Understanding changes in echocardiographic parameters at different ages following fetal growth restriction: a systematic review and meta-analysis.

Fetal growth restriction (FGR) increases cardiovascular risk by cardiac remodeling and programming. This systematic review and meta-analysis across species examines the use of echocardiography in FGR offspring at different ages. PubMed and Embase.com were searched for animal and human studies reporting on echocardiographic parameters in placental insufficiency-induced FGR offspring. We included six animal and 49 human studies. Although unable to perform a meta-analysis of animal studies because of insufficient number of studies per individual outcome, all studies showed left ventricular dysfunction. Our meta-analyses of human studies revealed a reduced left ventricular mass, interventricular septum thickness, mitral annular peak velocity, and mitral lateral early diastolic velocity at neonatal age. No echocardiographic differences during childhood were observed, although the small age range and number of studies limited these analyses. Only two studies at adult age were performed. Meta-regression on other influential factors was not possible due to underreporting. The few studies on myocardial strain analysis showed small changes in global longitudinal strain in FGR offspring. The quality of the human studies was considered low and the risk of bias in animal studies was mostly unclear. Echocardiography may offer a noninvasive tool to detect early signs of cardiovascular predisposition following FGR. Clinical implementation yet faces multiple challenges including identification of the most optimal timing and the exact relation to long-term cardiovascular function in which echocardiography alone might be limited to reflect a child's vascular status. Future research should focus on myocardial strain analysis and the combination of other (non)imaging techniques for an improved risk estimation.NEW & NOTEWORTHY Our meta-analysis revealed echocardiographic differences between fetal growth-restricted and control offspring in humans during the neonatal period: a reduced left ventricular mass and interventricular septum thickness, reduced mitral annular peak velocity, and mitral lateral early diastolic velocity. We were unable to pool echocardiographic parameters in animal studies and human adults because of an insufficient number of studies per individual outcome. The few studies on myocardial strain analysis showed small preclinical changes in FGR offspring.

Practice variation in timing of antenatal corticosteroid administration in early-onset fetal growth restriction: A secondary analysis of the Dutch STRIDER study.

INTRODUCTION: In early-onset fetal growth restriction the fetus fails to thrive in utero due to unmet fetal metabolic demands. This condition is linked to perinatal mortality and severe neonatal morbidity. Maternal administration of corticosteroids in high-risk pregnancies for preterm birth at a gestational age between 24 and 34 weeks has been shown to reduce perinatal mortality and morbidity. Practice variation exists in the timing of the administration of corticosteroids based on umbilical artery monitoring findings in early-onset fetal growth restriction. The aim of this study was to examine differences in neonatal outcomes when comparing different corticosteroid timing strategies. MATERIAL AND METHODS: This was a post-hoc analysis of the Dutch STRIDER trial. We examined neonatal outcomes when comparing institutional strategies of early (umbilical artery pulsatility index >95th centile) and late (umbilical artery shows absent or reversed end-diastolic flow) administration of corticosteroids. The primary outcomes were neonatal mortality and a composite of neonatal mortality and neonatal morbidity, defined as bronchopulmonary dysplasia, intraventricular hemorrhage, necrotizing enterocolitis or retinopathy of prematurity. We also analyzed predictors for adverse neonatal outcomes, including gestational age at delivery, birthweight, maternal hypertensive disorders, and time interval between corticosteroids and birth. RESULTS: A total of 120 patients matched our inclusion criteria. In 69 (57.5%) the early strategy was applied and in 51 (42.5%) patients the late strategy. Median gestational age at delivery was 28 4/7 (± 3, 3/7) weeks. Median birthweight was 708 (± 304) g. Composite primary outcome was found in 57 (47.5%) neonates. No significant differences were observed in the primary outcome between the two strategies (neonatal mortality adjusted odds ratio [OR] 1.22, 95% CI 0.44-3.38; composite primary outcome adjusted OR 1.05, 95% CI 0.42-2.64). Only gestational age at delivery was a significant predictor for improved neonatal outcome (adjusted OR 0.91, 95% CI 0.86-0.96). CONCLUSIONS: No significant differences in neonatal outcomes were observed when comparing early and late strategy of antenatal corticosteroid administration on neonatal outcomes in pregnancies complicated by early-onset fetal growth restriction. We found no apparent risk contribution of interval between corticosteroid administration and delivery in multivariate analysis. Gestational age at delivery was found to be an important predictor of neonatal outcome.

Methods of induction of labor in women with obesity: A secondary analysis of two multicenter randomized controlled trials.

INTRODUCTION: Obesity is an increasing public health concern worldwide and can lead to more complications in pregnancy and childbirth. Women with obesity more often require induction of labor for various indications. The aim of this study is to assess which method of induction of labor is safest and most effective in women with obesity. MATERIAL AND METHODS: This is a secondary analysis of two randomized controlled trials about induction of labor. Women with a term singleton pregnancy in cephalic presentation, an unfavorable cervix, intact membranes and without a previous cesarean section were randomly allocated to cervical priming with a Foley catheter or vaginal prostaglandin-E2-gel (PROBAAT-I) or a Foley catheter or oral misoprostol (PROBAAT-II). The inclusion and exclusion criteria for the studies were identical. Induction methods were compared in women with obesity (body mass index ≥30.0). Main outcomes were cesarean section and postpartum hemorrhage (blood loss >1000 mL). RESULTS: A total of 2664 women, were included in the trials, 517 of whom were obese: 254 women with obesity received a Foley catheter, 176 oral misoprostol and 87 prostaglandin E2 (PGE2). A cesarean section was performed in 29.1% of women allocated to Foley vs 22.2% in the misoprostol and 23.0% in the PGE2 groups. Comparisons between groups revealed no statistically significant differences: the relative risk [RR] was 1.31 (95% confidence interval [CI] 0.94-1.84) in the Foley vs misoprostol group and 1.27 (95% CI 0.83-1.95) in the Foley vs PGE2 group. The rates of postpartum hemorrhage were comparable (10.6%, 11.4% and 6.9%, respectively; P = 0.512). In women with obesity, more often a switch to another method occurred in the Foley group, (20.1% vs 6.3% in misoprostol vs 1.1% in the PGE2 group; P < 0.001). The risk of a failed Foley placement was higher in women with obesity than in women without obesity (8.3% vs 3.2%; adjusted odds ratio 3.12, 95% CI 1.65-5.90). CONCLUSIONS: In women with obesity we found a nonsignificant trend towards an increased rate of cesarean sections in the group induced with a Foley catheter compared to oral misoprostol; however, the study lacked power for this subgroup analysis. The finding of a higher risk of failed placement of a Foley catheter in women with obesity can be used in shared decision making.

A nationwide Dutch cohort study shows relatively good pregnancy outcomes after kidney transplantation and finds risk factors for adverse outcomes.

Although numbers of pregnancy after kidney transplantation (KT) are rising, high risks of adverse pregnancy outcomes (APO) remain. Though important for pre-conception counselling and pregnancy monitoring, analyses of pregnancy outcomes after KT per pre-pregnancy estimated glomerular filtration rate-chronic kidney disease (eGFR-CKD)-categories have not been performed on a large scale before. To do this, we conducted a Dutch nationwide cohort study of consecutive singleton pregnancies over 20 weeks of gestation after KT. Outcomes were analyzed per pre-pregnancy eGFR-CKD category and a composite APO (cAPO) was established including birth weight under 2500 gram, preterm birth under 37 weeks, third trimester severe hypertension (systolic blood pressure over 160 and/or diastolic blood pressure over 110 mm Hg) and/or over 15% increase in serum creatinine during pregnancy. Risk factors for cAPO were analyzed in a multilevel model after multiple imputation of missing predictor values. In total, 288 pregnancies in 192 women were included. Total live birth was 93%, mean gestational age 35.6 weeks and mean birth weight 2383 gram. Independent risk factors for cAPO were pre-pregnancy eGFR, midterm percentage serum creatinine dip and midterm mean arterial pressure dip; odds ratio 0.98 (95% confidence interval 0.96-0.99), 0.95 (0.93-0.98) and 0.94 (0.90-0.98), respectively. The cAPO was a risk indicator for graft loss (hazard ratio 2.55, 1.09-5.96) but no significant risk factor on its own when considering pre-pregnancy eGFR (2.18, 0.92-5.13). This was the largest and most comprehensive study of pregnancy outcomes after KT, including pregnancies in women with poor kidney function, to facilitate individualized pre-pregnancy counselling based on pre-pregnancy graft function. Overall obstetric outcomes are good. The risk of adverse outcomes is mainly dependent on pre-pregnancy graft function and hemodynamic adaptation to pregnancy.

Predicting anticoagulant-related bleeding in patients with venous thromboembolism: a clinically oriented review.

Diagnosis of venous thromboembolism (VTE) requires prompt treatment with anticoagulants in therapeutic doses. Since these drugs are associated with the occurrence of haemorrhage, identification of patients at increased risk of major bleeding is of utmost clinical importance for defining the optimal treatment regimen and duration of anticoagulation. Current suggested prediction scores for bleeding risk in VTE patients have been derived from observational studies of moderate quality, or from patients with various indications for therapeutic anticoagulation other than VTE. To date, none of the scores have been adequately validated in cohorts that underwent dedicated monitoring and independent adjudication of bleeding complications. In addition, while the scarce available evidence has focused on patients treated with heparins and/or vitamin K antagonists, risk stratification scores for bleeding complications in VTE patients treated with non-vitamin K dependent anticoagulants have not yet been developed. This clinically oriented review covers the incidence and risk factors of anticoagulation-related bleeding in VTE patients treated with different anticoagulant drugs as well as the available bleeding-prediction scores. Further, we attempt to provide guidance for bleeding-prevention in clinical practice and speculate on developments in the near future that may fundamentally change our current thinking on VTE management.

No increase in Kidney Injury Molecule-1 and Neutrophil Gelatinase-Associated Lipocalin excretion following intravenous contrast enhanced-CT.

OBJECTIVES: To analyze kidney injury molecule-1 (KIM-1) and neutrophil gelatinase-associated lipocalin (N-GAL) excretion post-intravenous contrast enhanced-CT (CE-CT) in patients with chronic kidney disease (CKD). METHODS: Patients were enrolled in a trial on hydration regimes to prevent contrast-induced acute kidney injury (CI-AKI). Blood and urine samples were taken at baseline, 4 - 6, and 48 - 96 h post CE-CT. Urinary KIM-1 and N-GAL values were normalized for urinary creatinine levels, presented as medians with 2.5 - 97.5 percentiles. RESULTS: Of the enrolled 511 patients, 10 (2%) were lost to follow-up. CI-AKI occurred in 3.9% of patients (20/501). Median KIM-1 values were 1.2 (0.1 - 7.7) at baseline, 1.3 (0.1 - 8.6) at 4 - 6 h, and 1.3 ng/mg (0.1 - 8.1) at 48 - 96 h post CE-CT (P = 0.39). Median N-GAL values were 41.0 (4.4 - 3,174.4), 48.9 (5.7 - 3,406.1), and 37.8 µg/mg (3.5 - 3,200.4), respectively (P = 0.07). The amount of KIM-1 and N-GAL excretion in follow-up was similar for patients with and without CI-AKI (P-value KIM-1 0.08, P-value N-GAL 0.73). Neither patient characteristics at baseline including severe CKD, medication use, nor contrast dose were associated with increased excretion of KIM-1 or N-GAL during follow-up. CONCLUSION: KIM-1 and N-GAL excretion were unaffected by CE-CT both in patients with and without CI-AKI, suggesting that CI-AKI was not accompanied by tubular injury. KEY POINTS: • KIM-1 and N-GAL excretion were unaffected by intravenous contrast-enhanced CT (CE-CT). • Patient or procedure characteristics were not associated with increased KIM-1 or N-GAL excretion. • Performance of CE-CT in CKD patients is likely to be safe.

Association between micro particle-tissue factor activity, factor VIII activity and recurrent VTE in patients with acute pulmonary embolism.

Studies on the association between microparticle expressing tissue factor (MP-TF) activity, FVIII activity ( FVIII: C) and recurrent VTE yielded inconclusive results. We studied these associations in patients diagnosed with acute pulmonary embolism. Plasma levels of MP-TF and FVIII activity were measured in 277 patients with a first and 72 patients with a recurrent VTE. All patients were categorized based on the quintiles of MP-TF and FVIII activity in those with a single VTE. For both markers, odds ratios (ORs) for recurrent VTE were computed using patients in the lowest quintile as a reference group. No association was observed between MP-TF activity and recurrent VTE, with an OR of 1.4 (95 % CI 0.7-2.9) in the highest quintile of MP-TF activity. Compared with the reference group, patients in the highest quintile of FVIII: C were at increased risk of recurrent VTE, OR 4.2 (95 % CI 1.4-12.2). MP-TF activity was not associated with recurrent VTE whereas high FVIII: C levels were associated with a 4-fold increased risk of VTE recurrence. Future prospective studies are necessary to explore the potential of FVIII: C as a tool for risk stratification, either by itself or in combination with other pro-thrombotic markers.

A randomized comparison of 1-h sodium bicarbonate hydration versus standard peri-procedural saline hydration in patients with chronic kidney disease undergoing intravenous contrast-enhanced computerized tomography.

BACKGROUND: Guidelines recommend saline hydration for prophylaxis of contrast-induced acute kidney injury (CI-AKI) in patients with chronic kidney disease (CKD) undergoing intravenous contrast media-enhanced CT (CE-CT). The safety and efficacy of a brief hydration protocol using sodium bicarbonate in this population is unknown. We analysed whether 1-h sodium bicarbonate hydration prior to CE-CT is non-inferior to saline hydration prior to and after CE-CT in CKD patients. METHODS: We performed an open-label multicentre randomized trial. Patients were randomized to 250 mL of 1.4% sodium bicarbonate hydration prior to CE-CT or 1000 mL of 0.9% saline hydration prior to and, once again, after CE-CT. Primary outcome was the relative increase in serum creatinine 48-96 h post-CE-CT. Secondary outcomes were incidence of CI-AKI [serum creatinine increase >25%/>44 µmol/L (0.5 mg/dL)], recovery of renal function, the need for dialysis and 2-month hospital costs. RESULTS: Five hundred and seventy adult CKD patients undergoing CE-CT were randomized between 2010 and 2012, of whom 548 were included in the intention-to-treat population. Mean relative serum creatinine increase was 1.2% for sodium bicarbonate and 1.5% for saline (mean difference -0.3%; 95% confidence interval -2.7 to 2.1, P-value for non-inferiority <0.0001). CI-AKI occurred in 22 patients (4.1%); 8 (3.0%) randomized to sodium bicarbonate versus 14 (5.1%) to saline (P = 0.23). Renal function recovered in 75 and 69% of CI-AKI patients, respectively (P = 0.81). No patients developed a need for dialysis. Mean hydration costs per patient were €224 for the sodium bicarbonate and €683 for the saline regime (P < 0.001). Other healthcare costs were similar. CONCLUSIONS: Short hydration with sodium bicarbonate prior to CE-CT was non-inferior to peri-procedural saline hydration with respect to renal safety and may result in healthcare savings. [Netherlands Trial Register (http://www.trialregister.nl/trialreg/index.asp), Nr 2149, date of registration 23 December 2009.].

Pregnancy outcome predictors in systemic lupus erythematosus: a systematic review and meta-analysis.

BACKGROUND: To enhance patient-tailored preconception risk assessment for women with systemic lupus erythematosus (SLE), knowledge on risk factors associated with adverse pregnancy outcomes is required. Therefore, we did a systematic review and meta-analysis to identify and provide unambiguous effect sizes of preconception predictors of pregnancy outcomes in women with SLE. METHODS: In this systematic review and meta-analysis, we searched PubMed and Embase for studies reporting preconception predictors of pregnancy outcomes in women with SLE, from database inception to Aug 22, 2023. Studies were included if they presented original, quantitative data on pregnant women with SLE and reported on preconception risk factors on at least one of the outcomes as defined in the protocol. Studies were excluded if they had a sample size of less than 20 patients, were restricted to multiple pregnancies, had unclear timing of prognostication, or exclusively reported a composite outcome. Literature screening, data extraction, and risk-of-bias assessment (quality in prognostic studies tool) were done by two reviewers independently, in a blinded, standardised manner. The reported outcomes included livebirth, pre-eclampsia, small for gestational age, preterm birth, pregnancy loss before and after 20 weeks of gestation, and SLE flares. We computed pooled univariate odds ratios (ORs) and 95% CIs using a random effects model. We assessed heterogeneity using the I2 statistic and prediction intervals. This study is registered with PROSPERO, CRD42022344732. FINDINGS: Of the 6705 unique articles identified, 72 (1·1%) were included in the meta-analysis, comprising 10 355 pregnancies in 8065 women with SLE. One potentially eligible study was retracted and therefore removed from our analysis. Previous lupus nephritis was associated with decreased livebirth probability (OR 0·62 [95% CI 0·47-0·81]; I2=0%), increased risk of preterm birth (2·00 [1·55-2·57]; I2=17%), and increased risk of pre-eclampsia (3·11 [2·35-4·12]; I2=0%). Chronic hypertension was associated with increased risk of disease flare (2·50 [1·74-3·58]; I2=0%), preterm birth (2·65 [1·87-3·77]; I2=0%), and pre-eclampsia (5·86 [3·41-10·06]; I2=33%). SLE disease activity at conception or preconception was associated with increased risk of preterm birth (2·91 [1·96-4·33]; I2=21%) and pre-eclampsia (2·32 [1·40-3·83]; I2=0%). Secondary antiphospholipid syndrome was associated with decreased livebirth probability (0·40 [0·27-0·58]; I2=0%), increased risk of pregnancy loss after 20 weeks of gestation (2·77 [1·44-5·31]; I2=0%), and increased risk of preterm birth (1·65 [1·29-2·11]; I2=0%). Across studies, risk-of-bias assessment suggested considerable bias in study attrition and confounding. INTERPRETATION: We identified previous lupus nephritis, chronic hypertension, SLE disease activity before and at conception, and secondary antiphospholipid syndrome as predictors of adverse pregnancy outcomes in women with SLE. These findings contribute to an optimal patient-tailored risk assessment in preconception counselling. FUNDING: None.

Outpatient versus inpatient treatment in patients with pulmonary embolism: a meta-analysis.

Our aim was to study the safety of outpatient treatment in low risk patients with acute pulmonary embolism compared with inpatient treatment, the current clinical standard. We searched Medline, Web of Science, Cochrane and EMBASE databases and included studies on outpatient treatment of pulmonary embolism. The outcomes were 3-month recurrent venous thromboembolism, major bleeding and all-cause mortality. We identified 13 studies (1657 patients) with outpatients (discharge <24 h), three studies (256 patients) with early discharge patients (discharged within 72 h) and five studies (383 patients) with inpatients. The pooled incidence of recurrent venous thromboembolism was 1.7% (95% CI 0.92-3.1%) in outpatients, 1.1% (0.22-5.4%) in patients discharged early and 1.2% (0.16-8.1%) in inpatients. The pooled incidence of major bleeding was 0.97% (0.58-1.6%) in outpatients, 0.78% (0.16-3.7%) in early discharge patients and 1.0% (0.39-2.8%) in inpatients. The pooled incidence of mortality was 1.9% (0.79-4.6%) in outpatients, 2.3% (1.1-5.1%) in early discharge patients and 0.74% (0.04-11%) in inpatients. Incidences of recurrent venous thromboembolism, major bleeding and, after correction for malignancies, mortality were comparable between outpatients, patients discharged early and inpatients. We conclude that home treatment or early discharge of selected low-risk patients with pulmonary embolism is as safe as inpatient treatment.

Contrast-induced acute kidney injury and clinical outcomes after intra-arterial and intravenous contrast administration: risk comparison adjusted for patient characteristics by design.

BACKGROUND: Direct comparisons between risk of contrast induced acute kidney injury (CI-AKI) after intra-arterial versus intravenous contrast administration are scarce. We estimated and compared the risk of CI-AKI and its clinical course after both modes of contrast administration in patients who underwent both. METHODS: One hundred seventy patients who received both intra-arterial and intravenous contrast injections within one year between 2001 and 2010 were included. Primary outcome was occurrence of CI-AKI. Secondary outcomes were duration of hospital stay, the need for dialysis, recovery of renal function, and mortality. RESULTS: The risk of CI-AKI was 24/170 (14.0%, 95% CI 9.6-20.2) after intra-arterial contrast injection versus 20/170 (11.7%, 95% CI 7.7-17.5) after intravenous contrast administration, which led to a relative risk of 1.2 (95% CI 0.7-2.1). None of the patients had a need for dialysis. Median duration of hospital stay in CI-AKI patients was 15.0 days (2.5-97.5, percentile 1-92) after intra-arterial and 15.5 days (2.5-97.5, percentile 0-38) after intravenous contrast procedures. Renal function recovered after CI-AKI in 13/24 after intra-arterial and in 10/20 patients after intravenous contrast administration. Mortality risks in CI-AKI patients were slightly higher than in non-CI-AKI patients, hazard ratios 1.6 (95% CI 0.7-3.7) for intra-arterial and 1.7 (95% CI 0.7-4.4) for intravenous contrast administration, adjusted for confounders. CONCLUSION: The risk of CI-AKI, and its clinical course was similar after intra-arterial and intravenous contrast media administration, after adjustment by design for patient-related risk factors.

OPtimal TIming of antenatal COrticosteroid administration in pregnancies complicated by early-onset fetal growth REstriction (OPTICORE): study protocol of a multicentre, retrospective cohort study.

INTRODUCTION: Early-onset fetal growth restriction (FGR) requires timely, often preterm, delivery to prevent fetal hypoxia causing stillbirth or neurologic impairment. Antenatal corticosteroids (CCS) administration reduces neonatal morbidity and mortality following preterm birth, most effectively when administered within 1 week preceding delivery. Optimal timing of CCS administration is challenging in early-onset FGR, as the exact onset and course of fetal hypoxia are unpredictable. International guidelines do not provide a directive on this topic. In the Netherlands, two timing strategies are commonly practiced: administration of CCS when the umbilical artery shows (A) a pulsatility index above the 95thh centile and (B) absent or reversed end-diastolic velocity (a more progressed disease state). This study aims to (1) use practice variation to compare CCS timing strategies in early-onset FGR on fetal and neonatal outcomes and (2) develop a dynamic tool to predict the time interval in days until delivery, as a novel timing strategy for antenatal CCS in early-onset FGR. METHODS AND ANALYSIS: A multicentre, retrospective cohort study will be performed including pregnancies complicated by early-onset FGR in six tertiary hospitals in the Netherlands in the period between 2012 and 2021 (estimated sample size n=1800). Main exclusion criteria are multiple pregnancies and fetal congenital or genetic abnormalities. Routinely collected data will be extracted from medical charts. Primary outcome for the comparison of the two CCS timing strategies is a composite of perinatal, neonatal and in-hospital mortality. Secondary outcomes include the COSGROVE core outcome set for FGR. A multivariable, mixed-effects model will be used to compare timing strategies on study outcomes. Primary outcome for the dynamic prediction tool is 'days until birth'. ETHICS AND DISSEMINATION: The need for ethical approval was waived by the Ethics Committee (University Medical Center Utrecht). Results will be published in open-access, peer-reviewed journals and disseminated by presentations at scientific conferences. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov: NCT05606497.

Pregnancy outcome predictors in antiphospholipid syndrome: A systematic review and meta-analysis.

OBJECTIVE: To identify and assess the magnitude of effect of pregnancy outcome predictors in women with antiphospholipid syndrome (APS) by means of systematic review and meta-analysis. METHODS: PubMed and Embase were searched (13th June 2020) for studies reporting on pre-pregnancy risk factors of pregnancy outcomes in APS patients. Literature screening and data extraction were conducted by two reviewers independently, in a blinded standardized manner. Pooled univariate odds ratios (OR) were computed using a random effects model. Heterogeneity was assessed by I2%. RESULTS: The search yielded 3013 unique results; 27 records were included in this meta-analysis. Previous thrombosis was associated with a decreased live birth risk (OR 0.60, p < 0.01, I2 = 40%), increased neonatal mortality (OR 15.19, p < 0.01, I2 = 0%), an increased risk of antenatal or postpartum thrombosis (OR 6.26, p < 0.01, I2 = 0%) and an increased risk of delivering a small for gestational age neonate (SGA) (OR 2.60, p = 0.01, I2 = 0%). Patients with an APS laboratory category I (double or triple positivity) profile had a decreased live birth risk (OR 0.66, p < 0.01, I2 = 0%), an increased risk of SGA (OR 1.86, p = 0.01, I2 = 43%) and preterm birth (OR 1.35, p < 0.01, I2 = 49%). Triple positivity was associated with a decreased live birth risk (OR 0.33, p < 0.01, I2 = 68%), an increased risk of preeclampsia (OR 2.43, p = 0.02, I2 = 35%) and SGA (OR 2.47, p = 0.04, I2 = 61%). Patients with lupus anticoagulant positivity had an increased risk of preeclampsia (OR 2.10, p = 0.02, I2 = 48%), SGA (OR 1.78, p < 0.01, I2 = 0%) and preterm birth (OR 3.56, p = 0.01, I2 = 48%). Risk of bias assessment suggested considerable bias on study participation and statistical methods. CONCLUSIONS: The results of this meta-analysis identified previous thrombosis, laboratory category I, triple positivity and lupus anticoagulant positivity as the most important predictors of adverse pregnancy outcomes. This up-to-date knowledge, can be used in preconception counseling and tailoring of obstetric care.

Conflicting Effects of Fetal Growth Restriction on Blood Pressure Between Human and Rat Offspring: A Meta-Analysis.

Low birth weight is associated with hypertension. Low birth weight can result from fetal growth restriction (FGR) or prematurity. FGR is postulated to impact blood pressure (BP) by developmental programming. This systematic review and meta-analysis studies BP in human and animal offspring following FGR. Pubmed and Web of Science were searched for studies reporting on BP after placental insufficiency induced FGR compared with normal growth controls. Primary outcome was mean absolute BP difference (ΔBP mm Hg [95% CI]). Meta-analysis was performed using random-effects models. Subgroup analyses were executed on species, sex, age, pregnancy duration, and stress during BP readings. Due to large interspecies heterogeneity, analyses were performed separately for human (n=41) and animal (n=31) studies, the latter restricted to rats (n=27). Human studies showed a ΔBP between FGR and controls of -0.6 mm Hg ([95% CI, -1.7 to 0.6]; I2=91%). Mean ΔBP was -2.6 mm Hg (95% CI, -5.7 to 0.4) in women versus -0.5 mm Hg (95% CI, -3.7 to 2.7) in men. Subgroup analyses did not indicate age, gestational age, and stress during measurements as sources of heterogeneity. In rats, mean BP was 12.0 mm Hg ([95% CI, 8.8-15.2]; I2=81%) higher in FGR offspring. This difference was more pronounced in FGR males (13.6 mm Hg [95% CI, 10.3-17.0] versus 9.1 mm Hg [95% CI, 5.3-12.8]). Subgroup analyses on age showed no statistical interaction. BP readings under restrained conditions resulted in larger BP differences between FGR and control rats (15.3 mm Hg [95% CI, 11.6-18.9] versus 5.7 mm Hg [95% CI, 1.1-10.3]). Rat studies confirm the relation between FGR and offspring BP, while observational studies in humans do not show such differences. This may be due to the observational nature of human studies, methodological limitations, or an absence of this phenomenon in humans. Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: CRD42018091819.

Effect of No Prehydration vs Sodium Bicarbonate Prehydration Prior to Contrast-Enhanced Computed Tomography in the Prevention of Postcontrast Acute Kidney Injury in Adults With Chronic Kidney Disease: The Kompas Randomized Clinical Trial.

Importance: Prevention of postcontrast acute kidney injury in patients with stage 3 chronic kidney disease (CKD) by means of prehydration has been standard care for years. However, evidence for the need for prehydration in this group is limited. Objective: To assess the renal safety of omitting prophylactic prehydration prior to iodine-based contrast media administration in patients with stage 3 CKD. Design, Setting, and Participants: The Kompas trial was a multicenter, noninferiority, randomized clinical trial conducted at 6 hospitals in the Netherlands in which 523 patients with stage 3 CKD were randomized in a 1:1 ratio to receive no prehydration or prehydration with 250 mL of 1.4% sodium bicarbonate administered in a 1-hour infusion before undergoing elective contrast-enhanced computed tomography from April 2013 through September 2016. Final follow-up was completed in September 2017. Data were analyzed from January 2018 to June 2019. Interventions: In total, 262 patients were allocated to the no prehydration group and 261 were allocated to receive prehydration. Analysis on the primary end point was available in 505 patients (96.6%). Main Outcomes and Measures: The primary end point was the mean relative increase in serum creatinine level 2 to 5 days after contrast administration compared with baseline (noninferiority margin of less than 10% increase in serum creatinine level). Secondary outcomes included the incidence of postcontrast acute kidney injury 2 to 5 days after contrast administration, mean relative increase in creatinine level 7 to 14 days after contrast administration, incidences of acute heart failure and renal failure requiring dialysis, and health care costs. Results: Of 554 patients randomized, 523 were included in the intention-to-treat analysis. The median (interquartile range) age was 74 (67-79) years; 336 (64.2%) were men and 187 (35.8%) were women. The mean (SD) relative increase in creatinine level 2 to 5 days after contrast administration compared with baseline was 3.0% (10.5) in the no prehydration group vs 3.5% (10.3) in the prehydration group (mean difference, 0.5; 95% CI, -1.3 to 2.3; P < .001 for noninferiority). Postcontrast acute kidney injury occurred in 11 patients (2.1%), including 7 of 262 (2.7%) in the no prehydration group and 4 of 261 (1.5%) in the prehydration group, which resulted in a relative risk of 1.7 (95% CI, 0.5-5.9; P = .36). None of the patients required dialysis or developed acute heart failure. Subgroup analyses showed no evidence of statistical interactions between treatment arms and predefined subgroups. Mean hydration costs were €119 (US $143.94) per patient in the prehydration group compared with €0 (US $0) in the no prehydration group (P < .001). Other health care costs were similar. Conclusions and Relevance: Among patients with stage 3 CKD undergoing contrast-enhanced computed tomography, withholding prehydration did not compromise patient safety. The findings of this study support the option of not giving prehydration as a safe and cost-efficient measure. Trial Registration: Netherlands Trial Register Identifier: NTR3764.

Randomized trial of one-hour sodium bicarbonate vs standard periprocedural saline hydration in chronic kidney disease patients undergoing cardiovascular contrast procedures.

BACKGROUND: Guidelines advise periprocedural saline hydration for prevention of contrast induced-acute kidney injury (CI-AKI). We analysed whether 1-hour sodium bicarbonate hydration administered solely prior to intra-arterial contrast exposure is non-inferior to standard periprocedural saline hydration in chronic kidney disease (CKD) patients undergoing elective cardiovascular diagnostic or interventional contrast procedures. METHODS: We performed an open-label multicentre non-inferiority trial between 2011-2014. Patients were randomized to 1 hour pre-procedure sodium bicarbonate hydration (250 ml 1.4%, N = 168) or 4-12 hours saline hydration (1000 ml 0.9%, N = 165) prior to and following contrast administration (2000 ml of saline total). Primary outcome was the relative serum creatinine increase (%) 48-96 hours post contrast exposure. Secondary outcomes were: incidence of CI-AKI (serum creatinine increase>25% or >44µmol/L), recovery of renal function, the need for dialysis, and hospital costs within two months follow-up. RESULTS: Mean relative creatinine increase was 3.1% (95%CI 0.9 to 5.2%) in the bicarbonate and 1.1% (95%CI -1.2 to 3.5%) in the saline arm, mean difference 1.9% (95%CI -1.2 to 5.1%, p-non-inferiority <0.001). CI-AKI occurred in 11 (6.7%) patients randomized to sodium bicarbonate and 12 (7.5%) to saline (p = 0.79). Renal function did not fully recover in 40.0% and 44.4% of CI-AKI patients, respectively (p = 0.84). No patient required dialysis. Mean costs for preventive hydration and clinical preparation for the contrast procedure were $1158 for sodium bicarbonate vs. $1561 for saline (p < 0.001). CONCLUSION: Short hydration with sodium bicarbonate prior to elective cardiovascular diagnostic or therapeutic contrast procedures is non-inferior to standard periprocedural saline hydration in CKD patients with respect to renal safety and results in considerable healthcare savings. TRIAL REGISTRATION: Netherlands Trial Register (http://www.trialregister.nl/trialreg/index.asp), Nr NTR2699.