95th Centile Research Articles

BrainChart cortical thickness centile scores: a generalizable tool to detect age‐inappropriate cortical neurodegeneration in Alzheimer’s disease

AbstractBackgroundIdentifying age‐inappropriate cortical neurodegeneration on structural MRI is a key component of Alzheimer’s disease (AD) assessment. However, widely available reference standards that enable objective interpretation are lacking. BrainChart (www.BrainChart.io; https://github.com/BrainChart/Lifespan) calculates age and sex adjusted centile scores for structural MRI metrics using normative data from 101,457 participants across the lifecourse and can be applied across different datasets. We applied this approach to regional cortical thickness estimates and explored its utility in identifying patients with AD associated neurodegeneration.MethodsCross‐sectional BrainChart cortical thickness centile scores were calculated for 241 individuals with pathologically confirmed AD (median scan time prior to death 5.8 years), as well as 1432 cognitively normal participants (CN) from the NACC dataset. Area under the receiver operating characteristic curve (AUC) analyses were performed to identify the cortical regions that best identified patients with pathologically confirmed AD. This approach was then applied to 305 participants from the ADNI‐3 cohort, all of whom underwent clinical amyloid (florbetapir) PET and tau (flortaucipir) PET within 6 months of structural MRI (CN = 185; Mild Cognitive Impairment (MCI) = 95); AD = 26).ResultsThe top ten performing regions for differentiating pathologically confirmed AD from CN in the NACC dataset were entorhinal, middle temporal, inferior parietal, isthmus cingulate, fusiform, supramarginal, inferior temporal, superior temporal, precuneus and temporal pole. AUCs ranged from 0.72 – 0.77 (figure 1 and table 1). Combining these ten regions into a single model significantly improved diagnostic separability (AUC = 0.81, figure 1). Optimal cut‐points for individual regions ranged from the 25th centile to the 35th centile, with sensitivities ranging from 57.7% to 68.9%, and specificities ranging from 72.6% to 80.9%. Using progressively lower centile scores increased specificity but decreased sensitivity (table 1).In ADNI‐3 participants, a combined model of the same ten regions derived from the NACC dataset was able to discriminate amyloid and tau pet positive AD patients from amyloid and tau negative CN (AUC = 0.98), as well as amyloid and tau positive MCI patients from amyloid and tau negative CN (AUC = 0.85) (figure 2).ConclusionBrainChart age and sex adjusted cortical thickness centile scores, derived from an extensive normative dataset, represent a generalizable method for objectively identifying cortical neurodegeneration in AD.

BrainChart cortical thickness centile scores: a generalizable tool to detect age‐inappropriate cortical neurodegeneration in Alzheimer’s disease

AbstractBackgroundIdentifying age‐inappropriate cortical neurodegeneration on structural MRI is a key component of Alzheimer’s disease (AD) assessment. However, widely available reference standards that enable objective interpretation are lacking. BrainChart (www.BrainChart.io; https://github.com/BrainChart/Lifespan) calculates age and sex adjusted centile scores for structural MRI metrics using normative data from 101,457 participants across the lifecourse and can be applied across different datasets. We applied this approach to regional cortical thickness estimates and explored its utility in identifying patients with AD associated neurodegeneration.MethodCross‐sectional BrainChart cortical thickness centile scores were calculated for 241 individuals with pathologically confirmed AD (median scan time prior to death 5.8 years), as well as 1432 cognitively normal participants (CN) from the NACC dataset. Area under the receiver operating characteristic curve (AUC) analyses were performed to identify the cortical regions that best identified patients with pathologically confirmed AD. This approach was then applied to 305 participants from the ADNI‐3 cohort, all of whom underwent clinical amyloid (florbetapir) PET and tau (flortaucipir) PET within 6 months of structural MRI (CN = 185; Mild Cognitive Impairment (MCI) = 95); AD = 26).ResultThe top ten performing regions for differentiating pathologically confirmed AD from CN in the NACC dataset were entorhinal, middle temporal, inferior parietal, isthmus cingulate, fusiform, supramarginal, inferior temporal, superior temporal, precuneus and temporal pole. AUCs ranged from 0.72 – 0.77 (figure 1 and table 1). Combining these ten regions into a single model significantly improved diagnostic separability (AUC = 0.81, figure 1). Optimal cut‐points for individual regions ranged from the 25th centile to the 35th centile, with sensitivities ranging from 57.7% to 68.9%, and specificities ranging from 72.6% to 80.9%. Using progressively lower centile scores increased specificity but decreased sensitivity (table 1). In ADNI‐3 participants, a combined model of the same ten regions derived from the NACC dataset was able to discriminate amyloid and tau pet positive AD patients from amyloid and tau negative CN (AUC = 0.98), as well as amyloid and tau positive MCI patients from amyloid and tau negative CN (AUC = 0.85) (figure 2).ConclusionBrainChart age and sex adjusted cortical thickness centile scores, derived from an extensive normative dataset, represent a generalizable method for objectively identifying cortical neurodegeneration in AD.

Afferent venous perfusion of fetal liver: umbilical and portal blood-flow volumes in fetuses born small-for-gestational age.

To quantify the dynamic changes in the afferent venous flow volume of the liver in low-risk pregnancies with fetuses born small-for-gestational age. This was a prospective study of low-risk singleton pregnancies with estimated fetal weight (EFW) and birth weight ≤ 10th centile attending for a routine second- or third-trimester ultrasound examination. Their umbilical and portal blood-flow volumes were compared with those of a control group of fetuses born appropriate-for-gestational age from which normal reference ranges were constructed. Absolute and Z-score differences between the groups were assessed. In total, 133 fetuses were included in the study group and 362 in the control group. The mean umbilical blood-flow volume in the study group, both absolute and normalized per kg of EFW, was below that of the appropriate-for-gestational-age fetuses for most of the period of pregnancy studied (overall mean Z-score, -0.82 and -0.84, respectively). In contrast, the mean portal blood-flow volume, per kg of EFW, showed the opposite trend (overall mean Z-score, +0.86), reaching its maximum level (+1.43) in the late third trimester. This resulted in a steep decrease in the mean placental-to-portal-blood-flow volume ratio, from 14.4 at 24 weeks of gestation (above the 60th centile) to 4.7 at 38 weeks of gestation (15th centile), corresponding to Z-scores of +0.4 and -1.02, respectively. In fetuses born small-for-gestational age, the ratio of blood-flow volume in the umbilical vein to that in the portal vein decreases consistently during pregnancy, and to a greater extent compared with those born appropriate-for-gestational age, reaching a lower nadir in the third trimester. This additional redistribution of liver perfusion affects negatively fetal growth even in low-risk pregnancy, and should be taken into account when planning delivery. We suggest considering liver venous perfusion as an ancillary tool for monitoring small-for-gestational-age pregnancies. © 2023 International Society of Ultrasound in Obstetrics and Gynecology.

Weight growth velocity and growth outcomes in very-low-birth-weight infants developing major morbidities

BackgroundExtrauterine growth restriction (EUGR) is common in very-low-birth-weight-infants and may be associated with poor neurodevelopment. The growth velocity of preterm infants is increasing over decades, but the relationship between growth velocity, EUGR, and morbidities of preterm infants remains unknown. MethodsA total of 263 infants born between 2012 and 2020, with birthweight <1500 g and gestational age of 24–33 weeks, were included. Birthweight and weight on day of evaluation point (corrected gestational age 36 weeks or discharged, whenever comes first) were converted to age-specific and gender-specific Z-scores and analyzed by multivariable modeling. The average growth velocity was calculated by the exponential model. ResultsAverage growth velocity from birth to the evaluation point was 11.8 ± 0.3 g/kg/day. The maximum growth velocity from birth to week 8 postnatal occurred at week 4 postnatal (16.4 ± 0.9 g/kg/day). Infants with smaller birth weight, higher gestational age, and indication of intestinal surgery or those who need more days to achieve full enteral feeding were more favorable to have a weight lower than the 10th centile at the evaluation point. By contrast, most comorbidities of prematurity did not affect either lower age-specific weight Z-scores on the evaluation point or larger change in weight Z-score between birth and evaluation point. ConclusionEUGR was associated with gestational age and birth weight. Infants with moderate-to-severe bronchopulmonary dysplasia, high-grade intraventricular hemorrhage, or retinopathy of prematurity tend to have slower growth velocity at 3–5 weeks postnatal, but these did not contribute to EUGR.

Occurrence and dietary exposure to metals and pesticides in Citrus fruits: A probabilistic assessment of risk to health of Iranian consumers

The present study assessed the risk posed by simultaneous oral exposure to a mixture of 20 pesticides and seven metals in 405 Citrus fruit samples [(15 cultivars of orange, tangerine, grapefruit, lemon, and sweet lemon) × (3 zones of Iran) × (3 orchards in each zone) × (3 spots in each orchard)]. The levels of metals and pesticides in Citrus fruits were quantified by inductively coupled plasma-optical emission spectrometry (ICP-OES) and gas chromatography-mass spectrometry (GC-MS), respectively. Our probabilistic assessment indicated hazard index (HI) ˂1 at the 50th, 75th, and 95th centiles for oral exposure to non-carcinogenic metals (Al, Cd, Co, and Hg), revealing no major risk. Also, the incremental lifetime cancer risks (ILCRs) for As and Pb presented no carcinogenic risk at the three centiles, however, the ILCR ˃10−4 found for Ni at the 50th (3.00 ×10−4), 75th (4.30 ×10−4), and 95th (6.00 ×10−4) centiles identified a moderate risk. The HI values for organophosphorus compounds at the 50th, 75th, and 95th were 1.23, 2.12, and 3.04, respectively, indicated a moderate risk while for pyrethroids, no appreciable risk was found at any centiles.

Incidence and two-year neurodevelopmental outcomes of small-for-gestational-age preterm infants: how do they relate to using different neonatal anthropometric charts?

The effect of different neonatal anthropometric charts on the incidence and neurodevelopmental outcomes at two years (Y) corrected age of small-for-gestational-age (SGA) preterm infants has still not been fully explored. All preterm infants with a gestational age (GA) between 24.0 and 31.6 weeks (W), born from Jan-2004 to Dec-2017 in the Marche region (Italy) were studied. Intergrowth-21st, Beeby, Fenton, and Bertino anthropometric charts were used to classify infants with a birth weight less than 10th centile as SGA. Disabilities and neurodevelopmental scores assessed by Bayley-III Test were recorded at the 2Y follow-up visit. One thousand one hundred forty-seven preterm infants were evaluated. The incidence of SGA was significantly different among the study charts (from 12.9 to 17.5%). Nine hundred and twenty-seven study infants were assessed for neurodevelopmental outcomes at 2Y corrected age. The incidence of SGA with moderate cognitive impairment (COG Score: 70-84) and mild neurodevelopmental disability (NDD) were significantly different between the Intergrowth-21st and Bertino charts (31.7% vs. 19.6%, P=0.042; 30.8 vs. 19.2%, P=0.036; respectively). A statistically significant difference in COG Score was found between SGA preterm infants overlapping in all study charts and those classified as SGA only by the Intergrowth-21st chart (89.1±15.7 vs. 99.2±19.8; P=0.038). In a large cohort of preterm infants with a GA between 24.0 and 31.6W, the incidence and neurodevelopmental outcomes at 2Y corrected age of SGAs were significantly different depending on the anthropometric charts. These differences, albeit small, should be considered both in clinical practice and trials on SGA preterm infants.

Practice variation in timing of antenatal corticosteroid administration in early-onset fetal growth restriction: Asecondary analysis of the Dutch STRIDER study.

In early-onset fetal growth restriction the fetus fails to thrive in utero due to unmet fetal metabolic demands. This condition is linked to perinatal mortality and severe neonatal morbidity. Maternal administration of corticosteroids in high-risk pregnancies for preterm birth at a gestational age between 24 and 34 weeks has been shown to reduce perinatal mortality and morbidity. Practice variation exists in the timing of the administration of corticosteroids based on umbilical artery monitoring findings in early-onset fetal growth restriction. The aim of this study was to examine differences in neonatal outcomes when comparing different corticosteroid timing strategies. This was a post-hoc analysis of the Dutch STRIDER trial. We examined neonatal outcomes when comparing institutional strategies of early (umbilical artery pulsatility index >95th centile) and late (umbilical artery shows absent or reversed end-diastolic flow) administration of corticosteroids. The primary outcomes were neonatal mortality and a composite of neonatal mortality and neonatal morbidity, defined as bronchopulmonary dysplasia, intraventricular hemorrhage, necrotizing enterocolitis or retinopathy of prematurity. We also analyzed predictors for adverse neonatal outcomes, including gestational age at delivery, birthweight, maternal hypertensive disorders, and time interval between corticosteroids and birth. A total of 120 patients matched our inclusion criteria. In 69 (57.5%) the early strategy was applied and in 51 (42.5%) patients the late strategy. Median gestational age at delivery was 28 4/7 (± 3, 3/7) weeks. Median birthweight was 708 (± 304) g. Composite primary outcome was found in 57 (47.5%) neonates. No significant differences were observed in the primary outcome between the two strategies (neonatal mortality adjusted odds ratio [OR] 1.22, 95% CI 0.44-3.38; composite primary outcome adjusted OR 1.05, 95% CI 0.42-2.64). Only gestational age at delivery was a significant predictor for improved neonatal outcome (adjusted OR 0.91, 95% CI 0.86-0.96). No significant differences in neonatal outcomes were observed when comparing early and late strategy of antenatal corticosteroid administration on neonatal outcomes in pregnancies complicated by early-onset fetal growth restriction. We found no apparent risk contribution of interval between corticosteroid administration and delivery in multivariate analysis. Gestational age at delivery was found to be an important predictor of neonatal outcome.

Reference curves of motor function outcomes in young steroid-naïve males with Duchenne muscular dystrophy.

To investigate functional motor performance in a large cohort of young steroid-naïve males with Duchenne muscular dystrophy (DMD) and typically developing males, and to develop specific reference curves for both groups. Also, to describe associations between anthropometric values and functional motor outcomes. Cross-sectional data of 196 steroid-naïve males with DMD aged 4 to 8 years and 497 typically developing males aged 2 years 6 months to 8 years were included. Both groups were evaluated with the time to rise from the floor test, 10-metre walk/run test, 6-minute walk test, and North Star Ambulatory Assessment. Reference curves with centiles 5%, 10%, 25%, 50%, 75%, 90%, and 95% were estimated using quantile regression. Males with DMD scored significantly worse on all functional motor outcomes than age-matched typically developing males (p < 0.001): 89% to 95% of the males with DMD scored below the 5th centile of the typically developing males. No or weak correlations exist between anthropometric values and functional motor outcomes. The estimated reference curves can support consultation with families of young males with DMD and can support the evaluation of treatment for reaching motor skills and functional motor outcomes compared with typically developing males.

Cardiometabolic sex differences in adults born small for gestational age.

This study aimed to assess the cardiometabolic sex similarities and differences in adults born small for gestational age. This study was an ambispective cohort study from a birth registry in Barcelona, Spain, including 523 adult participants (20-40 years-old) subdivided as born small for gestational age (SGA, if birth weight <10th centile) or adequate fetal growth for gestational age (AGA). Cardiometabolic health was assessed by echocardiography, electrocardiogram, blood pressure measurement, vascular ultrasound, anthropometric measurements, and serum glycemia and lipid profile. Stratified analyses by sex were performed by estimation of adjusted absolute difference (AAD) using inverse probability weighting. Compared with AGA, the stratified analyses by sex showed a more pronounced reduction in ejection fraction [AAD: female -1.73 (95% CI -3.2 to -0.28) vs. male -1.33 (-3.19 to 0.52)] and increment in heart rate [female 3.04 (0.29-5.8) vs. male 2.25 (-0.82 to 5.31)] in SGA females compared with SGA males. In contrast, a more pronounced reduction in PR interval [female -1.36 (-6.15 to 3.42) vs. male -6.61 (-11.67 to -1.54)] and an increase in systolic blood pressure [female 0.06 (-2.7 to 2.81) vs. male 2.71 (-0.48 to 5.9)] and central-to-peripheral fat ratio [female 0.05 (-0.03 to 0.12) vs. male 0.40 (0.17-0.62)] were mainly observed in SGA male compared with SGA female. Sex differences were observed in the effect of SGA on cardiometabolic endpoints with female being more prone to cardiac dysfunction and male to electrocardiographic, vascular, and metabolic changes. Future research including sex-stratification data is warranted.

The role of the PLGF in the prediction of the outcome in pregnancies with a small for gestational age fetus.

To explore the value of measuring maternal serum PLGF in the prediction of the outcome of small for gestational age fetuses (SGA). Singleton pregnancies referred with suspicion of SGA in the third trimester were included if they had: no indication for nor signs of imminent delivery, fetal abdominal circumference (AC) at or below the 10th centile and/or estimated fetal weight (EFW) at or below the 10th centile and/or umbilical artery pulsatility index (Umb-PI) at or above the 90th centile for gestation. Women with pre-eclampsia at presentation were excluded. Maternal blood was drawn at the first (index) visit and analyzed retrospectively. Fifty-one fetuses were examined. Multiple regression analysis showed that family history of microsomia, index EFW and PLGF were significant predictors of the birthweight centile; index femur length centile and PLGF were significant predictors of pre-eclampsia; PLGF and index systolic blood pressure were significant predictors of iatrogenic preterm delivery < 37 weeks, whereas PLGF and index EFW were significant predictors of birthweight ≤ 5th centile and admission to the neonatal intensive care unit. For all outcomes, the addition of maternal-fetal parameters did not improve the prediction compared to PLGF alone. Using a cutoff of 0.3 MoM for PLGF would identify 94.1% of the pregnancies with iatrogenic preterm delivery and/or intra-uterine death and all of the cases that developed pre-eclampsia, for a screen positive rate of 54.9%. Women with PLGF ≤ 0.3 MoM had a poor fetal/maternal outcome (iatrogenic preterm delivery, pre-eclampsia, intra-uterine death) in 61.5% of cases. In pregnancies complicated by SGA, PLGF identifies a very high-risk group that may benefit from intense surveillance.

Gebeliğin birinci trimesterinde sistemik inflamatuar belirteçler ile yüksek uterin arter pulsatilite indeksi ilişkisi

Introduction: Preeclampsia is a serious complication of pregnancy leading to maternal and perinatal morbidity and mortality. The etiopathogenesis still remains unsolved, however, various theories currently become well-proved. The leading etiopathogenetic mechanisms are impaired placentation, and placental hypoxia, immune mechanisms, systemic inflammatory reaction, endothelial damage and maternal cardiovascular maladaptation. These mechanisms overlap and induce each other. There are some preventive interventions only if the patients at high-risk are identified timely. This study aimed to investigate the relationship between the inflammatory pathway and placental insufficiency in the first trimester, utilizing the clinical markers of both. It also aims to find out a cheap and easy test to identify those who absolutely need to undergo a comprehensive risk assessment. Methods: This retrospective observational study included 28 patients with high uterine artery resistance (pulsatility index &amp;gt;90th centile) in the first trimester as study group and 67 patients with normal uterine artery resistance in the first trimester as control group. The two groups were compared in terms of risk factors for preeclampsia. Neutrophil/lymphocyte ratio and platelet/lymphocyte ratio as systemic inflammatory markers were compared between the groups. ROC analysis was performed to obtain a cut-off value for predicting high uterine artery pulsatility index. Results: Demographic data, anamnestic and examination risk factors for preeclampsia did not differ between the groups. However, neutrophil/lymphocyte ratio and platelet/lymphocyte ratio were significantly higher in the patients with uterine artery pulsatility index above 90th centile. A cut off value of 3.58 and 136.9 of Neutrophil/lymphocyte ratio and platelet/lymphocyte ratio, respectively were determined for predicting first trimester uterine artery pulsatility index above 90th centile. Conclusions: Neutrophil/lymphocyte and platelet/lymphocyte ratio can simply be used to identify the patients who need referral for uterine artery doppler assessment. Keywords: preeclampsia, uterine artery, pulsatil flow, neutrophil, lymphocyte, placenta

Ultrasonographic cervical length screening at 20-24 weeks of gestation in twin pregnancies for prediction of spontaneous preterm birth: A 10-year Taiwanese cohort.

Shortened cervical length is one of the primary predictors for spontaneous preterm deliveries in twin pregnancies. However, there is lack of consensus regarding cut-off values. Recent evidence highlights that established cut-offs for cervical length screening might not always apply across different populations. This study aims to present the distribution of cervical length in Taiwanese twin pregnancies and to assess its predictive value for spontaneous preterm birth during mid-trimester screening. This retrospective analysis of cervical length screening in Taiwan evaluated 469 twin pregnancies between 20-24 weeks of gestation. Outcome data were obtained directly from the medical records of the delivery hospital. The study explored the predictive value of cervical length screening for spontaneous preterm birth and the characteristics of cervical length distribution in Taiwanese twin pregnancies. The average gestational age at screening was 22.7 weeks. Cervical length values displayed a non-normal distribution (p-value <0.001). The median, 5th and 95th centiles were 37.5 mm 25.1 mm, and 47.9 mm, respectively. Various cut-off values were assessed using different methods, yielding positive [negative] likelihood ratios for spontaneous preterm births between 32-37 weeks of gestational age (GA) (1.3-30.1 and [0.51-0.92]) and for very preterm births between 28-32 weeks GA (5.6-51.1 and [0.45-0.64]). The findings from our analysis of Taiwanese twin pregnancies uphold the moderate predictive potential of cervical length screening, consistent with prior investigations. The presented likelihood ratios for predicting preterm birth at different gestational ages equip clinicians with valuable tools to enhance their diagnostic rationale and resource utilization. By fine-tuning screening parameters according to the spontaneous preterm birth prevalence and clinical priorities of the particular population, healthcare providers can enhance patient care. Our data implies that a cervical length below 20 mm might provide an optimal balance between minimizing false negatives and managing false positives when predicting spontaneous preterm birth.

Clinical and genetic definition of serum bilirubin levels for the diagnosis of Gilbert syndrome and hypobilirubinemia.

Gilbert syndrome (GS) is genotypically predetermined by UGT1A1*28 homozygosity in Europeans and is phenotypically defined by hyperbilirubinemia using total bilirubin (TB) cutoff ≥1mg/dL (17μmol/L). The prevalence of illnesses associated with GS and hypobilirubinemia has never been studied prospectively. As TB varies with UGT1A1*28 genotyping, sex, and age, we propose stratified definitions of TB reference intervals and report the prevalence of illnesses and adjusted 15 years survival. UK Biobank with apparently healthy liver participants (middle-aged, n=138,125) were analyzed after the exclusion of of nonhealthy individuals. The stratified TB was classified as GS when TB >90th centile; <10th centile indicated hypobilirubinemia, and between the 10th and 90th centile was normobilirubinemia. We compared the prevalence and survival rates of 54 illnesses using odds ratio (OR), logistic regression, and Cox models adjusted for confounders, and causality by Mendelian randomizations. In women, we identified 10% (7,741/76,809) of GS versus 3.7% (2,819/76,809) using the historical cutoff of ≥1mg/dL (P<0.0001). When GS and hypobilirubinemia participants were compared with normobilirubinemia, after adjustment and Mendelian randomizations, only cholelithiasis prevalence was significantly higher (OR=1.50; 95% CI [1.3-1.7], P=0.001) in men with GS compared with normobilirubinemia and in causal association with bilirubin (P=0.04). No adjusted survival was significantly associated with GS or hypobilirubinemia. In middle-aged Europeans, the stratified TB demonstrates a careless GS underestimation in women when using the standard unisex 1mg/dL cutoff. The prevalence of illnesses is different in GS and hypobilirubinemia as well as survivals before adjusting for confounding factors. With the exception of cholelithiasis in men, these differences were no more significant after adjustment and Mendelian randomization.

EP20.04: How “short” is “short femur length”: 2.5th or 5th centile at 16–24 weeks of gestation?

EP20.04: How “short” is “short femur length”: 2.5th or 5th centile at 16–24 weeks of gestation?

Establishment of reference intervals for ultrasonographically derived caudal vena cava parameters from 110 healthy, lightly sedated cats

Objectives The present study aimed to establish reference intervals (RIs) for ultrasonographically derived caudal vena cava (CVC) parameters in healthy cats. Methods A prospective, observational, experimental single-centre study involving 110 cats was conducted. Two trained operators scanned all cats in a randomised order. Two sets of cine loops per cat were conducted by each operator from the subxiphoid view with cats in lateral recumbency. Two blinded raters measured the narrowest inspiratory (CVCinsp) and widest expiratory (CVCexp) diameter over two separate respiratory cycles for each operator (four measurements in total for each rater) at the point the CVC crosses the diaphragm. The CVC collapsibility index (CVCCI) was calculated. Reference intervals and limits were calculated for CVC parameters with outliers removed to include the central 95% of CVC values and the non-parametric 90% confidence intervals (90% CIs). The CVCCI interval included the central 95th (2.5th and 97.5th) centiles bounded by the 90% CI. Intra- and inter-rater and intra- and inter-operator reliabilities were calculated for each parameter using a two-way random-effects model. A Bland–Altman plot was used to visualise the CVCCI between the two raters. Results In total, 880 measurements were included for each diameter and 440 CVCCI values were calculated. The CVC diameters were normally distributed, whereas the CVCCI was not. The calculated RIs were 1.4–6.1 mm for CVCinsp and 2.2–6.7 mm for CVCexp. The median (range) CVCCI was 23% (11–36%) with 2.5th and 97.5th centiles of 2% and 67%, respectively. There was a moderate to good intra-rater and intra-operator reliability for CVC diameter. The intra-rater reliability for the CVCCI was moderate. The inter-rater and inter-operator reliabilities for the CVCCI were poor. Conclusions and relevance The CVC RIs determined from the subxiphoid site in cats appear to be wider than those reported in dogs, and rater and operator variability is present. Whether precise measurements of CVC parameters are suitable to guide clinical decisions remains to be determined.

Abdominal circumference growth velocity as a predictor of adverse perinatal outcomes in small-for-gestational-age fetuses

Objective To assess the predictive value of abdominal circumference growth velocity (ACGV) between the second and third trimesters to predict adverse perinatal outcomes in a cohort of small-for-gestational-age fetuses without evidence of placental insufficiency (i.e. fetal growth restriction). Material and methods This is a single-center retrospective cohort study of all singleton pregnancies with small-for-gestational-age fetuses diagnosed and delivered at a quaternary institution. Crude and adjusted odds ratios (ORs) and corresponding confidence intervals (CIs) were calculated via logistic regression models to assess the potential association between abnormal ACGV (i.e. ≤10th centile) and adverse perinatal outcomes defined as a composite outcome (i.e. umbilical artery pH <7.1, 5-min Apgar score <7, admission to the neonatal intensive care unit, hypoglycemia, intrapartum fetal distress requiring expedited delivery, and perinatal death). Furthermore, the area under the receiver-operating characteristic curve (AUC) of three logistic regression models based on estimated fetal weight and ACGV for predicting the composite outcome is also reported. Results A total of 154 pregnancies were included for analysis. The median birthweight for the cohort was 2,437 g (interquartile range [IQR] 2280, 2635). Overall, the primary composite outcome was relatively common (29.2%). In addition, there was a significant association between abnormal ACGV and adverse perinatal outcomes (OR 3.37, 95% CI 1.60, 7.13; adjusted OR 4.30, 95% CI 1.77, 10.49). Likewise, the AUC for the ACGV was marginally higher (0.64) than the estimated fetal weight (0.54) and ACGV + estimated fetal weight (0.54). Still, no significant difference was detected between the curves (p = 0.297). Conclusions Our results suggest that an ACGV below the 10th centile is a risk factor for adverse perinatal outcomes among small-for-gestational-age fetuses.

Cross-sectional observational study on correlation of obesity and overweight in children with insulin resistance based on HOMA-IR score

With improvements in lifestyle and healthcare throughout the world, there has been an increasing incidence of obesity among adults and children. It is important that obesity and its adverse effects be recognized in childhood and measures be taken right from childhood to tackle the long-term outcomes of the same. We have studied the correlation of scores like Homeostasis Model Assessment-Insulin Resistance (HOMA-IR) and its relation with Insulin resistance in children. Which helps as a tool in early recognition of lifestyle diseases in children. It was seen that of a total of 50 children of which 40 children were obese (BMI greater than 95th centile) and 10 children were overweight (BMI greater than 85th centile), 43 children had insulin resistance based on HOMA-IR score (cut-off=2.5) and 7 were non-insulin resistant. From our study, it has been concluded that HOMA-IR has a strong correlation with BMI and can be used as a surrogate marker of Insulin resistance.

Do neonatal birth weight thresholds for labor dystocia outcomes differ between short and normal stature women?

To determine if there is a correlation between maternal short stature and neonatal birth weight among women with adverse outcomes related to labor dystocia. The medical records of singleton deliveries with adverse obstetric outcomes related to labor dystocia during 2014-2020, in a single tertiary center, were reviewed. Outcomes included at least one of the following: cesarean delivery (CD) due to cephalopelvic disproportion (CPD), prolonged second stage, shoulder dystocia, third- or fourth-degree perineal tear. Maternal short stature was defined as height below the 10th centile (short stature group) and normal stature was defined as maternal height between the 10th and 90th centiles (normal stature group). Maternal and neonatal characteristics were compared between the groups. A total of 3295 women were included, among them, 307 in the short stature group (9.3%, height 1.52 ± 0.02 m) and 2988 in the normal stature group (90.7%, height 1.63 ± 0.04 m). Evaluating the entire cohort revealed similar neonatal birth weights comparing the short and normal stature groups. A subgroup analysis of women after CD due to CPD (n = 296) revealed lower neonatal birth weights in the short stature group (n = 31) compared with the normal stature group (n = 265) (3215 ± 411 vs 3484 ± 427 g, P = 0.001, respectively). Multivariable linear regression was performed for women who underwent CD due to CPD. After adjusting for obesity and diabetes mellitus, short stature and nulliparity were found to be independently associated with decreased neonatal birth weight (266 g less for short stature, P = 0.001, and 294 g less for nulliparity, P = 0.001). Among women with short stature, CD due to CPD occurs at lower neonatal birth weights.

A Flexible Regression Modeling Approach Applied to Observational Laboratory Virological Data Suggests That SARS-CoV-2 Load in Upper Respiratory Tract Samples Changes with COVID-19 Epidemiology.

(1) Background. Exploring the evolution of SARS-CoV-2 load and clearance from the upper respiratory tract samples is important to improving COVID-19 control. Data were collected retrospectively from a laboratory dataset on SARS-CoV-2 load quantified in leftover nasal pharyngeal swabs (NPSs) collected from symptomatic/asymptomatic individuals who tested positive to SARS-CoV-2 RNA detection in the framework of testing activities for diagnostic/screening purpose during the 2020 and 2021 winter epidemic waves. (2) Methods. A Statistical approach (quantile regression and survival models for interval-censored data), novel for this kind of data, was applied. We included in the analysis SARS-CoV-2-positive adults >18 years old for whom at least two serial NPSs were collected. A total of 262 SARS-CoV-2-positive individuals and 784 NPSs were included: 193 (593 NPSs) during the 2020 winter wave (before COVID-19 vaccine introduction) and 69 (191 NPSs) during the 2021 winter wave (all COVID-19 vaccinated). We estimated the trend of the median value, as well as the 25th and 75th centiles of the viral load, from the index episode (i.e., first SARS-CoV-2-positive test) until the sixth week (2020 wave) and the third week (2021 wave). Interval censoring methods were used to evaluate the time to SARS-CoV-2 clearance (defined as Ct < 35). (3) Results. At the index episode, the median value of viral load in the 2021 winter wave was 6.25 log copies/mL (95% CI: 5.50-6.70), and the median value in the 2020 winter wave was 5.42 log copies/mL (95% CI: 4.95-5.90). In contrast, 14 days after the index episode, the median value of viral load was 3.40 log copies/mL (95% CI: 3.26-3.54) for individuals during the 2020 winter wave and 2.93 Log copies/mL (95% CI: 2.80-3.19) for those of the 2021 winter wave. A significant difference in viral load shapes was observed among age classes (p = 0.0302) and between symptomatic and asymptomatic participants (p = 0.0187) for the first wave only; the median viral load value is higher at the day of episode index for the youngest (18-39 years) as compared to the older (40-64 years and >64 years) individuals. In the 2021 epidemic, the estimated proportion of individuals who can be considered infectious (Ct < 35) was approximately half that of the 2020 wave. (4) Conclusions. In case of the emergence of new SARS-CoV-2 variants, the application of these statistical methods to the analysis of virological laboratory data may provide evidence with which to inform and promptly support public health decision-makers in the modification of COVID-19 control measures.

Efficiency of the Cerebroplacental Ratio in Identifying High-Risk Late-Term Pregnancies.

Background and Objectives: Over the last few years, great interest has arisen in the role of the cerebroplacental ratio (CPR) to identify low-risk pregnancies at higher risk of adverse pregnancy outcomes. This study aimed to assess the predictive capacity of the CPR for adverse perinatal outcomes in all uncomplicated singleton pregnancies attending an appointment at 40-42 weeks. Materials and Methods: This is a retrospective cohort study including all consecutive singleton pregnancies undergoing a routine prenatal care appointment after 40 weeks in three maternity units in Spain and the United Kingdom from January 2017 to December 2019. The primary outcome was adverse perinatal outcomes defined as stillbirth or neonatal death, cesarean section or instrumental delivery due to fetal distress during labor, umbilical arterial cord blood pH < 7.0, umbilical venous cord blood pH < 7.1, Apgar score at 5 min < 7, and admission to the neonatal unit. Logistic mixed models and ROC curve analyses were used to analyze the data. Results: A total of 3143 pregnancies were analyzed, including 537 (17.1%) with an adverse perinatal outcome. Maternal age (odds ratio (OR) 1.03, 95% confidence interval (CI) 1.01 to 1.04), body mass index (OR 1.04, 95% CI 1.03 to 1.06), racial origin (OR 2.80, 95% CI 1.90 to 4.12), parity (OR 0.36, 95% CI 0.29 to 0.45), and labor induction (OR 1.79, 95% CI 1.36 to 2.35) were significant predictors of adverse perinatal outcomes with an area under the ROC curve of 0.743 (95% CI 0.720 to 0.766). The addition of the CPR to the previous model did not improve performance. Additionally, the CPR alone achieved a detection rate of only 11.9% (95% CI 9.3 to 15) when using the 10th centile as the screen-positive cutoff. Conclusions: Our data on late-term unselected pregnancies suggest that the CPR is a poor predictor of adverse perinatal outcomes.