Climate change exacerbates the environmental impacts of agriculture.

Agriculture's global environmental impacts are widely expected to continue expanding, driven by population and economic growth and dietary changes. This Review highlights climate change as an additional amplifier of agriculture's environmental impacts, by reducing agricultural productivity, reducing the efficacy of agrochemicals, increasing soil erosion, accelerating the growth and expanding the range of crop diseases and pests, and increasing land clearing. We identify multiple pathways through which climate change intensifies agricultural greenhouse gas emissions, creating a potentially powerful climate change-reinforcing feedback loop. The challenges raised by climate change underscore the urgent need to transition to sustainable, climate-resilient agricultural systems. This requires investments that both accelerate adoption of proven solutions that provide multiple benefits, and that discover and scale new beneficial processes and food products.

Pathogenic variants in KMT2C result in a neurodevelopmental disorder distinct from Kleefstra and Kabuki syndromes.

Trithorax-related H3K4 methyltransferases, KMT2C and KMT2D, are critical epigenetic modifiers. Haploinsufficiency of KMT2C was only recently recognized as a cause of neurodevelopmental disorder (NDD), so the clinical and molecular spectrums of the KMT2C-related NDD (now designated as Kleefstra syndrome 2) are largely unknown. We ascertained 98 individuals with rare KMT2C variants, including 75 with protein-truncating variants (PTVs). Notably, ∼15% of KMT2C PTVs were inherited. Although the most highly expressed KMT2C transcript consists of only the last four exons, pathogenic PTVs were found in almost all the exons of this large gene. KMT2C variant interpretation can be challenging due to segmental duplications and clonal hematopoesis-induced artifacts. Using samples from 27 affected individuals, divided into discovery and validation cohorts, we generated a moderate strength disorder-specific KMT2C DNA methylation (DNAm) signature and demonstrate its utility in classifying non-truncating variants. Based on 81 individuals with pathogenic/likely pathogenic variants, we demonstrate that the KMT2C-related NDD is characterized by developmental delay, intellectual disability, behavioral and psychiatric problems, hypotonia, seizures, short stature, and other comorbidities. The facial module of PhenoScore, applied to photographs of 34 affected individuals, reveals that the KMT2C-related facial gestalt is significantly different from the general NDD population. Finally, using PhenoScore and DNAm signatures, we demonstrate that the KMT2C-related NDD is clinically and epigenetically distinct from Kleefstra and Kabuki syndromes. Overall, we define the clinical features, molecular spectrum, and DNAm signature of the KMT2C-related NDD and demonstrate they are distinct from Kleefstra and Kabuki syndromes highlighting the need to rename this condition.

LINE1-mediated epigenetic repression of androgen receptor transcription causes androgen insensitivity syndrome.

Androgen insensitivity syndrome (AIS) is a difference of sex development (DSD) characterized by different degrees of undervirilization in individuals with a 46,XY karyotype despite normal to high gonadal testosterone production. Classically, AIS is explained by hemizygous mutations in the X-chromosomal androgen receptor (AR) gene. Nevertheless, the majority of individuals with clinically diagnosed AIS do not carry an AR gene mutation. Here, we present a patient with a 46,XY karyotype, born with undervirilized genitalia, age-appropriate testosterone levels and no uterus, characteristic for AIS. Diagnostic whole exome sequencing (WES) showed a maternally inherited LINE1 (L1) retrotransposon insertion in the 5' untranslated region (5'UTR) of the AR gene. Long-read nanopore sequencing confirmed this as an insertion of a truncated L1 element of ≈ 2.7 kb and showed an increased DNA methylation at the L1 insertion site in patient-derived genital skin fibroblasts (GSFs) compared to healthy controls. The insertion coincided with reduced AR transcript and protein levels in patient-derived GSFs confirming the clinical diagnosis AIS. Our results underline the relevance of retrotransposons in human disease, and expand the growing list of human diseases associated with them.

Timing of magnetic resonance imaging in pregnancy for outcome prediction in congenital diaphragmatic hernia.

PURPOSE: To evaluate the impact of the timing of MRI on the prediction of survival and morbidity in patients with CDH, and whether serial measurements have a beneficial value. METHODS: This retrospective cohort study was conducted in two perinatal centers, in Germany and Italy. It included 354 patients with isolated CDH having at least one fetal MRI. The severity was assessed with the observed-to-expected total fetal lung volume (o/e TFLV) measured by two experienced double-blinded operators. The cohort was divided into three groups according to the gestational age (GA) at which the MRI was performed (< 27, 27-32, and > 32 weeks' gestation [WG]). The accuracy for the prediction of survival at discharge and morbidity was analyzed with receiver operating characteristic (ROC) curves. Multiple logistic regression analyses and propensity score matching examined the population for balance. The effect of repeated MRI was evaluated in ninety-seven cases. RESULTS: There were no significant differences in the prediction of survival when the o/e TFLV was measured before 27, between 27 and 32, and after 32 WG (area under the curve [AUC]: 0.77, 0.79, and 0.77, respectively). After adjustment for confounding factors, it was seen, that GA at MRI was not associated with survival at discharge, but the risk of mortality was higher with an intrathoracic liver position (adjusted odds ratio [aOR]: 0.30, 95% confidence interval [95%CI] 0.12-0.78), lower GA at birth (aOR 1.48, 95%CI 1.24-1.78) and lower o/e TFLV (aOR 1.13, 95%CI 1.06-1.20). ROC curves showed comparable prediction accuracy for the different timepoints in pregnancy for pulmonary hypertension, the need of extracorporeal membrane oxygenation, and feeding aids. Serial measurements revealed no difference in change rate of the o/e TFLV according to survival. CONCLUSION: The timing of MRI does not affect the prediction of survival rate or morbidity as the o/e TFLV does not change during pregnancy. Clinicians could choose any gestational age starting mid second trimester for the assessment of severity and counseling.

Maternal and fetal outcomes after planned cesarean or vaginal delivery in twin pregnancy: a comparison between 2 third level birth centers.

BACKGROUND: Twin pregnancy is associated with higher risks of adverse perinatal outcomes for both the mother and the babies. Among the many challenges in the follow-up of twin pregnancies, the mode of delivery is the last but not the least decision to be made, with the main influencing factors being amnionicity and fetal presentation. The aim of the study was to compare perinatal outcomes in two European centers using different protocols for twin birth in case of non-cephalic second twin; the Italian patients being delivered mainly by cesarean section with those in Belgium being routinely offered the choice of vaginal delivery (VD). METHODS: This was a dual center international retrospective observational study. The population included 843 women with a twin pregnancy ≥ 32 weeks (dichorionic or monochorionic diamniotic pregnancies) and a known pregnancy outcome. The population was stratified according to chorionicity. Demographic and pregnancy data were reported per pregnancy, whereas neonatal outcomes were reported per fetus. We used multiple logistic regression models to adjust for possible confounding variables and to compute the adjusted odds ratio (adjOR) for each maternal or neonatal outcome. RESULTS: The observed rate of cesarean delivery was significantly higher in the Italian cohort: 85% for dichorionic pregnancies and 94.4% for the monochorionic vs 45.2% and 54.4% respectively in the Belgian center (p-value < 0.001). We found that Belgian cohort showed significantly higher rates of NICU admission, respiratory distress at birth and Apgar score of < 7 after 5 min. Despite these differences, the composite severe adverse outcome was similar between the two groups. CONCLUSION: In this study, neither the presentation of the second twin nor the chorionicity affected maternal and severe neonatal outcomes, regardless of the mode of delivery in two tertiary care centers, but VD was associated to a poorer short-term neonatal outcome.

Biallelic variants in CSMD1 are implicated in a neurodevelopmental disorder with intellectual disability and variable cortical malformations.

CSMD1 (Cub and Sushi Multiple Domains 1) is a well-recognized regulator of the complement cascade, an important component of the innate immune response. CSMD1 is highly expressed in the central nervous system (CNS) where emergent functions of the complement pathway modulate neural development and synaptic activity. While a genetic risk factor for neuropsychiatric disorders, the role of CSMD1 in neurodevelopmental disorders is unclear. Through international variant sharing, we identified inherited biallelic CSMD1 variants in eight individuals from six families of diverse ancestry who present with global developmental delay, intellectual disability, microcephaly, and polymicrogyria. We modeled CSMD1 loss-of-function (LOF) pathogenesis in early-stage forebrain organoids differentiated from CSMD1 knockout human embryonic stem cells (hESCs). We show that CSMD1 is necessary for neuroepithelial cytoarchitecture and synchronous differentiation. In summary, we identified a critical role for CSMD1 in brain development and biallelic CSMD1 variants as the molecular basis of a previously undefined neurodevelopmental disorder.

Cell-free DNA screening for common autosomal trisomies using rolling-circle replication in twin pregnancies.

OBJECTIVE: To evaluate the performance of prenatal screening for common autosomal trisomies in twin pregnancies through the use of rolling-circle replication (RCR)-cfDNA as a first-tier test. METHOD: Prospective multicenter study. Women who underwent prenatal screening for trisomy (T) 21, 18 and 13 between January 2019 and March 2022 in twin pregnancies were included. Patients were included in two centers. The primary endpoint was the rate of no-call results in women who received prenatal screening for common autosomal trisomies by RCR-cfDNA at the first attempt, compared to that in prospectively collected samples from 16,382 singleton pregnancies. The secondary endpoints were the performance indices of the RCR-cfDNA. RESULTS: 862 twin pregnancies underwent screening for T21, T18 and T13 by RCR-cfDNA testing at 10-33 weeks' gestation. The RCR-cfDNA tests provided a no-call result from the first sample obtained from the patients in 107 (0.7%) singleton and 17 (2.0%) twin pregnancies. Multivariable regression analysis demonstrated that significant independent predictors of test failure were twin pregnancy and in vitro fertilization conception. All cases of T21 (n = 20/862; 2.3%), T18 (n = 4/862; 0.5%) and T13 (n = 1/862; 0.1%) were correctly detected by RCR-cfDNA (respectively, 20, 4 and 1 cases). Sensitivity was 100% (95% CI, 83.1%-100%), 100% (95% CI 39.8%-100%) and 100% (95% CI 2.5%-100%) for T21, T18 and T13, respectively, in twin pregnancies. CONCLUSION: The RCR-cfDNA test appears to have good accuracy with a low rate of no-call results in a cohort of twin pregnancies for the detection of the most frequent autosomal trisomies.

A simulation study to assess the potential benefits of MRI-based fetal weight estimation as a second-line test for suspected macrosomia.

OBJECTIVE: To simulate the outcomes of Boulvain's trial by using magnetic resonance imaging (MRI) for estimated fetal weight (EFW) as a second-line confirmatory imaging. STUDY DESIGN: Data derived from the Boulvain's trial and the study PREMACRO (PREdict MACROsomia) were used to simulate a 1000-patient trial. Boulvain's trial compared induction of labor (IOL) to expectant management in suspected macrosomia, whereas PREMACRO study compared the performance of ultrasound-EFW (US-EFW) and MRI-EFW in the prediction of birthweight. The primary outcome was the incidence of significant shoulder dystocia (SD). Cesarean delivery (CD), hyperbilirubinemia (HB), and IOL at < 39 weeks of gestation (WG) were selected as secondary outcomes. A subgroup analysis of the Boulvain's trial was performed to estimate the incidence of the primary and secondary outcomes in the true positive and false positive groups for the two study arms. Sensitivity, specificity, positive and negative predictive values (PPV, NPV) for the prediction of macrosomia by MRI-EFW at 36 WG were calculated, and a decision tree was constructed for each outcome. RESULTS: The PPV of US-EFW for the prediction of macrosomia in the PREMACRO trial was 56.3 %. MRI-EFW was superior to US-EFW as a predictive tool resulting in lower rates of induction for false-positive cases. Repeating Boulvain's trial using MRI-EFW as a second-line test would result in similar rates of SD (relative risk [RR]:0.36), CD (RR:0.84), and neonatal HB (RR:2.6), as in the original trial. Increasing the sensitivity and specificity of MRI-EFW resulted in a similar relative risk for SD as in Boulvain's trial, but with reduced rates of IOL < 39 WG, and improved the RR of CD in favor of IOL. We found an inverse relationship between IOL rate and incidence of SD for both US-EFW and MRI-EFW, although overall rates of IOL, CD, and neonatal HB would be lower with MRI-derived estimates of fetal weight. CONCLUSION: The superior accuracy of MRI-EFW over US-EFW for the diagnosis of macrosomia could result in lower rates of IOL without compromising the relative advantages of the intervention but fails to demonstrate a significant benefit to justify a replication of the original trial using MRI-EFW as a second-line test.

Postmortem imaging of fetuses at early gestations: A comparison of microfocus computed tomography with postmortem magnetic resonance at 9.4 T and postmortem ultrasound.

OBJECTIVE: To compare the diagnostic performance of postmortem ultrasound (PMUS), 9.4 T magnetic resonance imaging (MRI) and microfocus computed tomography (micro-CT) for the examination of early gestation fetuses. METHOD: Eight unselected fetuses (10-15 weeks gestational age) underwent at least 2 of the 3 listed imaging examinations. Six fetuses underwent 9.4 T MRI, four underwent micro-CT and six underwent PMUS. All operators were blinded to clinical history. All imaging was reported according to a prespecified template assessing 36 anatomical structures, later grouped into five regions: brain, thorax, heart, abdomen and genito-urinary. RESULTS: More anatomical structures were seen on 9.4 T MRI and micro-CT than with PMUS, with a combined frequency of identified structures of 91.9% and 69.7% versus 54.5% and 59.6 (p < 0.001; p < 0.05) respectively according to comparison groups. In comparison with 9.4 T MRI, more structures were seen on micro-CT (90.2% vs. 83.3%, p < 0.05). Anatomical structures were described as abnormal on PMUS in 2.7%, 9.4 T MRI in 6.1% and micro-CT 7.7% of all structures observed. However, the accuracy test could not be calculated because conventional autopsy was performed on 6 fetuses of that only one structure was abnormal. CONCLUSION: Micro-CT appears to offer the greatest potential as an imaging adjunct or non-invasive alternative for conventional autopsies in early gestation fetuses.

Assessment of whole-body MRI including diffusion-weighted sequences in the initial staging of breast cancer patients at high risk of metastases in comparison with PET-CT: a prospective cohort study.

OBJECTIVE: The aim of this study was to assess the diffusion-weighted whole-body-MRI (WBMRI) in the initial staging of breast cancer at high risk of metastases in comparison with positron emission tomography (PET)-CT. METHODS: Forty-five women were prospectively enrolled. The inclusion criteria were female gender, age >18, invasive breast cancer, an initial PET-CT, and a performance status of 0-2. The exclusion criteria were contraindication to WB-MRI and breast cancer recurrence. The primary outcome was the concordance of WB-MRI and PET-CT in the diagnosis of distant metastases, whereas secondary outcomes included their concordance for the primary tumor and regional lymph nodes (LN), as well as the agreement of WB-MRI interpretation between two radiologists. RESULTS: The mean age was 51.2 years with a median size of the primary tumor of 30 mm. Concordance between the two modalities was almost perfect for metastases staging, all sites included (k = 0.862), with excellent interobserver agreement. The accuracy of WB-MRI for detecting regional LN, distant LN, lung, liver, or bone metastases ranged from 91 to 96%. In 2 patients, WB-MRI detected bone metastases that were overlooked by PET-CT. WB-MRI showed a substantial agreement with PET-CT for staging the primary tumor, regional LN status, and stage (k = 0.766, k = 0.756, and k = 0.785, respectively) with a high interobserver agreement. CONCLUSION: WB-MRI including DWI could be a reliable and reproducible examination in the initial staging of breast cancer patients at high risk of metastases, especially for bone metastases and therefore could be used as a surrogate to PET-CT. CLINICAL RELEVANCE STATEMENT: Whole-body-MRI including DWI is a promising technique for detecting metastases in the initial staging of breast cancer at high risk of metastases. KEY POINTS: Whole-body-MRI (WB-MRI) was effective for detecting metastases in the initial staging of 45 breast cancer patients at high risk of metastases in comparison with PET-CT. Concordance between WB-MRI and PET-CT was almost perfect for metastases staging, all sites included, with excellent interobserver agreement. The accuracy of WB-MRI for detecting bone metastases was 92%.

Fetoscopic endoluminal tracheal occlusion vs expectant management for fetuses with severe left-sided congenital diaphragmatic hernia.

BACKGROUND: The treatment of fetuses with a congenital diaphragmatic hernia is challenging, but there is evidence that fetoscopic endoluminal tracheal occlusion has a benefit over expectant care. In addition, standardization and expertism have a great impact on survival and are probably crucial in centers that rely on expectant management with extracorporeal membrane oxygenation after birth. OBJECTIVE: This study aimed to examine the survival and morbidity rates of fetuses with a severe isolated left-sided congenital diaphragmatic hernia who underwent fetoscopic endoluminal tracheal occlusion vs expectant management in high-volume centers. STUDY DESIGN: This was a multicenter, retrospective study that included all consecutive fetuses with severe isolated left-sided congenital diaphragmatic hernia who were expectantly managed in a German center or who underwent fetoscopic endoluminal tracheal occlusion in 3 other European centers (Belgium, France, and Italy). Severe congenital diaphragmatic hernia was defined as having an observed to expected total fetal lung volume ≤35% with intrathoracic position of the liver diagnosed with magnetic resonance imaging. All magnetic resonance images were centralized, and lung volumes were measured by 2 experienced operators who were blinded to the pre- and postnatal data. Multiple logistic regression analyses were performed to examine the effect of the management strategy in the 2 groups on the short- and long-term outcomes. RESULTS: A total of 147 patients who were managed expectantly and 47 patients who underwent fetoscopic endoluminal tracheal occlusion were analyzed. Fetuses who were managed expectantly had lower observed to expected total fetal lung volumes (20.6%±7.5% vs 23.7%±6.8%; P=.013), higher gestational age at delivery (median weeks of gestation, 37.4; interquartile range, 36.6-38.00 vs 35.1; interquartile range, 33.1-37.2; P<.001), and more frequent use of extracorporeal membrane oxygenation (55.8% vs 4.3%; P<.001) than the fetuses who underwent fetoscopic endoluminal tracheal occlusion. The survival rates at discharge and at 2 years of age in the expectant management group were higher than the survival rates of the fetoscopic endoluminal tracheal occlusion group (74.3% vs 44.7%; P=.001 and 72.8% vs 42.5%; P=.001, respectively). After adjustment for maternal age, gestational age at birth, observed to expected total fetal lung volume, and birth weight Z-score, the odds ratios were 4.65 (95% confidence interval, 1.9-11.9; P=.001) and 4.37 (95% confidence interval, 1.8-11.0; P=.001), respectively. CONCLUSION: Fetuses with a severe isolated left-sided congenital diaphragmatic hernia had a higher survival rate when treated in an experienced center in Germany with antenatal expectant management and frequent use of extracorporeal membrane oxygenation during the postnatal period than fetuses who were treated with fetoscopic endoluminal tracheal occlusion in 3 centers in Belgium, France, and Italy.

Performance of fetal ultrasound and magnetic resonance imaging in predicting birthweight according to the test-to-delivery interval: A cohort study.

OBJECTIVE: To assess the influence of the test-to-delivery interval (TDI) on the performance of ultrasound (US) and magnetic resonance imaging (MRI) for predicting birthweight (BW). STUDY DESIGN: This is a secondary analysis of a prospective, single center, blinded cohort study that compared MRI and US for the prediction of BW ≥ 95th percentile in singleton pregnancies. Patients that were included in the initial study underwent US and MRI for estimation of fetal weight between 36 + 0/7 and 36 + 6/7 weeks of gestation (WG). The primary outcome of the current study was to report the changes of US and MRI sensitivity and specificity in the prediction of BW > 95th percentile, BW > 90th percentile, BW < 10th percentile, and BW < 5th percentile, according to the TDI. The secondary outcome was to represent the performance of both tools in the prediction of BW > 90th percentile when TDI is<2 weeks, between 2 and 4 weeks, and>4 weeks. Receiver operating characteristic (ROC) curves were constructed accordingly. RESULTS: 2378 patients were eligible for final analysis. For the prediction of BW > 95th or 90th percentile, the sensitivity of MRI remains high until 2 weeks, and it decreases slowly between 2 and 4 weeks, in contrast to the sensitivity of US which decreases rapidly 2 weeks after examination (p < 0.001). For the prediction of BW < 10th or 5th percentile, the sensitivity of both tools decreases in parallel between 1 and 2 weeks. The specificities of both tools remain high from examination till delivery. These findings are reproducible with the use of the antenatal customized and the postnatal national growth charts. CONCLUSION: The performance of MRI in the prediction of BW, especially in large-for-gestational age, is maximal when delivery occurs within two weeks of the examination, decreasing slightly thereafter, in contrast with the performance of US which decreases drastically over time.

Learning curve for fetal postmortem ultrasound.

OBJECTIVE: To determine the learning curve of fetal postmortem ultrasound (PMUS) and evaluate the evolution of its diagnostic performance over the past 8 years. METHODS: PMUS was performed by two fetal medicine specialists and two experts on 100 unselected fetuses of 12-38 weeks of gestation in a prospective, double-blind manner. 21 pre-defined internal structures were analyzed consecutively by the trainee alone and the expert, with a comparison of diagnosis and immediate feedback. The learning curves for examination duration, non-recognition of structures and final diagnoses were computed using cumulative summation analysis. Secondly, the expert PMUS diagnostic accuracy using autopsy as the gold standard was compared to the previously published data. RESULTS: The trainees reached expert level of PMUS at 28-36 cases for examination duration (12.1 ± 5.2 min), non-diagnostic rate (6.5%, 137/2100), and abnormality diagnosis. In a group of 33 fetuses ≥20 weeks who had an autopsy, the experts PMUS performance was improved after 8 years with a reduction of all organs non-diagnostic rate (6.5 %VS 11.4%, p < 0.01) and higher sensitivity for the heart (100% VS 40.9%, p < 0.01) and the abdomen (100%VS 56.5%, p < 0.05). CONCLUSION: PMUS offers a short learning curve for fetal medicine specialists and on-going improvement of diagnostic accuracy over time.

Reducing macrosomia-related birth complications in primigravid women: ultrasound- and magnetic resonance imaging-based models.

BACKGROUND: Many complications increase with macrosomia, which is defined as birthweight of ≥4000 g. The ability to estimate when the fetus would exceed 4000 g could help to guide decisions surrounding the optimal timing of delivery. To the best of our knowledge, there is no available tool to perform this estimation independent of the currently available growth charts. OBJECTIVE: This study aimed to develop ultrasound- and magnetic resonance imaging-based models to estimate at which gestational age the birthweight would exceed 4000 g, evaluate their predictive performance, and assess the effect of each model in reducing adverse outcomes in a prospectively collected cohort. STUDY DESIGN: This study was a subgroup analysis of women who were recruited for the estimation of fetal weight by ultrasound and magnetic resonance imaging at 36 0/7 to 36 6/7 weeks of gestation. Primigravid women who were eligible for normal vaginal delivery were selected. Multiparous patients, patients with preeclampsia spectrum, patients with elective cesarean delivery, and patients with contraindications for normal vaginal delivery were excluded. Of note, 2 linear models were built for the magnetic resonance imaging- and ultrasound-based models to predict a birthweight of ≥4000 g. Moreover, 2 formulas were created to predict the gestational age at which birthweight will reach 4000 g (predicted gestational age); one was based on the magnetic resonance imaging model, and the second one was based on the ultrasound model. This study compared the adverse birth outcomes, such as intrapartum cesarean delivery, operative vaginal delivery, anal sphincter injury, postpartum hemorrhage, shoulder dystocia, brachial plexus injury, Apgar score of <7 at 5 minutes of life, neonatal intensive care unit admission, and intracranial hemorrhage in the group of patients who delivered after the predicted gestational age according to the magnetic resonance imaging-based or the ultrasound-based models with those who delivered before the predicted gestational age by each model, respectively. RESULTS: Of 2378 patients, 732 (30.8%) were eligible for inclusion in the current study. The median gestational age at birth was 39.86 weeks of gestation (interquartile range, 39.00-40.57), the median birthweight was 3340 g (interquartile range, 3080-3650), and 63 patients (8.6%) had a birthweight of ≥4000 g. Prepregnancy body mass index, geographic origin, gestational age at birth, and fetal body volume were retained for the optimal magnetic resonance imaging-based model, whereas maternal age, gestational diabetes mellitus, diabetes mellitus type 1 or 2, geographic origin, fetal gender, gestational age at birth, and estimated fetal weight were retained for the optimal ultrasound-based model. The performance of the first model was significantly better than the second model (area under the curve: 0.98 vs 0.89, respectively; P<.001). The group of patients who delivered after the predicted gestational age by the first model (n=40) had a higher risk of cesarean delivery, postpartum hemorrhage, and shoulder dystocia (adjusted odds ratio: 3.15, 4.50, and 9.67, respectively) than the group who delivered before this limit. Similarly, the group who delivered after the predicted gestational age by the second model (n=25) had a higher risk of cesarean delivery and postpartum hemorrhage (adjusted odds ratio: 5.27 and 6.74, respectively) than the group who delivered before this limit. CONCLUSION: The clinical use of magnetic resonance imaging- and ultrasound-based models, which predict a gestational age at which birthweight will exceed 4000 g, may reduce macrosomia-related adverse outcomes in a primigravid population. The magnetic resonance imaging-based model is better for the identification of the highest-risk patients.

Sources of variation in nutrient loads collected through street sweeping in the Minneapolis-St. Paul Metropolitan Area, Minnesota, USA.

Excess non-point nutrient loading continues to impair urban surface waters. Because of the potential contribution of tree litterfall to nutrient pollution in stormwater, street sweeping is a promising management tool for reducing eutrophication in urban and suburban regions. However, nutrient concentrations and loads of material removed through street sweeping have not been well characterized, impeding the development of pollution reduction credits and improvement of models for stormwater management. We evaluated the role of canopy cover over streets, street sweeper type, season, and sweeping frequency in contributing to variation in concentrations and loads of nitrogen (N), phosphorus (P), and solids recovered in street sweepings, using analyses of samples collected during regular street sweeping operations in five cities in the Minneapolis-St. Paul Metropolitan Area, Minnesota, USA. We expected that nutrient concentrations and loads would be highest in seasons and places of higher tree litterfall. We also expected that regenerative-air sweepers would recover higher loads compared to mechanical broom sweepers. Total N and P concentrations in sweepings increased most strongly with canopy cover in June, October, and November. Total N and P recovered in street sweepings similarly increased with canopy cover in June, October, and November, and peaked in early summer and autumn, times of high litterfall. In contrast, total dry mass in sweepings was greatest in early spring, following winter snowmelt. However, nutrient loads and concentrations did not differ between sweeper types. Our results add to growing evidence of the importance of street trees in contributing nutrient pollution to urban surface waters. Street sweeping focused on high-canopy streets during early summer and autumn is likely an effective management tool for stormwater nutrient pollution.

Chest CT scan predictors of intensive care unit admission in hospitalized pregnant women with COVID-19: a case-control study.

PURPOSE: To investigate the role of chest computed tomography (CT) scan in the prediction of admission of pregnant women with COVID-19 into intensive care unit (ICU). METHODS: This was a single-center retrospective case-control study. We included pregnant women diagnosed with COVID-19 by reverse transcriptase polymerase chain reaction between February 2020 and July 2021, requiring hospital admission due to symptoms, who also had a CT chest scan at presentation. Patients admitted to the ICU (case group) were compared with patients who did not require ICU admission (control group). The CT scans were reported by an experienced radiologist, blinded to the patient's course and outcome, aided by an artificial intelligence software. Total CT scan score, chest CT severity score (CT-SS), total lung volume (TLV), infected lung volume (ILV), and infected-to-total lung volume ratio (ILV/TLV) were calculated. Receiver operating characteristic curves were constructed to test the sensitivity and specificity of each parameter. RESULTS: 8/28 patients (28.6%) required ICU admission. These also had lower TLV, higher ILV, and ILV/TLV. The area under the curve (AUC) for these three parameters was 0.789, 0.775, and 0.763, respectively. TLV, ILV, and ILV/TLV had good sensitivity (62.5%, 87.5%, and 87.5%, respectively) and specificity (84.2%, 70%, and 73.7%, respectively) for predicting ICU admission at the following selected thresholds: 2255 mL, 319 mL, and 14%, respectively. The performance of CT-SS, CT scan score, and ILV/TLV in predicting ICU admission was comparable. CONCLUSION: TLV, ILV, and ILV/TLV as measured by an artificial intelligence software on chest CT, may predict ICU admission in hospitalized pregnant women, symptomatic for COVID-19.

The impact of different growth charts on birthweight prediction: obstetrical ultrasound vs magnetic resonance imaging.

BACKGROUND: The estimation of fetal weight by fetal magnetic resonance imaging is a simple and rapid method with a high sensitivity in predicting birthweight in comparison with ultrasound. Several national and international growth charts are currently in use, but there is substantial heterogeneity among these charts due to variations in the selected populations from which they were derived, in methodologies, and in statistical analysis of data. OBJECTIVE: This study aimed to compare the performance of magnetic resonance imaging and ultrasound for the prediction of birthweight using 3 commonly used fetal growth charts: the INTERGROWTH-21st Project, World Health Organization, and Fetal Medicine Foundation charts. STUDY DESIGN: Data derived from a prospective, single-center, blinded cohort study that compared the performance of magnetic resonance imaging and ultrasound between 36+0/7 and 36+6/7 weeks of gestation for the prediction of birthweight ≥95th percentile were reanalyzed. Estimated fetal weight was categorized as above or below the 5th, 10th, 90th, and 95th percentile according to the 3 growth charts. Birthweight was similarly categorized according to the birthweight standards of each chart. The performances of ultrasound and magnetic resonance imaging for the prediction of birthweight <5th, <10th, >90th, and >95th percentile using the different growth charts were compared. Data were analyzed with R software, version 4.1.2. The comparison of sensitivity and specificity was done using McNemar and exact binomial tests. P values <.05 were considered statistically significant. RESULTS: A total of 2378 women were eligible for final analysis. Ultrasound and magnetic resonance imaging were performed at a median gestational age of 36+3/7 weeks, delivery occurred at a median gestational age of 39+3/7 weeks, and median birthweight was 3380 g. The incidences of birthweight <5th and <10th percentiles were highest with the Fetal Medicine Foundation chart and lowest with the INTERGROWTH-21st chart, whereas the incidences of birthweight >90th and >95th percentiles were lowest with the Fetal Medicine Foundation chart and highest with the INTERGROWTH-21st chart. The sensitivity of magnetic resonance imaging with an estimated fetal weight >95th percentile in the prediction of birthweight >95th percentile was significantly higher than that of ultrasound across the 3 growth charts; however, its specificity was slightly lower than that of ultrasound. In contrast, the sensitivity of magnetic resonance imaging with an estimated fetal weight <10th percentile for predicting birthweight <10th percentile was significantly lower than that of ultrasound in the INTERGROWTH-21st and Fetal Medicine Foundation charts, whereas the specificity and positive predictive value of magnetic resonance imaging were significantly higher than those of ultrasound for all 3 charts. Findings for the prediction of birthweight >90th percentile were close to those of birthweight >95th percentile, and findings for the prediction of birthweight <5th percentile were close to those of birthweight <10th percentile. CONCLUSION: The sensitivity of magnetic resonance imaging is superior to that of ultrasound for the prediction of large for gestational age fetuses and inferior to that of ultrasound for the prediction of small for gestational age fetuses across the 3 different growth charts. The reverse is true for the specificity of magnetic resonance imaging in comparison with that of ultrasound.

[Predictive factors of spontaneous pregnancies among women with diminished ovarian reserve patients treated with DHEA]. / Facteurs prédictifs de grossesse spontanée chez les femmes présentant une réserve ovarienne diminuée traitées par DHEA.

INTRODUCTION: Diminished ovarian reserve remains a challenge in the reproductive medicine field. Treatment options for these patients are limited and there is no consensus to make any recommendations. Regarding adjuvant supplements, DHEA could play a role in follicular recruitment and, therefore, may increase spontaneous pregnancy rate. MATERIALS AND METHODS: This study was a monocentric historical and observational cohort study carried out in the reproductive medicine department at the University Hospital, Femme-Mère-Enfant in Lyon. All women presenting with a diminished ovarian reserve treated with 75mg/day of DHEA were consecutively included. The main objective was to evaluate the spontaneous pregnancy rate. The secondary objectives were to identify predictive factors for pregnancy and the evaluation of treatment side effects. RESULTS: Four hundred and thirty-nine women were included. In all, 277 were analyzed, 59 had a spontaneous pregnancy (21.3%). The probability of being pregnant was respectively 13.2% (IC95 9-17.2%), 21.3% (IC95 15.1-27%) and 38.8% (IC95 29.3-48.4%) at 6, 12 and 24 months. Only 20.6% of patients complained of side effects. CONCLUSION: DHEA may improve spontaneous pregnancies in women with diminished ovarian reserve without any stimulation.

Cell-free DNA-based prenatal screening via rolling circle amplification: Identifying and resolving analytic issues.

OBJECTIVE: A rolling circle amplification (RCA) based commercial methodology using cell-free (cf)DNA to screen for common trisomies became available in 2018. Relevant publications documented high detection but with a higher than expected 1% false positive rate. Preliminary evidence suggested assay variability was an issue. A multi-center collaboration was created to explore this further and examine whether subsequent manufacturer changes were effective. METHODS: Three academic (four devices) and two commercial (two devices) laboratories provided run date, chromosome 21, 18, and 13 run-specific standard deviations, number of samples run, and reagent lot identifications. Temporal trends and between-site/device consistency were explored. Proportions of run standard deviations exceeding pre-specified caps of 0.4%, 0.4% and 0.6% were computed. RESULTS: Overall, 661 RCA runs between April 2019 and July 30, 2022 tested 39,756 samples. In the first 24, subsequent 9, and final 7 months, proportions of capped chromosome 21 runs dropped from 39% to 22% to 6.0%; for chromosome 18, rates were 76%, 36%, and 4.0%. Few chromosome 13 runs were capped using the original 0.60%, but capping at 0.50%, rates were 28%, 16%, and 7.6%. Final rates occurred after reformulated reagents and imaging software modifications were fully implemented across all devices. Revised detection and false positive rates are estimated at 98.4% and 0.3%, respectively. After repeat testing, failure rates may be as low as 0.3%. CONCLUSION: Current RCA-based screening performance estimates are equivalent to those reported for other methods, but with a lower test failure rate after repeat testing.