95th Centile Research Articles

Umbilical Vein Flows and Cardiac Size, Shape, and Ventricular Contractility in Fetuses With Estimated Weight Less-Than 10th Centile.

In a cohort of patients with estimated fetal weights (EFWs) <10th centile, we aimed 1) to compare the prevalence of abnormalities of fetal 4-chamber view (4CV) cardiac size, shape, and ventricular contractility in fetal growth restricted (FGR) and small-for-gestational-age (SGA) fetuses and 2) to compare umbilical vein flow (UVF) measurements to standard Doppler surveillance in predicting abnormalities of cardiac function. Prospective observational cohort study of fetuses with EFW <10th percentile. Measurements of size and shape used were 4CV transverse width, 4CV cardiac area, 4CV global sphericity index, and right-to-left ventricular mid-chamber width ratio. Variables of contractility used were fractional shortening change at the mid-ventricle chamber, global longitudinal strain, fractional area change, and left ventricular cardiac output. The UVF and standard Doppler surveillance including umbilical artery (UA), middle cerebral artery, and cerebroplacental ratio (CPR) were collected. Control data were from previously published studies. A total of 95 fetuses with EFWs <10th centile were included in the study. The rates of abnormalities of cardiac size and shape and ventricular contractility were all significantly elevated compared with normally grown control fetuses but similar between FGR and SGA fetuses. In a subset of 76 patients with UVF data, evaluation UVF identified more patients with any abnormality of contractility compared with UA (37.9 vs 17.2%, P = .02). The addition of UVF doubled the detection rate of ventricular contractility abnormalities. The addition of UVF should be considered in the surveillance of FGR and SGA fetuses to further stratify the severity of hypoxemia and to identify those at greater risk for future cardiovascular dysfunction.

Association of self-esteem and school connectedness with substance use among street children in southwestern Nigeria

ABSTRACT Objective The study aimed to determine the relationship between substance use, self-esteem and school connectedness among street children in southwestern Nigeria. Methods A cross-sectional survey of 358 street children in Oyo State Nigeria, was carried out. Data was collected using a semi-structured questionnaire. Appropriate scoring systems were used to assess the degree of self-esteem and school connectedness. The 50th centile was used as the cutoff point to define good self-esteem and school connectedness. Results Participants were aged 9–17 years, with a mean age of 16.2 ± 1.3 years; 208 (58.1%) were males. More than three-quarters (77.9%) had used psychoactive substances at some point in their lives, with local (herbal) psychoactive substances being the most frequent, followed by central nervous system depressants. One hundred and eighty (50.3%) of them were currently using psychoactive substances. The females had better self-esteem and school connectedness compared with the males, whereas substance use was more prevalent among the males. Good school connectedness was associated with lower use of psychoactive substances, but good self-esteem was associated only with reduced use of inhalants. Conclusion Promoting good school connectedness among street children may help in reducing the use of psychoactive substances among them.

The impact of the proposed revised Australia's microbiological monitoring programme for beef and sheep meat exported to the EU.

The European Commission asks scientific and technical assistance from EFSA to determine the impact of the revision of the Australian monitoring programme on its ability to detect microbiological contamination. Considering that, in 2010, the European Commission determined the current Australian monitoring programme to be equivalent to the EU requirements for microbiological monitoring further to an EFSA scientific assessment, the current and proposed programmes were described and the total number of alerts was compared using a probabilistic modelling approach. In the current programme, only beef and sheep carcasses are monitored using three-class moving window sampling plans, while in the proposed programme, carcass, bulk meat, primal and offal are monitored using four two-class sampling plans and Salmonella testing is excluded. The models revealed that the current programme provides a higher number of alerts for APC, while the proposed monitoring programme provides a higher number of alerts for E. coli. For APC and E. coli combined, the mean, 5th and 95th centiles of the uncertainty distribution of the total number of alerts in the current and the proposed monitoring programme are 201 [179, 227] and 172 [149, 194] for beef, and 199 [175, 222] and 2897 [2795, 3008] for sheep, respectively. For Salmonella, there are no alerts for the proposed programme since sampling is excluded while for the current programme, the estimated mean, 5th and 95th centiles of the uncertainty distribution of the number of alerts for a 5-year period were 143 [126, 144] for heifer/steer, 1.6 [0, 4] for cow/bull and 0 [0, 0] for lamb/sheep. Overall, for APC and E. coli, the estimated total number of alerts was similar (beef) or higher (sheep) for the proposed compared to the current programme. In contrast, Salmonella sampling is excluded from the proposed programme and thus cannot detect the number of current alerts.

Effect of non-optimal ambient temperature on preterm birth stratified by social positioning in Nepal: A space–time-stratified case-crossover study

BackgroundThe ongoing increase in the mean global temperature due to human induced climate change, indicates that women and infants will have higher exposure to heat events leading to adverse outcomes. The study investigates the effect of non-optimal ambient temperature on the risk of preterm birth stratified by social position in Nepal. MethodThis is a space–time-stratified case-crossover design, based on hospital-registered perinatal data between 2017 and 2021 (n = 47,807). A daily count of pregnant women residing in seven heat-prone districts was extracted together with their social status (ethnicity), obstetric complication and gestation of birth. The daily count of events was matched with the daily ambient temperature of their residence using the NOAA spatial temperature recording. Ambient temperature exposure was analysed using conditional Poisson regression and distributed lag non-linear models. FindingsIn the general population, with exposure to ambient temperature at the 75th centile (28 °C) the cumulative risk of preterm birth over 28 days was 1·29 times higher (RR, 1·29; 95% CI; 1·09, 1·54) than at median temperature (24.1 °C), and even higher among the socially disadvantaged population. Cumulative risk of preterm birth to cold ambient temperature at the 1st centile was high but not significant. Exposure to ambient temperature at the 90th centile (32·5 °C) had the highest cumulative risk of preterm birth for pregnant women from socially disadvantaged populations (RR 1·81; 95% CI; 1·28, 2·55). The delayed effect after exposure to temperatures above the 75th percentile was more prolonged in the disadvantaged than the advantaged social group. ConclusionAlthough exposure to cold with certain effect on preterm births, heat (increase in ambient temperature) carries a risk of preterm birth in Nepal, and is more profound among socially disadvantaged populations.

Ambient temperature and cardiovascular disease-related emergency room visits in Lanzhou, China from 2013 to 2019: A time-series study.

This study assessed the links between daily mean temperature and emergency room (ER) admissions for total and cause-specific cardiovascular diseases (CVD) in Lanzhou, China from 2013 to 2019. A quasi-Poisson Generalized Additive Model (GAM) and a Distributed Lag Non-Linear Model (DLNM) were used to determine the effects of temperature on total and cause-specific cardiovascular emergency visits. The relative risks (RR) at cold (hot) temperatures were calculated by comparing the 5th (95th) centile of temperature with the minimum morbidity temperature (MMT). Exposure-response curves demonstrating an inverted U-shape or an irregular M-shape association were observed between temperature and total and cause-specific CVD. The study found that both cold and hot temperatures had negative impacts on emergency room visits for various cardiovascular diseases. For people with total CVD, heart rhythm disturbances (HRD), or cerebrovascular diseases (CD), females were more sensitive to temperature than males, while for ischemic heart disease (IHD) and heart failure (HF), males were more vulnerable to temperature. The < 65 years old with total CVD, IHD, HRD, or CD was more susceptible to the effects of temperature. The results indicated that the relationship between temperature and total and cause-specific CVD was nonlinear, and susceptibility to temperature varied across disease subtype, gender, and age.

Title Isolated Absent or Hypoplastic Nasal Bone during Second Trimester Scan- Should it be Considered a Major Soft Marker?

Background: For many years, absent or hypoplastic nasal bone during prenatal scans has been reported to be associated with increased risk of chromosomal abnormalities. We aimed to study the association of isolated absent or hypoplastic nasal bone with chromosomal abnormalities and genetic syndromes. Methods: a retrospective observational study conducted at BLK Max foetal medicine unit, in which women with absent or hypoplastic nasal bone during second trimester scan between 16-24weeks of gestation were recruited over a period of 2 years, from June 2021 to June 2023. Nasal bone was defined as absent when no calcification was seen below the skin of the nasal bridge in mid sagittal view of facial profile, while defined as hypoplastic nasal bone when nasal bone length was &lt;5th centile for gestation according to gestation corrected Indian charts. Absent or hypoplastic nasal bone was defined as isolated - when there was absence of other second trimester soft markers, no other structural abnormalities were seen on the ultrasound and biochemistry screen was low risk. Results :A total of 3008 women were scanned during this period, among these 21 (0.69%) foetuses were found to have absent or hypoplastic nasal bone during second trimester scan. Thirteen (61.9%) fetuses were defined to have isolated absent (n-9) or hypoplastic (n-4) nasal bone which were included in the final analysis. Out of 13, 11 women opted for invasive testing where fluorescence in situ hybridisation (FISH) for 5 common aneuploidies and Microarray (750K) were sent on the amniotic fluid as a unit protocol, and 2 parents opted against any further genetic testing. In all tested cases, FISH and chromosomal microarray reports were reported as normal. All pregnancies were continued in our study group and had favourable foetal outcomes.

A probabilistic risk assessment of long-term exposure to metals and pesticides residues via consumption of cucurbit crops

Cucurbits contribute significantly to global food and are economically important for farm lands and greenhouses in Iran. The present study assessed the probabilistic risk posed to Iranian consumers through oral exposure to a mixture of pesticides and metals by consumption of cucurbit crops. A total of 180 samples of cucurbit crops including cucumber, courgette, pumpkin, Persian melon, watermelon, and melon were collected from different farm lands (i.e. open fields, 90 samples) and greenhouses (90 samples) in Iran and levels of pesticides and metals were quantified by GC-MS and ICP-OES, respectively. The mean levels of Cd, As, and Ni were above reference dose (RfD) in farmland crops, whereas only Ni levels were above RfD in greenhouse crops. In general, metals mean levels in farmland crops were statistically higher compared to greenhouse cucurbits. Concerning pesticides, in farmland crops, mean concentrations of carbaryl, methomyl, diazinon, malathion, and methamidophos were above the maximum residue limits (MRLs), while in greenhouse crops diazinon and methamidophos were above MRLs. Estimated incremental lifetime cancer risk (ILCR) and hazard index (HI) for metals reflected no health risk for both farmland and greenhouse crops. Based on probabilistic assessment, HI values for carbamates, pyrethroids, and organophosphorus contents in cucurbit crops from farmlands and greenhouses at the 50th, 80th and 95th centiles, indicated no risk for Iranian consumers. Agricultural policies should be updated by using the cultivars types with minimum contaminants-accumulation and raise the general awareness of Iranian farmers about careful use of pesticides and fertilizers in agricultural practices.

Effect of polygenic risk score for clinically significant prostate cancer in a screening program: The BARCODE 1 study results.

10500 Background: Incidence of prostate cancer (PCa) is increasing, but there is no internationally agreed population screening program. Studies using an age-based PSA approach show a high rate of false-positive results as well as over-diagnosis of indolent PCa. Genome wide association studies identify common germline variants to calculate a polygenic risk score (PRS) associated with PCa risk. The BARCODE1 study used PRS to target PCa screening to those at higher risk based on genotype. Methods: European men aged 55-69yrs were recruited via Primary Care in the UK. PRS was constructed by summing weighted risk alleles for 130 PCa risk variants using germline DNA from saliva samples via mailed kits. Men with a PRS &gt; 90th centile were invited for PCa screening using MRI and 12-core transperineal biopsy (including MRI fusion to target additional lesions where identified) irrespective of PSA result. Results: Invitation letters were sent to 40,292 men. 8,953 (22%) expressed an interest; 8,014 were eligible and sent a saliva kit. 6,644 consented; 6,393 were genotyped; 251 failed QC. A total of 6,142 participants had PRS calculated: 745 (12.1%) had a PRS &gt; 90th centile and were invited to screening. 558/745 participants attended screening (121 declined, 66 excluded on health grounds). 551 underwent MRI and 468 had prostate biopsy resulting in 187 (40.0%) diagnoses of PCa, overall PCa detection rate 2.8%. Mean age at diagnosis 64.1yrs (range 57-73; median 64). Using NCCN criteria (2023) 103/187 (55.1%) of cancers were Intermediate or High Risk; 40/187 (21.4%) were Intermediate Unfavourable/High/Very High Risk. 119/187 (63.6%) men had a PSA &lt;3.0ug/L; PPV of biopsy for PSA &gt; 3.0ug/L was 49.6%. PPV of MRI (presence of PI-RADS 3-5 lesion) 60.4%. PPV of PRS alone 40%. 103/187 (55.1%) had Gleason &gt;7; compared with 360/1014 (35.5%) p &lt; 0.001 in the PSA directed ERSPC study. Conclusions: A population PCa screening program using PRS risk-stratification enriches for clinically significant PCa requiring treatment. It detects a high proportion of clinically significant disease compared with PSA or MRI based screening programs and MRI missed a significant proportion (17-67%) of cancers found on biopsy. This is the first study to assess if this approach will be useful in population screening programs. Clinical trial information: NCT03857477 . [Table: see text]

First-trimester uterine artery Doppler and hypertensive disorders in twin pregnancies: Use of twin versus singleton references.

To determine the association of first-trimester uterine artery Doppler with hypertensive disorders of pregnancy in twin pregnancies. This was a retrospective cohort study of twin pregnancies followed at the University Hospital Center of Central Lisbon, Portugal, between January 2010 and December 2022. First-trimester uterine artery pulsatility index (UtA-PI) was determined and compared between twin pregnancies (n = 454) and singleton pregnancies (n = 908), matched to maternal and pregnancy characteristics. Maternal characteristics and mean UtA-PI were analyzed for gestational age, birth weight, gestational hypertension, early- and late-onset pre-eclampsia, HELLP (hemolysis, elevated liver enzymes, low platelets) syndrome, and preterm birth. Univariable and multivariable logistic regression models were used. The mean first-trimester UtA-PI was significantly lower in dichorionic twins than in singletons (P < 0.001). To study hypertensive disorders of pregnancy in twins, 390 pregnancies were included: 311 (79.7%) dichorionic and 79 (20.3%) monochorionic twins. The observed rates of early- and late-onset pre-eclampsia, gestational hypertension, and HELLP syndrome were 1.0%, 4.4%, 7.4%, and 1.5%, respectively. We achieved a 100% detection rate for early-onset pre-eclampsia using the UtA-PI 90th centile for twins. However, when singleton references were considered, the detection rate decreased to 50%. UtA-PI at or above the 95th centile was associated with increased odds for preterm birth before 32 weeks (adjusted odds ratio 4.1, 95% confidence interval 1.0-16.7, P = 0.043). Unless other major risk factors for hypertensive disorders are present, women with low UtA-PI will probably not benefit from aspirin prophylaxis. Close monitoring of all twin pregnancies for hypertensive disorders is still recommended.

Association between Doppler assessment and secondary cesarean delivery for intrapartum fetal compromise in small-for-gestational-age fetuses

PurposeTo elucidate the association between arterial and venous Doppler ultrasound parameters and the risk of secondary cesarean delivery for intrapartum fetal compromise (IFC) and neonatal acidosis in small-for-gestational-age (SGA) fetuses.MethodsThis single-center, prospective, blinded, cohort study included singleton pregnancies with an estimated fetal weight (EFW) < 10th centile above 36 gestational weeks. Upon study inclusion, all women underwent Doppler ultrasound, including umbilical artery (UA) pulsatility index (PI), middle cerebral artery (MCA) PI, fetal aortic isthmus (AoI) PI, umbilical vein blood flow (UVBF), and modified myocardial performance index (mod-MPI). Primary outcome was defined as secondary cesarean section due to IFC.ResultsIn total, 87 SGA pregnancies were included, 16% of which required a cesarean section for IFC. Those fetuses revealed lower UVBF corrected for abdominal circumference (AC) (5.2 (4.5–6.3) vs 7.2 (5.5–8.3), p = 0.001). There was no difference when comparing AoI PI, UA PI, ACM PI, or mod-MPI. No association was found for neonatal acidosis. After multivariate logistic regression, UVBF/AC remained independently associated with cesarean section due to IFC (aOR 0.61 [0.37; 0.91], p = 0.03) and yielded an area under the curve (AUC) of 0.78 (95% CI, 0.67–0.89). A cut-off value set at the 50th centile of UVBF/AC reached a sensitivity of 86% and specificity of 58% for the occurrence of cesarean section due to IFC (OR 8.1; 95% CI, 1.7–37.8, p = 0.003).ConclusionLow levels of umbilical vein blood flow (UVBF/AC) were associated with an increased risk among SGA fetuses to be delivered by cesarean section for IFC.

Urinary sFlt-1 and PlGF as preeclampsia predictors: sFlt-1/creatinine ratio improves the prediction value

ObjectivesTo evaluate the correlation between maternal serum and urinary soluble Fms-like tyrosine kinase-1 (sFlt-1) and placental growth factor (PlGF) levels and to assess their potential value in preeclampsia and fetal growth restriction. Study DesignThis case-control longitudinal prospective study was performed in 49 singleton pregnant women, divided into two clinical groups, low risk pregnancy (n = 23) and pregnancy complicated by preeclampsia (n = 26). Maternal serum and urinary sFlt-1 and PlGF levels were quantified by electrochemiluminescence. Every patient underwent an ultrasound for fetal biometry. Doppler assessment was done when estimated fetal weight was under the 10th centile. ROC curves were used to evaluate the predictive capability of serum and urinary angiogenic biomarkers and their ratios on preeclampsia. Linear regression was used to compare the values of serum and urinary sFlt-1 and PlGF and their ratios. ResultsUrine biomarkers were positively associated with their serum values, being the best associated urinary PlGF (R2 = 0.73), which also showed the highest predictive capability of preeclampsia of urine biomarkers (AUC 0.866). The predictive capability of urinary sFlt-1 was much lower (AUC 0.640), but increased when adjusting by serum creatinine, a more precise parameter (AUC 0.863). ConclusionsUrinary PlGF could be a lesser invasive alternative to circulating biomarkers to monitor pregnancies complicated with preeclampsia that need repeated controls of their pregnancy complication. Urinary sFlt-1 values need adjustment by serum creatinine to be reliable.

Placental growth factor and fetoplacental Doppler indices in combination predict preterm birth reliably in pregnancies complicated by fetal growth restriction.

To assess the association between placental biomarkers (placental growth factor (PlGF) and soluble fms-like tyrosine kinase-1 (sFlt-1)/PlGF ratio) and fetoplacental Doppler indices (umbilical artery (UA) pulsatility index (PI) and uterine artery (UtA) PI) in various combinations for predicting preterm birth (PTB) in pregnancies complicated by fetal growth restriction (FGR). This was a prospective observational cohort study, performed at Mater Mother's Hospital in Brisbane, Queensland, Australia, from May 2022 to June 2023, of pregnancies complicated by FGR and appropriate-for-gestational-age (AGA) pregnancies. Maternal serum PlGF levels, sFlt-1/PlGF ratio, UA-PI and UtA-PI were measured at 2-4-weekly intervals from recruitment until delivery. Harrell's concordance statistic (Harrell's C) was used to evaluate multivariable Cox proportional hazards regression models featuring various combinations of placental biomarkers and fetoplacental Doppler indices to ascertain the best combination to predict PTB (< 37 weeks). Multivariable Cox regression models were used with biomarkers as time-varying covariates. The study cohort included 320 singleton pregnancies, comprising 179 (55.9%) affected by FGR, defined according to a Delphi consensus, and 141 (44.1%) with an AGA fetus. In the FGR cohort, both low PlGF levels and elevated sFlt-1/PlGF ratio were associated with significantly shorter time to PTB. Low PlGF was a better predictor of PTB than was either sFlt-1/PlGF ratio or a combination of PlGF and sFlt-1/PlGF ratio (Harrell's C, 0.81, 0.78 and 0.79, respectively). Although both Doppler indices were significantly associated with time to PTB, in combination they were better predictors of PTB than was either UA-PI > 95th centile or UtA-PI > 95th centile alone (Harrell's C, 0.82, 0.75 and 0.76, respectively). Predictive utility for PTB was best when PlGF < 100 ng/L, UA-PI > 95th centile and UtA-PI > 95th centile were combined (Harrell's C, 0.88) (hazard ratio, 32.99; 95% CI, 10.74-101.32). Low maternal serum PlGF level (< 100 ng/L) and abnormal fetoplacental Doppler indices (UA-PI > 95th centile and UtA-PI > 95th centile) in combination have the greatest predictive utility for PTB in pregnancies complicated by FGR. Their assessment may help guide clinical management of these complex pregnancies. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

A Rare Case Report of Bardet–Biedl Syndrome: A Syndrome of Pentad Symptoms

Bardet–Biedl syndrome (BBS) is a clinically and genetically heterogeneous disorder that manifests as a result of primary cilia impairment, characterized by retinitis pigmentosa, obesity, mental retardation, hypogonadism, and polydactyly. The five findings together are called “the pentad” and are found in most of the cases. This is the case of a 14-year-old boy, 2nd issue of consanguineous marriage of his parents, having a positive family history, who presented with progressive dimness of vision, learning disability, increased hunger, and weight since childhood. Initially, there were impaired night vision and peripheral vision problems, and later loss of color vision. He had no hearing problem, anosmia, cold intolerance, or steroid-taking history. His intranatal and postnatal history was uneventful except slightly delayed developmental milestone. His body mass index was 32.7 kg/m2, waist–hip ratio was 1.08, height was in the 50th centile on the growth chart. He had polydactyly, high-arched palate, acanthosis nigricans, and buried penis; testicular volume was prepubertal. Laboratory findings revealed high triglyceride, impaired glucose tolerance, hypogonadotropic hypogonadism, and grade-III fatty liver. He had bony spicule-like pigmentation in the periphery of both eyes suggestive of retinitis pigmentosa. Based on these data, BBS was diagnosed. In conclusion, BBS is a rare clinical syndrome that may go unnoticed by many clinicians. Renal failure is the leading cause of morbidity and mortality in patients with BBS. Therefore, early detection of BBS is vital to halt the progression of renal impairment.

Prenatal prediction of adverse outcome using different charts and definitions of fetal growth restriction.

Antenatal growth assessment using ultrasound aims to identify small fetuses that are at higher risk of perinatal morbidity and mortality. This study explored whether the association between suboptimal fetal growth and adverse perinatal outcome varies with different definitions of fetal growth restriction (FGR) and different weight charts/standards. This was a retrospective cohort study of 17 261 singleton non-anomalous pregnancies at ≥ 24 + 0 weeks' gestation that underwent routine ultrasound at a tertiary referral hospital. Estimated fetal weight (EFW) and Doppler indices were converted into percentiles using a reference standard (INTERGROWTH-21st (IG-21)) and various reference charts (Hadlock, Fetal Medicine Foundation (FMF) and Swedish). Test characteristics were assessed using the consensus definition, Society for Maternal-Fetal Medicine (SMFM) definition and Swedish criteria for FGR. Adverse perinatal outcome was defined as perinatal death, admission to the neonatal intensive care unit at term, 5-min Apgar score < 7 and therapeutic cooling for neonatal encephalopathy. The association between FGR according to each definition and adverse perinatal outcome was compared. Multivariate logistic regression analysis was used to test the strength of association between ultrasound parameters and adverse perinatal outcome. Ultrasound parameters were also tested for correlation. IG-21, Hadlock and FMF fetal size references classified as growth-restricted 1.5%, 3.6% and 4.6% of fetuses, respectively, using the consensus definition and 2.9%, 8.8% and 10.6% of fetuses, respectively, using the SMFM definition. The sensitivity of the definition/chart combinations for adverse perinatal outcome varied from 4.4% (consensus definition with IG-21 charts) to 13.2% (SMFM definition with FMF charts). Specificity varied from 89.4% (SMFM definition with FMF charts) to 98.6% (consensus definition with IG-21 charts). The consensus definition and Swedish criteria showed the highest specificity, positive predictive value and positive likelihood ratio in detecting adverse outcome, irrespective of the reference chart/standard used. Conversely, the SMFM definition had the highest sensitivity across all investigated growth charts. Low EFW, abnormal mean uterine artery pulsatility index (UtA-PI) and abnormal cerebroplacental ratio were significantly associated with adverse perinatal outcome and there was a positive correlation between the covariates. Multivariate logistic regression showed that UtA-PI > 95th percentile and EFW < 5th percentile were the only parameters consistently associated with adverse outcome, irrespective of the definitions or fetal growth chart/standard used. The apparent prevalence of FGR varies according to the definition and fetal size reference chart/standard used. Irrespective of the method of classification, the sensitivity for the identification of adverse perinatal outcome remains low. EFW, UtA-PI and fetal Doppler parameters are significant predictors of adverse perinatal outcome. As these indices are correlated with one other, a prediction algorithm is advocated to overcome the limitations of using these parameters in isolation. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Stride Velocity 95th Centile Detects Decline in Ambulatory Function Over Shorter Intervals than the 6-Minute Walk Test or North Star Ambulatory Assessment in Duchenne Muscular Dystrophy.

Stride Velocity 95th Centile (SV95C) is the first wearable device-derived clinical outcome assessment (COA) to receive European Medicines Agency (EMA) qualification as a primary endpoint in ambulant patients with Duchenne muscular dystrophy (DMD) aged ≥4 years. To compare SV95C-in its first-ever clinical trial application as a secondary endpoint-with established motor function COAs used in the trial (Four-Stair Climb [4SC] velocity, North Star Ambulatory Assessment [NSAA], and Six-Minute Walk Distance [6MWD]). SV95C was a secondary endpoint in a subset (n = 47) of participants in the SPITFIRE/WN40227 trial of taldefgrobep alfa, which was discontinued due to lack of clinical benefit. Participants in the ≤48-week SV95C sub-study were 6-11 years old and received corticosteroids for ≥6 months pre-treatment. Pearson correlations were used to compare SV95C with the other COAs. Responsiveness and changes over time were respectively assessed via standardized response means (SRMs) based on absolute changes and mixed models for repeated measures. SV95C change at Week 24 was -0.07 m/s, with limited variability (standard deviation: 0.16, n = 27). The SRM for SV95C indicated moderate responsiveness to clinical change at the earliest timepoint (Week 12, n = 46), while those of the other COAs did not indicate moderate responsiveness until Week 36 (6MWD, n = 33) or Week 48 (4SC velocity, n = 20; NSAA total score, n = 20). Baseline correlations between SV95C and other COAs were strong (r = 0.611-0.695). Correlations between SV95C change from baseline to Week 48 and changes in other COAs were moderate to strong (r = 0.443-0.678).∥. Overall, SV95C demonstrated sensitivity to ambulatory decline over short intervals, low variability, and correlation with established COAs. Although the negative trial precluded demonstration of SV95C's sensitivity to drug effect, these findings support the continued use of SV95C in DMD clinical trials.

Adverse perinatal outcomes are strongly associated with degree of abnormality in uterine artery Doppler pulsatility index.

To investigate the association between varying degrees of abnormality in the Doppler uterine artery pulsatility index (UtA-PI) and adverse perinatal outcome. This was a prospective study of women with a singleton, non-anomalous pregnancy in whom UtA-PI was measured universally in midpregnancy and who gave birth in Oxford University Hospitals, Oxford, UK, between 2016 and 2023. Relative risk ratios (RRR) for the primary outcomes of extended perinatal mortality and live birth with a severe small-for-gestational-age (SGA) neonate were calculated using multinomial logistic regression, for early preterm birth (before 34 + 0 weeks' gestation) and late preterm/term birth (at or after 34 + 0 weeks). Risks were also investigated for iatrogenic preterm birth and a composite adverse outcome before 34 + 0 weeks. Overall, 33 364 pregnancies were included in the analysis. Compared to those with a normal UtA-PI, the risk of extended perinatal mortality with delivery before 34 + 0 weeks was higher in women with UtA-PI ≥ 90th percentile (RRR, 4.7 (95% CI, 2.7-8.0); P < 0.001), but this was not demonstrated in births at or after 34 + 0 weeks. The risk of live birth with severe SGA was associated strongly with abnormal UtA-PI for early births (RRR, 26.0 (95% CI, 11.6-58.2); P < 0.001) and later births (RRR, 2.3 (95% CI, 1.8-2.9); P < 0.001). Women with raised UtA-PI were more likely to have an early iatrogenic birth (RRR, 7.8 (95% CI, 5.5-11.2); P < 0.001). For each outcome before 34 + 0 weeks and the composite outcome, the risk increased significantly in association with the degree of abnormality in the UtA-PI (from < 90th, 90-94th, 95-98th to ≥ 99th percentile) (Ptrend < 0.001). When using the 90th percentile as opposed to the 95th, there was a significant improvement in the overall predictive accuracy (as determined by the area under the receiver-operating-characteristics curve) for the composite adverse outcome (χ2 = 6.64, P = 0.01) and iatrogenic preterm birth (χ2 = 4.10, P = 0.04). Elevated UtA-PI is a key predictor of iatrogenic preterm birth, severe SGA and perinatal loss up to 34+0 weeks' gestation. The 90th percentile for UtA-PI should be used, and management should be tailored according to the degree of abnormality, as pregnancies with very raised UtA-PI measurement constitute a group at extreme risk of adverse outcome. © 2024 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

P090 Real-world data on immuno-modulation therapies and body mass index in children and young people with juvenile idiopathic arthritis

Abstract Background/Aims There is some evidence that children and young people (CYP) with Juvenile Idiopathic Arthritis (JIA) who are overweight/obese have less favourable disease control and treatment outcomes. The aim of this study was to investigate any association between BMI and total number of immune modulation therapies used in CYP with JIA. Methods This was a retrospective observational study at a tertiary paediatric rheumatology centre. Cross-sectional data was captured in April 2022 from CYP receiving immunomodulation therapies for JIA. Data on diagnosis, treatments and weight/height at last routine follow-up was included. BMI was calculated for each patient and centile assigned using Royal College of Paediatrics and Child Health electronic BMI charts as follows: BMI ≥85th to 94th centile - overweight, ≥95th centile - obese, as per population monitoring British 1990 growth reference (UK90). Results 187 CYP were identified and 180 included (seven were excluded due to missing BMI data). Baseline demographic, disease and treatment data are summarised in Table A. 67% were female. Median (interquartile range (IQR)) age in years at diagnosis and follow-up was 4.3 (2.7, 8) and 11.9 (8.5, 14.4) respectively. At follow-up, 41.1% of CYP were either obese or overweight. The median (IQR) number of total immunomodulation therapies per patient according to BMI categories were: under/normal weight 2 (1, 3); overweight 3 (2, 3) and obese 3 (2, 5). The median (IQR) years of follow-up in under/normal weight, overweight and obese groups were 4.77 (2, 8.74); 5.27 (1.86, 7) and 5.5 (3, 9.1) respectively. Conclusion CYP that were overweight/obese received more therapies compared to under/normal weight. The high proportion (41%) of CYP in this study who were either overweight or obese is similar to prevalence (44.2%) for children in year six at school in this region. Corticosteroid use and limited physical activity is associated with inadequate control of joint inflammation and increased BMI but this data was not collected and is an important limitation, in addition to cross-sectional and retrospective study design. The overweight/obese group had longer follow-up and may have accumulated more therapies. Future research to evaluate optimal dosing of immunomodulation in CYP with high BMI is warranted. Disclosure K. Hartley: Grants/research support; NIHR BRC Internship. S. Jandial: None. F. McErlane: None. E. Sen: None. S. Sampath: None.

Selection of prenatal screening with nuchal translucency > 95th centile and below 99th centile: a 4-year observational study with real-world data.

We sought to analyze the genetic outcomes of fetuses with nuchal translucency (NT) > 95th centile, and determine whether prenatal genetic counseling, chromosomal microarray analysis (CMA) or non-invasive prenatal testing (NIPT) are truly beneficial for the outcomes of fetuses with increased NT > 95th centile and below 99th centile. A total of 535 pregnant women were included in this study, with a fetal NT > 95th centile at 11-13+6weeks of gestation from January 2017 to December 2020. 324 pregnant women with fetal NT > 95th centile and below 99th centile combined with other risk factors and NT > 99th centile received prenatal diagnostic karyotype analysis and CMA, and 211 pregnant women with fetal isolated increased NT > 95th centile and below 99th centile were selected to carry out NIPT. A total of 211 pregnant women who underwent NIPT were included in the study, NIPT results showed that 8 high-risk cases were confirmed by prenatal diagnosis. Overall, the detection rate of NIPT was 3.79%. A total of 324 pregnant women with fetal NT > 95th centile and below 99th centile, along with other risk factors, and those with fetal NT > 99th centile, received karyotype analysis and CMA for prenatal diagnosis. Among them, a total of 73 genetic abnormalities were detected, including 45 cases of chromosomal aneuploidy, 7 cases of structural abnormalities, and 21 cases of copy number variations (CNVs) with a size of less than 10Mb. In addition, the 73 women with genetic abnormalities are divided into three groups based on the NT measurement (Group 1: Fetuses with NT > 95th centile and below 99th centile, Group 2: Fetuses with NT > 99th centile, and Group 3: Fetuses with NT > 99th centile). 13.11% (8/61) of pathogenic genetic abnormalities (6 chromosomal aneuploidy, 1 structural abnormality, and 1 likely pathogenic CNV) will be missed if genetic counseling and prenatal genetic testing were not conducted in fetuses with increased NT > 95th centile and below 99th centile combined with other risks. Pathogenic CNVs were the most common abnormalities in group 3, and one likely pathogenic CNV was detected in group 1 and group 3, respectively, and a total of 14 CNVs of unknown clinical significance (VOUS) were detected. Through this study, we demonstrated that the critical value of NT > 95th centile for invasive detection or NIPT. Invasive testing combined with CMA may be recommended for fetuses with NT > 95th centile and below 99th centile and with other risks. But when isolated NT > 95th centile and below 99th centile, NIPT would be appropriate.

Centiles for the shock index among injured children in the prehospital setting

ObjectiveThe shock index (SI), the ratio of heart rate to systolic blood pressure, is a clinical tool for assessing injury severity. Age-adjusted SI models may improve predictive value for injured children in the out-of-hospital setting. We sought to characterize the proportion of children in the prehospital setting with an abnormal SI using established criteria, describe the age-based distribution of SI among injured children, and determine prehospital interventions by SI. MethodsWe performed a multi-agency retrospective cross-sectional study of children (<18 years) in the prehospital setting with a scene encounter for suspected trauma and transported to the hospital between 2018 and 2022 using the National Emergency Medical Services (EMS) Information System datasets. Our exposure of interest was the first calculated SI. We identified the proportion of children with an abnormal SI when using the SI, pediatric age-adjusted (SIPA); and the pediatric SI (PSI) criteria. We developed and internally validated an age-based distributional model for the SI using generalized additive models for location, scale, and shape to describe the age-based distribution of the SI as a centile or Z-score. We evaluated EMS interventions (basic airway interventions, advanced airway interventions, cardiac interventions, vascular access, intravenous fluids, and vasopressor use) in relation to both the SIPA, PSI, and distributional SI values. ResultsWe analyzed 1,007,863 pediatric EMS trauma encounters (55.0% male, median age 13 years [IQR, 8–16 years]). The most common dispatch complaint was for traffic/transport related injury (32.9%). When using the PSI and SIPA, 13.1% and 16.3% were classified as having an abnormal SI, respectively. There were broad differences in the percentage of encounters classified as having an abnormal SI across the age range, varying from 5.1 to 22.8% for SIPA and 3.7–20.1% for PSI. The SIPA values ranged from the 75th to 95th centiles, while the PSI corresponded to an SI greater than the 90th centile, except in older children. The centile distribution for SI declined during early childhood and stabilized during adolescence and demonstrated a difference of <0.1% at cutoff values. An abnormal PSI, SIPA and higher SI centiles (>90th centile and >95th centiles) were associated with interventions related to basic and advanced airway management, cardiac procedures, vascular access, and provision of intravenous fluids occurred with greater frequency at higher SI centiles. Some procedures, including airway management and vascular access, had a smaller peak at lower (<10th) centiles. DiscussionWe describe the empiric distribution of the pediatric SI across the age range, which may overcome limitations of extant criteria in identifying patients with shock in the prehospital setting. Both high and low SI values were associated with important, potentially lifesaving EMS interventions. Future work may allow for more precise identification of children with significant injury using cutpoint analysis paired to outcome-based criteria. These may additionally be combined with other physiologic and mechanistic criteria to assist in triage decisions.

Comparison of Left Ventricular Stroke Volume in 2nd- and 3rd-Trimester Fetuses Measured by the Product of VTI and Aortic Annular Area With That Assessed by Simpson's Single-Plane Rule Using the STE Technique.

The aim of the study was to compare left ventricle stroke volume in healthy, eutrophic fetuses in the 2nd and 3rd trimesters evaluated using the velocity time integral and aortic annulus area with left ventricular stroke volume measured using Simpson's single-plane rule and to determine the discrepancy equation. The study included 354 fetuses. In each fetus, during the same examination, simultaneous assessment of stroke volume was performed by pulsed-wave Doppler using the product of the velocity time integral and aortic annulus area and by the fetalHQ® software using Simpson's single-plane rule. The Mann-Whitney U test was used to compare the "product-derived" stroke volume and stroke volume using fetalHQ® software values in the 2nd and 3rd trimesters separately. The agreement between the two methods were verified using Bland-Altman analysis. A linear regression model was used to obtain the discrepancy equation. In the 2nd trimester, the mean percentage difference between both the techniques showed that the stroke volume values determined using pulsed-wave Doppler were, on average, 88% higher than the stroke volume values determined using fetalHQ®. The upper limit of agreement between the compared techniques was approximately 146% and the lower limit of agreement was equal to 29.6%. In the 3rd trimester, the results indicated that the stroke volume values determined using pulsed-wave Doppler were, on average, 76% higher than the stroke volume values determined using fetalHQ®. The upper limit of agreement between the compared techniques was approximately 129% and the lower limit of agreement was 23%. Based on the results of the linear regression models, discrepancy formulas of the stroke volume values were obtained. The equations to calculate the predicted mean and standard deviations were used to compute the reference intervals for the mean, 5th and 95th centiles. The calculation of left ventricular stroke volume using pulsed Doppler has higher result in relation to stroke volume determined using Simpson's rule significantly. The aortic annulus area showed a higher correlation regarding stroke volume than the velocity time integral in both the 2nd and 3rd trimesters. Stroke volume increased with the increase in aortic annulus area, whereas the velocity time integral remained relatively constant. The retrospective analysis of the collected material enabled the determination of the discrepancy equation.