Machine learning techniques for prediction in pregnancy complicated by autoimmune rheumatic diseases: Applications and challenges.

Autoimmune rheumatic diseases are chronic conditions affecting multiple systems and often occurring in young women of childbearing age. The diseases and the physiological characteristics of pregnancy significantly impact maternal-fetal health and pregnancy outcomes. Currently, the integration of big data with healthcare has led to the increasing popularity of using machine learning (ML) to mine clinical data for studying pregnancy complications. In this review, we introduce the basics of ML and the recent advances and trends of ML in different prediction applications for common pregnancy complications by autoimmune rheumatic diseases. Finally, the challenges and future for enhancing the accuracy, reliability, and clinical applicability of ML in prediction have been discussed. This review will provide insights into the utilization of ML in identifying and assisting clinical decision-making for pregnancy complications, while also establishing a foundation for exploring comprehensive management strategies for pregnancy and enhancing maternal and child health.

Carbapenem-resistant Gram-negative bacteria (CR-GNB) in ICUs: resistance genes, therapeutics, and prevention - a comprehensive review.

Intensive care units (ICUs) are specialized environments dedicated to the management of critically ill patients, who are particularly susceptible to drug-resistant bacteria. Among these, carbapenem-resistant Gram-negative bacteria (CR-GNB) pose a significant threat endangering the lives of ICU patients. Carbapenemase production is a key resistance mechanism in CR-GNB, with the transfer of resistance genes contributing to the extensive emergence of antimicrobial resistance (AMR). CR-GNB infections are widespread in ICUs, highlighting an urgent need for prevention and control measures to reduce mortality rates associated with CR-GNB transmission or infection. This review provides an overview of key aspects surrounding CR-GNB within ICUs. We examine the mechanisms of bacterial drug resistance, the resistance genes that frequently occur with CR-GNB infections in ICU, and the therapeutic options against carbapenemase genotypes. Additionally, we highlight crucial preventive measures to impede the transmission and spread of CR-GNB within ICUs, along with reviewing the advances made in the field of clinical predictive modeling research, which hold excellent potential for practical application.

Dimethylglycine Can Enhance the Cryopreservation of Red Blood Cells by Reducing Ice Formation and Oxidative Damage.

The cryopreservation of red blood cells (RBCs) holds great potential for ensuring timely blood transfusions and maintaining an adequate RBC inventory. The conventional cryoprotectants (CPAs) have a lot of limitations, and there is an obvious need for novel, efficient, and biocompatible CPAs. Here, it is shown for the first time that the addition of dimethylglycine (DMG) improved the thawed RBC recovery from 11.55 ± 1.40% to 72.15 ± 1.22%. We found that DMG could reduce the mechanical damage by inhibiting ice formation and recrystallization during cryopreservation. DMG can also scavenge reactive oxygen species (ROS) and maintain endogenous antioxidant enzyme activities to decrease oxidative damage during cryopreservation. Furthermore, the properties of thawed RBCs were found to be similar to the fresh RBCs in the control. Finally, the technique for order performance by similarity to ideal solution (TOPSIS) was used to compare the performance of glycerol (Gly), hydroxyethyl starch (HES), and DMG in cryopreservation, and DMG exhibited the best efficiency. This work confirms the use of DMG as a novel CPA for cryopreservation of RBCs and may promote clinical transfusion therapy.

Maternal vaginal fluids play a major role in the colonization of the neonatal intestinal microbiota.

Background: Caesarean section (CS) is associated with newborns' health risks due to the blocking of microbiome transfer. The gut microbiota of CS-born babies was different from those born vaginally, which may be attributed to reduced exposure to maternal vaginal microbes during labour. To understand the microbial transfer and reduce CS disadvantages, the effect of vaginal microbiota exposure on infant gut microbiota composition was evaluated using 16s rDNA sequencing-based techniques. Results: Pregnant women were recruited in the Women and Children's Hospital, School of Medicine, Xiamen University from June 1st to August 15th, 2017. Maternal faeces (n = 26), maternal vaginal fluids (n = 26), and neonatal transitional stools (n = 26) were collected, while the participants underwent natural delivery (ND) (n = 6), CS (n = 4) and CS with the intervention of vaginal seedings (I) (n = 16). 26 mothers with the median age 26.50 (25.00-27.25) years showed no substantial clinical differences. The newborns' gut microbiota altered among ND, CS and I, and clustered into two groups (PERMANOVA P = 0.001). Microbial composition of ND babies shared more features with maternal vaginal samples (PERMANOVA P = 0.065), while the microbiota structure of ND babies was obviously different from that of sample of maternal faeces. The genus Bacteroides in CS-born babies with intervention approached to vaginal-born neonates, compared with CS-born neonates without intervention. Conclusions: Neonatal gut microbiota was dependent on the delivery mode. And the gut microbiota CS newborns with vaginal seeding shared more features with those of ND babies, which hinted the aberrant gut microbiota composition initiated by CS might be partly mitigated by maternal vaginal microbiota exposure.

Effects of emergency/nonemergency cervical cerclage on the vaginal microbiome of pregnant women with cervical incompetence.

Background: Evaluation of the therapeutic effects of cerclage on preterm birth (PTB) caused by cervical incompetence remains challenging. The vaginal microbiome is associated with preterm births. Thus, this study aimed to analyse the vaginal microbiota of patients with cervical incompetence, explore the relationship between the composition of the vaginal microbiota before cervical cerclage and at term delivery, and assess the effect of cervical cerclage on the vaginal microbiota. Methods: Patients (n = 30) underwent cerclage performed by the same surgical team. Vaginal swabs were obtained pre-surgery and seven days post-surgery. A gestational age-matched cohort of healthy pregnant women (n = 20) (no particular abnormality during pregnancy, delivery at term) was used as the control group and sampled during a comparable pregnancy. All collected vaginal swabs were analysed by 16S rRNA gene sequencing. Results: When comparing the healthy control and cervical cerclage groups, the enriched microorganism in the healthy controls was G. Scardovia, and the enriched microorganism of the cerclage was G. Streptococcus. α diversity was significantly increased in patients who received cerclage with preterm delivery compared with those with full-term delivery, and the enriched microorganism was F. Enterococcus. A comparison before and after nonemergency cerclage suggested that the enriched microorganisms were G. Lactobacillus and F. Lactobacillaceae before surgery. After nonemergency cerclage, the enriched microorganisms were F. Enterobacteriaceae and C. Gammaproteobacteria. Vaginal microbiota diversity significantly increased, and the proportion of women with Lactobacillus spp.-depleted microbiomes increased after emergency cerclage. Significant differences in ß diversity were found between the groups. Before the emergency cerclage, the enriched microorganisms were G. Lactobacillus, O. Alteromonadales, and P. Firmicutes. After emergency cerclage, the enriched microorganisms were P. Actinobacteria, C. Actinobacteria, P. Proteobacteria, F. Bifidobacteriaceae, O. Bifidobacteriales, G. Gardnerella, and G. Veillonella. Conclusion: Cerclage (particularly emergency cerclage) may alter the vaginal microbiota by increasing microbiota diversity, decreasing vaginal Lactobacillus abundance, and increasing the abundance of pathogenic bacteria that are not conducive to pregnancy maintenance, thereby affecting surgical efficacy. Therefore, the role of the vaginal microbiome should be considered when developing treatment strategies for pregnant women with cervical incompetence. Clinical trial registration: https://www.chictr.org.cn, identifier ChiCTR2100046305.

Trehalose in Biomedical Cryopreservation-Properties, Mechanisms, Delivery Methods, Applications, Benefits, and Problems.

Cells and tissues are the foundation of translational medicine. At present, one of the main technological obstacles is their preservation for long-term usage while maintaining adequate viability and function. Optimized storage techniques must be developed to make them safer to use in the clinic. Cryopreservation is the most common long-term preservation method to maintain the vitality and function of cells and tissues. But, the formation of ice crystals in cells and tissues is considered to be the main mechanism that could harm cells and tissues during freezing and thawing. To reduce the formation of ice crystals, cryoprotective agents (CPAs) must be added to the cells and tissues to achieve the cryoprotective effect. However, conventional cryopreservation of cells and tissues often needs to use toxic organic solvents as CPAs. As a result, cryopreserved cells and tissues may need to go through a time-consuming washing process to remove CPAs for further applications in translational medicine, and multiple valuable cells are potentially lost or killed. Currently, trehalose has been researched as a nontoxic CPA due to its cryoprotective ability and stability during cryopreservation. Nevertheless, trehalose is a nonpermeable CPA, and the lack of an effective intracellular trehalose delivery method has become the main obstacle to its use in cryopreservation. This article illustrated the properties, mechanisms, delivery methods, and applications of trehalose, summarized the benefits and limits of trehalose, and summed up the findings and research direction of trehalose in biomedical cryopreservation.

Maternal Physiological Variations Induced by Chronic Gestational Hypoxia: 1H NMR-Based Metabolomics Study.

Metabolomics have been widely used in pregnancy-related diseases. However, physiological variations induced by chronic hypoxia during pregnancy are not well characterized. We aimed to investigate physiological variations induced by chronic hypoxia during pregnancy. A Sprague-Dawley (SD) pregnant rat model of chronic hypoxia was established. Plasma and urine metabolite profiles at different stages of the pregnancy were detected by 1H NMR (nuclear magnetic resonance). Multivariate statistical analysis was used to analyze changes in plasma and urine metabolic trajectories at different time-points. We identified hypoxia-induced changes in the levels of 30 metabolites in plasma and 29 metabolites in urine during different stages of pregnancy; the prominently affected metabolites included acetic acid, acetone, choline, citric acid, glutamine, isoleucine, lysine, and serine. Most significant hypoxia-induced changes in plasma and urine sample metabolites were observed on the 11th day of gestation. In summary, chronic hypoxia has a significant effect on pregnant rats, and may cause metabolic disorders involving glucose, lipids, amino acids, and tricarboxylic acid cycle. Metabolomics study of the effect of hypoxia during pregnancy may provide insights into the pathogenesis of obstetric disorders.

Tricine as a Novel Cryoprotectant with Osmotic Regulation, Ice Recrystallization Inhibition and Antioxidant Properties for Cryopreservation of Red Blood Cells.

The cryopreservation of red blood cells (RBCs) plays a key role in blood transfusion therapy. Traditional cryoprotectants (CPAs) are mostly organic solvents and may cause side effects to RBCs, such as hemolysis and membrane damage. Therefore, it is necessary to find CPAs with a better performance and lower toxicity. Herein, we report for the first time that N-[Tri(hydroxymethyl)methyl]glycine (tricine) showed a great potential in the cryopreservation of sheep RBCs. The addition of tricine significantly increased the thawed RBCs' recovery from 19.5 ± 1.8% to 81.2 ± 8.5%. The properties of thawed RBCs were also maintained normally. Through mathematical modeling analysis, tricine showed a great efficiency in cryopreservation. We found that tricine had a good osmotic regulation capacity, which could mitigate the dehydration of RBCs during cryopreservation. In addition, tricine inhibited ice recrystallization, thereby decreasing the mechanical damage from ice. Tricine could also reduce oxidative damage during freezing and thawing by scavenging reactive oxygen species (ROS) and maintaining the activities of endogenous antioxidant enzymes. This work is expected to open up a new path for the study of novel CPAs and promote the development of cryopreservation of RBCs.

Cryopreservation of Animals and Cryonics: Current Technical Progress, Difficulties and Possible Research Directions.

The basis of cryonics or medical cryopreservation is to safely store a legally dead subject until a time in the future when technology and medicine will permit reanimation after eliminating the disease or cause of death. Death has been debunked as an event occurring after cardiac arrest to a process where interjecting its progression can allow for reversal when feasible. Cryonics technology artificially halts further damages and injury by restoring respiration and blood circulation, and rapidly reducing temperature. The body can then be preserved at this extremely low temperature until the need for reanimation. Presently, the area has attracted numerous scientific contributions and advancement but the practice is still flooded with challenges. This paper presents the current progression in cryonics research. We also discuss obstacles to success in the field, and identify the possible solutions and future research directions.

Principles and Protocols For Post-Cryopreservation Quality Evaluation of Stem Cells in Novel Biomedicine.

Stem cell therapy is a thriving topic of interest among researchers and clinicians due to evidence of its effectiveness and promising therapeutic advantage in numerous disease conditions as presented by novel biomedical research. However, extensive clinical application of stem cells is limited by its storage and transportation. The emergence of cryopreservation technology has made it possible for living organs, tissues, cells and even living organisms to survive for a long time at deep low temperatures. During the cryopreservation process, stem cell preparations are subject to three major damages: osmotic damage, mechanical damage, and peroxidative damage. Therefore, Assessing the effectiveness and safety of stem cells following cryopreservation is fundamental to the quality control of stem cell preparations. This article presents the important biosafety and quality control parameters to be assessed during the manufacturing of clinical grade stem cell products, highlights the significance of preventing cryodamage. and provides a reference for protocols in the quality control of stem cell preparations.

Antifreeze Proteins: Novel Applications and Navigation towards Their Clinical Application in Cryobanking.

Antifreeze proteins (AFPs) or thermal hysteresis (TH) proteins are biomolecular gifts of nature to sustain life in extremely cold environments. This family of peptides, glycopeptides and proteins produced by diverse organisms including bacteria, yeast, insects and fish act by non-colligatively depressing the freezing temperature of the water below its melting point in a process termed thermal hysteresis which is then responsible for ice crystal equilibrium and inhibition of ice recrystallisation; the major cause of cell dehydration, membrane rupture and subsequent cryodamage. Scientists on the other hand have been exploring various substances as cryoprotectants. Some of the cryoprotectants in use include trehalose, dimethyl sulfoxide (DMSO), ethylene glycol (EG), sucrose, propylene glycol (PG) and glycerol but their extensive application is limited mostly by toxicity, thus fueling the quest for better cryoprotectants. Hence, extracting or synthesizing antifreeze protein and testing their cryoprotective activity has become a popular topic among researchers. Research concerning AFPs encompasses lots of effort ranging from understanding their sources and mechanism of action, extraction and purification/synthesis to structural elucidation with the aim of achieving better outcomes in cryopreservation. This review explores the potential clinical application of AFPs in the cryopreservation of different cells, tissues and organs. Here, we discuss novel approaches, identify research gaps and propose future research directions in the application of AFPs based on recent studies with the aim of achieving successful clinical and commercial use of AFPs in the future.

Off-label indications of aspirin in gynaecology and obstetrics outpatients at two Chinese tertiary care hospitals: a retrospective cross-sectional study.

OBJECTIVE: To investigate the prevalence of off-label aspirin indications and the level of scientific support for off-label indications of aspirin in gynaecology and obstetrics outpatients. DESIGN: A retrospective cross-sectional study. SETTING: Two tertiary hospitals (a general hospital and a women and children's specialised hospital) in Xiamen, a city located on the southeastern coast of China. PARTICIPANTS: A total of 4257 prescriptions were included for 2091 female patients aged >18 who visited the gynaecology and obstetrics outpatient clinics and received aspirin treatment. OUTCOME MEASURES: The primary measure of this study was the proportion of off-label indications and of off-label indications supported by strong scientific evidence. Evidence from clinical guidelines and Micromedex is shown using descriptive statements. On-label indications of drugs in the same class as aspirin were also referred to for off-label aspirin use without strong evidence support. RESULTS: All indications of aspirin on outpatient prescriptions were determined as off-label use in this study. The most frequent off-label indication was recurrent miscarriage (2244 prescriptions, 52.71%). Totally, 30.94% of the prescriptions were supported by strong evidence for indications, including recurrent miscarriage with antiphospholipid syndrome and prophylaxis for pre-eclampsia. No drugs in the same class as aspirin had on-label indications for off-label aspirin use without strong evidence support. CONCLUSIONS: This study demonstrated that all indications of aspirin used in gynaecology and obstetrics outpatients at the two tertiary hospitals were off-label and not always supported by strong evidence, implicating that physicians should be cautious when issuing off-label prescriptions. More original clinical research on off-label aspirin use is needed to provide reference for routine clinical practice.

Freeze-Thaw Pretreatment Can Improve Efficiency of Bacterial DNA Extraction From Meconium.

Although the presence of live microbes in utero remains under debate, newborn gastrointestinal bacteria are undoubtedly important to infant health. Measuring bacteria in meconium is an ideal strategy to understand this issue; however, the low efficiency of bacterial DNA extraction from meconium has limited its utilization. This study aims to improve the efficiency of bacterial DNA extraction from meconium, which generally has low levels of microflora but high levels of PCR inhibitors in the viscous matrix. The research was approved by the ethical committee of the Xiamen Maternity and Child Health Care Hospital, Xiamen, China. All the mothers delivered naturally, and their newborns were healthy. Meconium samples passed by the newborns within 24 h were collected. Each sample was scraped off of a sterile diaper, transferred to a 5-ml sterile tube, and stored at -80°C. For the assay, a freeze-thawing sample preparation protocol was designed, in which a meconium-InhibitEX buffer mixture was intentionally frozen 1-3 times at -20°C, -80°C, and (or) in liquid nitrogen. Then, DNA was extracted using a commercial kit and sequenced by 16S rDNA to verify the enhanced bacterial DNA extraction efficiency. Ultimately, we observed the following: (1) About 30 mg lyophilized meconium was the optimal amount for DNA extraction. (2) Freezing treatment for 6 h improved DNA extraction at -20°C. (3) DNA extraction efficiency was significantly higher with the immediate thaw strategy than with gradient thawing at -20°C, -80°C, and in liquid nitrogen. (4) Among the conditions of -20°C, -80°C, and liquid nitrogen, -20°C was the best freezing condition for both improving DNA extraction efficiency and preserving microbial species diversity in meconium, while liquid nitrogen was the worst condition. (5) Three freeze-thaw cycles could markedly enhance DNA extraction efficiency and preserve the species diversity of meconium microflora. We developed a feasible freeze-thaw pretreatment protocol to improve the extraction of microbial DNA from meconium, which may be beneficial for newborn bacterial colonization studies.

Predictive value of aberrant right subclavian artery for fetal chromosome aneuploidy in women of advanced maternal age.

BACKGROUND: In the entire population, an aberrant right subclavian artery (ARSA) is closely associated with chromosomal abnormalities. ARSA with additional ultrasonic findings would increase risk of chromosomal abnormalities. The risk of fetal chromosomal abnormalities increased exponentially with the maternal age. These risks in the advanced maternal age (AMA) group are uncertain. This study aimed to determine the incidence of ARSA in Chinese AMA and non-AMA women and the frequency of aneuploidy among AMA and non-AMA women with ARSA. METHODS: This retrospective study included 13,690 singleton pregnancies, were divided into AMA and non-AMA groups. Integrated obstetric ultrasonic screening, biochemical screening, noninvasive prenatal screening, and fetal karyotype analysis were analyzed. RESULTS: The overall incidence of ARSA was 0.69%, with no difference between age groups. The incidence of chromosomal abnormalities in the AMA group (37 / 2860) was much higher than that of the non-AMA group. The risk of chromosomal abnormalities significantly increased with both ARSA detected and additional ultrasound findings. With combined ARSA and AMA, the likelihood of the incidence of chromosomal abnormalities increased. Chimerism (45X / 46XX) was found with isolated ARSA in AMA pregnancies. CONCLUSION: There is a high prevalence of chromosomal abnormalities in fetuses of AMA women. ARSA increases the risk of chromosomal abnormalities in both age groups, especially combined with ARSA. When ARSA occurs in AMA women, it confers a high likelihood of chromosomal abnormalities.

Three-dimensional sonographic minute structure analysis of fetal cerebellar vermis development and malformations: utilizing volume contrast imaging.

PURPOSE: To obtain three-dimensional ultrasonic (3D US) structural details and biometrics of the fetal cerebellar vermis and evaluate the value of developmental and malformation identification. METHODS: The 3D US minute structure of the fetal cerebellar vermis in mid-sagittal view was detected in normal fetuses (n = 438; 16-41 weeks). Biometric sizes were measured to establish the stage-specific norms and reproducibility analysis. Additionally, 28 fetuses with suspected abnormal posterior fossa contents were assessed to analyze the clinical value. RESULTS: The minute structure of normal fetuses, including cerebellar vermis contours and the fastigial recess of the fourth ventricle, were visible around Week 19. The main lobules and fissures were apparent around Week 22, and all nine lobules, fissures, and the fourth ventricle were clearly displayed by Week 28. Cerebellar vermis biometric sizes (anterior-posterior length, cranio-caudal length, circumference, and surface area (SA)) grew in a linear fashion with high reliability, especially SA measurements (for intraclass, ICC 0.989, 95% CI (0.980-0.994); for interclass, ICC 0.992, 95% CI (0.984-0.996)). On the middle sagittal section of 3D US, the SA reduced at least 50% in the Dandy-Walker group with no recognizable cerebellar vermis structures showing. The SA in vermian hypoplasia malformation reduced during [Formula: see text] to 50% with the primary/secondary fissures absent or partly absent and arborization of the lobules reduced. That would be an important diagnosis and antidiastole clue. Combined with minute structural observation, sonographic diagnoses were accurate in 88% of cases. CONCLUSION: Minute structures obtained by 3D US were clinically useful in the evaluation of cerebellar vermis development and cerebellar vermis malformations.

The relationship of lung cancer with menstrual and reproductive factors may be influenced by passive smoking, cooking oil fumes, and tea intake: A case-control study in Chinese women.

The aim of this study was to investigate the association of menstrual and reproductive factors with risk of lung cancer in women. Potential etiological clues related to lung cancer in women are identified to inform preventive strategies.Case-control study of 477 newly diagnosed women with lung cancer and 479 age-matched (±2 years) controls. Data on menstrual and reproductive factors and history of oral contraceptive use were obtained on personal interviews using a structured questionnaire. Risk factors were analyzed by unconditional logistic regression analysis.Maternal age ≥25 years at first birth appeared to protect against female lung cancer [odds ratios (ORs): 0.511, 95% confidence interval (CI), 0.376-0.693]. Age at menopause > 50 years and use of contraceptives was associated with an increased risk of lung cancer in women (OR: 1.471, 95% CI, 1.021-2.119 and OR: 1.844, 95% CI: 1.111-3.061, respectively). Age ≥13 years at menarche was associated with a decreased risk of lung adenocarcinoma (OR: 0.563, 95% CI, 0.317-0.997). There was significant heterogeneity in the levels of cooking oil fume (COF) exposure (Pheterogeneity = .015). Higher levels of exposure to passive smoking, COF, and lack of tea intake were associated with an increased risk of lung cancer.Menstrual and reproductive factors are considered to play a role in the development of lung cancer in women. Exposure to passive smoking, COF, and lack of tea intake appeared to significantly modify the relationship.

Maternal hypoxia increases the susceptibility of adult rat male offspring to high-fat diet-induced nonalcoholic fatty liver disease.

Exposure to an adverse intrauterine environment increases the risk for adult metabolic syndrome. However, the influence of prenatal hypoxia on the risk of fatty liver disease in offspring is unclear. The purpose of the present study was to evaluate the role of reduced fetal oxygen on the development and severity of high-fat (HF) diet-induced nonalcoholic fatty liver disease (NAFLD). Based on design implicating 2 factors, ie, maternal hypoxia (MH) and postnatal HF diet, blood lipid and insulin levels, hepatic histology, and potential molecular targets were evaluated in male Sprague Dawley rat offspring. MH associated with postnatal HF diet caused a significant increase in plasma concentration of triglycerides, free fatty acids, low-density lipoprotein cholesterol, and insulin. Histologically, a more severe form of NAFLD with hepatic inflammation, hepatic resident macrophage infiltration, and progression toward nonalcoholic steatohepatitis was observed. The lipid homeostasis changes and insulin resistance caused by MH plus HF were accompanied by a significant down-regulation of insulin receptor substrate 2 (IRS-2), phosphoinositide-3 kinase p110 catalytic subunit, and protein kinase B. In MH rats, insulin-stimulated IRS-2 and protein kinase B (AKT) phosphorylation were significantly blunted as well as insulin suppression of phosphoenolpyruvate carboxykinase and glucose-6-phosphatase. Meanwhile, a significant up-regulation of lipogenic pathways was noticed, including sterol-regulatory element-binding protein-1 and fatty acid synthase in liver. Our results indicate that maternal hypoxia enhances dysmetabolic liver injury in response to an HF diet. Therefore, the offspring born in the context of maternal hypoxia may require special attention and follow-up to prevent the early development of NAFLD.

The effect of fetal congenital heart disease on in utero urine production rate.

OBJECTIVES: To evaluate the influence of congenital heart disease (CHD) or congestive heart failure (CHF) on fetal urine production rate (UPR) and to establish normal reference intervals. METHODS: A cross-sectional study was performed on normal fetuses (n = 314) and on fetuses with CHD (n = 49). CHD cases were divided into groups on the basis of heart function as defined by Huhta score: with CHF (n = 11) and without CHF (n = 38). Fetal bladder volume was measured by two-dimensional as well as three-dimensional ultrasound with the Virtual Organ Computer-aided Analysis technique. RESULTS: In normal fetuses, UPR increased with gestational age from a mean value of 4.5 mL/h at 21 weeks to 66.5 mL/h at 40 weeks. There were no significant differences in UPR between CHD cases without CHF and controls (P = 0.581). However, fetuses with CHF had decreased UPR values (Controls vs. CHF, P = 0.007) compared with the controls. The interobserver and intraobserver variability for assessment of UPR was better using three-dimensional rather than two-dimensional US. CONCLUSIONS: Fetal UPR can be reproducibly measured by the Virtual Organ Computer-aided Analysis technique. It appears that heart function, rather than CHD, affects fetal UPR. Fetal UPR may therefore be an additional indicator of CHF.