Composite Adverse Outcome Research Articles

Clinical impact of circulating biomarkers in prediction of adverse cardiac events in patients with congenital heart disease. A systematic review

IntroductionPatients with congenital heart disease (ConHD) are at increased risk for adverse cardiac events. Predicting long-term outcomes and guidance of patient management might benefit from a range of (new) biomarkers. This is a rapidly evolving field with potentially large consequences for clinical decision making. With a systematic review of available biomarkers in ConHD we identified the clinical role of these markers, knowledge gaps and future research directions. MethodsWe systematically reviewed the literature on associations between blood biomarkers and outcome measures (mortality or composite adverse outcomes in patients with ConHD. ResultsThe inclusion criteria were met by 102 articles. Biomarkers assessed in more than studies are discussed in the main text, those studied in 3 or less studies are summarized in the supplement. Thus, we discuss 15 biomarkers from 92 studies. These biomarkers were studied in 32,399 / 10,735 patients for the association with mortality and composite adverse outcomes, respectively. Biomarkers that were studied most and had statistically significant associations with mortality or composite adverse outcomes were (NT-pro)BNP, MELD-XI score, Hs-CRP, creatinine, albumin and sodium. Most of these biomarkers are involved in intracardiac processes associated with inflammation or are markers of renal function. ConclusionFor (NT-pro)BNP, clinical value for prediction of mortality and composite adverse outcomes in adult and paediatric ConHD has been shown. For MELD-XI, hs-CRP, albumin, creatinine, sodium, RDW, and GDF-15, correlations with mortality and composite adverse outcomes have been demonstrated in patient groups with mixed types of ConHD, but clinical utility needs additional exploration.

Abstract TP132: Safety-net Hospitals in the U.S. Have Worse Outcomes than Non-safety Net Hospitals for Ischemic Stroke

Background: Safety-net hospitals (SNHs) are crucial in serving uninsured, underinsured, and socioeconomically disadvantaged populations, who often face financial limitations and resource shortages compared to their counterparts. We hypothesized that patients with ischemic stroke treated at SNHs would have inferior outcomes compared to non-SNHs, which may be related to the patient's socioeconomic status and care allocation. Methods: The National Inpatient Sample Database was queried to identify adult patients (≥18 years) who were hospitalized for ischemic stroke from 2016 to 2019. Patients with safety-net features were those with Medicaid or no insurance. Hospitals were ranked based on the percentage of patients with safety-net features. Hospitals in the top quartile were defined as SNHs, and the remaining hospitals were defined as non-SNHs. The characteristics and outcomes of the patients with or without safety-net features treated at SNHs vs non-SNHs were compared after adjusting for patient and hospital characteristics. A composite overall outcome variable was also generated to include in-hospital mortality, acute renal failure, tracheostomy, and sepsis. Results: We identified a weighted total of 1,823,985 patients, including 501,345 treated at SNHs and 1,550,100 at non-SNHs. The patients treated at SNHs were more likely to be non-white, had lower socioeconomic status but higher neurological severity, and more frequently required endovascular thrombectomy. They were associated with higher in-hospital mortality (adjusted odds ratio [aOR] 1.14, 95% confidence interval [CI] 1.09-1.19, p<0.001) and composite outcome (aOR 1.17, 95% CI 1.14-1.19), and longer hospital length of stay (5.6±7.7 vs 4.5±5.4 days, p<0.001) (Figure 1). Patients without safety-net features who were cared at SNHs had higher neurological acuity and worse outcomes compared to those treated at non-SNHs including in-hospital mortality (aOR 1.14, 95% CI 1.09-1.19), acute respiratory failure (aOR 1.24, 95% CI 1.20-1.29), tracheostomy (aOR 1.45, 95% CI 1.30-1.63), acute renal failure (aOR 1.16, 95% CI 1.13-1.19), and sepsis (OR 1.42, 95% CI 1.33-1.51) (Figure 2). Conclusions: Patients treated for ischemic stroke at SNHs, regardless of their socioeconomic status and safety-net features, have higher in-hospital mortality and an increased risk for composite adverse outcomes. These findings support changes in resource allocation and efforts to improve the care of ischemic stroke in SNHs.

Reduced fetal movements and COVID-19 infection: a retrospective cohort study

BackgroundFetal movements are an important indicator of fetal well-being; therefore, reduced fetal movements (RFMs) can indicate fetal compromise. RFM is associated with fetal growth restriction (FGR) and intrauterine fetal death (IUFD). Studies have implied that COVID-19 infection increases the risk of adverse fetal outcomes, such as preterm birth and IUFD. It is unclear how COVID-19 infection may aggravate these fetal outcomes among women presenting with RFM.The aims of the study were to (1) determine whether adverse fetal outcomes in women with RFM increased in 2020 compared to 2019, the year before the pandemic, and (2) evaluate whether maternal COVID-19 infection during pregnancy was a risk factor for adverse fetal outcomes in comparison to previously established risk factors among women seeking care for RFM.MethodsAll women who sought care due to RFM and were delivered at Soder Hospital from 2019 to 2020 were included. Fetal composite outcomes were constructed and compared between women with RFM and COVID-19 and women with RFM but without COVID-19.ResultsCOVID-19 infection did not increase the risk of adverse fetal outcomes in women who sought care for RFM. A twofold risk for adverse fetal outcomes was found among all primiparous women vs. multiparous women with RFM (98/788 [12.4%] vs 37/644 [9.8%], AOR = 2.5, 95% CI (1.6–3.7).ConclusionThe proportion of adverse composite outcomes among women with RFM during the first year of the pandemic did not increase compared to the year before. Composite outcomes were marginally higher in the COVID-19-positive group compared to the COVID-19-negative group, but it was not statistically significant.

P-1035. Hypo- and hyper-inflammatory phenotypes both predict adverse clinical outcomes in patients with presumed and confirmed Pneumocystis jirovecii pneumonia without underlying human immunodeficiency virus infection

Abstract Background With the advent of highly effective antiretroviral therapies, the burden of Pneumocystis jirovecii pneumonia (PJP) has shifted from people living with human immunodeficiency virus (HIV) to other immunocompromised hosts. We hypothesize that amongst patients with PJP without underlying HIV, there are unique hypo- and hyper-inflammatory phenotypes that may predict clinical outcomes. Clinical characteristics of patients with PJP without underlying HIV, stratified by inflammatory phenotypes Clinical characteristics of patients with PJP without underlying HIV, stratified by inflammatory phenotypes Methods Consecutive patients with a diagnosis of PJP and a negative HIV test admitted to a tertiary hospital in Singapore were examined from 2006-2023. We included patients who had a C-reactive protein (CRP) measured within 48 hours of admission. The cohort was then divided into three groups stratified by CRP centiles, namely the hypo-inflammatory (up to 25th centile), normo-inflammatory (25th to 75th centile) and hyper-inflammatory (above 75th centile) groups. Clinical profile and outcomes were compared amongst the three groups. A composite adverse outcome consisting of in-hospital mortality or need for mechanical ventilation was evaluated. Multivariable analysis showing predictors of adverse outcome (death or mechanical ventilation) in patients with PJP without underlying HIV Results A total of 62 patients were examined, of which 16 were in the hypo-inflammatory group (CRP< 30 mg/L), 32 were in the normo-inflammatory group (CRP 30-135 mg/L) and the remaining 16 were in the hyper-inflammatory group (CRP > 135 mg/L). Adjunctive corticosteroid use was also similar across the three groups. Importantly, mortality was highest in the hyper-inflammatory group (6.3 vs 13.3 vs 62.5%, p< 0.001). However, in terms of composite adverse outcome, both the hypo-inflammatory (37.5%) and hyperinflammatory groups (68.8%) had higher prevalence of adverse outcomes than the normo-inflammatory group (20.0%, p=0.005). On multivariable analyses, after adjusting for age and sex, the hyperinflammatory phenotype remained independently associated with adverse outcomes (adjusted OR 6.98, 95%CI 1.81 – 26.92, p=0.005) Composite adverse outcomes (death or mechanical ventilations) across the three groups of hypo-, normo- and hyper-inflammatory patients with PJP without underlying HIV Conclusion There may be a U-shaped relationship between C-reactive protein and clinical outcomes in patients with PJP without underlying HIV infection. Patients from both ends of the inflammatory spectrum had increased adverse outcomes in our study. These findings invite further study on the influence of degree of immunosuppression on subsequent inflammation and adverse outcomes among non-HIV infected immunocompromised hosts with PJP. Disclosures Paul Tambyah, MBBS (S'pore), Diplomate, American Board of Internal Medicine and Infectious Diseases, Moderna: Grant/Research Support|Sanofi-Pasteur: Grant/Research Support

P-1446. Impact of Social Determinants of Health on Infectious Outcomes in Patients Undergoing Amputation

Abstract Background Studies have demonstrated the impact of SDOH on outcomes following vascular surgery, but few have focused on risk factors for infectious complications following major amputation. Odds Ratios (Confidence Intervals) for Infectious Outcomes Based on Social Determinants of Health Methods Local data for the Society Vascular Surgery Vascular Quality Initiative, a multicenter registry of quality improvement, were queried for demographics, clinical, procedure, and outcomes of 371 patients with amputation as index procedure 6/1/2015 to 7/31/2023. Zip codes were used to derive CDC/ATSDR Social Vulnerability Index (SVI). The impact of SDOH and SVI on surgical outcomes with a focus on infection was evaluated by logistical regression with R v4.3.2. Primary outcomes for univariate analysis included surgical site infection (SSI), readmission for infection, composite infection-related outcome, organ system complications during index admission, mortality at 30 days, 1 year, 2 years, and 5 years, and composite surgical adverse outcome inclusive of infectious and non-infectious complications. Significant variables were selected for multivariate regression. Odds Ratios (Confidence Intervals) Additional Factors and Surgical Outcomes Based on Social Determinants of Health Results SDOH correlated with multiple parameters in univariate analysis (Fig 1, 2). Male patients had higher ASA score and uncontrolled infection as indication for amputation but were less likely to incur an SSI, or require above trans-metatarsal amputation. Publicly insured patients were more likely to be wheelchair bound or bedridden, or residing in a facility preoperatively, and had the highest risk of readmission for infection (OR=8.09), along with a higher risk of 2 year mortality. Patients with ongoing tobacco use had increased mortality at 1 (OR=1.9) and 2 years (OR=1.7). In multivariate analysis, male gender was associated with SSI (OR 0.25 CI 0.06-0.96). Composite infectious complication was associated with emergent procedure status (OR 2.96 CI 1.22-6.97). There was no significant difference in survival for SDOH derived subgroups (Fig 1) or composite surgical adverse outcome. Kaplan-Meier Survival Analysis for subgroups based on SDOH parameters Conclusion Association between demographic, clinical, and peri-operative complications, with focus on infection, provides opportunity to identify high-risk patients, and serves as a framework for additional interventions, such as close post-operative follow up, and robust involvement of social work and care management teams. Disclosures All Authors: No reported disclosures

Cerebral injury and long-term neurodevelopment impairment in children following severe fetomaternal transfusion: a retrospective cohort study

ObjectiveFetomaternal transfusion (FMT) is associated with increased perinatal mortality and morbidity, but data on postnatal outcomes are scarce. Our aim was to determine the incidence of adverse short-termand long-term sequelae...

Food Insecurity in Pregnancy, Receipt of Food Assistance, and Perinatal Complications

Food insecurity is a growing public health concern, but its association with perinatal complications remains unclear. To examine whether food insecurity in pregnancy was associated with the risk of perinatal complications and determine whether these potential associations differed by receipt of food assistance. This cohort study used data from a pregnancy survey conducted between June 22, 2020, and September 9, 2022, at Kaiser Permanente Northern California, an integrated health care system serving a diverse population of 4.6 million. Participants included individuals who delivered singletons. Data were analyzed from December 2023 to June 2024. Food insecurity in pregnancy assessed using the validated 2-item Hunger Vital Sign screener. Maternal (gestational diabetes, gestational hypertension, preeclampsia, cesarean delivery) and neonatal (preterm birth, neonatal intensive care unit [NICU] admission, small-for-gestational age [SGA], and large-for-gestational age [LGA]) complications extracted from the electronic health records, and a composite adverse perinatal outcome (APO) of maternal and neonatal complications. Modified Poisson regression models were adjusted for covariates and stratified by receipt of food assistance in pregnancy. Among 19 338 individuals, 2707 (14.0%) reported food insecurity in pregnancy. Individuals with food insecurity in pregnancy had a higher risk of gestational diabetes (adjusted relative risk [aRR], 1.13 [95% CI, 1.01-1.29]), preeclampsia (aRR, 1.28 [95% CI, 1.11-1.49]), preterm birth (aRR, 1.19 [95% CI, 1.02-1.38]), NICU admission (aRR, 1.23 [95% CI, 1.07-1.42]), and APO (aRR, 1.07 [95% CI, 1.02-1.13]) compared with individuals without food insecurity. Among 1471 individuals (7.6%) who received food assistance in pregnancy, associations of food insecurity in pregnancy with perinatal complications were attenuated to the null, except for preeclampsia (aRR, 1.64 [95% CI, 1.06-2.53]). On the contrary, the associations persisted among individuals who did not receive food assistance: gestational diabetes (aRR, 1.20 [95% CI, 1.04-1.37]), preeclampsia (aRR, 1.24 [95% CI, 1.06-1.46]), preterm birth (aRR, 1.23 [95% CI, 1.05-1.46]), NICU admission (aRR, 1.31 [95% CI, 1.12-1.52]), and APO (aRR, 1.12 [95% CI, 1.06-1.18]). In this cohort study, food insecurity in pregnancy was associated with a higher risk of perinatal complications, and these associations were overall attenuated to the null among individuals who received food assistance in pregnancy. These findings support clinical guidelines of screening for food insecurity in pregnancy and provide evidence to expand food assistance programs that may help improve maternal and neonatal outcomes.

Maternal and neonatal outcomes of Group B Streptococcus colonization: a retrospective study

BackgroundGroup B Streptococcus (GBS) colonization is one of the major causes of severe neonatal infections. The study was intended to identify GBS colonization in pregnant women, explore its potential risk factors, and analyze the impact of GBS on outcomes for both mothers and newborns.Material and MethodsA retrospective research was carried out on pregnant women who had undergone GBS screening and delivered from June 2020 to December 2022. Pregnant women between 35 and 37 weeks of gestation had GBS screening using real-time polymerase chain reaction (RT-PCR). The clinical characteristics and outcomes of mothers and newborns were collected. The risk factors linked to maternal GBS colonization and its impact on adverse outcomes for mothers and neonates were assessed using chi-square and logistic regression analyses. The composite neonatal adverse outcomes included low Apgar scores, neonatal pneumonia, neonatal hyperbilirubinemia, neonatal sepsis, or low birth weight.ResultsOverall, the rate of GBS positivity was 10.63% (551/5183), and the rate of maternal GBS screening was 88.4%. Diabetic pregnant women were more likely to become colonized with GBS. Our research revealed that GBS carriers experienced higher rates of fetal distress and neonatal adverse outcomes than non-GBS carriers. Fetal distress (OR, 1.940; 95% CI, 1.355 to 2.778, P < 0.001), neonatal sepsis (OR, 5.063; 95% CI, 2.536–10.109, P < 0.001), low Apgar scores (OR, 2.097; 95% CI, 1.184–3.715, P = 0.011), neonatal pneumonia (OR, 1.638; 95% CI, 1.039 to 2.582, P = 0.034) and neonatal hyperbilirubinemia (OR, 1.438; 95% CI, 1.080 to 1.915, P = 0.013) were significantly related to maternal GBS colonization. When we used the composite adverse neonatal outcomes as the dependent variable and analyzed the influencing factors, the logistic regression analysis revealed that GBS colonization was still significantly related to an elevated risk of adverse neonatal outcomes (OR = 1.752, 95% CI, 1.389–2.208; P < 0.001).ConclusionsDiabetes may be a risk factor for maternal GBS colonization. Moreover, in this study, GBS colonization correlated with neonatal adverse outcomes but not with maternal outcomes.

Cytokine Hemoadsorption versus Standard Care in Cardiac Surgery Using the Oxiris® Membrane: the OXICARD single center randomized trial.

Cardiac surgery can lead to dysregulation with a pro-inflammatory state, resulting in adverse outcomes. Hemadsorption using the AN69 membrane (Oxiris membrane) has the properties to chelate inflammatory cytokines. We hypothesized that in patients at high risk of inflammation, the use of the Oxiris membrane could decrease inflammation, preserve endothelial function, and improve postoperative outcomes. We conducted a randomized single-center study at Amiens University Hospital. The study population consisted of adult patients admitted for scheduled cardiac surgery with an expected cardiopulmonary bypass (CPB) time over 90 minutes. The patients were allocated to either the standard group or the Oxiris group. The intervention consisted of using the Oxiris membrane on a Prismaflex device at a blood flow rate of 450 ml/min during CPB. The primary outcome was the assessment of microcirculation on day 1 after surgery by measuring sublingual microcirculation using the microvascular flow index (MFI). MFI reflects the microcirculation flow type and is graded from 0 to 3 as follows: 0: no flow; 1: intermittent flow; 2: sluggish flow; 3: continuous flow. The secondary outcome was a composite adverse outcome within 30 days after surgery. Cytokines and endothelial biomarkers were measured in all patients at different time points. An intention-to-treat analysis was performed. From October 2019 to November 2022, we included 70 patients. Two patients were excluded from the Oxiris group: one patient did not undergo surgery and one procedure was performed under deep hypothermia. The MFI did not differ between groups on day 1 from baseline: difference Oxiris-standard at -0.17 [-0.44; 0.10]; P=0.2. The occurrence of a composite adverse outcome did not significantly differ between groups (14 [42%] for the Oxiris group vs 12 [35%] for the standard group; P=0.7). The overall variation in cytokines and angiopoietins did not significantly differ between groups. In patients scheduled for a cardiac surgery with prolonged CPB, we could not demonstrate the benefit on microcirculation and major cardiovascular events. URL: https://clinicaltrials.gov/study/NCT04201119. Identifier: NCT04201119.

Evaluation of Conventional and Combined Doppler Parameters in Preeclampsia: Diagnostic and Prognostic Insights.

Background: The aim of this study was to examine the relationship between conventional and novel Doppler parameters, including cerebroplacental ratio (CPR), cerebral-placental-uterine ratio (CPUR), umbilical-to-cerebral ratio (UCR), and amniotic-to-umbilical-cerebral ratio (AUCR), with the diagnosis of preeclampsia (PE) and adverse neonatal outcomes in PE cases. Methods: This prospective case-control study was conducted at the Ankara Etlik City Hospital Perinatology Clinic between November 2023 and May 2024. The study population was divided into two groups: Group 1, consisting of 74 patients diagnosed with preeclampsia, and Group 2, consisting of 80 healthy control patients. Composite adverse perinatal outcomes (CANOs) include presence of at least one adverse outcome: 5th-minute APGAR score < 7, transient tachypnea of the newborn (TTN), respiratory distress syndrome (RDS), need for continuous positive airway pressure (CPAP), need for mechanical ventilation, neonatal intensive care unit (NICU) admission, neonatal hypoglycemia, need for phototherapy, intraventricular hemorrhage (IVH), and neonatal sepsis. Results: The CPR, CPUR, and AUCR were significantly lower in the PE group compared to the control group, while the UCR was notably higher in the PE group. Among the combined ratios, the CPUR exhibited the highest diagnostic performance for both PE diagnosis and the prediction of CANOs. Additionally, while the UCR, CPR, and AUCR were significant for PE diagnosis, only AUCR demonstrated a significant association with the prediction of CANOs. Conclusions: Combined Doppler parameters, especially CPUR and AUCR, offer valuable insights into diagnosing PE and predicting CANOs. CPUR demonstrated the highest diagnostic accuracy, underscoring its potential utility in clinical settings.

Evaluation of an Alternative Screening Method for Gestational Diabetes Diagnosis During the COVID-19 Pandemic (DIABECOVID STUDY): An Observational Cohort Study.

Background: To evaluate the impact of applying alternative diagnostic criteria for gestational diabetes mellitus (GDM) during the COVID-19 pandemic on GDM prevalence, obstetrical and perinatal outcomes, and costs, as compared to the standard diagnostic method. Methods: A cohort of pregnant individuals undergoing GMD screening with the alternative GDM method, which uses plasma glucose (fasting or non-fasting) and HbA1c, was compared with a cohort of pregnant individuals undergoing the standard GDM screening method. Both cohorts were obtained from six hospitals across Catalonia, Spain, from April 2020 to April 2022. The primary outcome was large for gestational age rate at birth. The secondary outcomes were composite adverse outcomes, including pregnancy complications, delivery complications, and neonatal complications. The cost differences between screening methods were also evaluated. A similar analysis was performed in the subgroup diagnosed with GDM. Results: Data were collected from 1543 pregnant individuals in the standard screening group and 2197 in the alternative screening group. The standard screening group had a higher GDM diagnostic rate than the alternative screening group (10.8% vs. 6.9%, respectively; p < 0.0001). The primary outcome (large for gestational age rate) was similar between groups: 200/1543 (13.0%) vs. 303/2197 (13.8%). The adjusted OR for this outcome was 1.74 (95% CI: 0.74-4.10). An adjusted analysis showed no differences between groups in the composite adverse outcomes for pregnancy complications (OR: 1.11; 95% CI: 0.91-1.36), delivery complications (OR: 0.95; 95% CI: 0.75-1.19), and neonatal complications (OR: 1.28; 95% CI: 0.94-1.75). Among individuals diagnosed with GDM, the large for gestational age rate was similar between groups: 13/166 (7.8%) vs. 15/151 (9.9%). The OR adjusted for this outcome was 1.24 (95% CI: 0.51-3.09). An adjusted analysis showed no differences in the composite adverse outcomes for pregnancy complications (OR: 1.57; 95% CI: 0.84-2.98), delivery complications (OR: 1.21; 95% CI: 0.63-2.35), and neonatal complications (OR: 1.35; 95% CI: 0.61-3.04). The mean cost (which included expenses for consumables, equipment, and personnel) of the alternative screening method was 46.0 euros (22.3 SD), as compared to 85.6 euros (67.5 SD) for the standard screening method. Conclusions: In this Spanish population during the COVID-19 pandemic, GDM prevalence was lower in the alternative screening group than in the standard screening group. After adjusting for GDM risk factors, outcomes related to obstetrics, delivery, and neonatal complications were comparable between both groups. Finally, the alternative screening method was cheaper than the standard screening method.

Hospital admission of older patients with mild traumatic brain injury and traumatic intracranial hemorrhage: is it always necessary?

Background and importanceTraumatic intracranial hemorrhage (tICH) after mild traumatic brain injury (mTBI) is not uncommon in the elderly. Often, these patients are admitted to the hospital for observation. The necessity of admission in the absence of clinically important intracranial injuries is however unclear.ObjectivesThe objective of this study is to identify which factors additional to tICH affect the risk of this outcome and to evaluate the differences in the risk of adverse outcome in younger and older mTBI patients with tICH.Design, setting, and participantsThis retrospective study assessed adult (≥ 16 years) mTBI patients with tICH admitted to a Level 1 trauma center between January 2017 and October 2020.Outcome measures and analysisPatients were stratified into two groups, age < 65 years and age ≥ 65 years. Adverse outcome due to tICH was assessed using a composite adverse outcome which comprised either, a drop in GCS by more than 1 point, progression of or new neurological deficits, seizure activity, progression of tICH on repeated neuroimaging after clinical deterioration, a neurosurgical intervention, a readmission within three months of injury related to TBI, or death. Logistic regression analysis was used to identify independent predictors of the composite adverse outcome.Main resultsIn total, 332 mTBI patients with tICH were enrolled in our study. Older mTBI patients with tICH met the criteria for the composite adverse outcome significantly more often than younger patients (12.6% 95% CI 8.0–17.0% vs. 4.9%, 95% CI 1.0–9.0%, p = 0.033). The univariate analysis showed that a neurological deficit (OR 6.55, 95% CI 2.37–18.08) or a SDH on admission (OR 3.13, 95% CI 1.40–6.99) was positively associated with the composite adverse outcome in older patients. The presence of isolated traumatic SAH (tSAH) was associated with a decreased risk of the composite adverse outcome (OR 0.10, 95% CI 0.01–0.71). Multivariate analysis was not possible.ConclusionSerious adverse outcomes are frequently observed in older mTBI patients with tICH. Nonetheless, our findings suggest that older patients with an isolated tSAH are at low-risk for deterioration and may be directly discharged from the ED after a short period of observation.

Longitudinal Twin Growth Discordance Patterns and Adverse Perinatal Outcomes.

The objective of this study was to conduct a longitudinal assessment of inter-twin growth and Doppler discordance, to identify possible distinct patterns, and to investigate the predictive value of longitudinal discordance patterns for adverse perinatal outcomes in twin pregnancies. This retrospective cohort study included twin pregnancies followed and delivered at a tertiary University Hospital in London (UK), between 2010 and 2023. We included pregnancies with at least three ultrasound assessments after 18 weeks and delivery after 34 weeks' gestation. Monoamniotic twin pregnancies, pregnancies with twin-to-twin transfusion syndrome, genetic or structural abnormalities, or incomplete data were excluded. Data on chorionicity, biometry, Doppler indices, maternal characteristics, and obstetric as well as neonatal outcomes were extracted from electronic records. Doppler assessment included velocimetry of the umbilical artery, middle cerebral artery and cerebroplacental ratio. Inter-twin growth discordance was calculated for each scan. The primary outcome was a composite of perinatal mortality and neonatal morbidity. Statistical analysis involved multilevel mixed-effects regression models and unsupervised machine learning algorithms, specifically k-means clustering, to identify distinct patterns of inter-twin discordance and their predictive value. Predictive models were compared using the area under the receiver operating characteristics curve, calibration intercept, and slope, validated with repeated cross-validation. Analyses were performed using R, with significance set at p<0.05. Data from a total of 823 twin pregnancies (647 dichorionic, 176 monochorionic) were analyzed. Five distinct patterns of inter-twin growth discordance-low-stable (n=204, 24.8%), mild-decreasing (n=171, 20.8%), low-increasing (n=173, 21.0%), mild-increasing (n=189, 23.0%), and high-stable (n=86, 10.4%)-were derived using an unsupervised learning algorithm that clustered twin pairs based on the progression and patterns of discordance over gestation. In the high-stable cluster, the rates of perinatal morbidity (46.5%, 40/86) and mortality (9.3%, 8/86) were significantly higher, compared to the low-stable (reference) cluster (p<0.001). High-stable growth pattern was also associated with a significantly higher risk of composite adverse perinatal outcomes (Odds ratio 70.19, 95% confidence interval 24.18-299.03, p<0.001; adjusted Odds ratio 76.44, 95% confidence interval 25.39-333.02, p<0.001). The model integrating discordance pattern with CPR discordance at the last ultrasound before delivery demonstrated superior predictive accuracy, evidenced by the highest area under the receiver operating characteristics curve of 0.802 (95% confidence interval 0.712 - 0.892 0.046, p<0.001), compared to only discordance patterns (area under the receiver operating characteristics curve 0.785, 95% confidence interval 0.697 -0.873), intertwin weight discordance at the last ultrasound prior to delivery (area under the receiver operating characteristics curve 0.677, 95% confidence interval 0.545 - 0.809), combination of single measurements of estimated fetal weight and CPR discordance at the last ultrasound prior to delivery (area under the receiver operating characteristics curve 0.702, 95% confidence interval 0.586 -0.818) and single measurement of CPR discordance only at the last ultrasound (area under the receiver operating characteristics curve 0.633, 95% confidence interval 0.515 - 0.751). We identified five distinct trajectories of inter-twin fetal growth discordance using an unsupervised machine learning algorithm. Consistent high discordance is associated with increased rates of adverse perinatal outcomes, with a dose-response relationship. Additionally, a predictive model integrating discordance trajectory and CPR discordance at the last visit demonstrated superior predictive accuracy for the prediction of composite adverse perinatal outcomes, compared to either of these measurements alone or a single value of estimated fetal weight discordance at the last ultrasound prior to delivery.

Maternal and perinatal outcomes after implementation of a more active management in late- and postterm pregnancies in Sweden: A population-based cohort study.

The risk of perinatal death and severe neonatal morbidity increases gradually after 41 weeks of pregnancy. We evaluated maternal and perinatal outcomes after a national shift from expectancy and induction at 42+0 weeks to a more active management of late-term pregnancies in Sweden offering induction from 41+0 weeks or an individual plan aiming at birth or active labour no later than 42+0 weeks. Women with a singleton pregnancy lasting 41+0 weeks or more with a fetus in cephalic presentation (N = 150,370) were included in a nationwide, register-based cohort study. Elective cesarean sections were excluded. Outcomes during period 1, January 2017 to December 2019 (before the shift) versus outcomes during period 2, January 2020 to October 1, 2023 (after the shift) were analysed. For comparison, outcomes of pregnancies lasting 39+0 to 40+6 weeks (N = 358,548) were also studied. Primary outcomes were: First, peri/neonatal death (stillbirth or neonatal death before 28 days); second, composite adverse peri/neonatal outcome (peri/neonatal death, Apgar score <4 at 5 min, hypoxic ischemic encephalopathy grades 1-3, meconium aspiration syndrome, birth trauma, or admission to a neonatal intensive care unit (NICU) ≥4 days); third, composite adverse peri/neonatal outcome excluding admission to NICU; and fourth, emergency cesarean section. Secondary outcomes included the components of the primary composite outcomes. Relative risks (RRs) with 95% confidence intervals (CIs) for binary outcomes period 2 versus period 1 were computed using modified Poisson regression analyses with adjustments for maternal age, parity, body mass index (BMI), smoking, and educational level. Induction rates among pregnancies lasting 41+0 weeks or more increased from 33.7% in period 1 to 52.4% in period 2. Mean (standard deviation) gestational age at birth decreased from 290.7 (2.9) days to 289.6 (2.3) days. Infants born during period 2 were at lower risk of peri/neonatal death compared to infants born during period 1; 0.9/1,000 versus 1.7/1,000 born infants (adjusted RR 0.52; 95% CI [0.38, 0.69]; p < 0.001), and they had a lower risk of having the composite adverse neonatal outcome, both including (50.5/1,000 versus 53.9/1,000, adjusted RR 0.92; 95% CI [0.88, 0.96]; p < 0.001) or excluding NICU admission (18.5/1,000 versus 22.5/1,000, adjusted RR 0.79; 95% CI [0.74, 0.85]; p < 0.001). The cesarean section rate increased from 10.5% in period 1 to 11.9% in period 2 (adjusted RR 1.07; 95% CI [1.04, 1.10]; p < 0.001). For births at 39 to 40 weeks the adjusted RR for peri/neonatal death was 0.86 (95% CI [0.72, 1.02]). One limitation of the study is that we had no data on to what extent monitoring of fetal health was performed. A more active management of pregnancies lasting 41+0 weeks or more was associated with a decrease in peri/neonatal deaths, and a decrease in composite adverse peri/neonatal outcomes. Increased rate of emergency cesarean sections was observed. Women with pregnancies advancing towards 41 gestational weeks should be given balanced information on the benefits and risks of induction of labour at 41 weeks compared to expectant management until 42 weeks and be offered induction of labour at 41 weeks or active surveillance of pregnancies from 41 weeks in order to decrease peri/neonatal mortality.

Association between the dietary inflammatory index and adverse pregnancy outcomes.

Limited research exists on the association between preconception pro-inflammatory diets and adverse pregnancy outcomes, and this relationship remains poorly understood. To investigate the association between preconception dietary inflammatory potential, as measured by the Dietary Inflammatory Index (DII), and adverse pregnancy outcomes in nulliparous individuals. This was a secondary analysis of the data from the Nulliparous Outcomes Study: Mothers-to-be (nuMoM2b). Preconception dietary habits, assessed via food frequency questionnaires, were used to calculate DII scores based on 29 pro- and anti-inflammatory food items. Participants were categorized into DII quartiles (Q1-Q4), with Q1 representing the most anti-inflammatory and Q4 the most pro-inflammatory diets. The primary outcome was a composite of adverse pregnancy outcomes, including preterm birth, hypertensive disorders of pregnancy (preeclampsia, gestational hypertension, or eclampsia), small for gestational age (<5th percentile), and stillbirth. Secondary outcomes included the individual components of the primary outcome and gestational diabetes. Adjusted relative risks (aRR) and 95% confidence intervals (CIs) were calculated using modified Poisson regression, controlling for confounders. Among the 7,994 participants included, 1,829 (22.8%) experienced the primary outcome. Participants in Q4 had a significantly higher risk of the primary outcome compared to Q1 (25.9% vs. 22.1%; aRR 1.15, 95% CI 1.03-1.28) and a notably increased risk of stillbirth (0.9% vs. 0.3%; aRR 2.68, 95% CI 1.01-7.07). No significant associations were found for Q2 or Q3 compared to Q1 for the primary outcome (aRR 1.02, 95% CI 0.91-1.14; aRR 0.97, 95% CI 0.86-1.09, respectively). Other secondary outcomes were not statistically significant. Among individual food items, only folic acid was associated with a reduced risk of adverse pregnancy outcomes (aRR 0.97, 95% CI 0.94-0.99). A pro-inflammatory preconception diet was associated with an increased risk of composite adverse pregnancy outcomes, particularly stillbirth, among nulliparous individuals. These findings underscore the potential role of dietary interventions during the preconception period to mitigate these risks.

Neonatal outcomes between trial of labor and cesarean delivery for extreme preterm infants.

To compare adverse neonatal outcomes between trial of vaginal delivery and upfront cesarean delivery for singleton infants born at 24 to 28 weeks of gestation. This is a retrospective cohort study that was conducted at a university-affiliated tertiary medical center between 2011 and 2022, involving singleton pregnancies delivered between 240/7 and 276/7 weeks of gestation. Participants were divided into two groups based on their intended mode of delivery: a trial of labor (TOL) group and an upfront cesarean delivery (CD) group. The primary outcome was defined as neonatal death. The secondary outcome was defined as any of the following: intraventricular hemorrhage, necrotizing enterocolitis, bronchopulmonary dysplasia, neonatal sepsis, periventricular leukomalacia, disseminated intravascular coagulation, umbilical cord arterial PH <7.1, or use of postpartum mechanical ventilation. Analyses were performed using an intention-to-treat approach. Overall, 199 patients were enrolled, with 64 in the TOL group and 135 in the upfront CD group. Neonatal deaths occurred in 48 cases (24.2%) across the entire cohort, with no significant difference between the TOL (18.8%) and upfront CD (26.7%) groups (P = 0.223). Rates of other composite adverse outcome were comparable between the groups (26.6% vs. 31.9%, P = 0.448), respectively. A sub-analysis comparing patients with pre-existing contraindications for vaginal delivery, without maternal or fetal indications for delivery, to those in the TOL group who experienced spontaneous onset of labor showed no differences in primary or secondary outcomes between the groups. We found no difference in adverse neonatal outcomes between TOL and upfront CD for singletons born at 24-28 weeks gestation.

Optimal Cutoff Values and Utility of High-Sensitivity Troponin T and NT-proBNP for the Risk Stratification of Patients with Acute Pulmonary Embolism.

Guidelines recommend using high-sensitivity troponin T (hsTnT) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) to risk stratify hemodynamically stable patients with acute pulmonary embolism (PE). However, there are no evidence-based cutoff values defined for this clinical application. We performed a single-center, retrospective cohort study of patients with imaging-confirmed PE and hsTnT and/or NT-proBNP (ElecsysTM, Roche) measured 12 h before or 24 h after PE Response Team (PERT) activation. We excluded hypotensive patients. Our primary outcome was a composite of adverse outcomes or critical interventions within 7 days. We calculated the area under the receiver operating curve (AUC, ROC) for hsTnT and NT-proBNP and determined the optimal cutoffs using the distance from (0,1). We performed a subgroup analysis on patients with PE and right ventricular dysfunction on imaging. Two hundred thirty-four patients were included in the hsTnT analysis, and 727 in the NT-proBNP analysis. Mean age was 62 years (SD = 17) and 47% were female. The AUC for hsTnT was 0.64 (95% CI, 0.56-0.71) with an optimal cutoff of 46 ng/L, corresponding to a sensitivity of 59% (95% CI, 49-69) and a specificity of 61% (95% CI, 53-69). The AUC for NT-proBNP was 0.56 (95% CI, 0.51-0.61) with an optimal cutoff of 1092 pg/mL, corresponding to a sensitivity of 53% (95% CI, 45-61) and a specificity of 59% (95% CI, 55-63). We identified an optimal cutoff of 46 ng/L for hsTnT and 1092 pg/mL for NT-proBNP, though the AUC for both markers suggests low to moderate performance for the risk stratification of initially hemodynamically stable PERT patients. Use of these biomarkers to risk stratify PE may require reconsideration.

Clinical examination for identifying low-risk pregnancies suitable for expectant management beyond 40-41 gestational weeks: maternal and fetal outcomes.

There is an ongoing discussion on whether the benefits of term elective labor induction outweigh its potential risks. This study evaluated the utility of a comprehensive clinical examination in identifying low-risk pregnancies suitable for expectant management beyond gestational age 40‒41weeks and compared their outcomes with earlier labor induction by indication. Pregnant women (n = 722) with ≥ 40 + 0 gestational weeks referred to a tertiary hospital were included in this prospective cohort. The study population was divided into the primary induction group (induction before 42 + 0 gestational weeks) and the expectant management group (spontaneous labor onset or induction at 42 + 0 gestational weeks), by decision based on a primary consultation. The Chi-square test and logistic regression were applied. The outcome measures were composite adverse fetal outcome (admission to a neonatal intensive care unit, metabolic acidosis, or Apgar score < 7 at 5min), treatment with intrapartum antibiotics, intrapartum maternal fever ≥ 38°C, intrapartum cesarean section, and postpartum hemorrhage ≥ 1500ml. The main outcome measures did not differ significantly between the primary induction group (n = 258) and the expectant management group (n = 464): composite adverse fetal outcome (OR = 2.29, 95% CI = 0.92-5.68; p = 0.07), intrapartum cesarean section (OR = 1.00, 95% CI = 0.64-1.56; p = 1.00), postpartum hemorrhage ≥ 1500ml (OR = 1.89, 95% CI = 0.92-3.90; p = 0.09), intrapartum maternal fever ≥ 38°C (OR = 1.26, 95% CI = 0.83-1.93; p = 0.28), or treatment with intrapartum antibiotics (OR = 1.25, 95% CI = 0.77-2.02; p = 0.37). A comprehensive clinical examination at 40‒41 gestationalweeks can identify pregnancies that might be managed expectantly until 42gestationalweeks obtaining similar outcomes to those induced earlier.

Adverse Obstetric Outcomes in Pregnancies With Major Fetal Congenital Heart Defects

Understanding the risk profile of obstetric complications in pregnancies with fetal major congenital heart defects (MCHDs) is crucial for obstetric counseling and care. To investigate the risk of placenta-related adverse obstetric outcomes in pregnancies complicated by fetal MCHDs. This cohort study retrieved data from June 1, 2008, to June 1, 2018, from the Danish Fetal Medicine Database, which includes comprehensive data on more than 95% of all pregnancies in Denmark since the database was instituted in 2008. All singleton pregnancies that resulted in a live-born child after 24 weeks' gestation without chromosomal aberrations were included. A systematic search of the literature was performed in PubMed, Embase, and the Cochrane Library from inception to June 1, 2024, to compile existing knowledge and data on adverse obstetric outcomes among MCHD subtypes. Fetal MCHDs including 1 of 11 subtypes. The primary outcome was a composite adverse obstetric outcome defined as preeclampsia, preterm birth, fetal growth restriction, or placental abruption. Secondary outcomes consisted of each adverse obstetric event. Adjusted odds ratios (AORs) were computed using generalized estimating equations adjusted for maternal body mass index, age, smoking, and year of delivery. Meta-analyses were conducted using random-effects models to pool effect sizes for each MCHD subtype and adverse obstetric outcome. A total of 534 170 pregnancies were included in the Danish cohort, including 745 with isolated fetal MCHDs (median [IQR] maternal age, 29.0 [26.0-33.0] years) and 533 425 without MCHDs (median [IQR] maternal age, 30.0 [26.0-33.0] years). Pregnancies with fetal MCHDs exhibited a higher rate of adverse obstetric outcomes at 22.8% compared with 9.0% in pregnancies without fetal MCHDs (AOR, 2.96; 95% CI, 2.49-3.53). Preeclampsia (AOR, 1.83; 95% CI, 1.33-2.51), preterm birth at less than 37 weeks (AOR, 3.84; 95% CI, 3.15-4.71), and fetal growth restriction (AOR, 3.25; 95% CI, 2.42-4.38) occurred significantly more frequently in pregnancies with MCHDs. Except for fetal transposition of the great arteries (AOR, 1.19; 95% CI, 0.66-2.15), all MCHD subtypes carried a greater risk of adverse obstetric outcomes. The meta-analysis included 10 additional studies that supported these results. These findings suggest that nearly 1 in 4 women expecting a child with an MCHD, except transposition of the great arteries, may be at high risk of adverse obstetric outcomes.

Comparison of balloon catheter, oral misoprostol, or combination of both for cervical ripening in late-term and post-term nulliparous women: A Finnish randomized controlled multicenter pilot trial.

Nulliparous women beyond term have high rates of induction failure. The aim of this study was to compare delivery outcomes for balloon catheter, misoprostol, and combination of both in nulliparous late- and post-term women with unfavorable cervices. We intended to explore whether the combination strategy has lower cesarean section rate and is as safe as either method alone. The randomized multicenter pilot trial was carried out in the five university hospitals and the largest secondary care hospital of Finland March 1, 2018-March 31, 2022. A total of 273 nulliparous women with viable singleton fetus in cephalic presentation, intact amniotic membranes, and an unfavorable cervix at 41 + 0 gestational weeks were included. The study protocol was registered in the ISCTN registry (ISRCTN83219789). The women were randomized into cervical ripening by balloon catheter, oral misoprostol 50 μg every 4 h, or the combination use of both. The primary outcomes of the study were the rates of cesarean section and composite of adverse neonatal outcomes (5-min Apgar score <7, umbilical artery pH ≤7.05, or NICU admission). Ninety-seven women (35.5%) were allocated in the balloon catheter arm, 94 (34.4%) in the oral misoprostol arm, and 82 (30.0%) in the combination treatment arm. The rates of cesarean section (balloon catheter 23.7%, n = 23/97, vs. oral misoprostol 24.5%, n = 23/94, vs. combination 17.1%, n = 14/82) or composite adverse neonatal outcome (7.2% vs. 7.4% vs. 7.3%, respectively) were not statistically significantly different between the groups. The median (interquartile range) induction to delivery interval was the shortest in the combination treatment, 21.7 (15.1-33.2) h compared to balloon catheter 31.7 (21.9-44.5) h; p < 0.01 or oral misoprostol 37.0 (26.7-60.3) h; p < 0.01. The proportion of women with induction to delivery interval ≤24 h was significantly higher in the combination arm compared to balloon catheter (54.4% vs. 31.1%; p < 0.01) or oral misoprostol (54.4% vs. 21.1%; p < 0.001). Our findings confirm the effectiveness of combining balloon catheter and oral misoprostol for cervical ripening, showing shorter induction to delivery interval and comparable rates of cesarean section and neonatal outcomes compared to either method alone. These results advocate for a shift toward adopting combination strategy in the induction of nulliparous late- and post-term women.