BACKGROUND:Early fetal growth is a critical period for human development and of great importance for later life health. Detailed knowledge on normal and abnormal development of first trimester fetal and related structures is limited. This study aimed to construct first-trimester population distribution centiles for weeks of gestation and reference centiles for fetal crown to rump length, and yolk, gestational and amniotic sac between 6 and 13 weeks of gestation. METHODS:We used data from 3464 ultrasounds in 1609 pregnant women with information on first day of last menstrual period (LMP) and regular menstrual cycles participating in a population-based cohort study from preconception onwards. Ultrasound assessments were performed in a dedicated research center around 7, 9 and 11 weeks of gestation and included measurements of the crown to rump length, and diameters and volumes of the yolk, amniotic and gestational sac. Using Generalized Additive Modeling for Location, Size and Shape (GAMLSS), distribution and reference centiles were estimated for gestational age, crown to rump length, yolk sac, gestational sac and amniotic sac for the first trimester. RESULTS:We constructed distribution centiles for pregnancy dating based on first-trimester crown to rump length from 10 to 70 mm. Next, we generated gestational-age-based 5th, 10th, 25th, 50th, 75th, 90th, and 95th reference centiles for crown to rump length, and yolk, gestational and amniotic sac diameter and volume from 6 + 0 to 12 + 6 weeks of gestation. Length and diameter outcomes appeared to follow a nearly linear growth trajectory during this period of gestation. Confidence intervals showed that the centiles were most reliable between 6 + 0 and 12 + 6 weeks gestation. CONCLUSIONS:Using an urban population-based cohort in a high-income, Western country, we calculated descriptive population distribution centiles for LMP-based weeks of gestation, as well as reference charts for crown to rump length, yolk sac, gestational sac and amniotic sac for LMP-based gestational age. The latter are intended for use in clinical and population-based settings. Interpretation of these charts should proceed with the source population and potential bias in mind.
BACKGROUND:The increasing risk of complications after repeat induced abortions seriously threatens women's reproductive health and lives. This study aimed to identify risk factors for repeat abortion through time-stratified analysis to improve post-abortion care (PAC). METHODS:A prospective cohort study was conducted on patients undergoing abortion at Fengcheng Hospital, Fengxian District, Shanghai, between September 2022 and December 2024 (n = 557). Data were collected using structured questionnaires and hospital records. Participants were categorized into two groups based on the number of existing children: ≤1 birth (n = 133) and ≥2 births (n = 424). Univariate analyses were employed to identify variables with p < 0.05 for inclusion in multifactorial logistic regression models. Three time-stratified models (1-3, 4-6, and 7-12 months) were established to analyze the temporal characteristics of repeat abortion. RESULTS:Multiple regression analyses revealed significant associations between repeat abortion outcomes and several independent variables at different time intervals. Within 12 months, ethnic minorities exhibited 21.86-fold higher adjusted odds of repeat abortion compared to Han Chinese ethnicity (adjusted odds ratio (aOR) = 21.86, 95% CI: 4.92-97.17). Preoperative self-rating anxiety scale (SAS) scores ≥50 exhibited 83% risk reduction compared to SAS scores <50 (aOR = 0.17, 95% CI: 0.03-0.91). Preoperative self-rating depression scale (SDS) scores ≥53 revealed a 74% lower risk of repeat abortion compared to SDS scores <53 (aOR = 0.26, 95% CI: 0.07-0.94). Time-stratified analysis showed that the risk of repeat abortion was significantly higher among ethnic minorities from January to March (aOR = 35.56, 95% CI: 5.95-212.68). Furthermore, the risk was significantly higher among ethnic minorities from April to June (aOR = 32.73, 95% CI: 7.80-137.29). From July to December, ethnic minorities (aOR = 36.19, 95% CI: 9.69-135.18), a preoperative SAS score ≥50 (aOR = 0.15, 95% CI: 0.03-0.78), and a postoperative C-CSE score ≥30 (aOR = 0.21, 95% CI: 0.08-0.54) were significantly associated with repeat abortion. There were no significant differences in the incidence of repeat abortion across different time intervals. CONCLUSION:Ethnic minorities served as an independent risk factor for repeat abortion among Chinese women. However, due to the small sample size, our findings regarding the role of ethnic minorities should be interpreted cautiously. Additionally, psychological factors were identified as significant factors. In particular, preoperative anxiety (SAS ≥50) was associated with reduced odds of repeat abortion. This suggests that moderate anxiety may improve contraceptive adherence and lower the risk of repeat abortion. Postoperative contraceptive self-efficacy (C-CSE ≥30) protects against repeat abortion in the long term; therefore, enhancing contraceptive confidence is crucial for preventing repeat abortion.
OBJECTIVE:Eclampsia (E) and pre-eclampsia (PE) exhibit significant pathophysiological differences, yet the mitochondrial mechanisms underlying these differences are unclear. Our study conducted the first Mendelian randomization (MR) analysis to explore the specific causal effects of mitochondrial function-related proteins on E and PE, identifying actionable targets for precise prevention. METHODS:This two-sample Mendelian randomization study utilized three European-ancestry cohorts from FinnGen R12 (E/PE, E, and PE). Causal effects of mitochondrial proteins were estimated via the inverse variance weighted (IVW) method, with robustness confirmed through sensitivity analyses and MR-PRESSO for outlier removal. For mitochondrial genes identified through correction methods, we further conducted transcriptomic validation using independent GEO datasets to identify disease-causing genes associated with E/PE. RESULTS:The IVW results revealed distinct causal associations for E and PE. Specifically, 2,4-dienoyl-CoA reductase (DECR1) was associated with an increased risk of E (OR = 1.8788, 95% CI 1.0446-3.3791, p = 0.0352), while Serine-tRNA ligase (SerRS) showed a protective association with E (OR = 0.3090, 95% CI 0.1346-0.7097, p = 0.0056). For pre-eclampsia, Persulfide dioxygenase ETHE1 was associated with decreased risk (OR = 0.9341, 95% CI 0.8762-0.9958, p = 0.0367), while Transmembrane protein 70 (TMEM70) was associated with increased risk (OR = 1.0937, 95% CI 1.0023-1.1935, p = 0.0442). External validation using GEO datasets showed differential expression patterns of these genes in PE placental tissues. CONCLUSION:This MR study suggests distinct mitochondrial pathways for E and PE, with DECR1 and SerRS associated with E, and ETHE1 and TMEM70 with PE. These preliminary findings suggest non-overlapping genetic underpinnings and highlight the proteins as potential biomarkers for further investigation.
OBJECTIVE:To investigate the association between congenital uterine anomalies (CUAs) and placenta accreta spectrum (PAS), and to explore obstetric outcomes following hysteroscopic septal resection. METHODS:This retrospective cohort study included singleton pregnancies delivered at ≥22 weeks of gestation at a tertiary referral center between 2013 and 2024. PAS was diagnosed based on the 2019 International Federation of Gynecology and Obstetrics (FIGO) clinical or pathological criteria. The association between CUAs and PAS was evaluated using Firth's penalized logistic regression analysis. Sensitivity analyses were additionally performed using conventional logistic regression models. Obstetric outcomes following hysteroscopic septal resection were descriptively analyzed. RESULTS:Among 2,891 pregnancies, 31 (1.1%) involved CUAs, including 11 pregnancies following hysteroscopic septal resection. PAS occurred more frequently in the CUA group than in the non-CUA group (9.7% vs. 1.3%, p < 0.01). Firth's penalized logistic regression showed that CUAs were significantly associated with PAS (crude odds ratio [OR], 9.25; 95% confidence interval [CI], 2.42-26.1; p < 0.01). After adjustment for placenta previa or low-lying placenta, the association became stronger (adjusted OR, 21.8; 95% CI, 5.47-67.0; p < 0.001). Sensitivity analyses adjusting for advanced maternal age, assisted reproductive technology, and previous cesarean delivery showed consistent results. Cesarean delivery was significantly more common in pregnancies complicated by CUAs. In an exploratory descriptive analysis, no PAS cases were observed among following septal resection. CONCLUSION:CUAs may be a potential risk factor for PAS. In contrast, our exploratory analysis did not identify PAS cases following hysteroscopic septal resection. Large-scale multicenter studies using PAS defined according to the diagnostic criteria proposed by FIGO are essential to validate these findings and clarify the underlying mechanisms.
OBJECTIVE:This study aimed to evaluate the relationship between the Z-score of positive noninvasive prenatal testing (NIPT) results and the positive predictive value (PPV), as well as the correlation between Z-score and cell-free fetal DNA (cff-DNA) concentration, and the association between PPV and maternal age. METHODS:A total of 278 singleton pregnant women with high-risk NIPT results were included. Fetal karyotyping or copy number variation sequencing (CNV-Seq) was performed to confirm the presence of chromosomal abnormalities. The study evaluated the correlation between Z-scores of true positive NIPT results and the concentration of cff-DNA. Additionally, the study analyzed the association between NIPT Z-score and PPV, as well as the relationship between PPV and maternal age. Logistic regression analysis was used to assess the correlation between Z-scores and PPV. The diagnostic performance of Z-scores in detecting chromosomal aneuploidy was evaluated using receiver operating characteristic (ROC) curve analysis. RESULTS:Of the 242 pregnant women who opted for prenatal diagnosis through invasive amniocentesis, 184 cases were diagnosed as true positives. The total PPVs of NIPT screening for trisomy 21 (T21), trisomy 18 (T18), and trisomy 13 (T13) were 89.82%, 67.65%, and 26.83%, respectively. The Z-scores of T18 and T21 are positively correlated with the concentration of cff-DNA. The PPVs of T18 and T21 increase with rising Z-score. When 5 < Z ≤ 20, the PPV of T21 is the highest, while that for T13 is the lowest under the same Z-score. Furthermore, the PPV was found to be higher among pregnant women aged ≥35 years compared to those younger than 35 years. The ROC curve analysis showed that the optimal cutoff value of Z-scores for T21, T18, and T13 was 9.189, 14.08, and 13.72. The logistic regression analysis revealed that Z-scores of NIPT-positive results were significantly associated with the PPV at T21 (p < 0.001), T18 (p = 0.008), and T13 (p = 0.034). CONCLUSION:Z-score showed a positive correlation with cff-DNA concentration and PPV for T21 and T18. Based on these findings and current knowledge, we suggest that, a multi-parameter model (including Z-score, maternal age, cff-DNA%, and ultrasound markers) be evaluated in future studies to potentially improve NIPT accuracy and reduce false positives. This suggestion is speculative and requires prospective validation.
OBJECTIVE:To investigate the association between mid-pregnancy serum levels of insulin-like growth factor binding protein-1 (IGFBP-1) and chordin-like 1 (CHRDL1) and the occurrence of fetal growth restriction (FGR) in late pregnancy among women with gestational hypertension (GH). METHODS:This prospective nested case-control study was conducted within an established cohort of pregnant women with GH from January 2021 to January 2025. A total of 731 singleton pregnant women with GH at 20-24 gestational weeks were enrolled and followed up by dedicated nurses (those lost to follow-up were contacted at least three times) until late pregnancy (≥28 weeks), with 711 completing the entire follow-up. Based on prenatal ultrasound diagnosis, 106 cases of FGR were identified. These cases were individually matched in a 1:2 ratio (matching factors: maternal age, pre-pregnancy body mass index (BMI), and parity) with 212 controls selected from women without FGR, resulting in a final nested case-control sample of 318 participants. Fasting serum samples were collected at 20-24 weeks of gestation, and IGFBP-1 and CHRDL1 levels were measured by enzyme-linked immunosorbent assay (ELISA). FGR occurrence was assessed based on estimated fetal weight (EFW) monitored by B-ultrasound. Spearman's correlation analysis evaluated associations between mid-pregnancy serum concentrations of IGFBP-1 and CHRDL1 with EFW. Conditional logistic regression identified determinants of FGR development in late pregnancy within the GH cohort. The discriminative performance of mid-pregnancy serum IGFBP-1 and CHRDL1 for late-pregnancy FGR prediction was assessed using receiver operating characteristic (ROC) curve analysis. RESULTS:Among 731 pregnant women with GH, 20 (2.74%) were lost to follow-up, and 711 completed the entire follow-up; of these, 106 (14.91%) developed FGR. Following 1:2 matching with 212 controls, 318 participants were included in the nested analysis. Serum levels of IGFBP-1 and CHRDL1 were significantly higher in the FGR group compared with the control group (both p < 0.001). The two biomarkers were positively correlated with each other (r = 0.455, p < 0.05) and negatively correlated with EFW (r = -0.335, -0.304, both p < 0.05). Conditional logistic regression analysis revealed that elevated systolic blood pressure (SBP), diastolic blood pressure (DBP), IGFBP-1, and CHRDL1 were independent risk factors for FGR, while elevated triglycerides (TG) were protective factors. ROC curve analysis demonstrated that the area under the curve (AUC) for IGFBP-1 and CHRDL1 alone in predicting FGR was 0.734 (95%CI: 0.677-0.791) and 0.704 (95%CI: 0.645-0.762), respectively; the combined AUC was 0.801 (95%CI: 0.750-0.852). CONCLUSIONS:Elevated serum IGFBP-1 and CHRDL1 levels in mid-pregnancy are independent risk factors for FGR in late pregnancy among women with GH. The combination of these two biomarkers demonstrates favorable predictive value, providing an actionable biomarker panel for early identification of high-risk populations in clinical practice, enabling intensified monitoring and intervention initiation at 20-24 weeks of gestation, and ultimately improving perinatal outcomes.
INTRODUCTION:True labor is characterized by regular uterine contractions and cervical changes. However, the precise diagnosis of the "onset" of true labor is challenging, as the examination of cervical changes requires multiple timepoints, and it is a retrospective diagnosis. The objectives of this study are to determine the predictive performance of 1) cervical length, 2) cervicovaginal fluid fetal fibronectin, and 3) maternal angiogenic factors concentration [placental growth (PlGF), soluble fms-like tyrosine kinase-1 (sFlt-1), or its ratio (sFlt-1/PlGF)] for the identification of spontaneous true onset of labor at term within 24 h of the assessment in singleton pregnant women presenting with labor symptoms (i.e. differentiating true and false labor). MATERIAL AND METHODS:Design: A prospective observational cohort studySetting: Labor and Delivery unit, Bangkok, ThailandMethods: 146 singleton pregnancies with symptoms of labor were enrolled. A total of 132 patients underwent transvaginal measurements of cervical length and angiogenic factors, with cervicovaginal fluid fetal fibronectin available in 90 cases.Main Outcome Measures: The primary outcome was the spontaneous onset of true labor at term, defined as regular uterine contractions occurring at a frequency of at least 4 in 20 min with either cervical dilatation ≥4 cm or effacement of ≥ 80% or cervical changes or spontaneous rupture of membranes, followed by delivery within 24 h of the onset of true labor in women at ≥37th weeks of gestation. Predictive performance of individual biomarkers and the combined model was calculated to identify the spontaneous onset of true labor at term. RESULTS:The combination of cervical length and fetal fibronectin yielded significantly better predictive performance than the individual markers, with a sensitivity of 62.1%, a specificity of 90.6%, a positive predictive value of 92.3%, a negative predictive value of 56.9%, as well as a positive and a negative likelihood ratio of 6.62 and 0.42, respectively, for the identification of spontaneous true onset labor at term with delivery within 24 h of the assessment. CONCLUSION:Cervical length measurement with fetal fibronectin had a high specificity, positive predictive value, and positive likelihood ratio, but low negative predictive value and moderate negative likelihood ratio for identifying the spontaneous true onset of labor at term. This test may be used as a bedside test to rule in the diagnosis of true labor. However, its moderate sensitivity and negative likelihood ratio, along with a low negative predictive value, indicate that a negative result cannot safely discharge patients and may limit its use as a standalone triage test, warranting the search for other biomarkers.
OBJECTIVE:To compare the predictive performance of three Doppler ratio indices-cerebroplacental ratio (CPR), cerebral-placental-uterine ratio (CPUR), and uteroplacental-cerebral ratio (UCPR)-for adverse perinatal outcomes in late-onset fetal growth restriction (FGR). METHODS:This retrospective cohort study analyzed singleton pregnancies diagnosed with late-onset FGR (≥32 weeks) between October 2024 and January 2026. Doppler parameters-umbilical artery pulsatility index (UA-PI), middle cerebral artery pulsatility index (MCA-PI), and mean uterine artery pulsatility index (mean UtA-PI)-were retrieved at diagnosis. Three indices were calculated: CPR (MCA-PI/UA-PI), CPUR (CPR/mean UtA-PI), and UCPR ((UA-PI + mean UtA-PI)/MCA-PI). Univariable and multivariable logistic regression models (adjusting for estimated fetal weight percentile and gestational age) were constructed. Internal validation used bootstrap resampling (n = 1000). AUC pairwise comparisons employed the DeLong test, and decision curve analysis (DCA) evaluated clinical utility. RESULTS:Of 155 pregnancies, adverse perinatal outcomes occurred in 48 (31.0%). Affected pregnancies had earlier delivery (35.88 ± 1.17 vs. 37.74 ± 1.20 weeks, p < 0.001) and lower birth weight (1948.04 ± 213.15 vs. 2336.05 ± 306.45 g, p < 0.001). All indices differed significantly between groups (p < 0.05). In univariable analysis, CPUR achieved the highest AUC of 0.781 (95% CI: 0.698-0.856), followed by UCPR (0.777, 95% CI: 0.698-0.851) and CPR (0.740, 95% CI: 0.652-0.820). Optimal cutoffs were CPR ≤ 1.44, CPUR ≤ 1.38, and UCPR > 1.32. Pairwise comparisons revealed no statistically significant differences (all p > 0.05). In multivariable analysis, all ratios remained independently associated with adverse outcomes (CPR: aOR 0.37; CPUR: aOR 0.29; UCPR: aOR 2.71; all p < 0.001), with improved discrimination (AUC: 0.793-0.816). DCA demonstrated clinical benefit across threshold probabilities of 15-50%. CONCLUSIONS:In late-onset FGR, CPR, CPUR, and UCPR showed comparable predictive accuracy for adverse perinatal outcomes, each maintaining independent predictive value after adjustment for disease severity and gestational age. Statistically non-significant pairwise differences should not be interpreted as clinical equivalence; multicenter prospective studies are warranted. These indices may assist clinical decision-making in late-onset FGR management.
OBJECTIVE:To establish reference values for fetal heart rate (FHR) indices across time, frequency and nonlinear domains throughout pregnancy in a tertiary hospital population, considering sex. The influence of the number of fetuses, birth weight ,and time to delivery on FHR was evaluated. METHODS:This retrospective cohort study analyzed the initial FHR tracing upon hospital admission between 24° and 41° weeks of gestation, excluding cases in labor, with medication use, or a confirmed medical indication. Reference values were established using the Generalized Additive Models for Location Scale and Shape framework. Likelihood ratio test assessed whether including clinical variables significantly improved model fit. RESULTS:The cohort included 3219 fetuses, of which 48% were female and 91% singleton pregnancies. Median gestational age was 32+6. Birth weight was below p10 in 22% and above p90 in 9%. Median tracing duration was 42.5 min and median signal loss was 1.95%. Most indices were significantly associated with gestational age and several showed significant sex differences. Model fit significantly improved for multiple indices when including number of fetuses, birth weight, or time to delivery. CONCLUSIONS:This article presents gestational age- and sex-specific reference values for FHR in a large tertiary hospital population. The influence of gestational age was reaffirmed and significant differences related to sex, number of fetuses, birth weight, and time to delivery were identified. This enhances understanding of fetal autonomic regulation and supports a more individualized approach to predictive fetal monitoring. Further research is needed to determine the clinical utility of these reference values in practical monitoring and risk assessment.
OBJECTIVE:Umbilical venous catheterization (UVC) may fail because of resistance during catheter advancement, malposition, impaired catheter function, or procedure termination. Preprocedural predictors of failed UVC remain poorly defined. This study developed and internally validated a preprocedural model for failed UVC in neonates. METHODS:This single-center retrospective cohort study included 123 neonates who underwent UVC between April 2023 and May 2025. Candidate predictors were restricted to variables available before or at catheterization, including perinatal characteristics, Apgar scores, blood gas parameters, respiratory support, congenital anomalies, inflammatory markers, and coagulation indices. Failed UVC was defined as technical failure, positional failure, functional failure, or clinical termination. An Elastic Net penalized logistic regression model was developed and internally validated using 100 repetitions of stratified 10-fold cross-validation. RESULTS:UVC failure occurred in 40 of 123 neonates (32.5%). Failed UVC was associated with lower birth weight, more severe acidosis, impaired gas exchange, and coagulation abnormalities. During internal validation, the model showed high discrimination in this single-center cohort, with a mean AUC of 0.9999 (2.5th-97.5th percentile: 0.9997-1.0000) and a mean Brier score of 0.0062 (0.0038-0.0081). Base excess, PaCO2, birth weight, prothrombin time, activated partial thromboplastin time, and fibrinogen were consistently retained during repeated cross-validation. CONCLUSIONS:A preprocedural model based on routinely available clinical and laboratory indicators showed high internal performance for estimating failed UVC risk in this cohort. The retained predictors mainly reflected preprocedural illness severity. Observed UVC failure may also involve procedural context and local workflow. The model should be regarded as exploratory pending multicenter prospective external validation.
BACKGROUND:Low 5-minute Apgar scores are widely used as indicators of neonatal compromise and in perinatal performance assessments, but interpretation varies by case mix and local escalation and transfer protocols, especially in regional (non-tertiary) hospitals. This study examines delivery-room escalation, early neonatal care, and maternal and intrapartum risk factors associated with Apgar scores below 7. METHODS:The study used an unmatched case-control design of term infants (≥37 weeks' gestation) born at a regional Australian health service from 2018 to 2022. Cases were liveborn infants with a 5-minute Apgar score <7; controls had a score ≥7. Delivery-room escalation events, early postnatal disposition, and tertiary transfer were compared between groups. Multivariable logistic regression identified maternal and intrapartum factors associated with low Apgar scores, with significance at p < 0.05. RESULTS:Among 3,919 term births, the incidence of a 5-minute Apgar score below 7 was 2.32%, higher than the national average (1.4%). Cases had higher odds of requiring active resuscitation, delivery room escalation, and higher-acuity postnatal care. Resuscitation was performed in 100% of cases versus 41.8% of controls; code blue activation occurred in 40.7% of cases and 2.2% of controls. Special Care Nursery admission was in 81.3% of cases; 6.6% required tertiary transfer, whereas controls were more often managed on the postnatal ward (50.5%). Multivariable analysis identified cesarean delivery (aOR 2.60, 95% CI 1.21-5.58), prolonged rupture of membranes (aOR 2.91, 95% CI 1.06-7.95), and shoulder dystocia (aOR 9.38, 95% CI 1.07-82.54) as associated with Apgar <7. Intrapartum morphine use (aOR 0.13, 95% CI 0.05-0.38) and previous cesarean (aOR 0.31, 95% CI 0.11-0.87) were inversely associated and potentially protective. CONCLUSION:In this regional, non-tertiary setting, a low 5-minute Apgar score, reported more frequently, identifies a clinically meaningful "at-risk transition" phenotype associated with a substantial, quantifiable escalation burden. Rather than being interpreted as an isolated quality figure, it may also inform more nuanced local audits, benchmarking, and service planning.
OBJECTIVES:Respiratory distress syndrome (RDS) is common in preterm infants, accounting for significant healthcare resource utilization (HCRU). To address knowledge gaps in mature preterm infants, this study evaluated one-year post-discharge HCRU by surfactant administration. METHODS:This study included moderate (32 0/7-33 6/7 weeks) and late preterm infants (34 0/7-36 6/7 weeks) with RDS (ICD-10-CM P22.0) requiring >12 h of respiratory support during birth hospitalization at a Kaiser Permanente Hospital in Northern California (2019-2023). Nested logistic regression estimated adjusted odds ratios (aORs) for associations between surfactant receipt and one-year outcomes [any/respiratory emergency department (ED) visits and hospitalizations] across four sequential models: unadjusted; +birth/demographic factors; +clinical severity; +social factors. RESULTS:Among 1,674 infants, 316 (18.9%) received surfactant and had greater in-hospital severity (moderate-to-severe RDS 23.1% vs. 2.3%; invasive ventilation 25.6% vs. 1.3%; respiratory support ≥94 h 54.2% vs 26.1%; p < 0.001). After discharge, surfactant treated infants were more likely to have any ED visits and hospitalizations compared to non-treated infants. However, associations were attenuated and no longer significant after adjustment for birth/demographics, clinical severity and social factors for any ED visits (aOR:1.28 [0.93, 1.76]) and hospitalizations (aOR:1.33 [0.74, 2.40]). Respiratory ED visits remained elevated after adjustment while estimates for respiratory hospitalizations were imprecise. CONCLUSION:Among moderate and late preterm infants with RDS, surfactant receipt was associated with greater in-hospital severity. However, adjusting for severity when estimating odds of post-discharge outcomes resulted in small, inconsistent differences. Future studies should consider more precise measures of RDS severity and the impact of post-discharge factors on HCRU.
BACKGROUND:Gestational diabetes mellitus (GDM) arises from increasing insulin resistance during pregnancy combined with inadequate pancreatic β-cell adaptation and is associated with adverse pregnancy outcomes. Obesity and maternal hyperglycemia contribute to these risks, yet GDM is increasingly recognized as a heterogeneous condition. We evaluated whether pre-pregnancy BMI and oral glucose tolerance tests (OGTT)-derived fasting (FPG) and 2-hour glucose values show distinct associations with adverse pregnancy outcomes in a risk-based screened cohort. MATERIAL AND METHODS:We performed a post-hoc analysis of 4,431 OGTTs (2011-2016) from a Dutch risk-based screening cohort. Outcomes were described across predefined BMI and glucose categories, followed by multivariable logistic regression with BMI, FPG measured at the time of OGTT, and 2-hour glucose entered simultaneously and additionally adjusted for treatment status. Eight clinical subgroups combining BMI with fasting and 2-hour glucose thresholds were also explored. RESULTS:Higher BMI was mainly associated with hypertensive disorders of pregnancy and cesarean delivery. Higher FPG levels showed the broadest associations, including adverse maternal, delivery and neonatal outcomes. Higher 2-hour post-load glucose levels were primarily associated with fetal growth-related outcomes and neonatal hypoglycemia. Adjustment for treatment attenuated some 2-hour glucose-related associations but did not materially affect BMI- or FPG-related risks. CONCLUSIONS:In women undergoing OGTT because of risk factors or clinical suspicion of GDM, pre-pregnancy BMI, fasting glucose measured at the time of OGTT, and 2-hour post-load glucose demonstrate distinct patterns of association with adverse pregnancy outcomes. These findings suggest heterogeneous patterns of dysglycemia-related risk, alongside the independent contribution of BMI, in a risk-based screening population.
BACKGROUND:Aberrant right subclavian artery (ARSA) is the most frequent aortic-arch branching variant on prenatal sonography, and its clinical relevance is governed by the phenotypic context in which it is detected. Genotype-phenotype interpretation remains complicated by uneven genetic testing uptake and the additional anomaly burden carried in non-isolated cases. METHODS:This retrospective single-center cohort comprised 350 singleton pregnancies in which ARSA was diagnosed prenatally at a tertiary perinatology center between January 2020 and April 2025. Cases were classified as isolated ARSA (n = 200), ARSA with soft markers (n = 80), or non-isolated ARSA (n = 70). The primary outcome was chromosomal abnormalities, reported with explicit denominator separation: whole-cohort prevalence and diagnostic yield among invasively tested fetuses. The 22q11.2 deletion case definition required dual confirmation by FISH and chromosomal microarray analysis (CMA). Marker- and anomaly-specific yields were examined to identify findings most strongly linked to chromosomal and adverse pregnancy outcomes. RESULTS:Genetic evaluation acceptance varied by phenotype (75.0% isolated, 92.5% soft markers, 92.9% non-isolated; p < 0.001). Whole-cohort chromosomal-abnormality prevalence was 4.5%, 17.5%, and 32.9%; diagnostic yield among invasively tested fetuses was 6.0%, 18.9%, and 35.4%. Trisomy 21 was the most frequent abnormality across phenotypes. Five 22q11.2 deletions (1/1/3 across phenotypes) fulfilled the dual-confirmation criteria; all three non-isolated 22q11.2 cases harbored a conotruncal cardiac anomaly. Marker co-occurrence (≥2 markers, 43.8% of soft-markers) and concurrent major anomalies (≥2, 44.3% of non-isolated) drove yield. Live-birth rates were 97.5%, 87.5%, and 71.4% (p < 0.001). On multivariable logistic regression, ARSA with soft markers (adjusted OR 4.52; 95% CI 1.86-10.96) and non-isolated ARSA (adjusted OR 10.51; 95% CI 4.52-24.44) remained independent predictors of chromosomal abnormality (optimism-corrected AUC 0.708). A compound phenotype (major anomaly + ≥2 soft markers) was present in 25.7% of non-isolated fetuses. CONCLUSIONS:Phenotype-based classification of prenatal ARSA reveals a significant risk gradient for chromosomal abnormality and adverse pregnancy outcome, with co-occurring markers and conotruncal anomalies emerging as the strongest individual signals. The findings support risk-concordant counseling: conservative invasive testing in confirmed isolated ARSA, intensified evaluation when soft markers co-occur, and a compound-phenotype-aware, anatomy-directed approach, including CMA and 22q11.2-targeted testing for conotruncal lesions, in the non-isolated subgroup.
BACKGROUND:The use of antiretroviral therapy (ART) during pregnancy among women living with human immunodeficiency virus (HIV) may adversely affect their cardiometabolic health, but its influence on fetal growth remains underexplored. This study aimed to investigate the relationship between maternal cardiometabolic health and fetal growth in pregnant women living with HIV receiving ART in Mthatha, South Africa. METHODS:A pilot study included 21 HIV-positive and 53 HIV-negative pregnant women, measuring anthropometric parameters and blood pressure. Cardiometabolic risk factors were assessed, including dyslipidemia, glycemia, oxidative stress, endothelial function, and inflammatory markers. Noninvasive vascular function indicators, including uterine artery pulsatile index (UtA PI), flow-mediated slowing (FMS), carotid-femoral pulse wave velocity (cfPWV), and ankle-brachial index (ABI) were evaluated. Fetal growth parameters, including femur length (FL), biparietal diameter, head circumference (HC), abdominal circumference (AC), and estimated fetal weight, were recorded. Relationships between maternal health and fetal growth were analyzed with a significance threshold of p ≤ 0.05. RESULTS:Prehypertension was more common among pregnant women living with HIV (14.29% vs. 1.89%). Additionally, higher cfPWV, UtA, and LDL-C levels were noted in the HIV-positive group (p ≤ 0.05). A negative correlation (p ≤ 0.05) was found between maternal UtA PI and fetal growth parameters such as AC, FL and HC. CONCLUSION:Vascular dysfunction was observed in pregnant women living with HIV on ART coupled with an inverse association between maternal vascular function and fetal growth suggesting that impaired maternal vascular function may limit placental blood flow and potentially affect fetal growth.
OBJECTIVE:To investigate the associations of serum high-mobility group box-1 (HMGB1) and soluble cluster of differentiation antigen-14 (sCD14) with disease severity in neonatal jaundice, and to explore their relationship with phototherapy response. METHODS:A total of 345 neonates with hyperbilirubinemia (February 2023-May 2025) and 100 healthy controls were prospectively enrolled. Patients were stratified into mild (n = 273) and severe (n = 72) groups based on total serum bilirubin (TSB). Serum HMGB1 and sCD14 levels were measured by enzyme-linked immunosorbent assay (ELISA) according to the manufacturers' instructions with strict quality control. After intermittent phototherapy, response was classified as effective (n = 294) or ineffective (n = 51). Correlations were assessed by Spearman's rank test. Multivariable logistic regression and receiver operating characteristic (ROC) curve analyses were performed. RESULTS:Serum HMGB1 and sCD14 levels were elevated in jaundice patients versus controls, with further increases in severe versus mild hyperbilirubinemia (all p < 0.05). TSB, alanine aminotransferase (ALT), and aspartate aminotransferase (AST) showed similar patterns. HMGB1 and sCD14 positively correlated with TSB, AST, and ALT (all p < 0.05). AST, ALT, HMGB1, and sCD14 differed significantly between the effective and ineffective phototherapy groups (all p < 0.05). Multivariable logistic regression identified AST, ALT, HMGB1, and sCD14 as independent predictors of treatment failure (all p < 0.05). ROC analysis revealed AUCs of 0.75 for HMGB1 alone and 0.75 for sCD14 alone, with their combination yielding a significantly higher AUC of 0.83. CONCLUSIONS:In term neonates with non-hemolytic jaundice without severe comorbidities, serum HMGB1 and sCD14 levels are closely associated with disease severity and correlate with the efficacy of phototherapy. Their combined assessment may provide valuable reference indices for predicting phototherapy outcomes.
BACKGROUND:Gestational diabetes mellitus (GDM) affects 15.6% of pregnancies globally, with Vietnam exhibiting one of the highest prevalences at 21%. Current diagnostic approaches at 24-28 weeks limit early intervention opportunities. We developed a multi-modal machine learning framework integrating cell-free DNA (cfDNA) structural features and genetic information for early GDM prediction at 10-12 weeks of gestation in Vietnamese women. METHODS:We analyzed blood samples from 1,086 pregnant women (435 GDM cases, 651 controls) collected at 9-12 weeks. Two parallel analytical pathways were employed: cfDNA profiling extracting cfDNA-specific features (fragment length, end motifs, GC content, nucleosome patterns), and whole-genome imputation generating predictions for ∼19,000 omics traits. Component scores were developed using TabPFN classifier and integrated via logistic regression into a unified master score. RESULTS:Genome-wide analysis identified five omics traits with significant GDM associations: HSD11B1, NEK7, COMMD10, KLRC4, and OCEL1. Component score optimization revealed distinct patterns-cfDNA scores peaked at 200 features (AUC = 71.53), while genetics-based scores improved with up to 2,000 omics traits (AUC = 77.21). The final master score, integrating three components (gbSC2000, gbSCBH, cfSC200), achieved AUCs of 86.82-87.19 across validation cohorts with 70% sensitivity and 89% specificity. Addition-deletion analysis confirmed that both cfDNA and genetic components provided essential, non-redundant contributions. CONCLUSIONS:This multi-modal framework demonstrates superior performance compared to single-biomarker approaches, enabling risk stratification from very low (4% GDM prevalence) to very high risk (90% prevalence). At the cutoff 0.4, the model identifies 78% of future GDM cases at 10-12 weeks while maintaining an 18% false-positive rate, potentially enabling early interventions to prevent GDM development and associated complications.
PURPOSE:To develop a nomogram model for individualized prediction of fetal growth restriction (FGR) among pregnant women with iron deficiency anemia (IDA) and to evaluate its predictive performance and clinical utility. METHODS:A retrospective study was conducted on 351 pregnant women diagnosed with IDA between December 2017 and October 2024. After excluding 95 participants based on predefined criteria, 256 women were included and divided into a training cohort (n = 179) and an internal test cohort (n = 77) at a ratio of 7:3 for model construction and internal validation, respectively. Least absolute shrinkage and selection operator (LASSO) regression was used to identify independent risk factors and construct the nomogram. The model's performance was evaluated based on discrimination (ROC curve and AUC), calibration (calibration curves), and clinical utility (Decision Curve Analysis). RESULTS:Six independent predictors for FGR were identified: red blood cell count (RBC), hemoglobin (Hb), serum ferritin (SF), folic acid supplementation, gestational diabetes mellitus (GDM), and hypertensive disorders of pregnancy (HDP). The nomogram demonstrated excellent discriminative ability, with an AUC of 0.972 (95% CI: 0.946-0.998) in the training cohort and 0.950 (95% CI: 0.892-1.000) in the internal test cohort. Calibration curves showed high consistency between predicted and observed outcomes, and DCA confirmed the model's substantial net clinical benefit. CONCLUSION:The individualized nomogram model based on clinical and hematological parameters provides an accurate and practical tool for predicting FGR in women with gestational anemia due to IDA, offering substantial potential for clinical risk stratification and early intervention.
Background The uterus and its myometrium undergo several changes during delivery. In labor, the myometrium performs contractions to expel the newborn. In a cesarean section, however, the myometrium is incised. Little is known about labor-induced changes in biomarkers that are known to rise during injuries and exhaustion of another muscle, the heart. These markers can also be produced by the myometrium, especially damaged myometrium. Since labor is known to cause slight myocardial challenge, physiological changes in cardiac biomarkers in the context of labor versus after an incision of the uterus are of new interest. Here, we question whether cardiac biomarkers could also be produced by the uterus. If this were the case, the interpretation of the myocardial ischemic marker peripartum needed a revision. This study investigated whether cardiac biomarkers might be influenced by uterine activity or injuries from cesarean sections.Methods We conducted a prospective study on the peripartum trajectories of creatine kinase (CK, cardiac isoenzyme CK-MB), high-sensitivity cardiac troponin-T (hs-cTnt), and N-terminal pro-B-type natriuretic peptide (NT-Pro-BNP) in 44 cardiologically healthy pregnant women. The participants were stratified by delivery mode: cesarean section (CS, n = 24) versus vaginal delivery (VD, n = 20).Results Our findings indicate that ischemia biomarkers (hs-cTnT, CK and CK-MB) increase more during the postpartum period than they do after a cesarean section, whereas NT-Pro-BNP levels increase after cesarean section. These elevations remained within normal ranges and were not associated with clinical symptoms.Conclusion Biomarker levels differ based on delivery mode, indicating that mode of birth influences biomarker fluctuations postpartum within a physiological range. The incision of the uterus does not reveal higher marker levels than contractions do; therefore, this kind of myometrial damage is not associated with an increase in ischemic biomarkers. The observed elevations are linked to slight myocardial damage in the peripartum phase after labor, comparable to exercise. The myometrium does not appear to provide evidence for a clinically meaningful contribution based on peripheral measurements of highly sensitive troponin, CK and CKMB.
OBJECTIVE:To investigate the predictive value of the cerebroplacental-uterine ratio (CPUR) combined with multiple ultrasound parameters for adverse perinatal outcomes (APOs) in late-onset fetal growth restriction (FGR). METHODS:This retrospective study included 149 singleton pregnant women diagnosed with suspected late-onset FGR at our hospital from August 2023 to January 2025. Based on perinatal outcomes, they were divided into a non-adverse outcome group (105 cases) and an adverse outcome group (44 cases). Ultrasound parameters including umbilical artery pulsatility index (UA-PI), middle cerebral artery pulsatility index (MCA-PI), uterine artery pulsatility index (UtA-PI), cerebroplacental ratio (CPR), CPUR, aortic isthmus pulsatility index (AoI-PI), and estimated fetal weight (EFW) percentile were measured and compared between the two groups. Univariate analysis was used to screen significant variables, followed by binary logistic regression analysis to identify independent predictors. Receiver operating characteristic (ROC) curves were plotted to evaluate the predictive performance of individual indicators and combined models. RESULTS:The adverse outcome group had significantly higher levels of UA-PI, UtA-PI, AoI-PI, and a higher proportion of EFW <5th percentile compared to the non-adverse outcome group, while MCA-PI, CPR, and CPUR levels were significantly lower (all p < 0.001). Multivariate regression analysis showed that CPUR (OR = 0.061, 95% CI: 0.021-0.172), AoI-PI (OR = 14.003, 95% CI: 3.928-49.925), and EFW <5th percentile (OR = 3.386, 95% CI: 1.124-10.193) were independent predictors of APOs in late-onset FGR. ROC curve analysis revealed that the combined prediction model incorporating CPUR, AoI-PI, and EFW (<5th) had the best predictive performance, with an AUC of 0.932 (95% CI: 0.890-0.974), sensitivity of 84.1%, and specificity of 86.7%, outperforming any single indicator. CONCLUSION:CPUR, AoI-PI, and EFW (<5th) are independent predictors of APOs in late-onset FGR. The combined prediction model constructed from these three parameters demonstrates high predictive value and may provide a reference for early identification of high-risk fetuses and optimization of perinatal management.
