ABSTRACT
BACKGROUND: The Alterra adaptive prestent is a novel self-expanding device designed to provide a landing zone for the 29 mm SAPIEN 3 valve to treat pulmonary regurgitation in patients with a right ventricular outflow tract that is too large for a balloon expandable valve alone. The mechanism of fixation for the Alterra prestent is radial force from the self-expanding stent frame, combined with a unique set of flared "tines" that protrude from both ends of the stent. AIMS, METHODS, AND RESULTS: In this report, we describe 6 patients who underwent uncomplicated transcatheter pulmonary valve replacement with an Alterra adaptive prestent and SAPIEN 3 valve and had surveillance chest computed tomography (CT) scans performed 1 day to 21 months after implant. In each patient, the CT scan demonstrated extravascular extension of a portion of the Alterra prestent, without clinical sequelae, but with extension into the ascending aorta in 1 patient and contact with the ascending aorta, left pulmonary vein, or left atrial appendage in 3 others. CONCLUSIONS: Surveillance CT imaging shows that the Alterra prestent can perforate the pulmonary artery and/or right ventricle. Although no sequelae were seen in these patients, prestent perforation has the potential to be clinically important. Implanters should be aware of this finding and its potential implications. As experience with the Alterra prestent grows, it will be important to further define the risk factors, incidence, and implications of this phenomenon.
Subject(s)
Heart Valve Prosthesis Implantation , Heart Valve Prosthesis , Predictive Value of Tests , Prosthesis Design , Humans , Male , Female , Treatment Outcome , Heart Valve Prosthesis Implantation/instrumentation , Heart Valve Prosthesis Implantation/adverse effects , Time Factors , Adult , Cardiac Catheterization/instrumentation , Cardiac Catheterization/adverse effects , Pulmonary Valve/diagnostic imaging , Pulmonary Valve/surgery , Pulmonary Valve/physiopathology , Pulmonary Valve Insufficiency/diagnostic imaging , Pulmonary Valve Insufficiency/physiopathology , Pulmonary Valve Insufficiency/surgery , Pulmonary Valve Insufficiency/etiology , Young Adult , Computed Tomography Angiography , Adolescent , Pulmonary Artery/diagnostic imaging , Pulmonary Artery/physiopathology , Tomography, X-Ray ComputedABSTRACT
BACKGROUND: Patients with d-transposition of the great arteries (d-TGA) who have undergone an arterial switch operation (ASO) can develop right ventricular outflow tract (RVOT) dysfunction with pulmonary regurgitation (PR) or stenosis. In these patients, treatment may include transcatheter pulmonary valve replacement (TPVR). Coronary compression is a contraindication occurring in 5% of typical TPVR cases. After ASO, there are various anatomical considerations that can confound TPVR, including potential coronary artery compression. Our goal is to understand feasibility of TPVR in patients following ASO. METHODS: This was a retrospective multicenter cohort study of patients with RVOT dysfunction after ASO who underwent cardiac catheterization with intention to perform TPVR from 2008 to 2020. RESULTS: Across nine centers, 33 patients met inclusion criteria. TPVR was successful in 22 patients (66%), 19 receiving a Melody valve and 3 a SAPIEN valve. RVOT stenosis in isolation or with PR dictated need for TPVR in nearly all patients. One serious adverse event occurred with valve embolization. After TPVR, the RVOT peak gradient decreased from 43 to 9 mm Hg (p < 0.001); PR was trivial/none in all but one patient, in whom it was mild. Coronary compression prohibiting TPVR occurred in eight patients (24%) and two patients (6%) had severe aortic regurgitation from aortic root deformation precluding TPVR. Seven patients underwent RVOT reintervention with a median of 5.3 years post-TPVR. CONCLUSIONS: TPVR in patients with d-TGA after ASO is feasible, but in this cohort, coronary compression or aortic root distortion precluded TPVR in one-third of patients. The rate of RVOT reintervention after TPVR was higher in this cohort of ASO patients that in prior studies.
ABSTRACT
This study describes right ventricle (RV) characteristics and right ventricle to pulmonary artery (RV-PA) conduit function pre- and post-repair in patients with tetraology of Fallot with major aortopulmonary collaterals (TOF/MAPCAs). We reviewed patients who underwent single-stage, complete unifocalization, and repair of TOF/MAPCAs between 2006 and 2019 with available pre- and early postoperative echocardiograms. For a subset of patients, 6-12 month follow-up echocardiogram was available. RV and left ventricle (LV) characteristics and RV-PA conduit function were reviewed. Wilcoxon signed rank test and McNemar's test were used. 170 patients were reviewed, 46 had follow-up echocardiograms. Tricuspid valve annular plane systolic excursion (TAPSE) Z-scores were reduced from pre- (Z-score 0.01) to post-repair (Z-score -4.5, p < 0.001), improved but remained abnormal at follow-up (Z-score -4.0, p < 0.001). RV fractional area change (FAC) and LV ejection fraction were not significantly different before and after surgery. Conduit regurgitation was moderate or greater in 11% at discharge, increased to 65% at follow-up. RV-PA conduit failure (severe pulmonary stenosis or severe pulmonary regurgitation) was noted in 61, and 63% had dilated RV (diastolic RV area Z-score > 2) at follow-up. RV dilation correlated with the severe conduit regurgitation (p = 0.018). Longitudinal RV function was reduced after complete repair of TOF/MAPCAs, with decreased TAPSE and preserved FAC and LV ejection fraction. TAPSE improved but did not normalize at follow-up. Severe RV-PA conduit dysfunction was observed prior to discharge in 11% of patients and in 61% at follow-up. RV dilation was common at follow-up, especially in the presence of severe conduit regurgitation.
Subject(s)
Cardiac Surgical Procedures , Heart Failure , Pulmonary Valve Stenosis , Tetralogy of Fallot , Humans , Heart Ventricles , Tetralogy of Fallot/diagnostic imaging , Tetralogy of Fallot/surgery , Retrospective Studies , Pulmonary Valve Stenosis/surgery , Ventricular Function, RightABSTRACT
Blood pressure gradient ( Δ P ) across an aortic coarctation (CoA) is an important measurement to diagnose CoA severity and gauge treatment efficacy. Invasive cardiac catheterization is currently the gold-standard method for measuring blood pressure. The objective of this study was to evaluate the accuracy of Δ P estimates derived non-invasively using patient-specific 0D and 3D deformable wall simulations. Medical imaging and routine clinical measurements were used to create patient-specific models of patients with CoA (N = 17). 0D simulations were performed first and used to tune boundary conditions and initialize 3D simulations. Δ P across the CoA estimated using both 0D and 3D simulations were compared to invasive catheter-based pressure measurements for validation. The 0D simulations were extremely efficient ( â¼ 15 s computation time) compared to 3D simulations ( â¼ 30 h computation time on a cluster). However, the 0D Δ P estimates, unsurprisingly, had larger mean errors when compared to catheterization than 3D estimates (12.1 ± 9.9 mmHg vs 5.3 ± 5.4 mmHg). In particular, the 0D model performance degraded in cases where the CoA was adjacent to a bifurcation. The 0D model classified patients with severe CoA requiring intervention (defined as Δ P ≥ 20 mmHg) with 76% accuracy and 3D simulations improved this to 88%. Overall, a combined approach, using 0D models to efficiently tune and launch 3D models, offers the best combination of speed and accuracy for non-invasive classification of CoA severity.
Subject(s)
Aortic Coarctation , Humans , Aortic Coarctation/diagnostic imaging , Blood Pressure , Magnetic Resonance Angiography/methods , Blood Flow Velocity , Computer SimulationABSTRACT
Objectives: It is well-known that right ventricle-to-pulmonary artery homograft conduit durability is worse for smaller conduits and smaller/younger patients. However, there is limited literature on age and conduit-size specific outcomes, or on the role of conduit oversizing. Methods: Patients diagnosed with tetralogy of Fallot and major aortopulmonary collateral arteries undergoing right ventricular outflow tract (RVOT) reconstruction with a valved aortic homograft conduit from November 2001 through March 2023, at our institution were included. Conduits were grouped and evaluated by diameter, diameter Z-score, and patient age at implant. The primary time-related outcome was freedom from RVOT reintervention. Factors associated with freedom from time-related outcomes were assessed with univariable Cox regression analysis. Results: A total of 863 RVOT conduits were implanted in 722 patients. On multivariable analysis, younger age, male sex, Alagille syndrome, smaller diameter of the conduit, and smaller Z-score were associated with shorter freedom from reintervention. Among patients with smaller diameter conduits, larger Z-scores were associated with longer freedom from conduit reintervention (P < .001). Transcatheter interventions were commonly used to extend conduit lifespan across ages and conduit sizes. Conclusions: Larger conduit diameter, older age, and higher conduit Z-score were associated with longer freedom from reintervention in patients undergoing RVOT reconstruction in this cohort. Oversizing of conduits, even beyond a Z-score of 4, is generally appropriate.
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BACKGROUND: Transcatheter pulmonary valve replacement (TPVR) has expanded and evolved since its initial commercial approval in the United States in 2010. OBJECTIVES: This study sought to characterize real-world practice, including patient selection, procedural outcomes, complications, and off-label usage. METHODS: Characteristics and outcomes for patients undergoing balloon-expandable TPVR were collected from the American College of Cardiology National Cardiovascular Data Registry IMPACT (Improving Pediatric and Adult Congenital Treatment) Registry. RESULTS: Between April 2016 and March 2021, 4,513 TPVR procedures were performed in patients with a median age of 19 years, 57% with a Melody (Medtronic Inc) and 43% with a SAPIEN (Edwards Lifesciences) valve. Most implanting centers performed <10 cases annually. One-third of transcatheter pulmonary valve implants were into homograft conduits, one-third were into bioprosthetic valves (BPVs), 25% were in native or patched right ventricular outflow tracts (RVOTs), and 6% were into Contegra (Medtronic Inc) conduits. Over the course of the study period, SAPIEN valve use grew from â¼25% to 60%, in large part because of implants in patients with a native/patched RVOT. Acute success was achieved in 95% of patients (95.7% in homografts, 96.2% in BPVs, 94.2% in native RVOTs, and 95.4% in Contegra conduits). Major adverse events occurred in 2.4% of procedures, more commonly in patients with a homograft (2.9%) or native RVOT (3.4%) than a prior BPV (1.4%; P = 0.004). CONCLUSIONS: This study describes novel population data on the use and procedural outcomes of TPVR with balloon-expandable valves. Over time, there has been increasing use of TPVR to treat regurgitant native RVOT anatomy, with the SAPIEN valve more commonly used for this application.
Subject(s)
Heart Valve Prosthesis , Pulmonary Valve , Transcatheter Aortic Valve Replacement , Adult , Humans , Child , Young Adult , Pulmonary Valve/diagnostic imaging , Pulmonary Valve/surgery , Treatment Outcome , RegistriesABSTRACT
BACKGROUND: Anatomic selection for Harmony valve implant is determined with the aid of a screening report and perimeter plot (PP) that depicts the perimeter-derived radius along the right ventricular outflow tract (RVOT) and projects device oversizing. The PP provides an estimation of suitability for implant, but its sensitivity as a screening method is unknown. This study was performed to describe anatomic features and outcomes in patients who underwent Harmony TPV25 implant despite a PP that predicted inadequate oversizing. METHODS: We reviewed RVOT anatomic features and measurements in patients who underwent transcatheter pulmonary valve replacement with the Harmony TPV25 device despite a PP that predicted inadequate oversizing. RESULTS: This study included 22 patients. There were no unsuccessful implants or adverse valve-related events. Anatomic features varied, but all patients fit into 1 of 3 anatomic types characterized by differences in RVOT dimensions. Type 1 patients (n=9) had a long RVOT with a choke point and a wide main pulmonary artery. Type 2 patients (n=6) had a short RVOT that was pyramidal in shape, with no choke point, and extensive main pulmonary artery lengthening/expansion during systole. Type 3 patients (n=7) had a short, bulbous main pulmonary artery with a choke point and an open pulmonary artery bifurcation. CONCLUSIONS: Transcatheter pulmonary valve replacement with the Harmony valve is feasible in some patients whose PP fit analysis predicts inadequate oversizing. All cases in this series fit into 1 of 3 anatomic patterns, which are not identified in the screening report. Implanters must review cases individually to assess the feasibility of the implant.
Subject(s)
Cardiac Catheterization , Heart Valve Prosthesis Implantation , Heart Valve Prosthesis , Prosthesis Design , Pulmonary Valve , Humans , Pulmonary Valve/surgery , Pulmonary Valve/diagnostic imaging , Pulmonary Valve/physiopathology , Heart Valve Prosthesis Implantation/instrumentation , Heart Valve Prosthesis Implantation/adverse effects , Cardiac Catheterization/instrumentation , Cardiac Catheterization/adverse effects , Treatment Outcome , Male , Female , Adolescent , Young Adult , Child , Adult , Retrospective Studies , Predictive Value of Tests , Pulmonary Valve Insufficiency/surgery , Pulmonary Valve Insufficiency/physiopathology , Pulmonary Valve Insufficiency/diagnostic imaging , Patient Selection , Clinical Decision-Making , Recovery of Function , HemodynamicsABSTRACT
BACKGROUND: Evidence for the efficacy of cardiac resynchronization therapy (CRT) in pediatric and congenital heart disease (CHD) has been limited to surrogate outcomes. OBJECTIVES: This study aimed to assess the impact of CRT upon the risk of transplantation or death in a retrospective, high-risk, controlled cohort at 5 quaternary referral centers. METHODS: Both CRT patients and control patients were <21 years of age or had CHD; had systemic ventricular ejection fraction <45%; symptomatic heart failure; and significant electrical dyssynchrony (QRS duration z score >3 or single-site ventricular pacing >40%) at enrollment. Patients with CRT were matched with control patients via 1:1 propensity score matching. CRT patients were enrolled at CRT implantation; control patients were enrolled at the outpatient clinical encounter where inclusion criteria were first met. The primary endpoint was transplantation or death. RESULTS: In total, 324 control patients and 167 CRT recipients were identified. Mean follow-up was 4.2 ± 3.7 years. Upon propensity score matching, 139 closely matched pairs were identified (20 baseline indices). Of the 139 matched pairs, 52 (37.0%) control patients and 31 (22.0%) CRT recipients reached the primary endpoint. On both unadjusted and multivariable Cox regression analysis, the risk reduction associated with CRT for the primary endpoint was significant (HR: 0.40; 95% CI: 0.25-0.64; P < 0.001; and HR: 0.44; 95% CI: 0.28-0.71; P = 0.001, respectively). On longitudinal assessment, the CRT group had significantly improved systemic ventricular ejection fraction (P < 0.001) and shorter QRS duration (P = 0.015), sustained to 5 years. CONCLUSIONS: In pediatric and CHD patients with symptomatic systolic heart failure and electrical dyssynchrony, CRT was associated with improved heart transplantation-free survival.
Subject(s)
Cardiac Resynchronization Therapy , Heart Defects, Congenital , Heart Failure, Systolic , Heart Transplantation , Humans , Child , Retrospective Studies , Heart Defects, Congenital/therapy , Heart Failure, Systolic/therapyABSTRACT
BACKGROUND: Transcatheter pulmonary valve replacement (TPVR) with the self-expanding Harmony valve (Medtronic) is an emerging treatment for patients with native or surgically repaired right ventricular outflow tract (RVOT) pulmonary regurgitation (PR). Limited data are available since U.S. Food and Drug Administration approval in 2021. OBJECTIVES: In this study, the authors sought to evaluate the safety and short-term effectiveness of self-expanding TPVR in a real-world experience. METHODS: This was a multicenter registry study of consecutive patients with native RVOT PR who underwent TPVR through April 30, 2022, at 11 U.S. CENTERS: The primary outcome was a composite of hemodynamic dysfunction (PR greater than mild and RVOT mean gradient >30 mm Hg) and RVOT reintervention. RESULTS: A total of 243 patients underwent TPVR at a median age of 31 years (Q1-Q3: 19-45 years). Cardiac diagnoses were tetralogy of Fallot (71%), valvular pulmonary stenosis (21%), and other (8%). Acute technical success was achieved in all but 1 case. Procedural serious adverse events occurred in 4% of cases, with no device embolization or death. Hospital length of stay was 1 day in 86% of patients. Ventricular arrhythmia prompting treatment occurred in 19% of cases. At a median follow-up of 13 months (Q1-Q3: 8-19 months), 98% of patients had acceptable hemodynamic function. Estimated freedom from the composite clinical outcome was 99% at 1 year and 96% at 2 years. Freedom from TPVR-related endocarditis was 98% at 1 year. Five patients died from COVID-19 (n = 1), unknown causes (n = 2), and bloodstream infection (n = 2). CONCLUSIONS: In this large multicenter real-world experience, short-term clinical and hemodynamic outcomes of self-expanding TPVR therapy were excellent. Ongoing follow-up of this cohort will provide important insights into long-term outcomes.
Subject(s)
Heart Valve Prosthesis Implantation , Heart Valve Prosthesis , Pulmonary Valve Insufficiency , Pulmonary Valve , Humans , Adult , Pulmonary Valve/surgery , Heart Valve Prosthesis Implantation/adverse effects , Cardiac Catheterization/adverse effects , Treatment Outcome , Pulmonary Valve Insufficiency/surgery , Pulmonary Valve Insufficiency/etiology , Registries , Prosthesis Design , Retrospective StudiesABSTRACT
Introduction: Primary central nervous system lymphoma (PCNSL) is a rare type of non-Hodgkin's lymphoma that affects brain parenchyma, eyes, cerebrospinal fluid, and spinal cord. Diagnosing PCNSL can be challenging because imaging studies often show similar patterns as other brain tumors, and stereotactic brain lesion biopsy conformation is invasive and not always possible. This study aimed to validate a previous proteomic profiling (PMID: 32610669) of cerebrospinal fluid (CSF) and develop a CSF-based proteomic panel for accurate PCNSL diagnosis and differentiation. Methods: CSF samples were collected from patients of 30 PCNSL, 30 other brain tumors, and 31 tumor-free/benign controls. Liquid chromatography tandem-mass spectrometry targeted proteomics analysis was used to establish CSF-based proteomic panels. Results: Final proteomic panels were selected and optimized to diagnose PCNSL from tumor-free controls or other brain tumor lesions with an area under the curve (AUC) of 0.873 (95%CI: 0.723-0.948) and 0.937 (95%CI: 0.807- 0.985), respectively. Pathways analysis showed diagnosis panel features were significantly enriched in pathways related to extracellular matrices-receptor interaction, focal adhesion, and PI3K-Akt signaling, while prion disease, mineral absorption and HIF-1 signaling were significantly enriched with differentiation panel features. Discussion: This study suggests an accurate clinical test panel for PCNSL diagnosis and differentiation with CSF-based proteomic signatures, which may help overcome the challenges of current diagnostic methods and improve patient outcomes.
Subject(s)
Biomarkers, Tumor , Brain Neoplasms , Proteomics , Humans , Proteomics/methods , Biomarkers, Tumor/cerebrospinal fluid , Brain Neoplasms/cerebrospinal fluid , Brain Neoplasms/diagnosis , Female , Male , Middle Aged , Aged , Diagnosis, Differential , Adult , Lymphoma, Non-Hodgkin/cerebrospinal fluid , Lymphoma, Non-Hodgkin/diagnosisABSTRACT
Background: Markers of aging hold promise in the context of colorectal cancer (CRC) care. Utilizing high-resolution metabolomic profiling, we can unveil distinctive age-related patterns that have the potential to predict early CRC development. Our study aims to unearth a panel of aging markers and delve into the metabolomic alterations associated with aging and CRC. Methods: We assembled a serum cohort comprising 5,649 individuals, consisting of 3,002 healthy volunteers, 715 patients diagnosed with colorectal advanced precancerous lesions (APL), and 1,932 CRC patients, to perform a comprehensive metabolomic analysis. Results: We successfully identified unique age-associated patterns across 42 metabolic pathways. Moreover, we established a metabolic aging clock, comprising 9 key metabolites, using an elastic net regularized regression model that accurately estimates chronological age. Notably, we observed significant chronological disparities among the healthy population, APL patients, and CRC patients. By combining the analysis of circulative carcinoembryonic antigen levels with the categorization of individuals into the "hypo" metabolic aging subgroup, our blood test demonstrates the ability to detect APL and CRC with positive predictive values of 68.4% (64.3%, 72.2%) and 21.4% (17.8%, 25.9%), respectively. Conclusions: This innovative approach utilizing our metabolic aging clock holds significant promise for accurately assessing biological age and enhancing our capacity to detect APL and CRC.
Subject(s)
Colorectal Neoplasms , Precancerous Conditions , Humans , Metabolomics , Aging , Healthy VolunteersABSTRACT
Background: Though Aspirin and intravenous immunoglobulin (IVIG) remain the standard treatments for Kawasaki Disease (KD) to minimize coronary artery damage, the duration and dosage of aspirin are inconsistent across hospitals. However, the lack of multi-center randomized trials prevents definitive answers to the impact of high-dose aspirin. Methods: This clinical trial was structured as a prospective, evaluator-blinded, multi-center randomized controlled trial with two parallel arms, aiming to assess the effectiveness of IVIG as a standalone primary therapy of KD in comparison to the combination of IVIG with high-dose aspirin therapy. KD patients were enrolled between September, 2016 and August, 2019. A final cohort of 134 patients were randomly assigned to the standard and test groups with 69 and 65 patients, respectively. The Standard group received IVIG (2 g/kg) along with aspirin (80-100 mg/kg/day) until fever subsided for 48 hours. The test group received IVIG (2 g/kg) alone. Following the initial treatment, both groups received a daily aspirin dose (3-5 mg/kg) for six weeks. The primary outcome measure was the occurrence of coronary artery lesions (CAL) at the 6-8 weeks mark. The secondary outcome is IVIG resistance. Results: The overall rate of CAL in test group decreased from 10.8% at diagnosis to 1.5% and 3.1% at 6 weeks and 6 months, respectively. The CAL rate of standard group declined from 13.0% to 2.9% and 1.4%, with no statistically significant difference (P>0.1) in the frequency of CAL between the two groups. Furthermore, no statistically significant differences were found for treatment (P>0.1) and prevention (P>0.1) effect between the two groups. Conclusions: This marks the first prospective multi-center randomized controlled trial comparing the standard treatment of KD using IVIG plus high-dose aspirin against IVIG alone. Our analysis indicates that addition of high-dose aspirin during initial IVIG treatment is neither statistically significant nor clinically meaningful for CAL reduction. Registration: URL: http://www.clinicaltrials.gov ; identifier: NCT02951234. What is New?: This study represents the first multi-center randomized controlled trial investigating the efficacy of high-dose aspirin or intravenous immunoglobulin (IVIG) during the acute stage of KD. This study assessed the impact of discontinuing high-dose aspirin (80-100 mg/kg/day) on the occurrence of CAL during the acute phase treatment of Kawasaki Disease.No significant differences were observed between high-dose aspirin plus IVIG treatment and IVIG alone treatment in terms of the frequency of abnormal coronary artery abnormalities. Additionally, our analysis revealed no statistically significant differences in either the treatment effect (the number of cases successfully treated) or prevention effect (the prevention of new cases) between these two treatments. What Are the Clinical Implications?: Comparison analysis indicated the non-inferiority between two groups with or without high-dose aspirin.Administering the standard 2 g/kg/day IVIG without high-dose aspirin (80-100 mg/kg/day) during the acute phase therapy for KD does not increase the risk of coronary artery lesions, which are a primary cause of morbidity and mortality in KD patients.Addition of high-dose aspirin during initial IVIG treatment is not statistically significant or clinically meaningful.
ABSTRACT
Background: Pregnancy triggers longitudinal metabolic alterations in women to allow precisely-programmed fetal growth. Comprehensive characterization of such a "metabolic clock" of pregnancy may provide a molecular reference in relation to studies of adverse pregnancy outcomes. However, a high-resolution temporal profile of metabolites along a healthy pregnancy remains to be defined. Methods: Two independent, normal pregnancy cohorts with high-density weekly urine sampling (discovery: 478 samples from 19 subjects at California; validation: 171 samples from 10 subjects at Alabama) were studied. Urine samples were profiled by liquid chromatography-mass spectrometry (LC-MS) for untargeted metabolomics, which was applied for gestational age dating and prediction of time to delivery. Results: 5,473 urinary metabolic features were identified. Partial least-squares discriminant analysis on features with robust signals (n = 1,716) revealed that the samples were distributed on the basis of the first two principal components according to their gestational age. Pathways of bile secretion, steroid hormone biosynthesis, pantohenate, and CoA biosynthesis, benzoate degradation, and phenylpropanoid biosynthesis were significantly regulated, which was collectively applied to discover and validate a predictive model that accurately captures the chronology of pregnancy. With six urine metabolites (acetylcholine, estriol-3-glucuronide, dehydroepiandrosterone sulfate, α-lactose, hydroxyexanoy-carnitine, and l-carnitine), models were constructed based on gradient-boosting decision trees to date gestational age in high accordance with ultrasound results, and to accurately predict time to delivery. Conclusion: Our study characterizes the weekly baseline profile of the human pregnancy metabolome, which provides a high-resolution molecular reference for future studies of adverse pregnancy outcomes.