic patients (MPE of -3.94, P < 0.001) though this difference did not persist later in pregnancy. Sonographic and clinical weight predictions in the late third trimester were more accurate than earlier third-trimester sonographic assessments, hence continuous follow up and assessments closer to term are important. In women with diabetes, no adjustments in weight prediction methods are necessary. Accurately predicting birth weights for abnormally small or large fetuses remains challenging, indicating the need for improved screening and diagnostic strategies.

Relationship between growth and ambulation loss in Duchenne muscular dystrophy boys on steroids.

Treatment with glucocorticoids (GCs) is part of the standard of care in Duchenne muscular dystrophy, but excess weight gain and height stunting are common side-effects. It is still unclear how these growth-related side-effects affect motor function. This retrospective cohort study utilized 2228 observations from 648 participants in the UK NorthStar database who had growth and ambulation data recorded between 2006 and 2020. Joint modelling was used to analyse the effect of longitudinal growth centiles on loss of ambulation with respect to GC type and regimen. Loss of ambulation was observed in 113 patients. National estimates of loss of ambulation age were updated by GC group and showed no significant association between loss of ambulation risk and absolute growth centile. However, yearly drift in weight and/or height centile had an associated risk effect on loss of ambulation. Over a 2-year period, a yearly drift in weight from the 50th to the 75th, 75th to the 90th and 90th to the 95th centile was associated with 138%, 118% and 64% increased risk of loss of ambulation, respectively. Conversely, a 2-year drift in height from the 50th to the 25th, 25th to the 10th and 10th to the 5th centile was associated with 53%, 49% and 35% decreased risk of loss of ambulation, respectively. Our results suggest a complex relationship between growth and loss of ambulation in Duchenne muscular dystrophy boys on chronic GCs, the first step in understanding the effects of drugs which also affect growth patterns.

Combined first-trimester screening and invasive diagnostics for atypical chromosomal aberrations: Danish nationwide study of prenatal profiles and detection compared with NIPT.

Our aim was to examine the prenatal profiles of pregnancies affected by an atypical chromosomal aberration, focusing on pathogenic copy-number variants (pCNVs). We also wanted to quantify the performance of combined first-trimester screening (cFTS) and a second-trimester anomaly scan in detecting these aberrations. Finally, we aimed to estimate the consequences of a policy of using non-invasive prenatal testing (NIPT) rather than invasive testing with chromosomal microarray analysis (CMA) to manage pregnancies identified as high risk by cFTS. This was a retrospective review of the Danish Fetal Medicine Database of all pregnant women who underwent cFTS and a risk assessment for trisomy 21 between 1 January 2008 and 31 December 2018. Chromosomal aberrations diagnosed prenatally, postnatally or from fetal tissue following pregnancy loss or termination of pregnancy were identified. Chromosomal aberrations were grouped into one of six categories: triploidy; common trisomy (13, 18 or 21); monosomy X; other sex-chromosome aberration (SCA); pCNV; and rare autosomal trisomy (RAT) or mosaicism. The prevalence of each aberration category was stratified by the individual cFTS markers and trisomy 21 risk estimate, and the size of each pCNV diagnosed by CMA was calculated. We retrieved data on 565 708 pregnancies, of which 3982 (0.70%) were diagnosed with a fetal chromosomal aberration. cFTS identified 87% of the common trisomies, but it also performed well in identifying triploidies (86%), monosomy X (92%), atypical SCAs (58%) and RATs or mosaicisms (70%). pCNVs comprised 27% (n = 1091) of the chromosomal aberrations diagnosed overall, and the prevalence increased during the study period, as prenatal CMA was increasingly being performed. In pregnancies with a maternal age < 30 years, nuchal translucency (NT) thickness ≤ 95th centile, pregnancy-associated plasma protein-A (PAPP-A) ≥ 1 multiple of the median, or trisomy 21 risk of ≤ 1 in 1000, the prevalence of pCNVs exceeded significantly the prevalence of trisomies 21, 18 and 13. Pregnancies affected by a pCNV had significantly increased NT and decreased levels of the maternal biomarkers PAPP-A and β-human chorionic gonadotropin compared with unaffected pregnancies. However, only 23% of these pregnancies screened positive on cFTS and 51% of pCNVs were not detected until after birth. Among high-risk pregnancies, pCNVs comprised 14% of diagnosed aberrations, and when other atypical aberrations were considered, conventional NIPT (screening for trisomies 21, 18 and 13 and monosomy X) would miss 27% of all pathogenic aberrations diagnosed from invasive testing following a high-risk cFTS result. Thus, 1 in 26 pregnancies at high risk following cFTS would be affected by a chromosomal aberration despite a normal result from conventional NIPT. In a contingent screening model using NIPT for the 'intermediate'-risk group (trisomy 21 risk of 1 in 100-299), 50% of the aberrations would be missed. In our cohort, 79% of the pCNVs diagnosed were < 5Mb and therefore not detectable using current forms of 'genome-wide' NIPT. As a by-product of screening for trisomies 21, 18 and 13, most triploidies and the majority of atypical SCAs, RATs and mosaicisms are detected before birth. However, only 23% of pCNVs are associated with a high-risk result according to cFTS and only half are diagnosed before birth. Replacing invasive testing with NIPT for high-risk pregnancies would substantially decrease the first-trimester detection of pathogenic chromosomal anomalies. © 2024 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Utility of placental biomarkers and fetoplacental Dopplers in predicting likely placental pathology in early and late fetal growth restriction – A prospective study

IntroductionThe aim of this study was to evaluate the association between placental abnormalities, placental biomarkers, and fetoplacental Dopplers in a cohort of pregnancies complicated by fetal growth restriction (FGR). We also ascertained the risk of perinatal mortality, severe neurological morbidity, and severe non-neurological morbidity by type of placental abnormality. MethodsThis was a prospective cohort study. Multivariable logistic regression was used to evaluate the effect of early vs. late FGR, placental biomarkers and fetoplacental Dopplers on Maternal Vascular Malperfusion (MVM) which was the commonest placental abnormality identified. ResultsThere were 161 (53.5 %) early FGR and 140 (46.5 %) late FGR cases. MVM abnormalities were present in 154 (51.2 %), VUE in 45 (14.6 %), FVM in 16 (5.3 %), DVM in 14 (4.7 %) and CHI in 4 (1.3 %) cases. The odds of MVM were higher in early compared to late FGR cohort (OR 1.89, 95%CI 1.14, 3.14, p = 0.01). Low maternal PlGF levels <100 ng/L (OR 2.34, 95%CI 1.27,4.31, p = 0.01), high sFlt-1 level (OR 2.13, 95%CI 1.35, 3.36, p = 0.001) or elevated sFlt-1/PlGF ratio (OR 3.48, 95%CI 1.36, 8.91, p = 0.01) were all associated with MVM. Increased UA PI > 95th centile (OR 2.91, 95%CI 1.71, 4.95, p=<0.001) and mean UtA PI z-score (OR 1.74, 95%CI 1.15, 2.64, p = 0.01) were associated with higher odds of MVM. Rates of severe non-neurological morbidity were highest in the MVM, FVM, and CHI cohorts (44.8 %, 50 %, and 50 % respectively). ConclusionMVM was the commonest placental abnormality in FGR, particularly in early-onset disease. Low maternal PlGF levels, high sFlt-1 levels, elevated sFlt-1/PlGF ratio, and abnormal fetoplacental Dopplers were also significantly associated with MVM. MVM, FVM, and CHI abnormalities were associated with lower median birthweight, higher rates of preterm birth, operative birth for non-reassuring fetal status, and severe neonatal non-neurological morbidity.

Interplay between physical activity volume and intensity with modeled life expectancy in women and men: A prospective cohort analysis

BackgroundThere is a lack of research examining the interplay between objectively measured physical activity volume and intensity with life expectancy. MethodsIndividuals from UK Biobank with wrist-worn accelerometer data were included. The average acceleration and intensity gradient were extracted to describe the physical activity volume and intensity profile. Mortality data were obtained from national registries. Adjusted life expectancies were estimated using parametric flexible survival models. Results40,953 (57.1%) women (median age = 61.9 years) and 30,820 (42.9%) men (63.1 years) were included. Over a median follow-up of 6.9 years, there were 1719 (2.4%) deaths (733 in women; 986 in men). At 60 years, life expectancy was progressively longer for higher physical activity volume and intensity profiles, reaching 95.6 years in women and 94.5 years in men at the 90th centile for both volume and intensity, corresponding to 3.4 (95% confidence interval (95%CI): 2.4–4.4) additional years in women and 4.6 (95%CI: 3.6–5.6) additional years in men compared to those at the 10th centiles. An additional 10-min or 30-min daily brisk walk was associated with 0.9 (95%CI: 0.5–1.3) and 1.4 (95%CI: 0.9–1.9) years longer life expectancy, respectively, in inactive women; and 1.4 (95%CI: 1.0–1.8) and 2.5 (95%CI: 1.9–3.1) years in inactive men. ConclusionHigher physical activity volumes were associated with longer life expectancy, with a higher physical activity intensity profile further adding to a longer life. Adding as little as a 10-min brisk walk to daily activity patterns may result in a meaningful benefit to life expectancy.

Handwriting speed in juvenile idiopathic arthritis using the detailed assessment of speed of handwriting

BackgroundHandwriting is a commonly reported functional limitation for children with juvenile idiopathic arthritis (JIA). The aim of this study was to evaluate handwriting in children with JIA.FindingsTwelve children (mean age 13.0 years, SD = 1.9; range 9.1 to 15.6 years) with JIA completed the Detailed Assessment of Speed of Handwriting (DASH). The presence of hand and wrist arthritis, grip strength, disability, pain, and quality of life (QOL) was also assessed. The mean DASH score was 34.5th percentile (SD = 22.5). Eight (75%) scored below the 50th centile. DASH scores were negatively associated with grip strength (r = -0.31).ConclusionsHandwriting difficulties are common in children with JIA. Handwriting assessment may be helpful to direct treatments, and advocate for support and accommodations in school.

Can the neutrophil-to-lymphocyte ratio be used as an early marker of small fetuses for gestational age? A prospective study.

Small-for-gestational-age (SGA) fetuses are at increased risk of mortality and morbidity, and less than 30% will be detected by any ultrasound scan within 4 weeks before delivery. Our aim was to evaluate the relationship between neutrophil/lymphocyte ratio (NLR) in the first trimester of pregnancy and SGA fetuses. We performed a prospective study between June 2021 and August 2022, to evaluate the relationship between the neutrophil to lymphocyte ratio in maternal blood in the first trimester of pregnancy, with the birth of an SGA fetus. One hundred ninety-four participants with singleton pregnancies between 11 + 1 and 13 + 6 weeks of gestation were recruited. Pregnancies affected with diagnosed fetal chromosomal abnormalities, or chronic pathologies were excluded. SGA was defined as birthweight less than the 10th centile (N = 42) and severe SGA as birthweight less than the 3rd centile for gestation (N = 10) according to a locally derived descriptive charts. The NLR value measured in the first trimester was compared between these two groups and controls. We found no statistically significant difference in NLR, (3.5 +/-1.2 vs. 3.4+/-1.2, p-value of 0.78) when comparing the SGA less than the 10th centile group to the control group. NLR was also not different between severe SGA and controls (3.6+/-1.4 vs. 3.4+/-1.2 p-value of 0.78). We found no association between first-trimester NLR ratio and SGA.

Reference ranges of peripheral-muscle oxygenation in term neonates delivered by Caesarean section during immediate transition after birth.

To establish reference ranges of peripheral-muscle regional oxygen saturation (prSO2) and peripheral fractional tissue oxygen extraction (pFTOE) during the first 15 min after birth in stable term neonates. Secondary outcome parameters of prospective observational studies in healthy term neonates delivered by Caesarean section were analysed. prSO2 was measured on the right forearm using the INVOS 5100C monitor. pFTOE was calculated out of prSO2 and arterial oxygen saturation (SpO2). Centile charts (10th-90th) of prSO2 and pFTOE were defined during the first 15 min after birth. Three-hundred-five term neonates with a mean gestational age and birth weight of 39.0 ± 0.9 weeks and 3321 ± 454 g, respectively, were included. The 50th centiles of prSO2 were 39% (minute two), 52% (minute five), 71% (minute 10), and 73% (minute 15). The 50th centiles of pFTOE were 0.529 (minute two), 0.378 (minute five), 0.237 (minute 10), and 0.231 (minute 15). Reference ranges of prSO2 and pFTOE were established for term neonates delivered by Caesarean section during the immediate transition after birth. These reference ranges increase knowledge of physiological processes taking place immediately after birth and are necessary for possible future clinical applications.

Identification of copy-number variants in patients with overgrowth disorders.

Overgrowth syndromes (OGS) comprise a heterogeneous group of disorders whose main characteristic is that the weight, height or the head circumference are above the 97th centile or 2-3 standard deviations above the mean for age, gender, and ethnic group. Several copy-number variants (CNVs) have been associated with the development of OGS, such as the 5q35 microdeletion or the duplication of the 15q26.1-qter, among many others. In this study, we have applied 850K SNP-arrays to 112 patients and relatives with OGS from the Spanish OverGrowth Registry Initiative. We have identified CNVs associated with the disorder in nine individuals (8%). Subsequently, whole genome sequencing (WGS) analysis was performed in these nine samples in order to better understand these genomic imbalances. All the CNVs were detected by both techniques, settling that WGS is a useful tool for CNV detection. We have found six patients with genomic abnormalities associated with previously well-established disorders and three patients with CNVs of unknown significance, which may be related to OGS, based on scientific literature. In this report, we describe these findings and comment on genes associated with OGS that are located within the CNV regions.

Impact of the Choice of Diagnostic Criteria and Growth Reference on the Prevalence of Extrauterine Growth Restriction in Extremely-Low-Birthweight Infants.

Variable diagnostic criteria and growth charts have been used for extrauterine growth restriction (EUGR). The objective was to assess the prevalence and concordance of EUGR in extremely-low-birthweight (ELBW) infants with the most frequent diagnostic criteria and growth charts. An observational, retrospective and multicenter study was conducted from 2011 to 2020 including ELBW infants from the Spanish SEN1500 Network. EUGR prevalence was calculated at discharge using different definitions: cross-sectional (anthropometry less than the 10th centile), longitudinal (decrease of more than 1 SD from birth to discharge), "true" cross-sectional and "true" longitudinal (using the criteria previously described, excluding infants small for gestational age at birth). Concordance among Fenton, Olsen and INTERGROWTH-21st was assessed with Fleiss' Kappa coefficient. The prevalence of EUGR was variable with the different definitions and growth references studied in the 7914 ELBW infants included. Overall, it was higher with Fenton for all the EUGR criteria studied by weight and length. The agreement among growth charts was substantial (κ > 0.6) for all the definitions except for longitudinal EUGR by weight (moderate, κ = 0.578). The prevalence of EUGR was variable in our cohort with the different diagnostic criteria and growth charts. The agreement among charts was good for all the definitions of EUGR except longitudinal EUGR by weight.